Familial hypomagnesaemia, Hypercalciuria and Nephrocalcinosis associated with a novel mutation of the highly conserved leucine residue 116 of Claudin 16 in a Chinese patient with a delayed diagnosis: A case report

Background: Sixty mutations of claudin 16 coding gene have been reported in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) patients. Recent investigations revealed that a highly conserved glycine-leucine-tryptophan (115G-L-W117) motif in the first extracellular segment (ESC1) of claudin 16 might be essential for stabilization of the appropriately folded ECS1 structure and conservation of normal claudin 16 function. However, neither missense nor nonsense mutation has ever been described in this motif. Our study aimed at identifying mutations in a Chinese patient with FHHNC and exploring the association between genotype and phenotype. Case presentation: A 33-year-old female presented with 4 years history of recurrent acute pyelonephritis without other notable past medical history. Her healthy parents, who aged 56 and 53 respectively, were second cousins, and her only sibling died from renal failure without definite cause at age 25. Renal ultrasound imaging demonstrated atrophic kidneys and bilateral nephrocalcinosis. The laboratory workup revealed impaired renal function (Stage CKD IV), hypocalcemia and mild hypomagnesemia, accompanied with marked renal loss of magnesium and hypercalciuria. During the follow-up, treatment with calcitriol and calcium but not with magnesium was difficult to achieve normal serum calcium levels, whereas her serum magnesium concentration fluctuated within normal ranges. In the end, the patient unavoidably reached ESRD at 36 years old. The clinical features and family history suggested the diagnosis of FHHNC. To make a definite diagnosis, we use whole-exome sequencing to identify the disease-causing mutations and Sanger sequencing to confirm the mutation co-segregation in the family. As a result, a novel homozygous mutation (c.346C > G, p.Leu116Val) in115G-L-W117motif of claudin 16 was identified. Her parents, grandmother and one of her cousins carried heterozygous p.Leu116Val, whereas 200 unrelated controls did not carry this mutation. Conclusions: We described a delayed diagnosis patient with FHHNC in the Chinese population and identified a novel missense mutation in the highly conserved115G-L-W117motif of claudin 16 for the first time. According to the reported data and the information deduced from 3D modeling, we speculate that this mutation probably reserve partial residual function which might be related to the slight phenotype of the patient

Isospin effect on nuclear stopping in intermediate energy Heavy Ion Collisions

By using the Isospin Dependent Quantum Molecular Dynamics Model (IQMD), we study the dependence of nuclear stopping Q_{ZZ}/A and R in intermediate energy heavy ion collisions on system size, initial N/Z, isospin symmetry potential and the medium correction of two-body cross sections. We find the effect of initial N/Z ratio, isospin symmetry potential on stopping is weak. The excitation function of Q_{ZZ}/A and R depends on the form of medium correction of two-body cross sections, the equation of state of nuclear matter (EOS). Our results show the behavior of the excitation function of Q_{ZZ}/A and R can provide clearer information of the isospin dependence of the medium correction of two-body cross sections.Comment: 3 pages including 4 figure

Identification of a novel TSC2 c.3610G > A, p.G1204R mutation contribute to aberrant splicing in a patient with classical tuberous sclerosis complex: a case report

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in any organ systems. Mutations in the TSC1 or TSC2 gene lead to the dysfunction of hamartin or tuberin proteins, which cause tuberous sclerosis complex. Case presentation: We describe the clinical characteristics of patients from a Chinese family with tuberous sclerosis complex and analyze the functional consequences of their causal genetic mutations. A novel heterozygous mutation (c.3610G > A) at the last nucleotide of exon 29 in TSC2 was identified. On the protein level, this variant was presumed to be a missense mutation (p.Gly1204Arg). However, the splicing assay revealed that this mutation also leads to the whole TSC2 exon 29 skipping, besides the wild-type transcript. The mutated transcript results in an in-frame deletion of 71 amino acids (p.Gly1133_Thr1203del) and its ratio with the normal splice product is of about 44:56. Conclusions: The novel c.3610G > A TSC2 mutation was identified in association with tuberous sclerosis complex. And it was proven to code both for a missense-carrying transcript (56%), and for an isoform lacking exon 29 (44%)

Measurement of the Michel Parameter xi" in Polarized Muon Decay and Implications on Exotic Couplings of the Leptonic Weak Interaction

The Michel parameter xi" has been determined from a measurement of the longitudinal polarization of positrons emitted in the decay of polarized and depolarized muons. The result, xi" = 0.981 +- 0.045stat +- 0.003syst, is consistent with the Standard Model prediction of unity, and provides an order of magnitude improvement in the relative precision of this parameter. This value sets new constraints on exotic couplings beyond the dominant V-A description of the leptonic weak interaction.Comment: 15 pages, 16 figures, 3 tables; submitted to Phys. Rev.

