194 research outputs found
Atomic motion in tilted optical lattices
This paper presents a formalism describing the dynamics of a quantum particle
in a one-dimensional, time-dependent, tilted lattice. The formalism uses the
Wannier-Stark states, which are localized in each site of the lattice, and
provides a simple framework allowing fully-analytical developments. Analytic
solutions describing the particle motion are explicit derived, and the
resulting dynamics is studied.Comment: 6 pages, 2 figs, submitted to EPJD, Springer Verlag styl
Wavepacket reconstruction via local dynamics in a parabolic lattice
We study the dynamics of a wavepacket in a potential formed by the sum of a
periodic lattice and of a parabolic potential. The dynamics of the wavepacket
is essentially a superposition of ``local Bloch oscillations'', whose frequency
is proportional to the local slope of the parabolic potential. We show that the
amplitude and the phase of the Fourier transform of a signal characterizing
this dynamics contains information about the amplitude and the phase of the
wavepacket at a given lattice site. Hence, {\em complete} reconstruction of the
the wavepacket in the real space can be performed from the study of the
dynamics of the system.Comment: 4 pages, 3 figures, RevTex
Revisiting the effect of pharmaceuticals on transmission stage formation in the malaria parasite Plasmodium falciparum
Malaria parasites rely on specialized stages, called gametocytes, to ensure human-to-human transmission. The formation of these sexual precursor cells is initiated by commitment of blood stage parasites to the sexual differentiation pathway. Plasmodium falciparum, the most virulent of six parasite species infecting humans, employs nutrient sensing to control the rate at which sexual commitment is initiated, and the presence of stress-inducing factors, including antimalarial drugs, has been linked to increased gametocyte production in vitro and in vivo. These observations suggest that therapeutic interventions may promote gametocytogenesis and malaria transmission. Here, we engineered a P. falciparum reporter line to quantify sexual commitment rates after exposure to antimalarials and other pharmaceuticals commonly prescribed in malaria-endemic regions. Our data reveal that some of the tested drugs indeed have the capacity to elevate sexual commitment rates in vitro. Importantly, however, these effects are only observed at drug concentrations that inhibit parasite survival and only rarely result in a net increase of gametocyte production. Using a drug-resistant parasite reporter line, we further show that the gametocytogenesis-promoting effect of drugs is linked to general stress responses rather than to compound-specific activities. Altogether, we did not observe evidence for mechanistic links between the regulation of sexual commitment and the activity of commonly used pharmaceuticals in vitro. Our data hence does not support scenarios in which currently applied therapeutic interventions would promote the spread of drug-resistant parasites or malaria transmission in general
Super Bloch oscillations in the Peyrard-Bishop-Holstein model
Recently, polarons in the Peyrard-Bishop-Holstein model under DC electric
fields were established to perform Bloch oscillations, provided the
charge-lattice coupling is not large. In this work, we study this model when
the charge is subjected to an applied field with both DC and AC components.
Similarly to what happens in the rigid lattice, we find that the carrier
undergoes a directed motion or coherent oscillations when the AC field is
resonant or detuned with respect to the Bloch frequency, respectively. The
electric density current and its Fourier spectrum are also studied to reveal
the frequencies involved in the polaron dynamics
Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri
The development of systemic approaches in biology has put emphasis on
identifying genetic modules whose behavior can be modeled accurately so as to
gain insight into their structure and function. However most gene circuits in a
cell are under control of external signals and thus quantitative agreement
between experimental data and a mathematical model is difficult. Circadian
biology has been one notable exception: quantitative models of the internal
clock that orchestrates biological processes over the 24-hour diurnal cycle
have been constructed for a few organisms, from cyanobacteria to plants and
mammals. In most cases, a complex architecture with interlocked feedback loops
has been evidenced. Here we present first modeling results for the circadian
clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock
genes have been shown to play a central role in Ostreococcus clock. We find
that their expression time profiles can be accurately reproduced by a minimal
model of a two-gene transcriptional feedback loop. Remarkably, best adjustment
of data recorded under light/dark alternation is obtained when assuming that
the oscillator is not coupled to the diurnal cycle. This suggests that coupling
to light is confined to specific time intervals and has no dynamical effect
when the oscillator is entrained by the diurnal cycle. This intringuing
property may reflect a strategy to minimize the impact of fluctuations in
daylight intensity on the core circadian oscillator, a type of perturbation
that has been rarely considered when assessing the robustness of circadian
clocks
The nonlinear Schroedinger equation for the delta-comb potential: quasi-classical chaos and bifurcations of periodic stationary solutions
The nonlinear Schroedinger equation is studied for a periodic sequence of
delta-potentials (a delta-comb) or narrow Gaussian potentials. For the
delta-comb the time-independent nonlinear Schroedinger equation can be solved
analytically in terms of Jacobi elliptic functions and thus provides useful
insight into the features of nonlinear stationary states of periodic
potentials. Phenomena well-known from classical chaos are found, such as a
bifurcation of periodic stationary states and a transition to spatial chaos.
The relation of new features of nonlinear Bloch bands, such as looped and
period doubled bands, are analyzed in detail. An analytic expression for the
critical nonlinearity for the emergence of looped bands is derived. The results
for the delta-comb are generalized to a more realistic potential consisting of
a periodic sequence of narrow Gaussian peaks and the dynamical stability of
periodic solutions in a Gaussian comb is discussed.Comment: Enhanced and revised version, to appear in J. Nonlin. Math. Phy
PD-1T TILs as a predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC
PURPOSE
Durable clinical benefit to PD-1 blockade in NSCLC is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCLC.
EXPERIMENTAL DESIGN
PD-1T TILs were digitally quantified in120 baseline samples from advanced NSCLC patients treated with PD-1 blockade. Primary outcome was Disease Control (DC) at 6 months. Secondary outcomes were DC at 12 months and survival. Exploratory analyses addressed the impact of lesion-specific responses, tissue sample properties and combination with other biomarkers on the predictive value of PD-1T TILs.
RESULTS
PD-1T TILs as a biomarker reached 77% sensitivity and 67% specificity at 6 months, and 93% and 65% at 12 months, respectively. Particularly, a patient group without clinical benefit was reliably identified, indicated by a high negative predictive value (NPV) (88% at 6 months, 98% at 12 months). High PD-1T TILs related to significantly longer progression-free (HR 0.39, 95% CI: 0.24-0.63, p<0.0001) and overall survival (HR 0.46, 95% CI: 0.28-0.76, p<0.01). Predictive performance was increased when lesion-specific responses and samples obtained immediately before treatment were assessed. Notably, the predictive performance of PD-1TTILs was superior to PD-L1 and TLS in the same cohort.
CONCLUSIONS
This study established PD-1T TILs as predictive biomarker for clinical benefit to PD-1 blockade in advanced NSCLC patients. Most importantly, the high NPV demonstrates an accurate identification of a patient group without benefit
Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells
© 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.Peer reviewe
Neddylation inhibition upregulates PDâL1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/1/ijc32379_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/2/ijc32379-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149569/3/ijc32379.pd
- âŠ