Cerebrofaciothoracic dysplasia: four new patients with a recurrent TMCO1 pathogenic variant.

Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1

Theory for Metal Hydrides with Switchable Optical Properties

Recently it has been discovered that lanthanum, yttrium, and other metal hydride films show dramatic changes in the optical properties at the metal-insulator transition. Such changes on a high energy scale suggest the electronic structure is best described by a local model based on negatively charged hydrogen (H$^-$) ions. We develop a many-body theory for the strong correlation in a H$^-$ ion lattice. The metal hydride is described by a large $U$-limit of an Anderson lattice model. We use lanthanum hydride as a prototype of these compounds, and find LaH$_3$ is an insulator with a substantial gap consistent with experiments. It may be viewed either as a Kondo insulator or a band insulator due to strong electron correlation. A H vacancy state in LaH$_3$ is found to be highly localized due to the strong bonding between the electron orbitals of hydrogen and metal atoms. Unlike the impurity states in the usual semiconductors, there is only weak internal optical transitions within the vacancy. The metal-insulator transition takes place in a band of these vacancy states.Comment: 18 pages, 16 figures and 6 tables. Submitted to PR

Utility of irritable bowel syndrome subtypes and most troublesome symptom in predicting disease impact and burden

Background Little is known about the characteristics of individuals with irritable bowel syndrome (IBS) according to stool subtype or the most troublesome symptom reported by the individual, or whether these are useful in predicting the impact of IBS. Methods We collected demographic, gastrointestinal, and psychological symptoms, healthcare usage and direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. Key Results We recruited 752 people with Rome IV IBS. Individuals with IBS-D reported a poorer disease-specific quality of life than those with IBS-C or IBS-M (mean (SD) IBS-QOL 45.3 (23.0) for IBS-D, vs. 52.3 (19.9) for IBS-C, vs. 49.4 (22.0) for IBS-M, p = 0.005). Mean (SD) IBS-QOL scores were also lower amongst those who reported diarrhea (44.8 (22.3)) or urgency (44.6 (22.3)) as their most troublesome symptom, compared with those reporting abdominal pain (52.2 (22.9)), constipation (49.5 (21.8)), or abdominal bloating or distension (50.4 (21.3)). However, there were no differences in mean EQ-5D scores, IBS severity, levels of anxiety, depression, somatoform symptom-reporting, or gastrointestinal symptom-specific anxiety. Direct healthcare costs of IBS were similar across all subtypes and all most troublesome symptom groups, although some differences in work productivity and social leisure activities were detected. Conclusions and Inferences There appears to be limited variation in the characteristics of individuals with Rome IV IBS based on both stool subtypes and most troublesome symptom reported, suggesting that gastrointestinal symptoms alone have limited ability to predict disease impact and burden

Samarium-153 labelled microparticles for liver tumour targeted therapy with imaging functionality

Samarium-153 (153Sm) are widely used in radia-tion synovectomy and pain management for patients with bone metastases. However, its therapeutic application has not been fully explored. 153Sm has been proven to be useful for imaging purposes. This provides a beneficial alternative for therapy with pure beta emitter especially for liver radioembolization with Yttrium-90 (90Y). This study aimed to develop an alterna-tive radioembolic agent using 153Sm and biocompatible resin microparticles for liver cancer therapy. The ion-exchange resin; Amberlite IR-120 H+ commercially available in large beads were crushed and sieved to 20 – 40 μm and labelled with 152SmCl3 salt prior to neutron activation. Administered activity of 3 GBq 153Sm was aimed based on the standard activity used by the 90Y SIR-Spheres. 6 hours irradiation in 1.494 x 1012 n.cm-2.s-1 flux produced 3.1 GBq.g-1 immediately after activa-tion. Characterization of the microparticles, gamma spectros-copy, and in-vitro radiolabelling studies were carried out and compared to a commercially available resin readily made in 20 – 40 μm, Fractogel EMD SO3- (S). 153Sm-Amberlite micropar-ticles possess a superior and suitable characteristics for liver radioembolization with added imaging capabilities

Kondo effect in multielectron quantum dots at high magnetic fields

We present a general description of low temperature transport through a quantum dot with any number of electrons at filling factor $1<\nu <2$. We provide a general description of a novel Kondo effect which is turned on by application of an appropriate magnetic field. The spin-flip scattering of carriers by the quantum dot only involves two states of the scatterer which may have a large spin. This process is described by spin-flip Hubbard operators, which change the angular momentum, leading to a Kondo Hamiltonian. We obtain antiferromagnetic exchange couplings depending on tunneling amplitudes and correlation effects. Since Kondo temperature has an exponential dependence on exchange couplings, quantitative variations of the parameters in different regimes have important experimental consequences. In particular, we discuss the {\it chess board} aspect of the experimental conductance when represented in a grey scale as a function of both the magnetic field and the gate potential affecting the quantum dot

