Synthesis of a Molecular Charm Bracelet via Click Cyclization and Olefin Metathesis Clipping

We describe the synthesis of a polycatenated cyclic polymer, a structure that resembles a molecular charm bracelet. Ruthenium-catalyzed ring-opening metathesis polymerization of an aminocontaining cyclic olefin monomer in the presence of a chain transfer agent generated an α,ω-diazide functionalized polyamine. Cyclization of the resulting linear polyamine using pseudo-high-dilution coppercatalyzed click cyclization produced a cyclic polymer in 19% yield. The click reaction was then further employed to remove linear contaminants from the cyclic polymer using azide- and alkyne-functionalized scavenging resins, and the purified cyclic polymer product was characterized by gel permeation chromatography, ^1H NMR spectroscopy, and IR spectroscopy. Polymer hydrogenation and conversion to the corresponding polyammonium species enabled coordination and interlocking of diolefin polyether fragments around the cyclic polymer backbone using ruthenium-catalyzed ring-closing olefin metathesis to afford a molecular charm bracelet structure. This charm bracelet complex was characterized by ^1H NMR spectroscopy, and the catenated nature of the small rings was confirmed using two-dimensional diffusion-ordered NMR spectroscopy

The Effects of Slow Deep Breathing on Measures of Microvascular and Autonomic Function in an Irritable Bowel Syndrome Population

Irritable Bowel Syndrome (IBS) is a functional disorder linked to disruptions in autonomic nervous system regulation, which could impair vascular homeostasis. Studies have shown that slow, deep breathing reduces muscle sympathetic nerve activity and arterial stiffness; however, its effects on autonomic regulation in adults with IBS have not been previously investigated. Moreover, the effects of breathing on microvascular endothelium function are unknown. PURPOSE: To investigate the effects of slow, deep breathing on measures of autonomic function and microvascular endothelial function in adults with IBS. METHODS: Adults (ages 18-65 years) with a formal diagnosis of IBS were enrolled and randomized to 4-week controlled breathing or time-control conditions. The experimental group followed a 20-minute slow, deep breathing video 4 to 6 days per week while the control group maintained their regular activity. To assess autonomic function, heart rate variability (HRV) and exercise heart rate recovery (HRR) were measured at baseline and week 4. The HRV test was accompanied by respiration rate measurements to ensure no significant deviations in respiration occurred between assessments as this could impact HRV. Exercise HRR was assessed 30, 60, and 120 seconds following a Balke treadmill VO2 max test. Laser Doppler flowmetry was assessed at baseline (33°C) and in response to local heating up to 43.5°C while blood pressure was measured throughout for the calculation of cutaneous vascular conductance (CVC). RESULTS: Of the 14 participants enrolled, 12 (n=6 for control and experimental groups) completed the study. At baseline, age (p = 0.47) and body mass index (p=0.14) were similar between groups. Respiration rate was similar between HRV assessments in both groups. In the experimental group, %CVC max significantly increased (p = 0.027) at week 4 while HRR was unchanged. A tendency toward a time by group interaction was observed for HRV low frequency to high frequency (LF/HF) ratio (p = 0.066) with slight reductions in the breathing group and increases in the control group. In the control group, %CVC max and HRR were unaltered, though HRR at 120 seconds tended to improve (p=0.08). CONCLUSIONS: Preliminary results from this ongoing study suggest that microvascular endothelial function can improve with 4 weeks of slow, deep breathing exercises in adults with IBS. These alterations in vascular function were unaccompanied by significant changes in autonomic function though trends were observed in HRV. Results show that slow, deep breathing is a viable alternative to physical exercise for improving microvascular function. Findings also suggest that this intervention could result in improved sympathovagal balance in adults with IBS and potentially other individuals with functional disorders

Interaction Properties of the Periodic and Step-like Solutions of the Double-Sine-Gordon Equation

The periodic and step-like solutions of the double-Sine-Gordon equation are investigated, with different initial conditions and for various values of the potential parameter $\epsilon$. We plot energy and force diagrams, as functions of the inter-soliton distance for such solutions. This allows us to consider our system as an interacting many-body system in 1+1 dimension. We therefore plot state diagrams (pressure vs. average density) for step-like as well as periodic solutions. Step-like solutions are shown to behave similarly to their counterparts in the Sine-Gordon system. However, periodic solutions show a fundamentally different behavior as the parameter $\epsilon$ is increased. We show that two distinct phases of periodic solutions exist which exhibit manifestly different behavior. Response functions for these phases are shown to behave differently, joining at an apparent phase transition point.Comment: 17pages, 15 figure