Diffusion in simple fluids

Computed self diffusion coefficients for the Lennard-Jones and hard sphere fluids are related by Dej = DNs(aB) exp (--e/2kB T) where σB=σLJ(2/[1+ii(1+2kBT/ε)])1/6, the effective hard sphere diameter, is the (average) distance of closest approach in collisions between molecules which interact with the positive part of the LJ potential, and the Arrhenius term reflects the influence of the negative part. σLJ and ε are the size and well depth parameters. Measured diffusion coefficients of the halomethane liquids are reproduced by the equation over wide ranges of temperature and density and do not reveal any influence of the inelastic effects associated with molecular anisotropy

Fermi-surface induced modulation in an optimally doped YBCO superconductor

We have observed a Fermi-surface (FS) induced lattice modulation in a YBCO superconductor with a wavevector along CuO chains, {\it i.e.} ${\bf q}_1$=(0,$\delta$,0). The value of $\delta\sim0.21$ is twice the Fermi wavevector ($2{\bf k}_F$) along {\bf b*} connecting nearly nested FS `ridges'. The ${\bf q}_1$ modulation exists only within O-vacancy-ordered islands (characterized by ${\bf q}_0$=$(\frac14,0,0))$ and persists well above and below $T_c$. Our results are consistent with the presence of a FS-induced charge-density wave

INTEGRAL/SPI γ -ray line spectroscopy : Response and background characteristics

© 2018 ESO. Reproduced with permission from Astronomy & Astrophysics. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.Context. The space based γ-ray observatory INTEGRAL of the European Space Agency (ESA) includes the spectrometer instrument "SPI". This is a coded mask telescope featuring a 19-element Germanium detector array for high-resolution γ-ray spectroscopy, encapsulated in a scintillation detector assembly that provides a veto for background from charged particles. In space, cosmic rays irradiate spacecraft and instruments, which, in spite of the vetoing detectors, results in a large instrumental background from activation of those materials, and leads to deterioration of the charge collection properties of the Ge detectors.Aim. We aim to determine the measurement characteristics of our detectors and their evolution with time, that is, their spectral response and instrumental background. These incur systematic variations in the SPI signal from celestial photons, hence their determination from a broad empirical database enables a reduction of underlying systematics in data analysis. For this, we explore compromises balancing temporal and spectral resolution within statistical limitations. Our goal is to enable modelling of background applicable to spectroscopic studies of the sky, accounting separately for changes of the spectral response and of instrumental background.Methods. We use 13.5 years of INTEGRAL/SPI data, which consist of spectra for each detector and for each pointing of the satellite. Spectral fits to each such spectrum, with independent but coherent treatment of continuum and line backgrounds, provides us with details about separated background components. From the strongest background lines, we first determine how the spectral response changes with time. Applying symmetry and long-term stability tests, we eliminate degeneracies and reduce statistical fluctuations of background parameters, with the aim of providing a self-consistent description of the spectral response for each individual detector. Accounting for this, we then determine how the instrumental background components change in intensities and other characteristics, most-importantly their relative distribution among detectors.Results. Spectral resolution of Ge detectors in space degrades with time, up to 15% within half a year, consistently for all detectors, and across the SPI energy range. Semi-annual annealing operations recover these losses, yet there is a small long-term degradation. The intensity of instrumental background varies anti-correlated to solar activity, in general. There are significant differences among different lines and with respect to continuum. Background lines are found to have a characteristic, well-defined and long-term consistent intensity ratio among detectors. We use this to categorise lines in groups of similar behaviour. The dataset of spectral-response and background parameters as fitted across the INTEGRAL mission allows studies of SPI spectral response and background behaviour in a broad perspective, and efficiently supports precision modelling of instrumental background.Peer reviewedFinal Published versio

Mining State-Based Models from Proof Corpora

Interactive theorem provers have been used extensively to reason about various software/hardware systems and mathematical theorems. The key challenge when using an interactive prover is finding a suitable sequence of proof steps that will lead to a successful proof requires a significant amount of human intervention. This paper presents an automated technique that takes as input examples of successful proofs and infers an Extended Finite State Machine as output. This can in turn be used to generate proofs of new conjectures. Our preliminary experiments show that the inferred models are generally accurate (contain few false-positive sequences) and that representing existing proofs in such a way can be very useful when guiding new ones.Comment: To Appear at Conferences on Intelligent Computer Mathematics 201