Probing pocket depth reduction after non‐surgical periodontal therapy: Tooth‐related factors

Background To investigate tooth-related factors that influence the reduction of probing pocket depths (PPD) after non-surgical periodontal therapy (NST). Methods Seven hundred forty-six patients with a total of 16,825 teeth were included and retrospectively analyzed. PPD reduction after NST was correlated with the tooth-related factors; tooth type, number of roots, furcation involvement, vitality, mobility, and type of restoration; using logistic multilevel regression for statistical analysis. Results NST was able to reduce probing depth overall stratified probing depths (1.20 ± 1.51 mm, p ≤ 0.001). The reduction was significantly higher at teeth with higher probing depths at baseline. At pockets with PPD ≥ 6 mm, PPD remains high after NST. Tooth type, number of roots, furcation involvement, vitality, mobility, and type of restoration are significantly and independently associated with the rate of pocket closure. Conclusions The tooth-related factors: tooth type, number of roots, furcation involvement, vitality, mobility, and type of restoration had a significant and clinically relevant influence on phase I and II therapy. Considering these factors in advance may enhance the prediction of sites not responding adequately and the potential need for additional treatment, such as re-instrumentation or periodontal surgery, to ultimately achieve the therapy end points

Continuous wave-pumped wavelength conversion in low-loss silicon nitride waveguides

In this Letter we introduce a complementary metal-oxide semiconductor (CMOS)-compatible low-loss Si3N4 waveguide platform for nonlinear integrated optics. The waveguide has a moderate nonlinear coefficient of 285 W∕km, but the achieved propagation loss of only 0.06 dB∕cm and the ability to handle high optical power facilitate an optimal waveguide length for wavelength conversion. We observe a constant quadratic dependence of the four-wave mixing (FWM) process on the continuous-wave (CW) pump when operating in the C-band, which indicates that the waveguide has negligible high-power constraints owing to nonlinear losses. We achieve a conversion efficiency of −26.1 dB and idler power generation of −19.6 dBm. With these characteristics, we present for the first time, to the best of our knowledge, CW-pumped data conversion in a non-resonant Si3N4 waveguide

Wavelength Conversion in Low Loss Si3N4 Waveguides

We show wavelength conversion in a compact Si3N4 waveguide. Combining low loss, long length, relatively large nonlinear coefficient, high-power handling and absence of two-photon absorption, this platform is promising for integrated nonlinear optics applications

Book Reviews

TO SECURE THESE RIGHTS The Report of the President\u27s Committee on Civil Rights with An Introduction by Charles S. Wilson, Committee Chairman. New York: Simon and Schuster, 1947. Pp. xii, 178. $1.00.. ====================== ROSCOE POUND By Paul Sayre Iowa City: College of Law Committee State University of Iowa, 1948. Pp. 412.$4.50. ====================== A NATIONAL POLICY FOR THE OIL INDUSTRY By Eugene V. Rostow New Haven: Yale University Press, 1948. Pp. XVI, 173. $2.50. ===================== THE TRADE OF NATIONS By Michael A. Heilperin New York: Alfred A. Knopf, 1947. Pp. xix, 234.$3.00. ==================== AMERICA\u27S ECONOMIC SUPREMACY By Brooks Adams New York: Harper & Brothers, Inc., 1947. Pp. 194. $2.50

Orbitrap-Based Mass and Charge Analysis of Single Molecules

Native mass spectrometry is nowadays widely used for determining the mass of intact proteins and their noncovalent biomolecular assemblies. While this technology performs well in the mass determination of monodisperse protein assemblies, more real-life heterogeneous protein complexes can pose a significant challenge. Factors such as co-occurring stoichiometries, subcomplexes, and/or post-translational modifications, may especially hamper mass analysis by obfuscating the charge state inferencing that is fundamental to the technique. Moreover, these mass analyses typically require measurement of several million molecules to generate an analyzable mass spectrum, limiting its sensitivity. In 2012, we introduced an Orbitrap-based mass analyzer with extended mass range (EMR) and demonstrated that it could be used to obtain not only high-resolution mass spectra of large protein macromolecular assemblies, but we also showed that single ions generated from these assemblies provided sufficient image current to induce a measurable charge-related signal. Based on these observations, we and others further optimized the experimental conditions necessary for single ion measurements, which led in 2020 to the introduction of single-molecule Orbitrap-based charge detection mass spectrometry (Orbitrap-based CDMS). The introduction of these single molecule approaches has led to the fruition of various innovative lines of research. For example, tracking the behavior of individual macromolecular ions inside the Orbitrap mass analyzer provides unique, fundamental insights into mechanisms of ion dephasing and demonstrated the (astonishingly high) stability of high mass ions. Such fundamental information will help to further optimize the Orbitrap mass analyzer. As another example, the circumvention of traditional charge state inferencing enables Orbitrap-based CDMS to extract mass information from even extremely heterogeneous proteins and protein assemblies (e.g., glycoprotein assemblies, cargo-containing nanoparticles) via single molecule detection, reaching beyond the capabilities of earlier approaches. We so far demonstrated the power of Orbitrap-based CDMS applied to a variety of fascinating systems, assessing for instance the cargo load of recombinant AAV-based gene delivery vectors, the buildup of immune-complexes involved in complement activation, and quite accurate masses of highly glycosylated proteins, such as the SARS-CoV-2 spike trimer proteins. With such widespread applications, the next objective is to make Orbitrap-based CDMS more mainstream, whereby we still will seek to further advance the boundaries in sensitivity and mass resolving power

