المؤلفون: Slepenkin, Anatoli, Pal, Sukumar, Rasley, Amy, Coleman, Matthew, De La Maza, Luis

المصدر: npj Vaccines. 9(1)

الوصف: It is recommended that the adjuvant Montanide ISA 720 VG be used at a concentration of 70% v/v. At this concentration, Montanide causes at the site of immunization a local granuloma that can last for several weeks. To determine the safety and protective efficacy of a Chlamydia muridarum MOMP vaccine, formulated with CpG-1826 and four different concentrations of Montanide (70%, 50%, 30% and 10%), BALB/c (H-2d) female mice were immunized twice intramuscularly. Local reactogenicity was significant for vaccines formulated with 70% or 50% Montanide but not for those inoculated with 30% or 10% Montanide. Robust humoral and cell mediated memory immune responses were elicited by the 70%, 50% and 30% Montanide formulations. Mice were challenged intranasally with 104 C. muridarum inclusion forming units (IFU). Based on changes in body weight, lungss weight and number of IFU recovered, mice vaccinated with the 70%, 50% and 30% Montanide formulations were significantly protected, but not mice receiving 10% Montanide. To conclude, we recommend the 30% Montanide concentration to be tested in humans and animal models to determine its safety and efficacy, in comparison to the 70% Montanide concentration currently used. The 30% Montanide formulation could significantly facilitate licensing of this adjuvant for human use.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8gc5w5dsTest
https://escholarship.org/content/qt8gc5w5ds/qt8gc5w5ds.pdfTest

المؤلفون: Prasanna, Tejas, Coleman, Matthew S. B., Thompson, Todd A.

مصطلحات موضوعية: Astrophysics - High Energy Astrophysical Phenomena

الوصف: The neutrino-driven wind cooling phase of proto-neutron stars (PNSs) follows successful supernovae. Wind models without magnetic fields or rotation fail to achieve the necessary conditions for production of the third $r$-process peak, but robustly produce a weak $r$-process in neutron-rich winds. Using 2D magnetohydrodynamic simulations with magnetar-strength magnetic fields and rotation, we show that the PNS rotation rate significantly affects the thermodynamic conditions of the wind. We show that high entropy material is quasi-periodically ejected from the closed zone of the PNS magnetosphere with the required thermodynamic conditions to produce heavy elements. We show that maximum entropy $S$ of the material ejected depends systematically on the magnetar spin period $P_{\star}$ and scales as $S \propto P_{\star}^{-5/6}$ for sufficiently rapid rotation. We present results from simulations at a constant neutrino luminosity representative of $\sim 1-2$ s after the onset of cooling for $P_{\star}$ ranging from 5 ms to 200 ms and a few simulations with evolving neutrino luminosity where we follow the evolution of the magnetar wind until $10-14$ s after the onset of cooling. We estimate at magnetar polar magnetic field strength $B_0=3\times 10^{15}$ G, $10^{15}$ G, and $5\times 10^{14}$ G that neutron-rich magnetar winds can respectively produce at least $\sim 2-5\times 10^{-5}$ M$_{\odot}$, $\sim 3-4\times 10^{-6}$ M$_{\odot}$, and $\sim 2.5\times 10^{-8}$ M$_{\odot}$ of material with the required parameters for synthesis of the third $r-$process peak, within $1-2$ s, 10 s, and 14 s in that order after the onset of cooling. We show that proton-rich magnetar winds can have favorable conditions for production of $p-$nuclei, even at a modest $B_0=5\times 10^{14}$ G.
Comment: 21 pages, 14 figures

الوصول الحر: http://arxiv.org/abs/2402.06003Test

المؤلفون: Burrows, Adam, Wang, Tianshu, Vartanyan, David, Coleman, Matthew S. B.

مصطلحات موضوعية: Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Astrophysics of Galaxies, Astrophysics - Solar and Stellar Astrophysics

الوصف: Using twenty long-term 3D core-collapse supernova simulations, we find that lower compactness progenitors that explode quasi-spherically due to the short delay to explosion experience smaller neutron star recoil kicks in the $\sim$100$-$200 km s$^{-1}$ range, while higher compactness progenitors that explode later and more aspherically leave neutron stars with kicks in the $\sim$300$-$1000 km s$^{-1}$ range. In addition, we find that these two classes are correlated with the gravitational mass of the neutron star. This correlation suggests that the survival of binary neutron star systems may in part be due to their lower kick speeds. We also find a correlation of the kick with both the mass dipole of the ejecta and the explosion energy. Furthermore, one channel of black hole birth leaves masses of $\sim$10 $M_{\odot}$, is not accompanied by a neutrino-driven explosion, and experiences small kicks. A second is through a vigorous explosion that leaves behind a black hole with a mass of $\sim$3.0 $M_{\odot}$ kicked to high speeds. We find that the induced spins of nascent neutron stars range from seconds to $\sim$10 milliseconds, {but do not yet see a significant spin/kick correlation for pulsars.} We suggest that if an initial spin biases the explosion direction, a spin/kick correlation {would be} a common byproduct of the neutrino mechanism of core-collapse supernovae. Finally, the induced spin in explosive black hole formation is likely large and in the collapsar range. This new 3D model suite provides a greatly expanded perspective and appears to explain some observed pulsar properties by default.
Comment: 16 pages, 7 figures. Accepted to ApJ

الوصول الحر: http://arxiv.org/abs/2311.12109Test

المؤلفون: Prasanna, Tejas, Coleman, Matthew S. B., Raives, Matthias J., Thompson, Todd A.

المصدر: Monthly Notices of the Royal Astronomical Society 2023, Volume 526, Issue 2, pp.3141-3155

مصطلحات موضوعية: Astrophysics - High Energy Astrophysical Phenomena

الوصف: Rapidly rotating magnetars have been associated with gamma-ray bursts (GRBs) and super-luminous supernovae (SLSNe). Using a suite of 2D magnetohydrodynamic simulations at fixed neutrino luminosity and a couple of evolutionary models with evolving neutrino luminosity and magnetar spin period, we show that magnetars are viable central engines for powering GRBs and SLSNe. We also present analytic estimates of the energy outflow rate from the proto-neutron star (PNS) as a function of polar magnetic field strength $B_0$, PNS angular velocity $\Omega_{\star}$, PNS radius $R_{\star}$ and mass outflow rate $\dot{M}$. We show that rapidly rotating magnetars with spin periods $P_{\star}\lesssim 4$ ms and polar magnetic field strength $B_0\gtrsim 10^{15}$ G can release $10^{50}-5\times 10^{51}$ ergs of energy during the first $\sim2$ s of the cooling phase. Based on this result, it is plausible that sustained energy injection by magnetars through the relativistic wind phase can power GRBs. We also show that magnetars with moderate field strengths of $B_0\lesssim 5\times 10^{14}$ G do not release a large fraction of their rotational kinetic energy during the cooling phase and hence, are not likely to power GRBs. Although we cannot simulate to times greater than $\sim 3-5$ s after a supernova, we can hypothesize that moderate field strength magnetars can brighten the supernova light curves by releasing their rotational kinetic energy via magnetic dipole radiation on timescales of days to weeks, since these do not expend most of their rotational kinetic energy during the early cooling phase.
Comment: 15 pages, 13 Figures

الوصول الحر: http://arxiv.org/abs/2305.16412Test

المؤلفون: Liu, Zhongrui, Gu, Kevin, Shelby, Megan, Gilbile, Deepshika, Lyubimov, Artem, Russi, Silvia, Cohen, Aina, Narayanasamy, Sankar, Botha, Sabine, Kupitz, Christopher, Sierra, Raymond, Poitevin, Fredric, Gilardi, Antonio, Lisova, Stella, Coleman, Matthew, Frank, Matthias, Kuhl, Tonya

المصدر: Acta Crystallographica Section D: Structural Biology. 79(Pt 10)

مصطلحات موضوعية: X-ray crystallography, XFELs, cyclic olefin copolymer, fixed targets, microfluidics, room-temperature SFX, sample delivery, serial crystallography, synchrotrons

الوصف: Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip, 21, 4831-4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70 Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/54v4b3xhTest

المؤلفون: Gu, Kevin, Liu, Zhongrui, Narayanasamy, Sankar, Shelby, Megan, Chan, Nicholas, Coleman, Matthew, Frank, Matthias, Kuhl, Tonya

المصدر: Biomicrofluidics. 17(5)

الوصف: The development of x-ray free electron laser (XFEL) light sources and serial crystallography methodologies has led to a revolution in protein crystallography, enabling the determination of previously unobtainable protein structures and near-atomic resolution of otherwise poorly diffracting protein crystals. However, to utilize XFEL sources efficiently demands the continuous, rapid delivery of a large number of difficult-to-handle microcrystals to the x-ray beam. A recently developed fixed-target system, in which crystals of interest are enclosed within a sample holder, which is rastered through the x-ray beam, is discussed in detail in this Perspective. The fixed target is easy to use, maintains sample hydration, and can be readily modified to allow a broad range of sample types and different beamline requirements. Recent innovations demonstrate the potential of such microfluidic-based fixed targets to be an all-around workhorse for serial crystallography measurements. This Perspective will summarize recent advancements in microfluidic fixed targets for serial crystallography, examine needs for future development, and guide users in designing, choosing, and utilizing a fixed-target sample delivery device for their system.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8qm3574cTest

المؤلفون: Raives, Matthias J., Coleman, Matthew S. B., Thompson, Todd A.

المصدر: MNRAS, 526, 3, 4418-4434 (2023)

مصطلحات موضوعية: Astrophysics - Solar and Stellar Astrophysics, Astrophysics - High Energy Astrophysical Phenomena

الوصف: We consider the general problem of a Parker-type non-relativistic isothermal wind from a rotating and magnetic star. Using the magnetohydrodynamics (MHD) code athena++, we construct an array of simulations in the stellar rotation rate $\Omega_\ast$ and the isothermal sound speed $c_T$, and calculate the mass, angular momentum, and energy loss rates across this parameter space. We also briefly consider the three dimensional case, with misaligned magnetic and rotation axes. We discuss applications of our results to the spindown of normal stars, highly-irradiated exoplanets, and to nascent highly-magnetic and rapidly-rotating neutron stars born in massive star core collapse.8
Comment: 19 pages, 13 figures; v2: published version after minor revisions

الوصول الحر: http://arxiv.org/abs/2302.05462Test

المؤلفون: Vartanyan, David, Burrows, Adam, Wang, Tianshu, Coleman, Matthew S. B., White, Christopher J.

مصطلحات موضوعية: Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Solar and Stellar Astrophysics, General Relativity and Quantum Cosmology

الوصف: We calculate the gravitational-wave (GW) signatures of detailed 3D core-collapse supernova simulations spanning a range of massive stars. Most of the simulations are carried out to times late enough to capture more than 95% of the total GW emission. We find that the f/g-mode and f-mode of proto-neutron star oscillations carry away most of the GW power. The f-mode frequency inexorably rises as the proto-neutron star (PNS) core shrinks. We demonstrate that the GW emission is excited mostly by accretion plumes onto the PNS that energize modal oscillations and also high-frequency (``haze") emission correlated with the phase of violent accretion. The duration of the major phase of emission varies with exploding progenitor and there is a strong correlation between the total GW energy radiated and the compactness of the progenitor. Moreover, the total GW emissions vary by as much as three orders of magnitude from star to star. For black-hole formation, the GW signal tapers off slowly and does not manifest the haze seen for the exploding models. For such failed models, we also witness the emergence of a spiral shock motion that modulates the GW emission at a frequency near $\sim$100 Hertz that slowly increases as the stalled shock sinks. We find significant angular anisotropy of both the high- and low-frequency (memory) GW emissions, though the latter have very little power.
Comment: accepted to PRD

الوصول الحر: http://arxiv.org/abs/2302.07092Test

المؤلفون: Jernigan, Rebecca J, Logeswaran, Dhenugen, Doppler, Diandra, Nagaratnam, Nirupa, Sonker, Mukul, Yang, Jay-How, Ketawala, Gihan, Martin-Garcia, Jose M, Shelby, Megan L, Grant, Thomas D, Mariani, Valerio, Tolstikova, Alexandra, Sheikh, Michelle Z, Yung, Mimi Cho, Coleman, Matthew A, Zaare, Sahba, Kaschner, Emily K, Rabbani, Mohammad Towshif, Nazari, Reza, Zacks, Michele A, Hayes, Brandon, Sierra, Raymond G, Hunter, Mark S, Lisova, Stella, Batyuk, Alexander, Kupitz, Christopher, Boutet, Sebastien, Hansen, Debra T, Kirian, Richard A, Schmidt, Marius, Fromme, Raimund, Frank, Matthias, Ros, Alexandra, Chen, Julian J-L, Botha, Sabine, Fromme, Petra

المصدر: Structure (London, England : 1993). 31(2)

مصطلحات موضوعية: Humans, Crystallography, X-Ray, Lasers, Temperature, Electrons, COVID-19, SARS-CoV-2, NSP15, NendoU, X-ray free-electron laser, serial femtosecond crystallography, Prevention, Infectious Diseases, Emerging Infectious Diseases, Vaccine Related, Biodefense, Infection, Chemical Sciences, Biological Sciences, Information and Computing Sciences, Biophysics

الوصف: NendoU from SARS-CoV-2 is responsible for the virus's ability to evade the innate immune system by cleaving the polyuridine leader sequence of antisense viral RNA. Here we report the room-temperature structure of NendoU, solved by serial femtosecond crystallography at an X-ray free-electron laser to 2.6 Å resolution. The room-temperature structure provides insight into the flexibility, dynamics, and other intrinsic properties of NendoU, with indications that the enzyme functions as an allosteric switch. Functional studies examining cleavage specificity in solution and in crystals support the uridine-purine cleavage preference, and we demonstrate that enzyme activity is fully maintained in crystal form. Optimizing the purification of NendoU and identifying suitable crystallization conditions set the benchmark for future time-resolved serial femtosecond crystallography studies. This could advance the design of antivirals with higher efficacy in treating coronaviral infections, since drugs that block allosteric conformational changes are less prone to drug resistance.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9v8937bnTest

المؤلفون: Coleman, Matthew S. B., Burrows, Adam

مصطلحات موضوعية: Astrophysics - High Energy Astrophysical Phenomena

الوصف: Using simulations of non-rotating supernova progenitors, we explore the kicks imparted to and the spins induced in the compact objects birthed in core collapse. We find that the recoil due to neutrino emissions can be a factor affecting core recoil, comparable to and at times larger than the corresponding kick due to matter recoil. This result would necessitate a revision of the general model of the origin of pulsar proper motions. In addition, we find that the sign of the net neutrino momentum can be opposite to the sign of the corresponding matter recoil. As a result, at times the pulsar recoil and ejecta can be in the same direction. Moreover, our results suggest that the duration of the dipole in the neutrino emissions can be shorter than the duration of the radiation of the neutron-star binding energy. This allows a larger dipole asymmetry to arise, but for a shorter time, resulting in kicks in the observed pulsar range. Furthermore, we find that the spin induced by the aspherical accretion of matter can leave the residues of collapse with spin periods comparable to those inferred for radio pulsars and that there seems to be a slight anti-correlation between the direction of the induced spin and the net kick direction. This could explain such a correlation among observed radio pulsars. Finally, we find that the kicks imparted to black holes are due to the neutrino recoil alone, resulting in birth kicks $\le$100 km s$^{-1}$ most of the time.
Comment: 29 pages, 24 figures, accepted for publication in MNRAS

الوصول الحر: http://arxiv.org/abs/2209.02711Test