66 research outputs found
The long-time dynamics of two hydrodynamically-coupled swimming cells
Swimming micro-organisms such as bacteria or spermatozoa are typically found
in dense suspensions, and exhibit collective modes of locomotion qualitatively
different from that displayed by isolated cells. In the dilute limit where
fluid-mediated interactions can be treated rigorously, the long-time
hydrodynamics of a collection of cells result from interactions with many other
cells, and as such typically eludes an analytical approach. Here we consider
the only case where such problem can be treated rigorously analytically, namely
when the cells have spatially confined trajectories, such as the spermatozoa of
some marine invertebrates. We consider two spherical cells swimming, when
isolated, with arbitrary circular trajectories, and derive the long-time
kinematics of their relative locomotion. We show that in the dilute limit where
the cells are much further away than their size, and the size of their circular
motion, a separation of time scale occurs between a fast (intrinsic) swimming
time, and a slow time where hydrodynamic interactions lead to change in the
relative position and orientation of the swimmers. We perform a multiple-scale
analysis and derive the effective dynamical system - of dimension two -
describing the long-time behavior of the pair of cells. We show that the system
displays one type of equilibrium, and two types of rotational equilibrium, all
of which are found to be unstable. A detailed mathematical analysis of the
dynamical systems further allows us to show that only two cell-cell behaviors
are possible in the limit of , either the cells are attracted to
each other (possibly monotonically), or they are repelled (possibly
monotonically as well), which we confirm with numerical computations
Finite-temperature mutual information in a simple phase transition
We study the finite-temperature behavior of the Lipkin-Meshkov-Glick model,
with a focus on correlation properties as measured by the mutual information.
The latter, which quantifies the amount of both classical and quantum
correlations, is computed exactly in the two limiting cases of vanishing
magnetic field and vanishing temperature. For all other situations, numerical
results provide evidence of a finite mutual information at all temperatures
except at criticality. There, it diverges as the logarithm of the system size,
with a prefactor that can take only two values, depending on whether the
critical temperature vanishes or not. Our work provides a simple example in
which the mutual information appears as a powerful tool to detect
finite-temperature phase transitions, contrary to entanglement measures such as
the concurrence.Comment: 12 pages, 9 figures, published versio
Nearby young stars selected by proper motion. I. Four new members of the Beta Pictoris moving group from the Tycho-2 catalog
We describe a procedure to identify stars from nearby moving groups and
associations out of catalogs of stars with large proper motions. We show that
from the mean motion vector of a known or suspected moving group, one can
identify additional members of the group based on proper motion data and
photometry in the optical and infrared, with minimal contamination from
background field stars. We demonstrate this technique by conducting a search
for low-mass members of the Beta Pictoris Moving Group in the Tycho-2 catalog.
All known members of the moving group are easily recovered, and a list of 51
possible candidates is generated. Moving group membership is evaluated for 33
candidates based on X-ray flux from ROSAT, Halpha line emission, and radial
velocity measurement from high-resolution infrared spectra obtained at Infrared
Telescope Facility. We confirm three of the candidates to be new members of the
group: TYC 1186-706-1, TYC 7443-1102-1, and TYC 2211-1309-1 which are late-K
and early-M dwarfs 45-60pc from the Sun. We also identify a common proper
motion companion to the known Beta Pictoris Moving Group member TYC
7443-1102-1, at a 26".3 separation; the new companion is associated with the
X-ray source 1RXS J195602.8-320720. We argue that the present technique could
be applied to other large proper motion catalogs to identify most of the
elusive, low-mass members of known nearby moving groups and associations.Comment: To appear in the Astronomical Journal. Version 2 includes some
editing, corrected typos, and revised reference
Non-detection of Helium in the upper atmospheres of TRAPPIST-1b, e and f
We obtained high-resolution spectra of the ultra-cool M-dwarf TRAPPIST-1
during the transit of its planet `b' using two high dispersion near-infrared
spectrographs, IRD instrument on the Subaru 8.2m telescope and HPF instrument
on the 10m Hobby-Eberly Telescope. These spectroscopic observations are
complemented by a photometric transit observation for planet `b' using the
APO/ARCTIC, which assisted us to capture the correct transit times for our
transit spectroscopy. Using the data obtained by the new IRD and HPF
observations, as well as the prior transit observations of planets `b', `e' and
`f' from IRD, we attempt to constrain the atmospheric escape of the planet
using the He I triplet 10830 {\AA} absorption line. We do not detect evidence
for any primordial extended H-He atmospheres in all three planets. To limit any
planet related absorption, we place an upper limit on the equivalent widths of
<7.754 m{\AA} for planet `b', <10.458 m{\AA} for planet `e', and <4.143 m{\AA}
for planet `f' at 95% confidence from the IRD data, and <3.467 m{\AA} for
planet `b' at 95% confidence from HPF data. Using these limits along with a
solar-like composition isothermal Parker wind model, we attempt to constrain
the mass-loss rates for the three planets. For TRAPPIST-1b, our models exclude
the highest possible energy-limited rate for a wind temperature <5000 K. This
non-detection of extended atmospheres having low mean-molecular weight in all
three planets aids in further constraining their atmospheric composition by
steering the focus towards the search of high molecular weight species in their
atmospheres.Comment: 11 pages; 4 figures; Accepted for publication in A
Subtilase-mediated biogenesis of the expanded family of SERINE RICH ENDOGENOUS PEPTIDES
Plant signalling peptides are typically released from larger precursors by proteolytic cleavage to regulate plant growth, development and stress responses. Recent studies reported the characterization of a divergent family of Brassicaceae-specific peptides, SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs), and their perception by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2). Here, we reveal that the SCOOP family is highly expanded, containing at least 50 members in the Columbia-0 reference Arabidopsis thaliana genome. Notably, perception of these peptides is strictly MIK2-dependent. How bioactive SCOOP peptides are produced, and to what extent their perception is responsible for the multiple physiological roles associated with MIK2 are currently unclear. Using N-terminomics, we validate the N-terminal cleavage site of representative PROSCOOPs. The cleavage sites are determined by conserved motifs upstream of the minimal SCOOP bioactive epitope. We identified subtilases necessary and sufficient to process PROSCOOP peptides at conserved cleavage motifs. Mutation of these subtilases, or their recognition motifs, suppressed PROSCOOP cleavage and associated overexpression phenotypes. Furthermore, we show that higher-order mutants of these subtilases show phenotypes reminiscent of mik2 null mutant plants, consistent with impaired PROSCOOP biogenesis, and demonstrating biological relevance of SCOOP perception by MIK2. Together, this work provides insights into the molecular mechanisms underlying the functions of the recently identified SCOOP peptides and their receptor MIK2
Growing stock monitoring by European National Forest Inventories: Historical origins, current methods and harmonisation
peer reviewedWood resources have been essential for human welfare throughout history. Also nowadays, the volume of growing stock (GS) is considered one of the most important forest attributes monitored by National Forest Inventories (NFIs) to inform policy decisions and forest management planning. The origins of forest inventories closely relate to times of early wood shortage in Europe causing the need to explore and plan the utilisation of GS in the catchment areas of mines, saltworks and settlements. Over time, forest surveys became more detailed and their scope turned to larger areas, although they were still conceived as stand-wise inventories. In the 1920s, the first sample-based NFIs were introduced in the northern European countries. Since the earliest beginnings, GS monitoring approaches have considerably evolved. Current NFI methods differ due to country-specific conditions, inventory traditions, and information needs. Consequently, GS estimates were lacking international comparability and were therefore subject to recent harmonisation efforts to meet the increasing demand for consistent forest resource information at European level. As primary large-area monitoring programmes in most European countries, NFIs assess a multitude of variables, describing various aspects of sustainable forest management, including for example wood supply, carbon sequestration, and biodiversity. Many of these contemporary subject matters involve considerations about GS and its changes, at different geographic levels and time frames from past to future developments according to scenario simulations. Due to its historical, continued and currently increasing importance, we provide an up-to-date review focussing on large-area GS monitoring where we i) describe the origins and historical development of European NFIs, ii) address the terminology and present GS definitions of NFIs, iii) summarise the current methods of 23 European NFIs including sampling methods, tree measurements, volume models, estimators, uncertainty components, and the use of air- and space-borne data sources, iv) present the recent progress in NFI harmonisation in Europe, and v) provide an outlook under changing climate and forest-based bioeconomy objectives
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Strategies to model AL amyloidosis in mice.
International audienceMonoclonal immunoglobulin (Ig) deposition in AL amyloidosis is a severe complication of lymphoproliferative disorders. Research on this disease suffers from the lack of animal models, as they could allow for the testing of new innovative therapeutic strategies. We are trying to develop a transgenic animal model for this disease by overexpressing Ig light chain (LC) sequences cloned from AL amyloidosis patients. After several unsuccessful attempts using additional transgenesis due to low LC expression, we currently are following a strategy of targeted insertion of human LC sequences in the mouse endogenous kappa LC locus. We describe here the first data from this âknock-inâ model and propose future prospects to increase the rates of free LC and mimic the human disease. Absence of amyloid deposits in such models would raise the possibility of a resistance to AL amyloidosis in mice and question the feasibility of a reliable animal model for this disease
A rat model expressing a human amyloidogenic kappa light chain
International audienceNo abstract availabl
Light chain deposition disease and proximal tubulopathy in two successive kidney allografts.
International audienceLight chain proximal tubulopathy (LCPT) is a rare kidney disease associated with plasma cell dyscrasias, characterized by light chain deposits in the proximal tubular cells, with or without crystal formation. We describe an exceptional case of LCPT without crystal formation in a kidney allograft, in a patient who underwent two renal transplants for a light chain deposition disease (LCDD) complicating smoldering myeloma. This is the first description of this association in successive kidney allografts. We concisely describe pathology of LCDD and LCPT and discuss potential pathophysiological mechanisms relating these two conditions
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