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The time–energy information of ultrashort X-ray free-electron laser pulses generated by the Linac Coherent Light Source is measured with attosecond resolution via angular streaking of neon 1s photoelectrons. The X-ray pulses promote electrons from the neon core level into an ionization continuum, where they are dressed with the electric field of a circularly polarized infrared laser. This induces characteristic modulations of the resulting photoelectron energy and angular distribution. From these modulations we recover the single-shot attosecond intensity structure and chirp of arbitrary X-ray pulses based on self-amplified spontaneous emission, which have eluded direct measurement so far. We characterize individual attosecond pulses, including their instantaneous frequency, and identify double pulses with well-defined delays and spectral properties, thus paving the way for X-ray pump/X-ray probe attosecond free-electron laser science.

Since the early days of Dirac flux quantization, magnetic monopoles have been sought after as a potential corollary of quantized electric charge. As opposed to magnetic monopoles embedded into the theory of electromagnetism, Weyl semimetals (WSM) exhibit Berry flux monopoles in reciprocal parameter space. As a function of crystal momentum, such monopoles locate at the crossing point of spin-polarized bands forming the Weyl cone. Here, we report momentum-resolved spectroscopic signatures of Berry flux monopoles in TaAs as a paradigmatic WSM. We carried out angle-resolved photoelectron spectroscopy at bulk-sensitive soft X-ray energies (SX-ARPES) combined with photoelectron spin detection and circular dichroism. The experiments reveal large spin- and orbital-angular-momentum (SAM and OAM) polarizations of the Weyl-fermion states, resulting from the broken crystalline inversion symmetry in TaAs. Supported by first-principles calculations, our measurements image signatures of a topologically non-trivial winding of the OAM at the Weyl nodes and unveil a chirality-dependent SAM of the Weyl bands. Our results provide directly bulk-sensitive spectroscopic support for the non-trivial band topology in the WSM TaAs, promising to have profound implications for the study of quantum-geometric effects in solids. Weyl semimetals exhibit Berry flux monopoles in momentum-space, but direct experimental evidence has remained elusive. Here, the authors reveal topologically non-trivial winding of the orbital-angular-momentum at the Weyl nodes and a chirality-dependent spin-angular-momentum of the Weyl bands, as a direct signature of the Berry flux monopoles in TaAs.

A single cesium atom trapped within the mode of an optical cavity is used to generate single photons on demand. The photon wave packets are emitted as a Gaussian beam with temporal profile and repetition rate controlled by external driving fields. Each generation attempt is inferred to succeed with a probability near unity, whereas the efficiency for creating an unpolarized photon in the total cavity output is$0.69 \\pm 0.10$, as limited by passive cavity losses. An average of 1.4 × 104photons are produced by each trapped atom. These results constitute an important step in quantum information science, for example, toward the realization of distributed quantum networking.

Well-founded data management systems are of vital importance for ocean observing systems as they ensure that essential data are not only collected but also retained and made accessible for analysis and application by current and future users. Effective data management requires collaboration across activities including observations, metadata and data assembly, quality assurance and control (QA/QC), and data publication that enables local and interoperable discovery and access, and secure archiving that guarantees long-term preservation. To achieve this, data should be Findable, Accessible, Interoperable, and Reusable (FAIR). Here, we outline how these principles apply to ocean data, and illustrate them with a few examples. In recent decades, ocean data managers, in close collaboration with international organizations, have played an active role in the improvement of environmental data standardization, accessibility and interoperability through different projects, enhancing access to observation data at all stages of the data life cycle and fostering the development of integrated services targeted to research, regulatory and operational users. As ocean observing systems evolve and an increasing number of autonomous platforms and sensors are deployed, the volume and variety of data increases dramatically. For instance, there are more than 70 data catalogues that contain metadata records for the polar oceans, a situation that makes comprehensive data discovery beyond the capacity of most researchers. To better serve research, operational, and commercial users, more efficient turnaround of quality data in known formats and made available through web services is necessary. In particular, automation of data workflows will be critical to reduce friction throughout the data value chain. Adhering to the FAIR principles with free, timely and unrestricted access to ocean observation data is beneficial for the originators, has obvious benefits for users and is an essential foundation for the development of new services made possible with big data technologies.

