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During homeostasis, immune cells perform daily housekeeping functions to maintain heart health by acting as sentinels for tissue damage and foreign particles. Resident immune cells compose 5% of the cellular population in healthy human ventricular tissue. In response to injury, there is an increase in inflammation within the heart due to the influx of immune cells. Some of the most common immune cells recruited to the heart are macrophages, dendritic cells, neutrophils, and T-cells. In this review, we will discuss what is known about cardiac immune cell heterogeneity during homeostasis, how these cell populations change in response to a pathology such as myocardial infarction or pressure overload, and what stimuli are regulating these processes. In addition, we will summarize technologies used to evaluate cell heterogeneity in models of cardiovascular disease.

Background: Left ventricular pressure overload (LVPO) can develop from antecedent conditions, like aortic stenosis, and is associated with increased myocardial collagen content that can lead to increases in myocardial stiffness. Alleviation of LVPO in patients undergoing surgical aortic valve replacement (SAVR) resulted in reduced but persistent fibrosis evident in biopsies taken 5-yrs following SAVR. Little is known regarding cellular mechanisms that contribute to ECM turnover following hemodynamic unloading. Objective: Determine the time course of ECM remodeling after alleviation of LVPO. Methods: Transverse aortic constriction (TAC) was used to induce LVPO. Following 4wks of TAC, alleviation of LVPO was performed by removing the TAC band (unTAC). Five time points were assessed: Control no TAC, 4wk TAC, 4wk TAC+2wk unTAC, 4wk TAC+4wk unTAC, and 4wk TAC+6wk unTAC for cardiomyocyte cross-sectional area (CSA), collagen volume fraction (CVF), collagen degradation, and myocardial stiffness. Results: CSA increased by 47% at 4wk TAC vs control. Compared to 4wk TAC, CSA decreased by 20% at 2wk unTAC, but returned to control levels by 6wk unTAC. CVF increased by 204% at 4wk TAC vs control. Although CVF was similar between 4wk TAC and 2wk unTAC, 2wk unTAC demonstrated robust increases in markers of collagen degradation (cathepsin K, pro-matrix metalloproteinase 2 (pro-MMP2), MMP3, and MMP8). CVF significantly decreased at 4wk unTAC compared to 2wk unTAC. However, the markers of collagen degradation were reduced by 4wk- and 6wk unTAC likely contributing to persistent fibrosis. Furthermore, passive stiffness remained elevated at 6wk unTAC. Conclusion: In LVPO hearts, hypertrophy and fibrosis were present. Although cardiomyocyte hypertrophy fully regressed with normalization of hemodynamic load, increased myocardial stiffness and elevated interstitial fibrosis were persistent.

Left ventricular pressure overload (LVPO) can develop from antecedent diseases such as aortic valve stenosis and systemic hypertension and is characterized by accumulation of myocardial extracellular matrix (ECM). Evidence from patient and animal models supports limited reductions in ECM following alleviation of PO, however, mechanisms that control the extent and timing of ECM regression are undefined. LVPO, induced by 4 wk of transverse aortic constriction (TAC) in mice, was alleviated by removal of the band (unTAC). Cardiomyocyte cross-sectional area, collagen volume fraction (CVF), myocardial stiffness, and collagen degradation were assessed for: control, 2-wk TAC, 4-wk TAC, 4-wk TAC + 2-wk unTAC, 4-wk TAC + 4-wk unTAC, and 4-wk TAC + 6-wk unTAC. When compared with 4-wk TAC, 2-wk unTAC resulted in increased reactivity of collagen hybridizing peptide (CHP) (representing initiation of collagen degradation), increased levels of collagenases and gelatinases, decreased levels of collagen cross-linking enzymes, but no change in CVF. When compared with 2-wk unTAC, 4-wk unTAC demonstrated decreased CVF, which did not decline to control values. At 4-wk and 6-wk unTAC, CHP reactivity and mediators of ECM degradation were reduced versus 2-wk unTAC, whereas levels of tissue inhibitor of metalloproteinase (TIMP)-1 increased. ECM homeostasis changed in a time-dependent manner after removal of LVPO and is characterized by early increases in collagen degradation, followed by a later dampening of this process. Tempered ECM degradation with time is predicted to contribute to the finding that normalization of hemodynamic overload alone does not completely regress myocardial fibrosis. NEW & NOTEWORTHY In this study, a murine model demonstrated persistent interstitial fibrosis and myocardial stiffness following alleviation of pressure overload.

In human heart failure and in murine hearts with left-ventricular pressure overload (LVPO), increases in fibrosis are associated with increases in myocardial stiffness. Secreted protein acidic and rich in cysteine (SPARC) is shown to be necessary for both cardiac fibrosis and increases in myocardial stiffness in response to LVPO; however, cellular sources of cardiac SPARC are incompletely defined. Irradiation and bone marrow transfer were undertaken to test the hypothesis that SPARC expression by bone marrow-derived cells is an important mediator of fibrosis in LVPO. In recipient SPARC-null mice transplanted with donor wild-type (WT) bone marrow and subjected to LVPO, levels of fibrosis similar to that of WT mice were found despite the lack of SPARC expression by resident cells. In recipient WT mice with donor SPARC-null bone marrow, significantly less fibrosis versus that of WT mice was found despite the expression of SPARC by resident cells. Increases in myocardial stiffness followed a similar pattern to that of collagen deposition. Myocardial macrophages were significantly reduced in SPARC-null mice with LVPO versus that of WT mice. Recipient SPARC-null mice transplanted with donor WT bone marrow exhibited an increase in cardiac macrophages versus that of SPARC-null LVPO and donor WT mice with recipient SPARC-null bone marrow. Expression of vascular cellular adhesion molecule (VCAM), a previously identified binding partner of SPARC, was assessed in all groups and with the exception of WT mice, increases in VCAM immunoreactivity with LVPO were observed. However, no differences in VCAM expression between bone marrow transplant groups were noted. In conclusion, SPARC expression by bone marrow-derived cells was critical for fibrotic deposition of collagen and influenced the expansion of myocardial macrophages in response to LVPO. NEW & NOTEWORTHY Myocardial fibrosis and the resultant increases in LV and myocardial stiffness represent pivotal consequences of chronic pressure overload (PO). In this study, a murine model of cardiac fibrosis induced by PO was used to demonstrate a critical function of SPARC in bone marrow-derived cells that drives cardiac fibrosis and increases in cardiac macrophages.

The importance of understanding factors that contribute to surface wettability is highlighted in this new organic chemistry laboratory experiment, which aims to introduce the application of organic chemistry at the interface of polymer chemistry and material science. Polydimethylsiloxane (PDMS), a hydrophobic silicon-based rubber, is polymerized and molded onto templates of varying roughnesses and textures to introduce topology that changes surface hydrophilicity. The topological changes are assessed through optical microscopy imaging, and the wettability is analyzed by measuring the contact angle using an inexpensive digital camera. The molds are treated with boiling water which generates hydroxyl groups on the surface. Successful chemical modification of the polymer surface is confirmed using attenuated total reflection infrared (ATR-IR) analysis, and wettability is assessed through contact angle measurement. Postlab questions focus on the wettability of the physically and chemically modified surfaces and their potential use as scaffolding for tissue engineering. This adaptable experiment is designed to reinforce concepts such as intermolecular forces, introduce polymer structure and synthesis, showcase polymer applications in biological research, and provide an introduction to surface wettability in a visually interesting manner.

Background Instructors often try to promote student engagement with discussion boards in learning management systems (LMS) like Canvas. Although convenient, alternatives like the social media platform Reddit may be more effective. Method A non-randomized controlled trial compared the use of Canvas and Reddit in two sections of two undergraduate psychology courses ( N = 77). Engagement was measured as the number and word-count of posts and responses and complemented with self-reported data. Results There was no difference between platforms in total number of posts or replies. In one course, the average word count per post was higher in Reddit than Canvas ( r = .44). However, in the other course, the average word count per post ( r = .47) and per reply ( r = .39) was significantly lower in Reddit. Neither course observed a significant difference in students’ perceived value of the discussion board. Conclusion This study provided no consistent evidence that Reddit supports student engagement relative to Canvas, and combined with additional survey data, it is possible that hosting the discussion board on Reddit may even be detrimental. Teaching Implications Given the issues we identified with moving discussion boards to Reddit, and the benefits of using Canvas, we recommend using a traditional LMS like Canvas.

Heart failure is a leading cause of hospitalizations and mortality worldwide. Heart failure with a preserved ejection fraction (HFpEF) represents a significant clinical challenge due to the lack of available treatment modalities for patients diagnosed with HFpEF. One symptom of HFpEF is impaired diastolic function that is associated with increases in left ventricular stiffness. Increases in myocardial fibrillar collagen content is one factor contributing to increases in myocardial stiffness. Cardiac fibroblasts are the primary cell type that produce fibrillar collagen in the heart. However, relatively little is known regarding phenotypic changes in cardiac fibroblasts in HFpEF myocardium. In the current study, cardiac fibroblasts were established from left ventricular epicardial biopsies obtained from patients undergoing cardiovascular interventions and divided into three categories: Referent control, hypertension without a heart failure designation (HTN (-) HFpEF), and hypertension with heart failure (HTN (+) HFpEF). Biopsies were evaluated for cardiac myocyte cross-sectional area (CSA) and collagen volume fraction. Primary fibroblast cultures were assessed for differences in proliferation and protein expression of collagen I, Membrane Type 1-Matrix Metalloproteinase (MT1-MMP), and α smooth muscle actin (αSMA). Biopsies from HTN (-) HFpEF and HTN (+) HFpEF exhibited increases in myocyte CSA over referent control although only HTN (+) HFpEF exhibited significant increases in fibrillar collagen content. No significant changes in proliferation or αSMA was detected in HTN (-) HFpEF or HTN (+) HFpEF cultures versus referent control. Significant increases in production of collagen I was detected in HF (-) HFpEF fibroblasts, whereas significant decreases in MT1-MMP levels were measured in HTN (+) HFpEF cells. We conclude that epicardial biopsies provide a viable source for primary fibroblast cultures and that phenotypic differences are demonstrated by HTN (-) HFpEF and HTN (+) HFpEF cells versus referent control.

We report on a first measurement with a sensitive opto-mechanical force sensor designed for the direct detection of coupling of real chameleons to matter. These dark energy candidates could be produced in the Sun and stream unimpeded to Earth. The KWISP detector installed on the CAST axion search experiment at CERN looks for tiny displacements of a thin membrane caused by the mechanical effect of solar chameleons. The displacements are detected by a Michelson interferometer with a homodyne readout scheme. The sensor benefits from the focusing action of the ABRIXAS X-ray telescope installed at CAST, which increases the chameleon flux on the membrane. A mechanical chopper placed between the telescope output and the detector modulates the incoming chameleon stream. We present the results of the solar chameleon measurements taken at CAST in July 2017, setting an upper bound on the force acting on the membrane of $80$~pN at 95\% confidence level. The detector is sensitive for direct coupling to matter $10^4 \leq\beta_m \leq 10^8$, where the coupling to photons is locally bound to $\beta_\gamma \leq 10^{11}$., Comment: 21 pages, 12 figures

Extracellular matrix (ECM) remodeling occurs in response to various cardiac insults including infarction, pressure overload and dilated myopathies. Each type of remodeling necessitates distinct types of ECM turnover and deposition yet an increase in myocardial fibrillar collagen content is appreciated as a contributing feature to cardiac dysfunction in each of these pathologies. In addition, aging, is also associated with increases in cardiac collagen content. The importance of characterizing differences in ECM composition and processes used by cardiac fibroblasts in the assembly of fibrotic collagen accumulation is critical for the design of strategies to reduce and ultimately regress cardiac fibrosis. Collagen cross-linking is one factor that influences collagen deposition and insolubility with direct implications for tissue properties such as stiffness. In this review, three different types of collagen cross-links shown to be important in cardiac fibrosis will be discussed; those catalyzed by lysyl oxidases, those catalyzed by transglutaminases, and those that result from non-enzymatic modification by the addition of advanced glycation end products. Insight into cellular mechanisms that govern collagen cross-linking in the myocardium will provide novel pathways for exploring new treatments to treat diseases associated with cardiac fibrosis.

Çetin, Serkant Ali (Dogus Author) -- Arık, Metin (Dogus Author) -- Yıldız, Süleyman Cenk (Dogus Author) Although they have not yet been detected, axions and axion-like particles (ALPs) continue to maintain the interest (even increasingly so) of the rare-event searches community as viable candidates for the Dark Matter of the Universe but also as a solution for several other puzzles of astrophysics. Their property of coupling to photons has inspired different experimental methods for their detection, one of which is the helioscope technique. The CERN Axion Solar Telescope (CAST) is the most sensitive helioscope built up to date and has recently published part of the latest data taken with the magnet bores gradually filled with He-3, probing the mass range up to 1.17 eV. The International AXion Observatory (IAXO) is being proposed as a facility where different axion studies can be performed, with the primary goal to study axions coming from the Sun. Designed to maximize sensitivity, it will improve the levels reached by CAST by almost 5 orders of magnitude in signal detection, that is more than one order of magnitude in terms of gay. Here we will summarize the most important aspects of the helioscopes, and focus mainly on IAXO, based on the recent papers [1, 2].

Physics of plasmas 27(4), 043103 (2020). doi:10.1063/1.5134846, The Facility for Antiproton and Ion Research (FAIR) will employ the World's highest intensity relativistic beams of heavy nuclei to uniquely create and investigate macroscopic (millimeter-sized) quantities of highly energetic and dense states of matter. Four principal themes of research have been identified: properties of materials driven to extreme conditions of pressure and temperature, shocked matter and material equation of state, basic properties of strongly coupled plasma and warm dense matter, and nuclear photonics with a focus on the excitation of nuclear processes in plasmas, laser-driven particle acceleration, and neutron production. The research program, principally driven by an international collaboration of scientists, called the HED@FAIR collaboration, will evolve over the next decade as the FAIR project completes and experimental capabilities develop. The first programmatic research element, called “FAIR Phase 0, officially began in 2018 to test components, detectors, and experimental techniques. Phase-0 research employs the existing and enhanced infrastructure of the GSI Helmholtzzentrum für Schwerionenforschung (GSI) heavy-ion synchrotron coupled with the PHELIX high-energy, high-intensity laser. The “FAIR Day one” experimental program, presently scheduled to begin in 2025, commences the use of FAIR's heavy-ion synchrotron, coupled to new experimental and diagnostic infrastructure, to realize the envisaged high-energy-density-science research program., Published by American Institute of Physics, [S.l.]

To develop best practices for laboratory safety and for chemical product and supplies management accountability, the freely-available online platform, Quartzy, was integrated within an interdisciplinary science department at a small Mid-Atlantic liberal-arts college. This was done to ensure the accuracy of purchase records, the appropriate use of storage and handling protocols, and for a continually updated chemical inventory system. Quartzy also facilitated the digital tracking and dispersal of the College’s hazardous waste inventory. Since the implementation of the Quartzy platform, the science department achieved significant cost-savings during the procurement of laboratory supplies and equipment, and it developed a sense of ownership towards the common goal of lowering the College's environmental impact as it relates to its managing of laboratory-generated hazardous wastes.

