Demonstration of deterministic and high fidelity squeezing of quantum information

By employing at recent proposal (R. Filip, P. Marek and U.L. Andersen, Phys. Rev. A {\bf 71}, 042308 (2005) \cite{Filip05.pra}), we experimentally demonstrate a universal, deterministic and high-fidelity squeezing transformation of an optical field. It relies only on linear optics, homodyne detection, feedforward and an ancillary squeezed vacuum state, thus direct interaction between a strong pump and the quantum state is circumvented. We demonstrate three different squeezing levels for a coherent state input. This scheme is highly suitable for the fault-tolerant squeezing transformation in a continuous variable quantum computer.Comment: 5 pages, 4 figure

Association of Genetic Risks with Autism Spectrum Disorder and Early Neurodevelopmental Delays among Children without Intellectual Disability

IMPORTANCE Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. OBJECTIVE To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. MAIN OUTCOMES AND MEASURES Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. RESULTS Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, −1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, −1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, −5.28; SE, 1.40; P \u3c .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, −5.30; SE 1.30; P \u3c .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, −6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, −6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling–associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, −5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, −5.38; SE, 1.74; P = .002). CONCLUSIONS AND RELEVANCE In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills

Polygenic Risk Score Analysis Revealed Shared Genetic Background in Attention Deficit Hyperactivity Disorder and Narcolepsy

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n=876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g.,P-value threshold \u3c 0.05,β[SE], 5.815 [1.774];P=0.002) and inattention domain(e.g.,P-value threshold \u3c 0.05,β[SE], 5.734 [1.761];P=0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD

Conservation of Silk Genes in Trichoptera and Lepidoptera

Larvae of the sister orders Trichoptera and Lepidoptera are characterized by silk secretion from a pair of labial glands. In both orders the silk filament consists of heavy (H)- and light (L)-chain fibroins and in Lepidoptera it also includes a P25 glycoprotein. The L-fibroin and H-fibroin genes of Rhyacophila obliterata and Hydropsyche angustipennis caddisflies have exon/intron structuring (seven exons in L-fibroin and two in H-fibroin) similar to that in their counterparts in Lepidoptera. Fibroin cDNAs are also known in Limnephilus decipiens, representing the third caddisfly suborder. Amino acid sequences of deduced L-fibroin proteins and of the terminal H-fibroin regions are about 50% identical among the three caddisfly species but their similarity to lepidopteran fibroins is <25%. Positions of some residues are conserved, including cysteines that were shown to link the L-fibroin and H-fibroin by a disulfide bridge in Lepidoptera. The long internal part of H-fibroins is composed of short motifs arranged in species-specific repeats. They are extremely uniform in R. obliterata. Motifs (SX)n, GGX, and GPGXX occur in both Trichoptera and Lepidoptera. The trichopteran H-fibroins further contain charged amphiphilic motifs but lack the strings of alanines or alanine-glycine dipeptides that are typical lepidopteran motifs. On the other hand, sequences composed of a motif similar to ERIVAPTVITR surrounded by the (SX)4-6 strings and modifications of the GRRGWGRRG motif occur in Trichoptera and not in Lepidoptera

SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain

The newly identified SYLF lipid-binding domain of SH3YL1 mediates phosphoinositide binding during dorsal membrane morphogenesis

Volume-based parameters on FDG PET may predict the proliferative potential of soft-tissue sarcomas

Introduction: Soft-tissue sarcomas (STS) are rare types of tumors that have variable levels of tumor differentiation. F-18 fluorodeoxyglucose positron emission tomography (FDG PET) has been established as an useful tool for STS patients, and the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are reported to be useful in various cancers. We compared the diagnostic value of four PET parameters (maximum standardized uptake value [SUVmax], SUVmean, MTV, and TLG) from two acquisition timings for predicting the expression of the pathological marker of cell proliferation Ki-67, based on pathological investigation. Materials and methods: In this retrospective study, we investigated 20 patients (59±19 years old, 18-87 years old) with pathologically confirmed STS who underwent FDG PET before surgical intervention. The patients fasted ≥6 h before the intravenous injection of FDG. The whole body was scanned twice; at an early phase (61.5±2.6 min) and at a delayed phase (118.0±2.1 min) post-injection. The SUVmax, SUVmean, MTV, and TLG of the primary lesion were measured with a tumor boundary determined by SUV ≥2.0. Ki-67 was measured using MIB-1 immunohistochemistry. We used Pearson's correlation coefficient to analyze the relationships between the PET parameters and Ki-67 expressions. The Kaplan-Meier analysis with the log-rank test was performed to compare overall survival between high-group and low-group at each of the four PET parameters and Ki-67 expression. Results: All four PET parameters at each phase showed significant correlations with Ki-67. Among them, the Pearson's correlation coefficient (r) was largest for TLG (r=0.76 and 0.77 at the early and delayed phases, respectively), followed by MTV (0.70 and 0.72), SUVmax (r=0.65 and 0.66), and SUVmean (r=0.62 and r=0.64). From early to delayed phases, the SUVmax and SUVmean both increased in all 20 patients, whereas the MTV and TLG increased in 13/20 (65%) and 16/20 (80%) patients, respectively. None of the %increases of the PET parameters were significantly correlated with Ki-67. The overall survival was shorter for high-SUVmax, high-SUVmean, high-TLG, and high-Ki-67 groups than the other groups, although the difference did not reach statistical significance. Conclusion: The SUVmax, SUVmean, MTV, and TLG acquired at both 1 and 2 h after injection showed significant correlations with Ki-67. Among them, correlation coefficient with Ki-67 expression was highest for TLG, although the best parameter should be determined in a larger population. The delayed-phase FDG PET was equally useful as that of early-phase to predict tumor aggressiveness in STS

Assessment of early changes in H-3-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression

Background: The purpose of this study was to evaluate whether early changes in 3'-deoxy-3'-H-3-fluorothymidine (H-3-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). Methods: An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of H-3-FLT and F-18-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. Results: High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of H-3-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 +/- 0.09, 0.36 +/- 0.06, 0.59 +/- 0.11% ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of F-18-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 +/- 2.4%, 6.2 +/- 1.8%,and 10.4 +/- 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group. Conclusion: In our animal model, H-3-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in H-3-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer