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Machine learning algorithms have proven to be effective for essential quantum computation tasks such as quantum error correction and quantum control. Efficient hardware implementation of these algorithms at cryogenic temperatures is essential. Here we utilize magnetic topological insulators as memristors (termed magnetic topological memristors) and introduce a cryogenic in-memory computing scheme based on the coexistence of a chiral edge state and a topological surface state. The memristive switching and reading of the giant anomalous Hall effect exhibit high energy efficiency, high stability and low stochasticity. We achieve high accuracy in a proof-of-concept classification task using four magnetic topological memristors. Furthermore, our algorithm-level and circuit-level simulations of large-scale neural networks demonstrate software-level accuracy and lower energy consumption for image recognition and quantum state preparation compared with existing magnetic memristor and complementary metal-oxide-semiconductor technologies. Our results not only showcase a new application of chiral edge states but also may inspire further topological quantum-physics-based novel computing schemes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Early language skills are considered important precursors of early mathematical development. Prior research extensively explored the association between vocabulary and early numeracy. However, few studies have delved into the specific impact of mathematical language on this association. This study investigated the extent to which mathematical language mediates the relation between general vocabulary knowledge and early numeracy competence. A total of 180 Hong Kong kindergarteners (mean age = 4.66 years, SD = 0.63) were individually tested on their Chinese general vocabulary knowledge, mathematical language, and early numeracy competence online. Path analysis showed that when children's age and family income were statistically controlled, general vocabulary knowledge had a direct positive association with early numeracy competence as well as an indirect link through mathematical language. The findings highlighted the pivotal role of mathematical vocabulary in the learning of mathematics in early childhood. Future directions for examining the role of mathematical language in early numeracy development across different languages are further discussed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Molecular residual disease detected by circulating tumor DNA (ctDNA) has been reported to be predictive of patients' outcomes in various types of cancers after curative intent treatment. Nevertheless, additional detailed information regarding the association of longitudinal ctDNA detection with long-term follow-up in lung cancer is needed. Here, we report on a cohort of patients with NSCLC who underwent definitive surgery and ctDNA analysis in the pre-operative, adjuvant, and surveillance settings., Method: Plasma samples were collected from 46 patients with clinical stage II-III NSCLC before surgery (n = 46), after surgery (n = 45), and every six months until two years thereafter (n = 78). A clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction-next-generation sequencing assay was used for the detection and quantification of ctDNA in retrospectively analyzed plasma samples., Results: Circulating tumor DNA was detected in the first postoperative (within 51 days after surgery) plasma samples in 13% (6/45) of patients (landmark analysis). All of them had disease recurrence within a median of 9.1 months. These patients had shorter recurrence-free and overall survivals than those without detectable ctDNA at a landmark time point ( p < 0.01) and in multivariate analyses ( p < 0.03). Longitudinally (considering all postoperative follow-up time points), ctDNA was detected in 13 patients, all of whom experienced disease recurrence (positive predictive value = 100%). Three patients who had central nervous system-only metastases did not have detectable ctDNA., Conclusions: The presence of ctDNA post-surgery or during surveillance identifies patients with NSCLC at high risk of recurrence. Serial testing is important to detect disease recurrence earlier (lead-time: 3.2 months)., Competing Interests: Dr. Ohara has received honoraria from AstraZeneca. Dr. Suda has received research funding from AstraZeneca and Guardant, and has received honoraria from Chugai Pharmaceuticals, Amgen, Daiichi-Sankyo, Taiho, Boehringer Ingelheim, and AstraZeneca. Dr. Hamada has received honoraria from AstraZeneca, Chugai Pharmaceuticals, and Bristol-Myers Squibb. Dr. Tsutani has received research funding from AstraZeneca, and Chugai Pharmaceuticals and has received honoraria from AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceuticals, Merck Sharp & Dohme, Ono Pharmaceuticals, and Roche; and has been on the advisory board of AstraZeneca, Chugai Pharmaceuticals, and Ono Pharmaceuticals. Dr. Mitsudomi has received research funding from AstraZeneca, Ono Pharmaceuticals, Merck Sharp & Dohme, Brigde Bio, Boehringer Ingelheim, Pfizer, Taiho and Chugai Pharmaceuticals; has received honoraria from AstraZeneca, Chugai Pharmaceuticals, Bristol-Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Taiho, Eli-Lilly, Novartis, Pfizer, Amgen, Takeda, Bristol Meyers Squibb and Ono Pharmaceuticals; has been on the advisory board of Taiho; and has been on the consulting fees of AstraZeneca, Ono, Bristol Meyers Squibb, Regeneron and Novartis. Dr. Kalashnikova, Dr. Sudhaman, Dr. Cheung, Dr. Krainock, Mr. Sethi, Mr. Feeney, and Dr. Liu are employees at Natera, Inc. with stock or option to own stock. Dr. Liu also received grants (funding to Mayo Clinic) from Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, and Tesaro; travel support from AstraZeneca, Genomic Health, and Ionis; and Ad hoc advisory board meetings (all funds to Mayo Clinic): AstraZeneca, Celgene, Roche and /Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Background and Aims: There is currently a dearth of tools to assess parents' use of effective interactive strategies for supporting early mathematics learning. One potential such strategy is sustained shared thinking. This study therefore constructed and validated a scale for measuring parents' use of sustained shared thinking during joint mathematics activities with young children, and examined its antecedents and outcomes., Methods: Four hundred and sixty-six parents completed a questionnaire about their conceptions of mathematics teaching and learning, home practices, as well as their kindergarten children's approach and avoidance motivation to learn mathematics. Additionally, the children were tested on numeration skills., Results and Conclusion: Results showed that our new scale has three factors: exchanging ideas with children about mathematical problem-solving processes, creating a child-centred atmosphere for mathematics learning, and engaging children in mathematical thinking. Parents' uses of these three strategies were predicted by their constructivist conception of mathematics teaching and learning, and were differentially associated with the children's numeration skills, approach, and avoidance motivation to learn mathematics. Potential uses of our new scale in future home mathematics environment research are discussed., (© 2024 British Psychological Society.)

