Partition function zeros at first-order phase transitions: Pirogov-Sinai theory

This paper is a continuation of our previous analysis [BBCKK] of partition functions zeros in models with first-order phase transitions and periodic boundary conditions. Here it is shown that the assumptions under which the results of [BBCKK] were established are satisfied by a large class of lattice models. These models are characterized by two basic properties: The existence of only a finite number of ground states and the availability of an appropriate contour representation. This setting includes, for instance, the Ising, Potts and Blume-Capel models at low temperatures. The combined results of [BBCKK] and the present paper provide complete control of the zeros of the partition function with periodic boundary conditions for all models in the above class.Comment: 46 pages, 2 figs; continuation of math-ph/0304007 and math-ph/0004003, to appear in J. Statist. Phys. (special issue dedicated to Elliott Lieb

Direct Detection of Photoinduced Charge Transfer Complexes in Polymer:Fullerene Blends

We report transient electron paramagnetic resonance (trEPR) measurements with sub-microsecond time resolution performed on a P3HT:PCBM blend at low temperature. The trEPR spectrum immediately following photoexcitation reveals signatures of spin-correlated polaron pairs. The pair partners (positive polarons in P3HT and negative polarons in PCBM) can be identified by their characteristic g-values. The fact that the polaron pair states exhibit strong non-Boltzmann population unambiguously shows that the constituents of each pair are geminate, i.e. originate from one exciton. We demonstrate that coupled polaron pairs are present even several microseconds after charge transfer and suggest that they embody the intermediate charge transfer complexes which form at the donor/acceptor interface and mediate the conversion from excitons into free charge carriers

Double Doping of a Low-Ionization-Energy Polythiophene with a Molybdenum Dithiolene Complex

Doping of organic semiconductors is crucial for tuning the charge-carrier density of conjugated polymers. The exchange of more than one electron between a monomeric dopant and an organic semiconductor allows the polaron density to be increased relative to the number of counterions that are introduced into the host matrix. Here, a molybdenum dithiolene complex with a high electron affinity of 5.5 eV is shown to accept two electrons from a polythiophene that has a low ionization energy of 4.7 eV. Double p-doping is consistent with the ability of the monoanion salt of the molybdenum dithiolene complex to dope the polymer. The transfer of two electrons to the neutral dopant was also confirmed by electron paramagnetic resonance spectroscopy since the monoanion, but not the dianion, of the molybdenum dithiolene complex features an unpaired electron. Double doping allowed an ionization efficiency of 200% to be reached, which facilitates the design of strongly doped semiconductors while lessening any counterion-induced disruption of the nanostructure

Chemical Doping of Conjugated Polymers with the Strong Oxidant Magic Blue

Molecular doping of organic semiconductors is a powerful tool for the optimization of organic electronic devices and organic thermoelectric materials. However, there are few redox dopants that have a sufficiently high electron affinity to allow the doping of conjugated polymers with an ionization energy of more than 5.3\ua0eV. Here, p-doping of a broad palette of conjugated polymers with high ionization energies is achieved by using the strong oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate (Magic Blue). In particular diketopyrrolopyrrole (DPP)-based copolymers reach a conductivity of up to 100 S cm−1 and a thermoelectric power factor of 10 \ub5W m−1 K−2. Further, both electron paramagnetic resonance (EPR) as well as a combination of spectroelectrochemistry and chronoamperometry is used to estimate the charge-carrier density of the polymer PDPP-3T doped with Magic Blue. A molar attenuation coefficient of 6.0\ua0\ub1\ua00.2 7 103 m2 mol−1 is obtained for the first polaronic sub-bandgap absorption of electrochemically oxidized PDPP-3T. Comparison with chemically doped PDPP-3T suggests a charge-carrier density on the order of 1026 m−3, which yields a charge-carrier mobility of up to 0.5 cm2 V−1 s−1 for the most heavily doped material

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2

Background: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson’s disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro. Methodology/Principal Findings: Here, we show that the rho guanine nucleotide exchange factor ARHGEF7 and the small GTPase CDC42 are interacting with LRRK2 in vitro and in vivo. GTPase activity of full-length LRRK2 increases in the presence of recombinant ARHGEF7. Interestingly, LRRK2 phosphorylates ARHGEF7 in vitro at previously unknown phosphorylation sites. We provide evidence that ARHGEF7 might act as a guanine nucleotide exchange factor for LRRK2 and that R1441C mutant LRRK2 with reduced GTP hydrolysis activity also shows reduced binding to ARHGEF7. Conclusions/Significance: Downstream effects of phosphorylation of ARHGEF7 through LRRK2 could be (i) a feedback control mechanism for LRRK2 activity as well as (ii) an impact of LRRK2 on actin cytoskeleton regulation. A newly identified familial mutation N1437S, localized within the GTPase domain of LRRK2, further underlines the importance of the GTPas

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Leaf segmentation in plant phenotyping: a collation study

Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape characteristics, the presence of occlusions and variability in leaf shape and pose, as well as imaging conditions, render this problem challenging. The aim of this paper is to compare several leaf segmentation solutions on a unique and first-of-its-kind dataset containing images from typical phenotyping experiments. In particular, we report and discuss methods and findings of a collection of submissions for the first Leaf Segmentation Challenge of the Computer Vision Problems in Plant Phenotyping workshop in 2014. Four methods are presented: three segment leaves by processing the distance transform in an unsupervised fashion, and the other via optimal template selection and Chamfer matching. Overall, we find that although separating plant from background can be accomplished with satisfactory accuracy (>>90 % Dice score), individual leaf segmentation and counting remain challenging when leaves overlap. Additionally, accuracy is lower for younger leaves. We find also that variability in datasets does affect outcomes. Our findings motivate further investigations and development of specialized algorithms for this particular application, and that challenges of this form are ideally suited for advancing the state of the art. Data are publicly available (online at http://​www.​plant-phenotyping.​org/​datasets) to support future challenges beyond segmentation within this application domain

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), but the underlying pathophysiological mechanisms and the normal function of this large multidomain protein remain speculative. To address the role of this protein in vivo, we generated three different LRRK2 mutant mouse lines. Mice completely lacking the LRRK2 protein (knock-out, KO) showed an early-onset (age 6 weeks) marked increase in number and size of secondary lysosomes in kidney proximal tubule cells and lamellar bodies in lung type II cells. Mice expressing a LRRK2 kinase-dead (KD) mutant from the endogenous locus displayed similar early-onset pathophysiological changes in kidney but not lung. KD mutants had dramatically reduced full-length LRRK2 protein levels in the kidney and this genetic effect was mimicked pharmacologically in wild-type mice treated with a LRRK2-selective kinase inhibitor. Knock-in (KI) mice expressing the G2019S PD-associated mutation that increases LRRK2 kinase activity showed none of the LRRK2 protein level and histopathological changes observed in KD and KO mice. The autophagy marker LC3 remained unchanged but kidney mTOR and TCS2 protein levels decreased in KD and increased in KO and KI mice. Unexpectedly, KO and KI mice suffered from diastolic hypertension opposed to normal blood pressure in KD mice. Our findings demonstrate a role for LRRK2 in kidney and lung physiology and further show that LRRK2 kinase function affects LRRK2 protein steady-state levels thereby altering putative scaffold/GTPase activity. These novel aspects of peripheral LRRK2 biology critically impact ongoing attempts to develop LRRK2 selective kinase inhibitors as therapeutics for PD

PEDIA: prioritization of exome data by image analysis.

PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene. CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis