Single-Molecule Force Spectroscopy Studies of Fibrin ‘A–a’ Polymerization Interactions via the Atomic Force Microscope

Fibrin, the polymerized form of the soluble plasma protein fibrinogen, plays a critical role in hemostasis as the structural scaffold of blood clots. The primary functions of fibrin are to withstand the shear forces of blood flow and provide mechanical stability to the clot, protecting the wound. While studies have investigated the mechanical properties of fibrin constructs, the response to force of critical polymerization interactions such as the A-a knob-hole interaction remains unclear. Herein, the response of the A-a bond to force was examined at the single-molecule level using the atomic force microscope. Force spectroscopy methodology was developed to examine the A-a interaction while reducing the incidence of both nonspecific and multiple molecule interactions. The rupture of this interaction resulted in a previously unreported characteristic force profile comprised of up to four events. We hypothesized that the first event represented reorientation of the fibrinogen molecule, the second and third represented unfolding of structures in the D region of fibrinogen, and the last event was the rupture of the A-a bond weakened by prior structural unfolding. The configuration, molecular extension, and kinetic parameters of each event in the characteristic pattern were examined to compare the unfolding of fibrin to other proteins unfolded by force. Fitting the pattern with polymer models showed that the D region of fibrinogen could lengthen by ~50% of the length of a fibrin monomer before rupture of the A-a bond. Analysis showed that the second and third events had kinetic parameters similar to other protein structures unfolded by force. Studies of the dependence of the characteristic pattern on calcium, concentration of sodium chloride, pH, and temperature demonstrated that the incidence of the last event was affected by solution conditions. However, only low pH and high temperatures reduced the probability that an interaction was characteristic, indicating that the force required to rupture the A-a bond was less sensitive than the bond's resilience to structural unfolding to solution conditions. The structural unfolding that precedes the rupture of the A-a bond may prove significant in the polymerization and mechanical properties of fibrin

Qualitative assessment of a Context of Consumption Framework to inform regulation of cigarette pack design in the U.S.

INTRODUCTION Researchers and regulators need to know how changes to cigarette packages can influence population health. We sought to advance research on the role of cigarette packaging by assessing a theory-informed framework from the fields of design and consumer research. The selected Context of Consumption Framework posits cognitive, affective, and behavioral responses to visual design. To assess the Framework’s potential for guiding research on the visual design of cigarette packaging in the U.S., this study seeks to understand to what extent the Context of Consumption Framework converges with how adult smokers think and talk about cigarette pack designs. METHODS Data for this qualitative study came from six telephone-based focus groups conducted in March 2017. Two groups consisted of lesbian, gay, and bisexual participants; two groups of participants with less than four years college education; one group of LGB and straight identity; and one group the general population. All groups were selected for regional, gender, and racial/ethnic diversity. Participants (n=33) represented all nine U.S. Census divisions. We conducted a deductive qualitative analysis. RESULTS Cigarette package designs captured the participants’ attention, suggested the characteristics of the product, and reflected (or could be leveraged to convey) multiple dimensions of consumer identity. Particular to the affective responses to design, our participants shared that cigarette packaging conveyed how the pack could be used to particular ends, created an emotional response to the designs, complied with normative expectations of a cigarette, elicited interest when designs change, and prompted fascination when unique design characteristics are used. CONCLUSIONS Use of the Context of Consumption Framework for cigarette product packaging design can inform regulatory research on tobacco product packaging. Researchers and regulators should consider multiple cognitive, affective, and behavioral responses to cigarette pack design

Electron paramagnetic resonance and optical absorption study of acceptors in CdSiP2 crystals

Cadmium silicon diphosphide (CdSiP2) is a nonlinear material often used in optical parametric oscillators (OPOs) to produce tunable laser output in the mid-infrared. Absorption bands associated with donors and acceptors may overlap the pump wave- length and adversely affect the performance of these OPOs. In the present investigation, electron paramagnetic resonance (EPR) is used to identify two unintentionally present acceptors in large CdSiP2 crystals. These are an intrinsic silicon-on-phosphorus anti- site and a copper impurity substituting for cadmium. When exposed to 633 nm laser light at temperatures near or below 80 K, they convert to their neutral paramagnetic charge states (Si0P and Cu0Cd) and can be monitored with EPR. The corresponding donor serving as the electron trap is the silicon-on-cadmium antisite (Si2+ before illumina- above 90 K quickly destroys the EPR signals from both acceptors and the associated donor. Broad optical absorption bands peaking near 0.8 and 1.4 μm are also pro- duced at low temperature by the 633 nm light. These absorption bands are associated with the Si0P and Cu0Cd acceptors. © 2018 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1063/1.504180

Intrinsic Point Defects (Vacancies and Antisites) in CdGeP\u3csub\u3e2\u3c/sub\u3e Crystals