Porphyromonas gingivalis, a Gram-negative anaerobic bacterium commonly found in human subgingival plaque, is a major etiologic agent for periodontitis and has been associated with multiple systemic pathologies. Many P. gingivalis strains have been identified and different strains possess different virulence factors. Current oral microbiome approaches (16S or shotgun) have been unable to differentiate P. gingivalis strains. This study presents a new approach that aims to improve the accuracy of strain identification, using a detection method based on sequencing of the intergenic spacer region (ISR) which is variable between P. gingivalis strains. Our approach uses two-step PCR to amplify only the P. gingivalis ISR region. Samples are then sequenced with an Illumina sequencer and mapped to specific strains. Our approach was validated by examining subgingival plaque from 153 participants with and without periodontal disease. We identified the avirulent strain ATCC33277/381 as the most abundant strain across all sample types. The W83/W50 strain was significantly enriched in periodontitis, with 13% of participants harboring that strain. Overall, this approach can have significant implications not only for the diagnosis and treatment of periodontal disease but also for other diseases where P. gingivalis or its toxins have been implicated, such as Alzheimer's disease.

Gene expression requires the targeting of transcription factors (TFs) to regulatory sequences often occluded within nucleosomes. To comprehensively examine TF nucleosome binding, we developed Pioneer-Seq. In Pioneer-seq a library of thousands of nucleosomes are formed from sequences containing a TF binding site (TFBS) variant in all possible nucleosome orientations and within the linker regions. Pioneer-seq has the unique ability to simultaneously examine nucleosomes created with various nucleosome positioning sequences and examine binding to in vivo targeted nucleosomes (ITNs). Pioneer-seq can be applied to address various mechanistic models for TF-nucleosome binding directly and can be used to uncover inherent TF-interaction differences. To demonstrate Pioneer-seq, we examined nucleosome binding by OCT4, SOX2, KLF4, and c-MYC. Our results demonstrate that all studied TFs can bind at nucleosome edges and nucleosome sequence is the primary factor regulating TF binding. In addition, KLF4 can bind to a non-canonical TFBS located 20 bp from the nucleosome dyad. Examination of ITNs showed binding differences between the TFs, with KLF4 and SOX2 binding more often near nucleosome centers. Overall, our results demonstrate differences in how TF recognizes their TFBS within a nucleosome and begins to define the mechanistic requirements for pioneer factor binding.

Conventional lasers (from table-top systems to microscopic devices) typically operate in the so-called weak-coupling regime, involving large numbers of atoms and photons; individual quanta have a negligible impact on the system dynamics. However, this is no longer the case when the system approaches the regime of strong coupling for which the number of atoms and photons can become quite small. Indeed, the lasing properties of a single atom in a resonant cavity have been extensively investigated theoretically 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Here we report the experimental realization of a one-atom laser operated in the regime of strong coupling. We exploit recent advances 12 in cavity quantum electrodynamics that allow one atom to be isolated in an optical cavity in a regime for which one photon is sufficient to saturate the atomic transition. The observed characteristics of the atom–cavity system are qualitatively different from those of the familiar many-atom case. Specifically, our measurements of the intracavity photon number versus pump intensity indicate that there is no threshold for lasing, and we infer that the output flux from the cavity mode exceeds that from atomic fluorescence by more than tenfold. Observations of the second-order intensity correlation function demonstrate that our one-atom laser generates manifestly quantum (nonclassical) light, typified by photon anti-bunching and sub-poissonian photon statistics.

Background: Resistance training (RT) is recommended as part of our national physical activity guidelines which includes working all major muscle groups on two or more days a week.Older adults can gain many health benefits from RT, such as increased muscle strength,increased muscle mass, and maintenance of bone density. Additionally, certain dimensions of health-related quality of life (HRQOL) have been shown to improve in older adults due to RT intervention. The purpose of this study was to use systematic review and meta-analytic techniques to examine the effect of RT on HRQOL in older adults. Methods: A systematic review of current studies (2008 thru 2017) was conducted using PubMed. Studies were included if they used a randomized controlled design, had RT as an intervention, measured HRQOL using the SF-36/12 assessment, and included adults 50+ years of age. Eight dimension scores (physical functioning, bodily pain, physical role function, general health, mental health, emotional role function, social function, and vitality) and two summary scores (physical component and mental component) were extracted. Ten meta-analyses were performed using standardized mean effect sizes and random effects models. Study quality,moderator and sensitivity analyses were conducted. Results: A total of 16 studies were included in the analyses with a mean Physiotherapy Evidence Database (PEDro) score of 4.9 (SD=1.0). Among the mental health measures, RT had the greatest effect on mental health (Effect size [ES]=0.64, 95% CI: 0.30-0.99, I2=79.7). Among the physical health measures, RT had the largest effect on body pain (ES=0.81, 95% CI: 0.26-1.35, I2=85.9).Initially, RT did not significantly affect measures of emotional role function, social function or physical role function. However, after removing a single study, RT significantly increased all HRQOL measures. Conclusion: The meta-analytic evidence presented in this research clearly supports the promotion of RT in improving HRQOL in older adults.