Interference and interaction effects in multi-level quantum dots

Using renormalization group techniques, we study spectral and transport properties of a spinless interacting quantum dot consisting of two levels coupled to metallic reservoirs. For strong Coulomb repulsion $U$ and an applied Aharonov-Bohm phase $\phi$, we find a large direct tunnel splitting $|\Delta|\sim (\Gamma/\pi)|\cos(\phi/2)|\ln(U/\omega_c)$ between the levels of the order of the level broadening $\Gamma$. As a consequence we discover a many-body resonance in the spectral density that can be measured via the absorption power. Furthermore, for $\phi=\pi$, we show that the system can be tuned into an effective Anderson model with spin-dependent tunneling.Comment: 5 pages, 4 figures included, typos correcte

Normal Cones and Thompson Metric

The aim of this paper is to study the basic properties of the Thompson metric $d_T$ in the general case of a real linear space $X$ ordered by a cone $K$. We show that $d_T$ has monotonicity properties which make it compatible with the linear structure. We also prove several convexity properties of $d_T$ and some results concerning the topology of $d_T$, including a brief study of the $d_T$-convergence of monotone sequences. It is shown most of the results are true without any assumption of an Archimedean-type property for $K$. One considers various completeness properties and one studies the relations between them. Since $d_T$ is defined in the context of a generic ordered linear space, with no need of an underlying topological structure, one expects to express its completeness in terms of properties of the ordering, with respect to the linear structure. This is done in this paper and, to the best of our knowledge, this has not been done yet. The Thompson metric $d_T$ and order-unit (semi)norms $|\cdot|_u$ are strongly related and share important properties, as both are defined in terms of the ordered linear structure. Although $d_T$ and $|\cdot|_u$ are only topological (and not metrical) equivalent on $K_u$, we prove that the completeness is a common feature. One proves the completeness of the Thompson metric on a sequentially complete normal cone in a locally convex space. At the end of the paper, it is shown that, in the case of a Banach space, the normality of the cone is also necessary for the completeness of the Thompson metric.Comment: 36 page

FtsZ-dependent elongation of a coccoid bacterium

A mechanistic understanding of the determination and maintenance of the simplest bacterial cell shape, a sphere, remains elusive compared with that of more complex shapes. Cocci seem to lack a dedicated elongation machinery, and a spherical shape has been considered an evolutionary dead-end morphology, as a transition from a spherical to a rod-like shape has never been observed in bacteria. Here we show that a Staphylococcus aureus mutant (M5) expressing the ftsZG193D allele exhibits elongated cells. Molecular dynamics simulations and in vitro studies indicate that FtsZG193D filaments are more twisted and shorter than wild-type filaments. In vivo, M5 cell wall deposition is initiated asymmetrically, only on one side of the cell, and progresses into a helical pattern rather than into a constricting ring as in wild-type cells. This helical pattern of wall insertion leads to elongation, as in rod-shaped cells. Thus, structural flexibility of FtsZ filaments can result in an FtsZ-dependent mechanism for generating elongated cells from cocci

The embedding method beyond the single-channel case: Two-mode and Hubbard chains

We investigate the relationship between persistent currents in multi-channel rings containing an embedded scatterer and the conductance through the same scatterer attached to leads. The case of two uncoupled channels corresponds to a Hubbard chain, for which the one-dimensional embedding method is readily generalized. Various tests are carried out to validate this new procedure, and the conductance of short one-dimensional Hubbard chains attached to perfect leads is computed for different system sizes and interaction strengths. In the case of two coupled channels the conductance can be obtained from a statistical analysis of the persistent current or by reducing the multi-channel scattering problem to several single-channel setups.Comment: 14 pages, 13 figures, submitted for publicatio

Asymptotic behavior of w in general quintom model

For the quintom models with arbitrary potential $V=V(\phi,\sigma)$, the asymptotic value of equation of state parameter w is obtained by a new method. In this method, w of stable attractors are calculated by using the ratio (d ln V)/(d ln a) in asymptotic region. All the known results, have been obtained by other methods, are reproduced by this method as specific examples.Comment: 8 pages, one example is added, accepted for publication in Gen. Rel. Gra