226 research outputs found
Directed flow in non-adiabatic stochastic pumps
We analyze the operation of a molecular machine driven by the non-adiabatic
variation of external parameters. We derive a formula for the integrated flow
from one configuration to another, obtain a "no-pumping theorem" for cyclic
processes with thermally activated transitions, and show that in the adiabatic
limit the pumped current is given by a geometric expression.Comment: 5 pages, 2 figures, very minor change
Intermediate statistics for a system with symplectic symmetry: the Dirac rose graph
We study the spectral statistics of the Dirac operator on a rose-shaped
graph---a graph with a single vertex and all bonds connected at both ends to
the vertex. We formulate a secular equation that generically determines the
eigenvalues of the Dirac rose graph, which is seen to generalise the secular
equation for a star graph with Neumann boundary conditions. We derive
approximations to the spectral pair correlation function at large and small
values of spectral spacings, in the limit as the number of bonds approaches
infinity, and compare these predictions with results of numerical calculations.
Our results represent the first example of intermediate statistics from the
symplectic symmetry class.Comment: 26 pages, references adde
The Impact of Atmospheric Dry Deposition Associated Microbes on the Southeastern Mediterranean Sea Surface Water following an Intense Dust Storm
This study explores the potential impacts of microbes deposited into the surface seawater of the southeastern Mediterranean Sea (SEMS) along with atmospheric particles on marine autotrophic and heterotrophic production. We compared in situ changes in autotrophic and heterotrophic microbial abundance and production rates before and during an intense dust storm event in early September 2015. Additionally, we measured the activity of microbes associated with atmospheric dry deposition (also referred to as airborne microbes) in sterile SEMS water using the same particles collected during the dust storm. A high diversity of prokaryotes and a low diversity of autotrophic eukaryotic algae were delivered to surface SEMS waters by the storm. Autotrophic airborne microbial abundance and activity were low, contributing ~1% of natural abundance in SEMS water and accounting for 1–4% to primary production. Airborne heterotrophic bacteria comprised 30–50% of the cells and accounted for 13–42% of bacterial production. Our results demonstrate that atmospheric dry deposition may supply not only chemical constitutes but also microbes that can affect ambient microbial populations and their activity in the surface ocean. Airborne microbes may play a greater role in ocean biogeochemistry in the future in light of the expected enhancement of dust storm durations and frequencies due to climate change and desertification processes
Lower bounds on dissipation upon coarse graining
By different coarse-graining procedures we derive lower bounds on the total
mean work dissipated in Brownian systems driven out of equilibrium. With
several analytically solvable examples we illustrate how, when, and where the
information on the dissipation is captured.Comment: 11 pages, 8 figure
Fluctuation relations and coarse-graining
We consider the application of fluctuation relations to the dynamics of
coarse-grained systems, as might arise in a hypothetical experiment in which a
system is monitored with a low-resolution measuring apparatus. We analyze a
stochastic, Markovian jump process with a specific structure that lends itself
naturally to coarse-graining. A perturbative analysis yields a reduced
stochastic jump process that approximates the coarse-grained dynamics of the
original system. This leads to a non-trivial fluctuation relation that is
approximately satisfied by the coarse-grained dynamics. We illustrate our
results by computing the large deviations of a particular stochastic jump
process. Our results highlight the possibility that observed deviations from
fluctuation relations might be due to the presence of unobserved degrees of
freedom.Comment: 19 pages, 6 figures, very minor change
Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial
Safety; Antifungal; CandidaemiaSeguridad; Antifúngico; CandidemiaSeguretat; Antifúngic; CandidèmiaBackground
Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration.
Methods
This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST.
Results
Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002–0.03 mg/L).
Conclusions
Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment.The study was funded by Amplyx, now a subsidiary of Pfizer Inc
The non-equilibrium steady state of sparse systems with nontrivial topology
We study the steady state of a multiply-connected system that is driven out
of equilibrium by a sparse perturbation. The prototype example is an -site
ring coupled to a thermal bath, driven by a stationary source that induces
transitions with log-wide distributed rates. An induced current arises, which
is controlled by the strength of the driving, and an associated topological
term appears in the expression for the energy absorption rate. Due to the
sparsity, the crossover from linear response to saturation is mediated by an
intermediate regime, where the current is exponentially small in ,
which is related to the work of Sinai on "random walk in a random environment".Comment: 6 pages, 4 figure
Relationship between thermohaline and biochemical patterns in the levantine upper and intermediate water masses, Southeastern Mediterranean Sea (2013–2021)
The relationships between the interannual variations of the Levantine intermediate water (LIW) core properties and the corresponding biochemical variations in the euphotic zone were systematically studied in the Southeastern Mediterranean during 2013–2021 and since 2002 based on a previous study. Salinity and temperature interannual fluctuations in the LIW continue to follow the Adriatic–Ionian Bimodal Oscillating System (BiOS) mechanism, with salinity and temperature peaks in the years 2008–2010, 2014–2015, and 2018–2019 coinciding with periods of anticyclonic circulation of the North Ionian Gyre (NIG). During these anticyclonic periods, the transport of Atlantic Water into the Levant is reduced together with the transport of LIW out of the basin. These interannual fluctuations are superimposed on a long-term warming trend clearly evident from previous studies, showing a maximal temperature in 2018–2019, higher than the previously mentioned temperature peaks by ~0.7°C and ~0.4°C. The enhanced warming in 2018–2019 has caused a decrease in density (sigma) values of the LIW core, which gave way to the shallowest record of this water mass (~110-m depth), bringing it well within the lower photic zone. We suggest that a higher level of nutrients became available, supporting the observed long-term rise of the intergraded chlorophyll a (Chl.a) (0.89 mg m−2 year−1), with a maximum recorded during 2018–2019. The long-term record of the mixed layer depths shows no significant change; thus, the uplift of nutrients during winter mixing cannot support the trend and variations of the integrated Chl.a. Additional biological parameters of specific pico-phytoplankton populations and integrated bacterial production and abundance were measured in 2013–2021, but the measurements were too sparse to follow a clear interannual dynamics. Yet significantly higher average levels for integrated primary production and bacterial abundances were observed during the anticyclonic period (as for Chl.a). The combined impacts of the BiOS mechanism and global warming, and hence the increase in LIW residence time and buoyancy, may impact the primary producers’ biomass at the photic zone. This latter feedback may slightly counter the enhanced oligotrophication due to enhanced stratification
reaction at intermediate energies
The reaction is considered at the energies between 200 MeV and
520 MeV. The Alt-Grassberger-Sandhas equations are iterated up to the lowest
order terms over the nucleon-nucleon t-matrix. The parameterized wave
function including five components is used. The angular dependence of the
differential cross section and energy dependence of tensor analyzing power
at the zero scattering angle are presented in comparison with the
experimental data
Spectral properties of quantized barrier billiards
The properties of energy levels in a family of classically pseudointegrable
systems, the barrier billiards, are investigated. An extensive numerical study
of nearest-neighbor spacing distributions, next-to-nearest spacing
distributions, number variances, spectral form factors, and the level dynamics
is carried out. For a special member of the billiard family, the form factor is
calculated analytically for small arguments in the diagonal approximation. All
results together are consistent with the so-called semi-Poisson statistics.Comment: 8 pages, 9 figure
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