261 research outputs found
Toward physical realizations of thermodynamic resource theories
Conventional statistical mechanics describes large systems and averages over
many particles or over many trials. But work, heat, and entropy impact the
small scales that experimentalists can increasingly control, e.g., in
single-molecule experiments. The statistical mechanics of small scales has been
quantified with two toolkits developed in quantum information theory: resource
theories and one-shot information theory. The field has boomed recently, but
the theorems amassed have hardly impacted experiments. Can thermodynamic
resource theories be realized experimentally? Via what steps can we shift the
theory toward physical realizations? Should we care? I present eleven
opportunities in physically realizing thermodynamic resource theories.Comment: Publication information added. Cosmetic change
Thermodynamic Tree: The Space of Admissible Paths
Is a spontaneous transition from a state x to a state y allowed by
thermodynamics? Such a question arises often in chemical thermodynamics and
kinetics. We ask the more formal question: is there a continuous path between
these states, along which the conservation laws hold, the concentrations remain
non-negative and the relevant thermodynamic potential G (Gibbs energy, for
example) monotonically decreases? The obvious necessary condition, G(x)\geq
G(y), is not sufficient, and we construct the necessary and sufficient
conditions. For example, it is impossible to overstep the equilibrium in
1-dimensional (1D) systems (with n components and n-1 conservation laws). The
system cannot come from a state x to a state y if they are on the opposite
sides of the equilibrium even if G(x) > G(y). We find the general
multidimensional analogue of this 1D rule and constructively solve the problem
of the thermodynamically admissible transitions.
We study dynamical systems, which are given in a positively invariant convex
polyhedron D and have a convex Lyapunov function G. An admissible path is a
continuous curve along which does not increase. For x,y from D, x\geq y (x
precedes y) if there exists an admissible path from x to y and x \sim y if
x\geq y and y\geq x. The tree of G in D is a quotient space D/~. We provide an
algorithm for the construction of this tree. In this algorithm, the restriction
of G onto the 1-skeleton of (the union of edges) is used. The problem of
existence of admissible paths between states is solved constructively. The
regions attainable by the admissible paths are described.Comment: Extended version, 31 page, 9 figures, 69 cited references, many minor
correction
Discovery of (R)-N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a novel orally bioavailable EAAT2 modulator with drug-like properties and potent antiseizure activity in vivo
[Image: see text] (R)-7 [(R)-AS-1] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. In vitro studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations. (R)-7 [(R)-AS-1] was not active in EAAT1 and EAAT3 assays and did not show significant off-target activity, including interactions with targets reported for marketed antiseizure drugs, indicative of a novel and unprecedented mechanism of action. Both in vivo pharmacokinetic and in vitro absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) profiles confirmed the favorable drug-like potential of the compound. Thus, (R)-7 [(R)-AS-1] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders
New national and regional bryophyte records, 72
ABSTRACT: New record of Sphagnum palustre L. to Graciosa Island (Azores).info:eu-repo/semantics/publishedVersio
Sub-National Revenue Mobilization in Latin America and Caribbean Countries: The Case of Venezuela
Evolution of the eukaryotic ARP2/3 activators of the WASP family: WASP, WAVE, WASH, and WHAMM, and the proposed new family members WAWH and WAML
<p>Abstract</p> <p>Background</p> <p>WASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and C-terminal VCA domains that harbour the ARP2/3-activating regions.</p> <p>Results</p> <p>To reveal the evolution of ARP2/3 activation by WASP family proteins we performed a "holistic" analysis by manually assembling and annotating all homologs in most of the eukaryotic genomes available. We have identified two new families: the WAML proteins (WASP and MIM like), which combine the membrane-deforming and actin bundling functions of the IMD domains with the ARP2/3-activating VCA regions, and the WAWH protein (WASP without WH1 domain) that have been identified in amoebae, Apusozoa, and the anole lizard. Surprisingly, with one exception we did not identify any alternative splice forms for WASP family proteins, which is in strong contrast to other actin-binding proteins like Ena/VASP, MIM, or NHS proteins that share domains with WASP proteins.</p> <p>Conclusions</p> <p>Our analysis showed that the last common ancestor of the eukaryotes must have contained a homolog of WASP, WAVE, and WASH. Specific families have subsequently been lost in many taxa like the WASPs in plants, algae, Stramenopiles, and Euglenozoa, and the WASH proteins in fungi. The WHAMM proteins are metazoa specific and have most probably been invented by the Eumetazoa. The diversity of WASP family proteins has strongly been increased by many species- and taxon-specific gene duplications and multimerisations. All data is freely accessible via <url>http://www.cymobase.org</url>.</p
Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer
Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease
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