Trotter Product Formulae for ∗ -Automorphisms of Quantum Lattice Systems.

We consider the dynamics t ↦ τ t of an infinite quantum lattice system that is generated by a local interaction. If the interaction decomposes into a finite number of terms that are themselves local interactions, we show that τ t can be efficiently approximated by a product of n automorphisms, each of them being an alternating product generated by the individual terms. For any integer m, we construct a product formula (in the spirit of Trotter) such that the approximation error scales as n - m . Our bounds hold in norm, pointwise for algebra elements that are sufficiently well approximated by finite volume observables.

Neuregulin-4 Is Required for Maintaining Soma Size of Pyramidal Neurons in the Motor Cortex.

The regulation of neuronal soma size is essential for appropriate brain circuit function and its dysregulation is associated with several neurodevelopmental disorders. A defect in the dendritic growth and elaboration of motor neocortical pyramidal neurons in neonates lacking neuregulin-4 (NRG4) has previously been reported. In this study, we investigated whether the loss of NRG4 causes further morphologic defects that are specific to these neurons. We analyzed the soma size of pyramidal neurons of layer (L)2/3 and L5 of the motor cortex and a subpopulation of multipolar interneurons in this neocortical region in Nrg4+/+ and Nrg4-/- mice. There were significant decreases in pyramidal neuron soma size in Nrg4-/- mice compared with Nrg4+/+ littermates at all stages studied [postnatal day (P)10, P30, and P60]. The reduction was especially marked at P10 and in L5 pyramidal neurons. Soma size was not significantly different for multipolar interneurons at any age. This in vivo phenotype was replicated in pyramidal neurons cultured from Nrg4-/- mice and was rescued by NRG treatment. Analysis of a public single-cell RNA sequencing repository revealed discrete Nrg4 and Erbb4 expression in subpopulations of L5 pyramidal neurons, suggesting that the observed defects were due in part to loss of autocrine Nrg4/ErbB4 signaling. The pyramidal phenotype in the motor cortex of Nrg4-/- mice was associated with a lack of Rotarod test improvement in P60 mice, suggesting that absence of NRG4 causes alterations in motor performance.

Radiation exposure and image quality in staged low-dose protocols for coronary dual-source CT angiography: a randomized comparison.

OBJECTIVE: To evaluate staged low-dose approaches for coronary CT angiography (CTA) in which a standard sequence was added if the low-dose sequence did not allow reliable rule-out of coronary stenosis. PATIENTS AND METHODS: A total of 176 consecutive patients referred for dual-source CTA were randomized to three protocols: group 1 using prospective ECG-triggering (100 kV, 330 mAs), group 2 a retrospectively gated "MinDose" sequence (100 kV, 330 mAs) and group 3 a standard spiral sequence (120 kV, 400 mAs). If image quality in low-dose groups 1 or 2 was non-diagnostic, an additional standard CT examination (as in group 3) was performed. RESULTS: Non-diagnostic image quality was found in 11/56, 4/55, and 2/65 patients (46/896, 4/880 and 3/1,040 coronary segments) in groups 1, 2 and 3, respectively. Median (interquartile ranges) volumes of contrast material, CTDI(vol), DLP and effective dose for low-dose groups 1 and 2 and for standard group 3 were 92.5 (11.3), 75.0 (2.5) and 75.0 (9.0) ml; 8.0 (1.4), 16.8 (4.8) and 48.1 (14.2) mGy; 108.0 (27.3), 246.0 (93.0) and 701.0 (207.8) mGy cm; and 1.5 (0.4), 3.4 (1.3) and 9.8 (2.9) mSv, respectively. CONCLUSION: A staged coronary CTA protocol with an initial low-dose approach and addition of a standard sequence--should image quality be too low--can lead to a substantial reduction in radiation exposure.

Image quality in a low radiation exposure protocol for retrospectively ECG-gated coronary CT angiography.

OBJECTIVE: The purpose of our study was to systematically compare the image quality of dual-source CT coronary angiography using 100 kV instead of 120 kV. SUBJECTS AND METHODS: One hundred patients with a body weight

Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders.

Deletions in the 15q11.2 region of the human genome are associated with neurobehavioral deficits, and motor development delay, as well as in some cases, symptoms of autism or schizophrenia. The cytoplasmic FMRP-interacting protein 1 (CYFIP1) is one of the four genes contained within this locus and has been associated with other genetic forms of autism spectrum disorders (ASD). In mice, Cyfip1 haploinsufficiency leads to alteration of dendritic spine morphology and defects in synaptic plasticity, two pathophysiological hallmarks of mouse models of ASD. At the behavioral level, however, Cyfip1 haploinsufficiency leads to minor phenotypes, not directly relevant for 15q11.2 deletion syndrome or ASD. A fundamental question is whether neuronal phenotypes caused by the mutation of Cyfip1 are relevant for the human condition. Here, we describe a synaptic cluster of ASD-associated proteins centered on CYFIP1 and the adhesion protein Neuroligin-3. Cyfip1 haploinsufficiency in mice led to decreased dendritic spine density and stability associated with social behavior and motor learning phenotypes. Behavioral training early in development resulted in alleviating the motor learning deficits caused by Cyfip1 haploinsufficiency. Altogether, these data provide new insight into the neuronal and behavioral phenotypes caused by Cyfip1 mutation and proof-of-concept for the development of a behavioral therapy to treat phenotypes associated with 15q11.2 syndromes and ASD.

Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates.

In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety. Re-expression of Nlgn3 in parvalbumin-expressing cells in transgenic animals rescued their social behavior and alleviated the phenotype of their wild-type littermates, further indicating that the social behavior of Nlgn3 knockout mice has a direct and measurable impact on wild-type animals' behavior. Finally, we showed that, unlike male mice, female mice lacking Nlgn3 were insensitive to their peers' behavior but modified the social behavior of their littermates. Altogether, our findings show that the environment is a critical factor in the development of behavioral phenotypes in transgenic and wild-type mice. In addition, these results reveal that the social environment has a sexually dimorphic effect on the behavior of mice lacking Nlgn3, being more influential in males than females.

In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways.

Most small cell lung cancer (SCLC) patients relapse within 12 months of starting combination chemotherapy plus radio-therapy, due to the development of acquired chemo- and radio-resistance. This phenomenon relates to the induction of tumour differentiation, resulting in apoptosis-resistant, morphologically variant (v-SCLC) cells, which lack the neuroendocrine expression of classic (c-) SCLC cells. In this study spontaneously adherent SCLC sublines were shown by differential gene expression analysis to provide an in vitro model of variant differentiation in SCLC, with down-regulation of neuroendocrine markers and up-regulation of epithelial differentiation markers cyclin D1, endothelin, the cell adhesion molecules CD 44 and integrin subunits alpha2, beta3 and beta4. The sensitivity of adherent SCLC sublines to etoposide, cyclophosphamide and gamma radiation was significantly diminished relative to parent suspension cell lines. Western blot analysis using phosphorylation-specific antibodies to Akt and MAP kinase revealed markedly elevated activation in adherent SCLC sublines, paralleled by increased levels of phosphorylated Bad protein and activated NF-kappaB. Subcultivation of the adherent sublines on uncoated surfaces reversed their adherent phenotype immediately and under these conditions Akt activity reverted to low levels. These results suggest that c-SCLC cells can differentiate spontaneously to v-SCLC and that the associated cellular adhesion may trigger Akt-dependent inhibition of apoptosis in SCLC cells, thus leading to acquired chemo- and radio-resistance.

Noninvasive assessment of coronary in-stent restenosis by dual-source computed tomography.

Assessment of coronary artery stents using computed tomographic angiography has been challenging. The technology of dual-source computed tomography (DSCT) provides higher temporal resolution that may allow more accurate evaluation of coronary stents. This study evaluated the accuracy of DSCT for the assessment of coronary artery in-stent restenosis. A total of 112 patients with 150 previously implanted coronary stents (diameter > or = 3.0 mm) were examined using DSCT (Definition; Siemens Medical Solutions, Forchheim, Germany) before conventional coronary angiography. Each stent was classified as assessable or not assessable. All assessable stents were further classified for the absence or presence of in-stent restenosis (>50% diameter reduction) using DSCT, and results were compared with those using quantitative coronary angiography. Mean stent diameter was 3.27 +/- 0.35 mm. Fifteen of 80 stents (19%) with a diameter of 3.0 mm were not assessable, and all 70 stents >3.0 mm were assessable. DSCT correctly identified 16 of 19 in-stent restenoses in 135 assessable stents, as well as the absence of in-stent restenosis in 110 of 116 stents (sensitivity 84%, specificity 95%, positive predictive value 73%, and negative predictive value 97% in assessable stents). In conclusion, DSCT may be useful to noninvasively detect in-stent restenosis, especially in stents with a relatively large diameter.