"Pair" Fermi contour and repulsion-induced superconductivity in cuprates

The pairing of charge carriers with large pair momentum is considered in connection with high-temperature superconductivity of cuprate compounds. The possibility of pairing arises due to some essential features of quasi-two-dimensional electronic structure of cuprates: (i) The Fermi contour with strong nesting features; (ii) The presence of extended saddle point near the Fermi level; (iii) The existence of some ordered state (for example, antiferromagnetic) close to the superconducting one as a reason for an appearing of "pair" Fermi contour resulting from carrier redistribution in momentum space. In an extended vicinity of the saddle point, momentum space has hyperbolic (pseudoeuclidean) metrics, therefore, the principal values of two-dimensional reciprocal reduced effective mass tensor have unlike signs. Rearrangement of holes in momentum space results in a rise of "pair" Fermi contour which may be defined as zero-energy line for relative motion of the pair. The superconducting gap arises just on this line. Pair Fermi contour formation inside the region of momentum space with hyperbolic metrics results in not only superconducting pairing but in a rise of quasi-stationary state in the relative motion of the pair. Such a state has rather small decay and may be related to the pseudogap regime of underdoped cuprates. It is concluded that the pairing in cuprates may be due to screened Coulomb repulsion. In this case, the superconducting energy gap in hole-doped cuprates exists in the region of hole concentration which is bounded both above and below. The superconducting state with positive condensation energy exists in more narrow range of doping level inside this region. Such hole concentration dependence correlates with typical phase diagram of cuprates.Comment: 23 pages, 11 figures. Submitted to Phys. Rev.

I Spy Transits and Pulsations: Empirical Variability in White Dwarfs Using Gaia and the Zwicky Transient Facility

We present a novel method to detect variable astrophysical objects and transient phenomena using anomalous excess scatter in repeated measurements from public catalogs of Gaia DR2 and Zwicky Transient Facility (ZTF) DR3 photometry. We first provide a generalized, all-sky proxy for variability using only Gaia DR2 photometry, calibrated to white dwarf stars. To ensure more robust candidate detection, we further employ a method combining Gaia with ZTF photometry and alerts. To demonstrate the efficacy, we apply this latter technique to a sample of roughly $12,100$ white dwarfs within 200 pc centered on the ZZ Ceti instability strip, where hydrogen-atmosphere white dwarfs are known to pulsate. Through inspecting the top $1\%$ samples ranked by these methods, we demonstrate that both the Gaia-only and ZTF-informed techniques are highly effective at identifying known and new variable white dwarfs, which we verify using follow-up, high-speed photometry. We confirm variability in all 33 out of 33 ($100\%$) observed white dwarfs within our top $1\%$ highest-ranked candidates, both inside and outside the ZZ Ceti instability strip. In addition to dozens of new pulsating white dwarfs, we also identify five white dwarfs highly likely to show transiting planetary debris; if confirmed, these systems would more than triple the number of white dwarfs known to host transiting debris.Comment: 30 pages, 14 figures, revised and accepted to ApJ on March 11, 202

Vascular smooth muscle cells remodel collagen matrices by long-distance action and anisotropic interaction

While matrix remodeling plays a key role in vascular physiology and pathology, the underlying mechanisms have remained incompletely understood. We studied the remodeling of collagen matrices by individual vascular smooth muscle cells (SMCs), clusters and monolayers. In addition, we focused on the contribution of transglutaminase 2 (TG2), which plays an important role in the remodeling of small arteries. Single SMCs displaced fibers in collagen matrices at distances up to at least 300 μm in the course of 8–12 h. This process involved both ‘hauling up’ of matrix by the cells and local matrix compaction at a distance from the cells, up to 200 μm. This exceeded the distance over which cellular protrusions were active, implicating the involvement of secreted enzymes such as TG2. SMC isolated from TG2 KO mice still showed compaction, with changed dynamics and relaxation. The TG active site inhibitor L682777 blocked local compaction by wild type cells, strongly reducing the displacement of matrix towards the cells. At increasing cell density, cells cooperated to establish compaction. In a ring-shaped collagen matrix, this resulted in preferential displacement in the radial direction, perpendicular to the cellular long axis. This process was unaffected by inhibition of TG2 cross-linking. These results show that SMCs are capable of matrix remodeling by prolonged, gradual compaction along their short axis. This process could add to the 3D organization and remodeling of blood vessels based on the orientation and contraction of SMCs