We performed a retrospective cohort study in order to examine recent trends in use of post-partum treatments and in-hospital mortality for congenital diaphragmatic hernia (CDH). Included were infants with CDH, born in 2003 to 2012 and hospitalized at ⩽7 days of age at one of 33 United States tertiary referral children’s hospitals with extracorporeal membrane oxygenation (ECMO) programs. In-hospital mortality as well as use of ECMO, surfactant and a variety of vasodilators were examined for trends during the study period. Inclusion criteria were met by 3123 infants with CDH. Among 2423 term or near-term infants, odds of death decreased annually for those with isolated or complex CDH. For 700 premature or low-birth weight infants with CDH, in-hospital mortality did not change. Among treatments for CDH, increasing with time in the study cohort were use of milrinone and sildenafil individually, and use of multiple vasodilators during the hospitalization. Survival improved in large subgroups of term or near-term infants with CDH in this 10-year multicenter cohort, temporally associated with increasing use of multiple vasodilators. Use of vasodilators for infants with CDH is increasing despite a lack of evidence supporting efficacy or safety. Prospective research is needed to clarify specific causal effects contributing to improving survival in these infants.

Muscle atrophy can result from inactivity or unloading on one hand or the induction of a catabolic state on the other. Muscle-specific ring finger 1 (MuRF1), a member of the tripartite motif family of E3 ubiquitin ligases, is an essential mediator of multiple conditions inducing muscle atrophy. While most studies have focused on the role of MuRF1 in protein degradation, the protein may have other roles in regulating skeletal muscle mass and metabolism. We therefore systematically evaluated the effect of MuRF1 on gene expression during denervation and dexamethasone-induced atrophy. We find that the lack of MuRF1 leads to few differences in control animals, but there were several significant differences in specific sets of genes upon denervation- and dexamethasone-induced atrophy. For example, during denervation, MuRF1 knockout mice showed delayed repression of metabolic and structural genes and blunted induction of genes associated with the neuromuscular junction. In the latter case, this pattern correlates with blunted HDAC4 and myogenin upregulation. Lack of MuRF1 caused fewer changes in the dexamethasone-induced atrophy program, but certain genes involved in fat metabolism and intracellular signaling were affected. Our results demonstrate a new role for MuRF1 in influencing gene expression in two important models of muscle atrophy.

Background Thymoglobulin is a T-cell-depleting polyclonal rabbit anti-human thymocyte antibody used clinically for immunosuppression in solid organ and hematopoietic stem-cell transplantation. By using a surrogate rabbit anti-mouse thymocyte globulin (mATG), we previously demonstrated that murine regulatory and memory T cells are preferentially spared from mATG depletion in vivo. The current studies were designed to determine whether different effector mechanisms are involved in differential depletion of T-cell subsets by mATG. Methods Complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and apoptotic mechanisms of depletion by mATG were evaluated in vitro and in vivo. Results In vitro, there was evidence of differential susceptibility of T-cell subsets by different effector mechanisms where naive and CD4 effector memory T cells show reduced susceptibility to apoptosis, whereas regulatory T cells are less susceptible to mATG-mediated complement-dependent cytotoxicity and ADCC. However, mATG treatment of mice depleted of ADCC effector cell types (neutrophils, natural killer cells, or macrophages) or deficient in complement C5 or Fas demonstrated that mATG depletion of all T-cell subsets is mediated primarily by macrophages and that the role of neutrophils, natural killer cells, and complement is minimal in vivo. Interestingly, the Fas/FasL pathway does play a role in regulatory T-cell depletion, which is likely a result of increased basal expression of Fas on these cells. Conclusions These data suggest that macrophages deplete most T cells by mATG in mice, but regulatory T cells are also uniquely susceptible to mATG-mediated Fas-dependent depletion.

In this paper we present a newly developed one-dimensional hydrodynamic simulation code and use it to determine the shock evolution in flyer plate impact experiments. The code is Lagrangian with artificial viscosity and uses shock Hugoniot data in its equation-of-state calculations instead of SESAME data tables. First shock calculations for transparent targets show a good agreement with theoretical predictions, making the code suitable for designing future flyer impact experiments at the Nevada Terawatt Facility.

Sheared flows have been predicted to stabilize the kink instability that disrupts the Z-pinch. Experiments conducted at the Nevada Terawatt Facility used conical wire arrays with the addition of a wire on axis to create a sheared flow. Multiframe laser images and time integrated pinhole images suggest that the sheared flow generated in this configuration is sufficient to suppress the kink instability.

The interaction which occurs between a plasma and an externally applied magnetic field is an important process in natural and laboratory plasmas. In experiments performed at the Nevada Terawatt Facility, a plasma flow was created by ablating a polyethylene target with a high-intensity laser (10 J in 1 ps, 10 TW). This laser-produced plasma interacted with an azimuthal magnetic field produced by passing a 0.6 MA (200 ns rise time) current through a straight cylindrical electrode. In the experiment, the plasma was observed to penetrate the magnetic field. The penetration is due to E × B drift caused by the polarization of the plasma plume.

Scaled experiments studying the interaction of shock waves with inhomogeneous background media are essential for understanding many astrophysical phenomena, since they can be used to test analytical theories and simulation codes. We are currently developing such experiments at the Nevada Terawatt Facility. We are using a pulsed power generator (1 MA peak current) to accelerate thin aluminum flyer plates. By impacting these foils on low-density foam targets, we will be able to carry out scaled experiments. We have demonstrated velocities of up to 8 km/s for 50 μm thick aluminum flyers, and are planning to further increase the flyer velocities. We have also carried out first impact tests with transparent polycarbonate targets. Several improvements for our setup are currently in planning, and these improvements will enable us to design scaled experiments for our facility.

Pattern matching, or querying, over annotations is a general purpose paradigm for inspecting, navigating, mining, and transforming annotation repositories—the common representation basis for modern pipelined text processing architectures. The open-ended nature of these architectures and expressiveness of feature structure-based annotation schemes account for the natural tendency of such annotation repositories to become very dense, as multiple levels of analysis get encoded as layered annotations. This particular characteristic presents challenges for the design of a pattern matching framework capable of interpreting ‘flat’ patterns over arbitrarily dense annotation lattices. We present an approach where a finite state device applies (compiled) pattern grammars over what is, in effect, a linearized ‘projection’ of a particular route through the lattice. The route is derived by a mix of static grammar analysis and runtime interpretation of navigational directives within an extended grammar formalism; it selects just the annotations sequence appropriate for the patterns at hand. For expressive and efficient pattern matching in dense annotations stores, our implemented approach achieves a mix of lattice traversal and finite state scanning by exposing a language which, to its user, provides constructs for specifying sequential, structural, and configurational constraints among annotations.

Experiments were performed at the Nevada Terawatt Facility to investigate the plasma penetration across an externally applied magnetic field. In experiment, a short-pulse laser ablates a polyethylene laser target, producing a plasma which interacts with an external magnetic field. The mechanism which allows the plasma to penetrate the applied magnetic field in experiment will be discussed.

Many astrophysical phenomena involve the interaction of a shock wave with an inhomogeneous background medium. Using scaled experiments with inhomogeneous foam targets makes it possible to study relevant physics in the laboratory to better understand the mechanisms of shock compression and to benchmark astrophysical simulation codes. First experiments on Zebra at the Nevada Terawatt Facility (NTF) have demonstrated flyer acceleration to sufficiently high velocities (up to 5 km/s) and that laser shadowgraphy can image sound fronts in transparent targets. Based on this, we designed an optimized setup to improve the flyer parameters (higher speed and mass) to create shock waves in transparent media. Once x-ray backlighting with the Leopard laser at NTF is operational, we will switch to foam targets with parameters relevant for laboratory astrophysics.

At the Nevada Terawatt Facility we investigated the generation of a sheared plasma flow using conical wire arrays with an additional wire located on the axis of the pinch. The additional center wire generates axial current carrying plasma that serves as a target for the plasma accelerated from the outer wires, generating a sheared plasma flow which leads to the growth of the Kelvin-Helmholtz instability. These experiments were conducted on Zebra, a 2 TW pulse power device capable of delivering a 1 MA current in 100 ns. This paper will focus on the implosion dynamics that lead to shear flow and the development of the Kelvin Helmholtz instability.