Cadmium germanium diphosphide (CdGeP2) crystals, with versatile terahertz-generating properties, belong to the chalcopyrite family of nonlinear optical materials. Other widely investigated members of this family are ZnGeP2 and CdSiP2. The room-temperature absorption edge of CdGeP2 is near 1.72 eV (720 nm). Cadmium vacancies, phosphorous vacancies, and germanium-on-cadmium antisites are present in as-grown CdGeP2 crystals. These unintentional intrinsic point defects are best studied below room temperature with electron paramagnetic resonance (EPR) and optical absorption. Prior to exposure to light, the defects are in charge states that have no unpaired spins. Illuminating a CdGeP2 crystal with 700 or 850 nm light while being held below 120 K produces singly ionized acceptors (VCd−) and singly ionized donors (GeCd+), as electrons move from VCd2− vacancies to GeCd2+ antisites. These defects become thermally unstable and return to their doubly ionized charge states in the 150–190 K range. In contrast, neutral phosphorous vacancies (VP0) are only produced with near-band-edge light when the crystal is held near or below 18 K. The VP0 donors are unstable at these lower temperatures and return to the singly ionized VP+ charge state when the light is removed. Spin-Hamiltonian parameters for the VCd− acceptors and VP0 donors are extracted from the angular dependence of their EPR spectra. Exposure at low-temperature to near-band-edge light also introduces broad optical absorption bands peaking near 756 and 1050 nm. A consistent picture of intrinsic defects in II-IV-P2 chalcopyrites emerges when the present CdGeP2 results are combined with earlier results from ZnGeP2, ZnSiP2, and CdSiP2

Measurement of the Neutron Radius of Pb-208 through Parity Violation in Electron Scattering

We report the first measurement of the parity-violating asymmetry A(PV) in the elastic scattering of polarized electrons from Pb-208. APV is sensitive to the radius of the neutron distribution (R-n). The result A(PV) = 0.656 +/- 0.060(stat) +/- 0.014(syst) ppm corresponds to a difference between the radii of the neutron and proton distributions R-n - R-p = 0.33(-0.18)(+0.16) fm and provides the first electroweak observation of the neutron skin which is expected in a heavy, neutron-rich nucleus

Parity Violation in Elastic Electron-Proton Scattering and the Proton's Strange Magnetic Form Factor

We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A=-4.92 +- 0.61 +- 0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections.Comment: 4 pages, 3 figures, submitted to Physical Review Letters, Sept 199

Final analysis of proton form factor ratio data at Q(2)=4.0, 4.8, and 5.6 GeV2

Precise measurements of the proton electromagnetic form factor ratio R = mu(p)G(E)(p)/G(M)(p) using the polarization transfer method at Jefferson Lab have revolutionized the understanding of nucleon structure by revealing the strong decrease of R with momentum transfer Q(2) for Q(2) greater than or similar to 1 GeV2, in strong disagreement with previous extractions of R from cross-section measurements. In particular, the polarization transfer results have exposed the limits of applicability of the one-photon-exchange approximation and highlighted the role of quark orbital angular momentum in the nucleon structure. The GEp-II experiment in Jefferson Lab\u27s Hall A measured R at four Q(2) values in the range 3.5 GeV2 \u3c = Q(2) \u3c = 5.6 GeV2. A possible discrepancy between the originally published GEp-II results and more recent measurements at higher Q(2) motivated a new analysis of the GEp-II data. This article presents the final results of the GEp-II experiment, including details of the new analysis, an expanded description of the apparatus, and an overview of theoretical progress since the original publication. The key result of the final analysis is a systematic increase in the results for R, improving the consistency of the polarization transfer data in the high-Q(2) region. This increase is the result of an improved selection of elastic events which largely removes the systematic effect of the inelastic contamination, underestimated by the original analysis

Electron Paramagnetic Resonance and Optical Absorption Study of Acceptors in CdSiP\u3csub\u3e2\u3c/sub\u3e Crystals

Cadmium silicon diphosphide (CdSiP2) is a nonlinear material often used in optical parametric oscillators (OPOs) to produce tunable laser output in the mid-infrared. Absorption bands associated with donors and acceptors may overlap the pump wavelength and adversely affect the performance of these OPOs. In the present investigation, electron paramagnetic resonance (EPR) is used to identify two unintentionally present acceptors in large CdSiP2 crystals. These are an intrinsic silicon-on-phosphorus antisite and a copper impurity substituting for cadmium. When exposed to 633 µm laser light at temperatures near or below 80 K, they convert to their neutral paramagnetic charge states (Si0P and Cu0Cd) and can be monitored with EPR. The corresponding donor serving as the electron trap is the silicon-on-cadmium antisite (Si2+Cd before illumination and Si+Cd after illumination). Removing the 633 µm light and warming the crystal above 90 K quickly destroys the EPR signals from both acceptors and the associated donor. Broad optical absorption bands peaking near 0.8 and 1.4 μm are also produced at low temperature by the 633 µm light. These absorption bands are associated with the Si0P and Cu0Cd acceptors