Micromechanical fracture modeling of asphalt concrete using a single-edge notched beam test

Cracks in asphalt pavements create irreversible structural and functional deficiencies that increase maintenance costs and decrease lifespan. Therefore, it is important to understand the fracture behavior of asphalt mixtures, which consist of irregularly shaped and randomly oriented aggregate particles and mastic. A two-dimensional clustered discrete element modeling (DEM) approach is implemented to simulate the complex crack behavior observed during asphalt concrete fracture tests. A cohesive softening model (CSM) is adapted as an intrinsic constitutive law governing material separation in asphalt concrete. A homogenous model is employed to investigate the mode I fracture behavior of asphalt concrete using a single-edge notched beam (SE(B)) test. Heterogeneous morphological features are added to numerical SE(B) specimens to investigate complex fracture mechanisms in the process zone. Energy decomposition analyses are performed to gain insight towards the forms of energy dissipation present in fracture testing of asphalt concrete. Finally, a heterogeneous model is used to simulate mixed-mode crack propagatio

The 67 Hz Feature in the Black Hole Candidate GRS 1915+105 as a Possible ``Diskoseismic'' Mode

The Rossi X-ray Timing Explorer (RXTE) has made feasible for the first time the search for high-frequency (~ 100 Hz) periodic features in black hole candidate (BHC) systems. Such a feature, with a 67 Hz frequency, recently has been discovered in the BHC GRS 1915+105 (Morgan, Remillard, & Greiner). This feature is weak (rms variability ~0.3%-1.6%), stable in frequency (to within ~2 Hz) despite appreciable luminosity fluctuations, and narrow (quality factor Q ~ 20). Several of these properties are what one expects for a ``diskoseismic'' g-mode in an accretion disk about a 10.6 M_sun (nonrotating) - 36.3 M_sun (maximally rotating) black hole (if we are observing the fundamental mode frequency). We explore this possibility by considering the expected luminosity modulation, as well as possible excitation and growth mechanisms---including turbulent excitation, damping, and ``negative'' radiation damping. We conclude that a diskoseismic interpretation of the observations is viable.Comment: 4 Pages, Latex (emulateapj.sty included), to Appear in ApJ Letters, Vol. 477, Final Version with Updated Reference

Oscillations of a ring-constrained charged drop

Free drops of uncharged and charged inviscid, conducting fluids subjected to small-amplitude perturbations undergo linear oscillations (Rayleigh, Proc. R. Soc. London, vol. 29, no. 196–199, 1879, pp. 71–97; Rayleigh, Philos. Mag., vol. 14, no. 87, 1882, pp. 184–186). There exist a countably infinite number of oscillation modes, n=2,3,… role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3en=2,3,…n=2,3,…, each of which has a characteristic frequency and mode shape. Presence of charge (Q role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eQQ) lowers modal frequencies and leads to instability when Q\u3eQR role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eQ\u3eQRQ\u3eQR (Rayleigh limit). The n=0 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3en=0n=0 and n=1 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3en=1n=1 modes are disallowed because they violate volume conservation and cause centre of mass (COM) motion. Thus, the first mode to become unstable is the n=2 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3en=2n=2 prolate–oblate mode. For free drops, there is a one-to-one correspondence between mode number and shape (Legendre polynomial Pn role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3ePnPn). Recent research has shifted to studying oscillations of spherical drops constrained by solid rings. Pinning the drop introduces a new low-frequency mode of oscillation (n=1 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3en=1n=1), one associated primarily with COM translation of the constrained drop. We analyse theoretically the effect of charge on oscillations of constrained drops. Using normal modes and solving a linear operator eigenvalue problem, we determine the frequency of each oscillation mode. Results demonstrate that for ring-constrained charged drops (RCCDs), the association between mode number and shape is lost. For certain pinning locations, oscillations exhibit eigenvalue veering as Q role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eQQ increases. While slightly charged RCCDs pinned at zeros of P2 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eP2P2 have a first mode that involves COM motion and a second mode that entails prolate–oblate oscillations, the modes flip as Q role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline-table; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eQQ increases. Thereafter, prolate–oblate oscillations of RCCDs adopt the role of being the first mode because they exhibit the lowest vibration frequency. At the Rayleigh limit, the first eigenmode – prolate–oblate oscillations – loses stability while the second – involving COM motion – remains stable