Drosophila poly suggests a novel role for the Elongator complex in insulin receptor-target of rapamycin signalling

Multi-cellular organisms need to successfully link cell growth and metabolism to environmental cues during development. Insulin receptor–target of rapamycin (InR–TOR) signalling is a highly conserved pathway that mediates this link. Herein, we describe poly, an essential gene in Drosophila that mediates InR–TOR signalling. Loss of poly results in lethality at the third instar larval stage, but only after a stage of extreme larval longevity. Analysis in Drosophila demonstrates that Poly and InR interact and that poly mutants show an overall decrease in InR–TOR signalling, as evidenced by decreased phosphorylation of Akt, S6K and 4E-BP. Metabolism is altered in poly mutants, as revealed by microarray expression analysis and a decreased triglyceride : protein ratio in mutant animals. Intriguingly, the cellular distribution of Poly is dependent on insulin stimulation in both Drosophila and human cells, moving to the nucleus with insulin treatment, consistent with a role in InR–TOR signalling. Together, these data reveal that Poly is a novel, conserved (from flies to humans) mediator of InR signalling that promotes an increase in cell growth and metabolism. Furthermore, homology to small subunits of Elongator demonstrates a novel, unexpected role for this complex in insulin signalling

Not All Arms of IgM Are Equal: Following Hinge-Directed Cleavage by Online Native SEC-Orbitrap-Based CDMS

Immunoglobulins M (IgM) are key natural antibodies produced initially in humoral immune response. Due to their large molecular weights and extensive glycosylation loads, IgMs represent a challenging target for conventional mass analysis. Charge detection mass spectrometry (CDMS) may provide a unique approach to tackle heterogeneous IgM assemblies, although this technique can be quite laborious and technically challenging. Here, we describe the use of online size exclusion chromatography (SEC) to automate buffer exchange and sample introduction, and demonstrate its adaptability with Orbitrap-based CDMS. We discuss optimal experimental parameters for online SEC-CDMS experiments, including ion activation, choice of column, and resolution. Using this approach, CDMS histograms containing hundreds of individual ion signals can be obtained in as little as 5 min from single injections of <1 μg of sample. To demonstrate the unique utility of online SEC-CDMS, we performed real-time kinetic monitoring of pentameric IgM digestion by the protease IgMBRAZOR, which cleaves specifically in the hinge region of IgM. Several digestion intermediates corresponding to processive losses of F(ab’)2 subunits could be mass-resolved and identified by SEC-CDMS. Interestingly, we find that for the J-chain linked IgM pentamer, cleavage of one of the F(ab’)2 subunits is much slower than the other four F(ab’)2 subunits, which we attribute to the symmetry-breaking interactions of the J-chain within the pentameric IgM structure. The online SEC-CDMS methodologies described here open new avenues into the higher throughput automated analysis of heterogeneous, high-mass protein assemblies by CDMS

Proteoform-resolved profiling of plasminogen activation reveals novel abundant phosphorylation site and primary N-terminal cleavage site

Plasminogen (Plg), the zymogen of plasmin (Plm), is a glycoprotein involved in fibrinolysis and a wide variety of other physiological processes. Plg dysregulation has been implicated in a range of diseases. Classically, human Plg is categorized into two types, supposedly having different functional features, based on the presence (type I) or absence (type II) of a single N-linked glycan. Using high-resolution native mass spectrometry, we uncovered that the proteoform profiles of human Plg (and Plm) are substantially more extensive than this simple binary classification. In samples derived from human plasma, we identified up to 14 distinct proteoforms of Plg, including a novel highly stoichiometric phosphorylation site at Ser339. To elucidate the potential functional effects of these post-translational modifications, we performed proteoform-resolved kinetic analyses of the Plg-to-Plm conversion using several canonical activators. This conversion is thought to involve at least two independent cleavage events: one to remove the N-terminal peptide and another to release the active catalytic site. Our analyses reveal that these processes are not independent but are instead tightly regulated and occur in a step-wise manner. Notably, N-terminal cleavage at the canonical site (Lys77) does not occur directly from intact Plg. Instead, an activation intermediate corresponding to cleavage at Arg68 is initially produced, which only then is further processed to the canonical Lys77 product. Based on our results, we propose a refined categorization for human Plg proteoforms. In addition, we reveal that the proteoform profile of human Plg is more extensive than that of rat Plg, which lacks, for instance, the here-described phosphorylation at Ser339

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO