A metric space
X
is rigid if the isometry group of
X
is trivial. The finite ultrametric spaces
X
with |
X
| ≥ 2 are not rigid since for every such
X
there is a self-isometry having exactly |
X
|−2 ...fixed points. Using the representing trees we characterize the finite ultrametric spaces
X
for which every self-isometry has at least |
X
|−2 fixed points. Some other extremal properties of such spaces and related graph theoretical characterizations are also obtained.
Film forming properties of semiconducting organic molecules comprising alkyl-chains combined with an aromatic unit have a decisive impact on possible applications in organic electronics. In ...particular, knowledge on the film formation process in terms of wetting or dewetting, and the precise control of these processes, is of high importance. In the present work, the subtle effect of temperature on the morphology and structure of dioctyl1benzothieno3,2-b1benzothiophene (C8-BTBT) films deposited on silica surfaces by spin coating is investigated in situ via X-ray diffraction techniques and atomic force microscopy. Depending on temperature, bulk C8-BTBT exhibits a crystalline, a smectic A and an isotropic phase. Heating of thin C8-BTBT layers at temperatures below the smectic phase transition temperature leads to a strong dewetting of the films. Upon approaching the smectic phase transition, the molecules start to rewet the surface in the form of discrete monolayers with a defined number of monolayers being present at a given temperature. The wetting process and layer formation is well defined and thermally stable at a given temperature. On cooling the reverse effect is observed and dewetting occurs. This demonstrates the full reversibility of the film formation behavior and reveals that the layering process is defined by an equilibrium thermodynamic state, rather than by kinetic effects.
On spaces extremal for the Gomory-Hu inequality Dovgoshey, O.; Petrov, E.; Teichert, H. -M.
P-adic numbers, ultrametric analysis, and applications,
04/2015, Letnik:
7, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Let (
X, d
) be a finite ultrametric space. In 1961 E.C. Gomory and T.C. Hu proved the inequality |Sp(
X
)| ⩽ |
X
| where Sp(
X
) = {
d
(
x, y
):
x, y
∈
X
}. Using weighted Hamiltonian cycles and ...weighted Hamiltonian paths we give new necessary and sufficient conditions under which the Gomory-Hu inequality becomes an equality. We find the number of non-isometric (
X, d
) satisfying the equality |Sp(
X
)| = |
X
| for given Sp(
X
). Moreover it is shown that every finite semimetric space
Z
is an image under a composition of mappings
f
:
X
→
Y
and
g
:
Y
→
Z
such that
X
and
Y
are finite ultrametric spaces,
X
satisfies the above equality,
f
is an
ɛ
-isometry with an arbitrary
ɛ
> 0, and
g
is a ball-preserving map.
A systematic review and a meta‐analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism ...on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC‐homozygotes, T‐allele carriers required an 8.3% (95% confidence interval (CI): 5.6–11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Clinical Pharmacology & Therapeutics (2012); 92 6, 746–756. doi:10.1038/clpt.2012.184
Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant ...c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI –28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000–0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.
The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is ...also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays. Tie2 downstream signalling in pericytes involves Calpain, Akt and FOXO3A. Ng2-Cre-driven deletion of pericyte-expressed Tie2 in mice transiently delays postnatal retinal angiogenesis. Yet, Tie2 deletion in pericytes results in a pronounced pro-angiogenic effect leading to enhanced tumour growth. Together, the data expand and revise the current concepts on vascular Angiopoietin/Tie signalling and propose a bidirectional, reciprocal EC-pericyte model of Tie2 signalling.