Nucleoside reverse-transcriptase inhibitor dosing errors in an outpatient HIV clinic in the electronic medical record era

Information on antiretroviral dosing errors among health care providers for outpatient human immunodeficiency virus (HIV)-infected patients is lacking. We evaluated factors associated with nucleoside reverse-transcriptase inhibitor dosing errors in a university-based HIV clinic using an electronic medical record. Overall, older age, minority race or ethnicity, and didanosine use were related to such errors. Impaired renal function was more common in older patients and racial or ethnic minorities and, in conjunction with fixed-dose combination drugs, contributed to the higher rates of errors in nucleoside reverse-transcriptase inhibitor dosing. Understanding the factors related to nucleoside reverse-transcriptase inhibitor dosing errors is an important step in the building of preventive tools

Precision Prediction for the Big-Bang Abundance of Primordial Helium

Within the standard models of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of \he to a theoretical uncertainty of less than 0.1 \pct $(\delta Y_P < \pm 0.0002)$, improving the current theoretical precision by a factor of 10. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\tau_n = 885.4 \pm 2.0 sec$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon-mass corrections to the weak rates; order-$\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code designed to control numerical errors to be less than 0.1\pct. Our predictions for the \EL[4]{He} abundance are presented in the form of an accurate fitting formula. Summarizing our work in one number, $Y_P(\eta = 5\times 10^{-10}) = 0.2462 \pm 0.0004 (expt) \pm < 0.0002 (theory)$. Further, the baryon density inferred from the Burles-Tytler determination of the primordial D abundance, $\Omega_B h^2 = 0.019\pm 0.001$, leads to the prediction: $Y_P = 0.2464 \pm 0.0005 (D/H) \pm < 0.0002 (theory) \pm 0.0005 (expt)$. This ``prediction'' and an accurate measurement of the primeval \he abundance will allow an important consistency test of primordial nucleosynthesis.Comment: Replaced fitting formulas - new versions differ by small but significant amount. Other minor changes. 30 pages, 17 figures, 5 table

Total and Bioavailable Chromium Along a Toposequence in San Luis Obispo, CA.

The presence of large quantities of Chromium metal in soil and plants is of major concern due to its toxicity to humans. Total (USEPA 3050a) and bioavailable (USEPA 1311) levels of chromium were measured along a serpentinic Central Coast toposequence. Soil from the surface and subsurface, as well as the above ground plants of the toposequence were determined and compared to several soil chemical and physical properties using a least squares regression. The binding environments and oxidation states were found through XANES and EXAFS x-ray spectroscopies. The total and bioavailable chromium concentrations of the soil averaged 1457.1 and 1.6 mg Cr/kg respectively, and the average total plant chromium was 115.2 mg Cr/kg. The difference between chromium in the soil surface and subsurface was not statistically significant. The concentrations of total soil and plant chromium were highest in the backslope positions with a value of 2528.8 mg Cr/kg in the soil and 288.5 mg Cr/kg in the above ground plants. Though the backslope positions had slightly elevated levels of Cr, slope position did not have a large influence on soil and plant total chromium levels. The soil chemical and physical properties did not show a significant linear relationship with chromium levels. The dominant form of chromium found in both the bulk-soil and plant samples was Cr3+, this agrees with the low amount of bioavailable chromium found at the site. Sepentinitic parent materials naturally lead to high chromium levels in soils and plants, so the ability to understand how chromium interacts with soil properties is crucial in the effective landscape management of areas rich in this metal

Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2

Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers opportunities to discover synergistic drug combinations. While combination antiviral drug treatments are standard for chronic RNA virus infections, no antiviral combination therapy has been approved for SARS-CoV-2. Here, we demonstrate that combining host-targeting antivirals (HTAs) that target TMPRSS2 and hence SARS-CoV-2 entry, with the DAA molnupiravir, which targets SARS-CoV-2 replication, synergistically suppresses SARS-CoV-2 infection in Calu-3 lung epithelial cells. Strong synergy was observed when molnupiravir, an oral drug, was combined with three TMPRSS2 (HTA) oral or inhaled inhibitors: camostat, avoralstat, or nafamostat. The combination of camostat plus molnupiravir was also effective against the beta and delta variants of concern. The pyrimidine biosynthesis inhibitor brequinar combined with molnupiravir also conferred robust synergistic inhibition. These HTA+DAA combinations had similar potency to the synergistic all-DAA combination of molnupiravir plus nirmatrelvir, the protease inhibitor found in paxlovid. Pharmacodynamic modeling allowed estimates of antiviral potency at all possible concentrations of each agent within plausible therapeutic ranges, suggesting possible in vivo efficacy. The triple combination of camostat, brequinar, and molnupiravir further increased antiviral potency. These findings support the development of HTA+DAA combinations for pandemic response and preparedness. IMPORTANCE Imagine a future viral pandemic where if you test positive for the new virus, you can quickly take some medicines at home for a few days so that you do not get too sick. To date, only single drugs have been approved for outpatient use against SARS-CoV-2, and we are learning that these have some limitations and may succumb to drug resistance. Here, we show that combinations of two oral drugs are better than the single ones in blocking SARS-CoV-2, and we use mathematical modeling to show that these drug combinations are likely to work in people. We also show that a combination of three oral drugs works even better at eradicating the virus. Our findings therefore bode well for the development of oral drug cocktails for at home use at the first sign of an infection by a coronavirus or other emerging viral pathogens.Peer reviewe

Pennsylvanian-Early Triassic stratigraphy in the Alborz Mountains (Iran)

New fieldwork was carried out in the central and eastern Alborz, addressing the sedimentary succession from the Pennsylvanian to the Early Triassic. A regional synthesis is proposed, based on sedimentary analysis and a wide collection of new palaeontological data. The Moscovian Qezelqaleh Formation, deposited in a mixed coastal marine and alluvial setting, is present in a restricted area of the eastern Alborz, transgressing on the Lower Carboniferous Mobarak and Dozdehband formations. The late Gzhelian–early Sakmarian Dorud Group is instead distributed over most of the studied area, being absent only in a narrow belt to the SE. The Dorud Group is typically tripartite, with a terrigenous unit in the lower part (Toyeh Formation), a carbonate intermediate part (Emarat and Ghosnavi formations, the former particularly rich in fusulinids), and a terrigenous upper unit (Shah Zeid Formation), which however seems to be confined to the central Alborz. A major gap in sedimentation occurred before the deposition of the overlying Ruteh Limestone, a thick package of packstone–wackestone interpreted as a carbonate ramp of Middle Permian age (Wordian–Capitanian). The Ruteh Limestone is absent in the eastern part of the range, and everywhere ends with an emersion surface, that may be karstified or covered by a lateritic soil. The Late Permian transgression was directed southwards in the central Alborz, where marine facies (Nesen Formation) are more common. Time-equivalent alluvial fans with marsh intercalations and lateritic soils (Qeshlaq Formation) are present in the east. Towards the end of the Permian most of the Alborz emerged, the marine facies being restricted to a small area on the Caspian side of the central Alborz. There, the Permo-Triassic boundary interval is somewhat similar to the Abadeh–Shahreza belt in central Iran, and contains oolites, flat microbialites and domal stromatolites, forming the base of the Elikah Formation. The P–T boundary is established on the basis of conodonts, small foraminifera and stable isotope data. The development of the lower and middle part of the Elikah Formation, still Early Triassic in age, contains vermicular bioturbated mudstone/wackestone, and anachronostic-facies-like gastropod oolites and flat pebble conglomerates. Three major factors control the sedimentary evolution. The succession is in phase with global sea-level curve in the Moscovian and from the Middle Permian upwards. It is out of phase around the Carboniferous–Permian boundary, when the Dorud Group was deposited during a global lowstand of sealevel. When the global deglaciation started in the Sakmarian, sedimentation stopped in the Alborz and the area emerged. Therefore, there is a consistent geodynamic control. From the Middle Permian upwards, passive margin conditions control the sedimentary evolution of the basin, which had its depocentre(s) to the north. Climate also had a significant role, as the Alborz drifted quickly northwards with other central Iran blocks towards the Turan active margin. It passed from a southern latitude through the aridity belt in the Middle Permian, across the equatorial humid belt in the Late Permian and reached the northern arid tropical belt in the Triassic