In-Situ and Experimental Evidence for Acidic Weathering of Rocks and Soils on Mars

Experimental data for alteration of synthetic Martian basalts at pH=0-1 indicate that chemical fractionations at low pH are vastly different from those observed during terrestrial weathering. Rock analyses from Gusev crater are well described by the relationships apparent from low pH experimental alteration data. A model for rock surface alteration is developed which indicates that a leached alteration zone is present on rock surfaces at Gusev. This zone is not chemically fractionated to a large degree from the underlying rock interior, indicating that the rock surface alteration process has occurred at low fluid-to-rock ratio. The geochemistry of natural rock surfaces analyzed by APXS is consistent with a mixture between adhering soil/dust and the leached alteration zone. The chemistry of rock surfaces analyzed after brushing with the RAT is largely representative of the leached alteration zone. The chemistry of rock surfaces analyzed after grinding with the RAT is largely representative of the interior of the rock, relatively unaffected by the alteration process occurring at the rock surface. Elemental measurements from the Spirit, Opportunity, Pathfinder and Viking 1 landing sites indicate that soil chemistry from widely separated locations is consistent with the low-pH, low fluid to rock ratio alteration relationships developed for Gusev rocks. Soils are affected principally by mobility of FeO and MgO, consistent with alteration of olivine-bearing basalt and subsequent precipitation of FeO and MgO bearing secondary minerals as the primary control on soil geochemistry

Reduced Stability and Increased Dynamics in the Human Proliferating Cell Nuclear Antigen (PCNA) Relative to the Yeast Homolog

Proliferating Cell Nuclear Antigen (PCNA) is an essential factor for DNA replication and repair. PCNA forms a toroidal, ring shaped structure of 90 kDa by the symmetric association of three identical monomers. The ring encircles the DNA and acts as a platform where polymerases and other proteins dock to carry out different DNA metabolic processes. The amino acid sequence of human PCNA is 35% identical to the yeast homolog, and the two proteins have the same 3D crystal structure. In this report, we give evidence that the budding yeast (sc) and human (h) PCNAs have highly similar structures in solution but differ substantially in their stability and dynamics. hPCNA is less resistant to chemical and thermal denaturation and displays lower cooperativity of unfolding as compared to scPCNA. Solvent exchange rates measurements show that the slowest exchanging backbone amides are at the β-sheet, in the structure core, and not at the helices, which line the central channel. However, all the backbone amides of hPCNA exchange fast, becoming undetectable within hours, while the signals from the core amides of scPCNA persist for longer times. The high dynamics of the α-helices, which face the DNA in the PCNA-loaded form, is likely to have functional implications for the sliding of the PCNA ring on the DNA since a large hole with a flexible wall facilitates the establishment of protein-DNA interactions that are transient and easily broken. The increased dynamics of hPCNA relative to scPCNA may allow it to acquire multiple induced conformations upon binding to its substrates enlarging its binding diversity

Timing and Trends for Municipal Wastewater, Lab-Confirmed Case, and Syndromic Case Surveillance of COVID-19 in Raleigh, North Carolina

Objectives. To compare 4 COVID-19 surveillance metrics in a major metropolitan area. Methods. We analyzed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater influent and primary solids in Raleigh, North Carolina, from April 10 through December 13, 2020. We compared wastewater results with lab-confirmed COVID-19 cases and syndromic COVID-like illness (CLI) cases to answer 3 questions: (1) Did they correlate? (2) What was the temporal alignment of the different surveillance systems? (3) Did periods of significant change (i.e., trends) align? Results. In the Raleigh sewershed, wastewater influent, wastewater primary solids, lab-confirmed cases, and CLI were strongly or moderately correlated. Trends in lab-confirmed cases and wastewater influent were observed earlier, followed by CLI and, lastly, wastewater primary solids. All 4 metrics showed sustained increases in COVID-19 in June, July, and November 2020 and sustained decreases in August and September 2020. Conclusions. In a major metropolitan area in 2020, the timing of and trends in municipal wastewater, lab-confirmed case, and syndromic case surveillance of COVID-19 were in general agreement