Abstract Background The blockade of lymphocyte trafficking from the lymph nodes (LNs) towards the intestinal mucosa is an effective approach for the treatment of ulcerative colitis (UC). Etrasimod is ...an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor (S1PR) modulator, which is currently also under investigation for Crohn’s disease (CD). The therapeutic mechanism of action of S1PR modulators in the context of inflammatory bowel disease (IBD) is not completely understood. It is hypothesized that both B and T- cell populations are affected by this treatment and are retained in the peripheral LNs, reducing circulating lymphocytes and resulting in fewer immune cells available to traffic in the gastrointestinal tract. Etrasimod has been reported to induce a partial and selective reduction of lymphocyte subsets in the blood of healthy subjects, but the direct effect of S1PR modulators on LN leukocytes has not been evaluated. The aim of this study was to investigate changes in leukocyte subpopulations in peripheral LNs and peripheral blood (PB) in response to S1PR inhibition with etrasimod in patients with CD. Methods CD patients with moderate to severe disease activity, participating in the Phase 2, double-blinded, non-placebo-controlled portion of the CULTIVATE trial, were eligible for this sub-study. At baseline and after 14 weeks of etrasimod induction treatment (2 or 3 mg/day), 10cc of PB and 4 ultrasound guided biopsy samples of an inguinal LN were obtained. The isolated peripheral blood mononuclear cells (PBMCs) and LN leukocyte populations, were analyzed at single cell level via high-dimensional immunophenotyping through mass cytometry (CyTOF) at both timepoints. Results We observed that in the LNs, the numbers/percentages of naïve, central and effector memory T-helper cells, as well as, of CD8+ naïve T-cells were increased after treatment with etrasimod. There was a decrease in the proportion of these cell populations in peripheral blood. Circulating naïve and memory B-cells were reduced, while these subsets where also slightly reduced in the LN compartment. Innate immune cell populations were not significantly altered. Conclusion Etrasimod induction treatment resulted in an increase of both naïve and central memory T-lymphocyte subsets in inguinal LNs, with a corresponding decrease in the periphery. The effect on the frequency of B-cells was not consistent in the LNs and PB, while innate immunotypes and T-regs, were not significantly affected. Despite the limited sample size, these selective effects were consistent with previously published PB immunophenotyping studies with etrasimod. This study was conducted as a collaboration between Amsterdam UMC and Pfizer.
We extend the classical SIR model of infectious disease spread to account for time dependence in the parameters, which also include diffusivities. The temporal dependence accounts for the changing ...characteristics of testing, quarantine and treatment protocols, while diffusivity incorporates a mobile population. This model has been applied to data on the evolution of the COVID-19 pandemic in the US state of Michigan. For system inference, we use recent advances; specifically our framework for Variational System Identification (Wang et al. in Comput Methods Appl Mech Eng 356:44–74, 2019;
arXiv:2001.04816
cs.CE) as well as Bayesian machine learning methods.
Film forming properties of semiconducting organic molecules comprising alkyl-chains combined with an aromatic unit have a decisive impact on possible applications in organic electronics. In ...particular, knowledge on the film formation process in terms of wetting or dewetting, and the precise control of these processes, is of high importance. In the present work, the subtle effect of temperature on the morphology and structure of dioctyl1benzothieno3,2-
b
1benzothiophene (C8-BTBT) films deposited on silica surfaces by spin coating is investigated
in situ via
X-ray diffraction techniques and atomic force microscopy. Depending on temperature, bulk C8-BTBT exhibits a crystalline, a smectic A and an isotropic phase. Heating of thin C8-BTBT layers at temperatures below the smectic phase transition temperature leads to a strong dewetting of the films. Upon approaching the smectic phase transition, the molecules start to rewet the surface in the form of discrete monolayers with a defined number of monolayers being present at a given temperature. The wetting process and layer formation is well defined and thermally stable at a given temperature. On cooling the reverse effect is observed and dewetting occurs. This demonstrates the full reversibility of the film formation behavior and reveals that the layering process is defined by an equilibrium thermodynamic state, rather than by kinetic effects.
Film forming properties of semiconducting organic molecules comprising alkyl-chains combined with an aromatic unit have a decisive impact on possible applications in organic electronics.
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