C57BL/6J (B6) and DBA/2J (D2) are two of the most commonly used inbred mouse strains in neuroscience research. However, the only currently available mouse genome is based entirely on the B6 strain sequence. Subsequently, oligonucleotide microarray probes are based solely on this B6 reference sequence, making their application for gene expression profiling comparisons across mouse strains dubious due to their allelic sequence differences, including single nucleotide polymorphisms (SNPs). The emergence of next-generation sequencing (NGS) and the RNA-Seq application provides a clear alternative to oligonucleotide arrays for detecting differential gene expression without the problems inherent to hybridization-based technologies. Using RNA-Seq, an average of 22 million short sequencing reads were generated per sample for 21 samples (10 B6 and 11 D2), and these reads were aligned to the mouse reference genome, allowing 16,183 Ensembl genes to be queried in striatum for both strains. To determine differential expression, 'digital mRNA counting' is applied based on reads that map to exons. The current study compares RNA-Seq (Illumina GA IIx) with two microarray platforms (Illumina MouseRef-8 v2.0 and Affymetrix MOE 430 2.0) to detect differential striatal gene expression between the B6 and D2 inbred mouse strains. We show that by using stringent data processing requirements differential expression as determined by RNA-Seq is concordant with both the Affymetrix and Illumina platforms in more instances than it is concordant with only a single platform, and that instances of discordance with respect to direction of fold change were rare. Finally, we show that additional information is gained from RNA-Seq compared to hybridization-based techniques as RNA-Seq detects more genes than either microarray platform. The majority of genes differentially expressed in RNA-Seq were only detected as present in RNA-Seq, which is important for studies with smaller effect sizes where the sensitivity of hybridization-based techniques could bias interpretation.

Limited research exists on carbohydrate intake and oral microbiome diversity and composition assessed with next-generation sequencing. We aimed to better understand the association between habitual carbohydrate intake and the oral microbiome, as the oral microbiome has been associated with caries, periodontal disease, and systemic diseases. We investigated if total carbohydrates, starch, monosaccharides, disaccharides, fiber, or glycemic load (GL) were associated with the diversity and composition of oral bacteria in subgingival plaque samples of 1204 post-menopausal women. Carbohydrate intake and GL were assessed from a food frequency questionnaire, and adjusted for energy intake. The V3–V4 region of the 16S rRNA gene from subgingival plaque samples were sequenced to identify the relative abundance of microbiome compositional data expressed as operational taxonomic units (OTUs). The abundance of OTUs were centered log(2)-ratio transformed to account for the compositional data structure. Associations between carbohydrate/GL intake and microbiome alpha-diversity measures were examined using linear regression. PERMANOVA analyses were conducted to examine microbiome beta-diversity measures across quartiles of carbohydrate/GL intake. Associations between intake of carbohydrates and GL and the abundance of the 245 identified OTUs were examined by using linear regression. Total carbohydrates, GL, starch, lactose, and sucrose intake were inversely associated with alpha-diversity measures. Beta-diversity across quartiles of total carbohydrates, fiber, GL, sucrose, and galactose, were all statistically significant (p for PERMANOVA p < 0.05). Positive associations were observed between total carbohydrates, GL, sucrose and Streptococcus mutans; GL and both Sphingomonas HOT 006 and Scardovia wiggsiae; and sucrose and Streptococcus lactarius. A negative association was observed between lactose and Aggregatibacter segnis, and between sucrose and both TM7_[G-1] HOT 346 and Leptotrichia HOT 223 . Intake of total carbohydrate, GL, and sucrose were inversely associated with subgingival bacteria alpha-diversity, the microbial beta-diversity varied by their intake, and they were associated with the relative abundance of specific OTUs. Higher intake of sucrose, or high GL foods, may influence poor oral health outcomes (and perhaps systemic health outcomes) in older women via their influence on the oral microbiome.