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Opposing Pressures of Speed and Efficiency Guide the Evolution of Molecular Machines.
Many biomolecular machines need to be both fast and efficient. How has evolution optimized these machines along the tradeoff between speed and efficiency? We explore this question using optimizable dynamical models along coordinates that are plausible evolutionary degrees of freedom. Data on 11 motors and ion pumps are consistent with the hypothesis that evolution seeks an optimal balance of speed and efficiency, where any further small increase in one of these quantities would come at great expense to the other. For FoF1-ATPases in different species, we also find apparent optimization of the number of subunits in the c-ring, which determines the number of protons pumped per ATP synthesized. Interestingly, these ATPases appear to more optimized for efficiency than for speed, which can be rationalized through their key role as energy transducers in biology. The present modeling shows how the dynamical performance properties of biomolecular motors and pumps may have evolved to suit their corresponding biological actions
Standards for Analysis of Ce, La, Pb, Rb, Se, Sr, Y, AND Zr in Rock Samples Using Laser-induced Breakdown Spectroscopy and X-ray Fluorescence
Analytical geochemistry has long depended on the availability of robust suites of rock standards with well-characterized compositions. Standard rock powders for wet chemistry and x-ray fluorescence were initially characterized and supplied to the community by the U.S. Geological Survey, which continues to distribute a few dozen standards. Many other rock standards have subsequently been developed by organizations such as the Centre de Recherches Ptrographiques et Gochimiques (CRPG) and Brammer Standard Company, Inc
Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings from a Randomized Trial
Background.
Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant.
Methods.
Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose.
Results.
One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses.
Conclusions.
GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates
The Simons Observatory: Magnetic Sensitivity Measurements of Microwave SQUID Multiplexers
The Simons Observatory (SO) will be a cosmic microwave background (CMB)
survey experiment with three small-aperture telescopes and one large-aperture
telescope, which will observe from the Atacama Desert in Chile. In total, SO
will field 70,000 transition-edge sensor (TES) bolometers in six spectral
bands centered between 27 and 280 GHz in order to achieve the sensitivity
necessary to measure or constrain numerous cosmological quantities. The SO
Universal Focal Plane Modules (UFMs) each contain a 150 mm diameter TES
detector array, horn or lenslet optical coupling, cold readout components, and
magnetic shielding. SO will use a microwave SQUID multiplexing (MUX)
readout at an initial multiplexing factor of 1000; the cold (100 mK)
readout components are packaged in a MUX readout module, which is part of
the UFM, and can also be characterized independently. The 100 mK stage TES
bolometer arrays and microwave SQUIDs are sensitive to magnetic fields, and
their measured response will vary with the degree to which they are
magnetically shielded. We present measurements of the magnetic pickup of test
microwave SQUID multiplexers as a study of various shielding configurations for
the Simons Observatory. We discuss how these measurements motivated the
material choice and design of the UFM magnetic shielding.Comment: 5 pages, 6 figures, conference proceedings submitted to IEEE
Transactions on Applied Superconductivit
HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice
Hepatitis C virus (HCV) is a blood-borne pathogen and a major cause of liver disease worldwide. Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection. Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism genes, which may contribute to oxidative stress. We also found that infection of chimeric SCID/Alb-uPA mice by HCV led to signs of hepatocyte damage and apoptosis, which in patients plays a role in activation of stellate cells, recruitment of macrophages, and the subsequent development of fibrosis. Infection of chimeric mice with HCV H77c also led an inflammatory response characterized by infiltration of monocytes and macrophages. There was increased apoptosis in HCV-infected human hepatocytes in H77c-infected mice but not in mice inoculated with a replication incompetent H77c mutant. Moreover, TUNEL reactivity was restricted to HCV-infected hepatocytes, but an increase in FAS expression was not. To gain insight into the factors contributing specific apoptosis of HCV infected cells, immunohistological and confocal microscopy using antibodies for key apoptotic mediators was done. We found that the ER chaperone BiP/GRP78 was increased in HCV-infected cells as was activated BAX, but the activator of ER stress–mediated apoptosis CHOP was not. We found that overall levels of NF-κB and BCL-xL were increased by infection; however, within an infected liver, comparison of infected cells to uninfected cells indicated both NF-κB and BCL-xL were decreased in HCV-infected cells. We conclude that HCV contributes to hepatocyte damage and apoptosis by inducing stress and pro-apoptotic BAX while preventing the induction of anti-apoptotic NF-κB and BCL-xL, thus sensitizing hepatocytes to apoptosis
The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth
We present new measurements of cosmic microwave background (CMB) lensing over
sq. deg. of the sky. These lensing measurements are derived from the
Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which
consists of five seasons of ACT CMB temperature and polarization observations.
We determine the amplitude of the CMB lensing power spectrum at
precision ( significance) using a novel pipeline that minimizes
sensitivity to foregrounds and to noise properties. To ensure our results are
robust, we analyze an extensive set of null tests, consistency tests, and
systematic error estimates and employ a blinded analysis framework. The
baseline spectrum is well fit by a lensing amplitude of
relative to the Planck 2018 CMB power spectra
best-fit CDM model and relative to
the best-fit model. From our lensing power
spectrum measurement, we derive constraints on the parameter combination
of
from ACT DR6 CMB lensing alone and
when combining ACT DR6 and Planck NPIPE
CMB lensing power spectra. These results are in excellent agreement with
CDM model constraints from Planck or
CMB power spectrum measurements. Our lensing measurements from redshifts
-- are thus fully consistent with CDM structure growth
predictions based on CMB anisotropies probing primarily . We find no
evidence for a suppression of the amplitude of cosmic structure at low
redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see
companion papers Madhavacheril et al and MacCrann et a
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