Well-posedness results for triply nonlinear degenerate parabolic equations

We study the well-posedness of triply nonlinear degenerate elliptic-parabolic-hyperbolic problem $$b(u)_t - {\rm div} \tilde{\mathfrak a}(u,\nabla\phi(u))+\psi(u)=f, \quad u|_{t=0}=u_0$$ in a bounded domain with homogeneous Dirichlet boundary conditions. The nonlinearities $b,\phi$ and $\psi$ are supposed to be continuous non-decreasing, and the nonlinearity $\tilde{\mathfrak a}$ falls within the Leray-Lions framework. Some restrictions are imposed on the dependence of $\tilde{\mathfrak a}(u,\nabla\phi(u))$ on $u$ and also on the set where $\phi$ degenerates. A model case is $\tilde{\mathfrak a}(u,\nabla\phi(u)) =\tilde{\mathfrak{f}}(b(u),\psi(u),\phi(u))+k(u)\mathfrak{a}_0(\nabla\phi(u)),$ with $\phi$ which is strictly increasing except on a locally finite number of segments, and $\mathfrak{a}_0$ which is of the Leray-Lions kind. We are interested in existence, uniqueness and stability of entropy solutions. If $b=\mathrm{Id}$, we obtain a general continuous dependence result on data $u_0,f$ and nonlinearities $b,\psi,\phi,\tilde{\mathfrak{a}}$. Similar result is shown for the degenerate elliptic problem which corresponds to the case of $b\equiv 0$ and general non-decreasing surjective $\psi$. Existence, uniqueness and continuous dependence on data $u_0,f$ are shown when $[b+\psi](\R)=\R$ and $\phi\circ [b+\psi]^{-1}$ is continuous

Chirality-induced asymmetric magnetic nucleation in Pt/Co/AlOx ultrathin microstructures

The nucleation of reversed magnetic domains in Pt/Co/AlO$_{x}$ microstructures with perpendicular anisotropy was studied experimentally in the presence of an in-plane magnetic field. For large enough in-plane field, nucleation was observed preferentially at an edge of the sample normal to this field. The position at which nucleation takes place was observed to depend in a chiral way on the initial magnetization and applied field directions. An explanation of these results is proposed, based on the existence of a sizable Dzyaloshinskii-Moriya interaction in this sample. Another consequence of this interaction is that the energy of domain walls can become negative for in-plane fields smaller than the effective anisotropy field.Comment: Published version, Physical Review Letters 113, 047203 (2014

An open trial assessment of "The Number Race", an adaptive computer game for remediation of dyscalculia

BACKGROUND: In a companion article [1], we described the development and evaluation of software designed to remediate dyscalculia. This software is based on the hypothesis that dyscalculia is due to a "core deficit" in number sense or in its access via symbolic information. Here we review the evidence for this hypothesis, and present results from an initial open-trial test of the software in a sample of nine 7–9 year old children with mathematical difficulties. METHODS: Children completed adaptive training on numerical comparison for half an hour a day, four days a week over a period of five-weeks. They were tested before and after intervention on their performance in core numerical tasks: counting, transcoding, base-10 comprehension, enumeration, addition, subtraction, and symbolic and non-symbolic numerical comparison. RESULTS: Children showed specific increases in performance on core number sense tasks. Speed of subitizing and numerical comparison increased by several hundred msec. Subtraction accuracy increased by an average of 23%. Performance on addition and base-10 comprehension tasks did not improve over the period of the study. CONCLUSION: Initial open-trial testing showed promising results, and suggested that the software was successful in increasing number sense over the short period of the study. However these results need to be followed up with larger, controlled studies. The issues of transfer to higher-level tasks, and of the best developmental time window for intervention also need to be addressed

Transcriptional regulation of two stage-specifically expressed genes in the protozoan parasite Toxoplasma gondii

The protozoan parasite Toxoplasma gondii differentially expresses two distinct enolase isoenzymes known as ENO1 and ENO2, respectively. To understand differential gene expression during tachyzoite to bradyzoite conversion, we have characterized the two T.gondii enolase promoters. No homology could be found between these sequences and no TATA or CCAAT boxes were evident. The differential activation of the ENO1 and ENO2 promoters during tachyzoite to bradyzoite differentiation was investigated by deletion analysis of 5′-flanking regions fused to the chloramphenicol acetyltransferase reporter followed by transient transfection. Our data indicate that in proliferating tachyzoites, the repression of ENO1 involves a negative distal regulatory region (nucleotides −1245 to −625) in the promoter whereas a proximal regulatory region in the ENO2 promoter directs expression at a low level. In contrast, the promoter activity of ENO1 is highly induced following the conversion of tachyzoites into resting bradyzoites. The ENO2 promoter analysis in bradyzoites showed that there are two upstream repression sites (nucleotides −1929 to −1067 and −456 to −222). Furthermore, electrophoresis mobility shift assays demonstrated the presence of DNA-binding proteins in tachyzoite and bradyzoite nuclear lysates that bound to stress response elements (STRE), heat shock-like elements (HSE) and other cis-regulatory elements in the upstream regulatory regions of ENO1 and ENO2. Mutation of the consensus AGGGG sequence, completely abolished protein binding to an oligonucleotide containing this element. This study defines the first characterization of cis-regulatory elements and putative transcription factors involved in gene regulation of the important pathogen T.gondii

High lipid order of Arabidopsis cell‐plate membranes mediated by sterol and DYNAMIN‐RELATED PROTEIN1A function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/1/tpj12674.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/2/tpj12674-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/3/tpj12674-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/4/tpj12674-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/5/tpj12674-sup-0004-FigS4.pd

Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma

BACKGROUND: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. RESULTS: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013). CONCLUSIONS: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Interoperable atlases of the human brain

International audienceThe last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different as-pects of the human brain including micro-and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topo-graphically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and represen-tation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Serum Alpha-Fetoprotein Predicts Treatment Outcome in Chronic Hepatitis C Patients Regardless of HCV Genotype

We examined the association between serum alpha-fetoprotein (AFP) level and sustained virological response (SVR) in 93 chronic hepatitis C patients. The SVR rate was much higher among patients with serum AFP levels below rather than above the median value (5.7 ng/ml) (58.7% and 19.2%, respectively; P<0.0001). Serum AFP should be added to the list of factors predictive of treatment response in chronic hepatitis C