Background: Parents' high academic expectations are positively associated with young children's mathematical abilities. However, minimal attention has been devoted to whether, and how, different ways of conveying the performance targets would result in different outcomes., Aims: The current study investigated whether and how parents' perfectionistic strivings and concerns were associated with young children's mathematical abilities through home mathematical activities, children's approach motivation to learn mathematics, and children's avoidance motivation to learn mathematics., Sample: Participants included 211 kindergarteners in Hong Kong and their parents., Methods: Data were collected through individual child tests and parent questionnaires., Results: Structural equation modelling revealed that parents' perfectionistic strivings had a direct positive link with children's mathematical abilities, an indirect link via approach motivation to learn mathematics, and an indirect link via home mathematical activities, and then approach motivation. Parents' perfectionistic concerns had a direct negative link with children's mathematical abilities, an indirect link via approach motivation to learn mathematics, and an indirect link via avoidance motivation to learn mathematics., Conclusions: Early childhood practitioners are recommended to raise parents' awareness of how to communicate high-performance targets to children in a constructive manner., (© 2024 British Psychological Society.)

This project involved a co-design process involving researchers and kindergarten teachers to produce learning activities that integrated fundamental movement skills (FMS) and mathematics. We piloted the co-designed activities (i.e., motor-math program) in a local kindergarten and examined the effects on FMS proficiency, mathematics skills, and accrued physical activity (PA). The participants comprised pupils (N = 39) from two matched kindergarten classes, in which we compared the motor-math program with typical mathematics lessons. All participants wore pedometers to measure their number of steps during class, one day per week. FMS proficiency (i.e., locomotor, object control) and mathematics skills (numeracy, geometry, math problem solving) were measured before and after implementation. Significant improvements in locomotor and object control skills were found only in the pilot group ( p < 0.001); there were no differences in the changes in mathematics skills between the pilot and comparison groups. During implementation days, the participants in the pilot group accrued significantly greater step counts ( p < 0.001) than those in the comparison group. Participating in the motor-math program appears to have benefits associated with improvements in FMS proficiency and accrued PA time, suggesting a promising potential for integrated activities as a means of PA promotion in kindergarten settings. Future work that examines the effects of the integration of movement with mathematics should consider randomization, greater sample size, and a longer intervention period.

Parent-child and teacher-child relationship closeness have been shown to be crucial for children's development of socioemotional competencies from preschool to school-age stages. However, less is known about the importance of developing close relationships with young infants and toddlers attending childcare group settings for their early socioemotional development. The current study aimed to address this gap and to explore how child gender may influence the associations. Participants included 378 Hong Kong Chinese children (196 girls; M age  = 22.05 months, SD = 9.81 months) enrolled in childcare centres, along with their parents and teachers. Parents reported on children's socioemotional competencies as well as their relationship closeness with children; teachers reported on their relationship closeness with children. Multiple group structural equation modelling was used to analyse the results. The findings showed that both parent-child and teacher-child closeness were positively associated with children's social competence, while teacher-child closeness was negatively associated with children's anxiety behaviour. Parents of girls reported greater parent-child closeness, higher levels of social competence, and higher levels of anxiety behaviours compared to parents of boys. Furthermore, teacher-child closeness was significantly associated with social competence exclusively among girls, while parent-child closeness was significantly associated with anxiety behaviours solely among boys. Findings are discussed in terms of the role of child gender in influencing the associations between parent-child closeness, teacher-child closeness, and children's socioemotional competencies in the earliest years., (© 2024. The Author(s).)

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68  Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68  Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis., Competing Interests: Conflict of InterestShing Kee Cheung, Sirong Chen, Yuet Hung Wong, Kwan Kit Wu, and Chi Lai Ho declare no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2022.)

Weighted gene co-expression network analysis (WGCNA) identified a cell-cycle module that is associated with poor prognosis and aggressiveness of glioma. One of the core members, Regulator of chromatin condensation 2 (RCC2) is a component of the chromosome passenger complex. Accumulating evidence suggests that RCC2 plays a vital role in the mitotic process and that abnormal RCC2 expression is involved in cancer development. Gene silencing experiments show that RCC2 is required for glioma cell proliferation and migration. RNA-Sequencing analysis reveals a dual role of RCC2 in both the cell cycle and metabolism. Specifically, RCC2 regulates G2/M progression via CDC2 phosphorylation at Tyrosine 15. Metabolomic analysis identifies a role for RCC2 in promoting the glycolysis and pentose phosphate pathway. RCC2 exerts effects on metabolism by stabilizing the transcription factor BACH1 at its C-terminus leading to the transcriptional upregulation of hexokinase 2 (HK2). These findings elucidate a novel PTEN/RCC2/BACH1/HK2 signaling axis that drives glioma progression through the dual regulation of mitotic cell cycle and glycolytic events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Theory of Mind (ToM) refers to the ability to represent one's own and others' mental states, and emotion understanding involves appropriately comprehending and responding to others' emotional cues in social interactions. Individual differences in mind and emotion understanding have been associated strongly with verbal ability and interaction and, as such, existing training for children's ToM and emotion understanding is mostly language-based. Building on the literature on embodied cognition, this study proposes that mind and emotion understanding could be facilitated by one's visuospatial experience in simulating other's frames of reference., Methods: This protocol consists of two training studies. Study 1 will examine if visuospatial perspective-taking training promotes ToM and emotion understanding. Participants will consist of 96 4.5-year-olds and will be randomly assigned to one of two training groups: the altercentric block building group (trained to be visuospatial perspective-takers), or the egocentric block building group (no visuospatial perspective-taking is involved). Study 2 will compare the engagement of visuospatial perspective-taking and verbal interaction in the development of mind and emotion understanding. Participants will consist of 120 4.5-year-olds. They will be randomly assigned to one of three training groups: the socialized altercentric block building (both visuospatial perspective-taking and verbal interaction), the parallel altercentric block building (visuospatial perspective-taking only), or the paired dialogic reading (verbal interaction only)., Conclusions: In terms of theoretical implications, the potential causal relationship between visuospatial perspective-taking and ToM and emotion understanding may shed new insights on what underlies the development of mental state understanding. The findings of this study also have practical implications: researchers and educators may popularize visuospatial perspective-taking training in the form of block-building games if it is found to be effective in complementing conventional language-based theory-of-mind training., (© 2022. The Author(s).)

Introduction: Sarcopenia is an important clinical syndrome in older people living with HIV (PLWH). With a change to the Asia sarcopenia definition in 2019, we aimed to determine whether health outcomes were associated with different definitions of sarcopenia among Asian PLWH., Methods: We performed a prospective cross-sectional study enrolling PLWH aged ≥35 years from January 2018 to November 2021. We defined sarcopenia by the Asia Working Group of Sarcopenia (AWGS) criteria in 2014 and 2019. AWGS-2014 included low muscle mass plus weak handgrip strength and/or slow gait speed. AWGS-2019 included low muscle mass plus low muscle strength or physical performance, while the presence of all defines severe sarcopenia. We measured appendicular skeletal muscle mass using dual-energy X-ray absorptiometry, handgrip strength, usual gait speed, five-time chair stand test and Short Physical Performance Battery. Correlations between each sarcopenia definition and health-related quality of life (using EQ-5D-5L and SF-36) and functional disability were determined., Results: One hundred and fifty Asian PLWH were enrolled, 132 (88%) were male, mean age was 60±10 years, duration of HIV diagnosis was 13 (IQR 8-18) years and current CD4 count was 574 (IQR 362-762) cells/mm 3 , 67 (45%) had multimorbidity, 64 (43%) had polypharmacy. Prevalence of sarcopenia by AWGS-2014, AWGS-2019 and severe sarcopenia was 17.3%, 27.3% and 18.0%, respectively. Age, education and polypharmacy were associated with sarcopenia. Sarcopenia (AWGS-2014) and severe sarcopenia were associated with mobility, physical functioning and physical component score (SF-36). All three criteria were associated with impaired instrumental activities of daily living (IADL). After age and sex adjustment, sarcopenia (AWGS-2014) (adjusted odds ratio/aOR 5.4, 95% confidence interval/CI 2.0-15.1) and severe sarcopenia (aOR 5.1, 95% CI 1.9-14.0) were associated with mobility and physical component score (SF-36) (β coefficients -5.3342, p = 0.022 and -5.412, p = 0.019). Sarcopenia (AWGS 2014) (aOR 5.2, 95% CI 1.7-16.2), sarcopenia (AWGS-2019) (aOR 4.5, 95% CI 1.5-13.1) and severe sarcopenia (aOR 3.5, 95% CI 1.1-10.9) were associated with impaired IADL in fully adjusted models., Conclusions: In a sample of Asian PLWH, 17.3%, 27.3% and 18.0% had sarcopenia as defined by AWGS-2014, AWGS-2019 and severe sarcopenia, respectively. Sarcopenia by AWGS-2014 and severe sarcopenia correlated with parameters of poor health outcomes, while sarcopenia by AWGS-2019 correlated with functional disability., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

The current study investigated the contributions of phonological awareness, rapid automatized naming (RAN), and vocabulary to early numeracy and print knowledge developmental trajectories. A total of 128 young Filipino children were tracked three times at mean ages of 4.5, 5.0, and 5.5 years. The initial level (the intercept) and the growth rate (the slope) of early numeracy and print knowledge were estimated. Results showed that phonological awareness, vocabulary, and age significantly predicted the initial level of early numeracy. RAN and vocabulary explained significant variance in the growth rate of early numeracy. Phonological awareness, RAN, and vocabulary accounted for unique variance in the initial level of print knowledge. Results highlight the differential roles of phonological awareness, RAN, and vocabulary knowledge in the development of early numeracy and print knowledge among Filipino children., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This article synthesizes findings from an international virtual conference, funded by the National Science Foundation (NSF), focused on the home mathematics environment (HME). In light of inconsistencies and gaps in research investigating relations between the HME and children's outcomes, the purpose of the conference was to discuss actionable steps and considerations for future work. The conference was composed of international researchers with a wide range of expertise and backgrounds. Presentations and discussions during the conference centered broadly on the need to better operationalize and measure the HME as a construct - focusing on issues related to child, family, and community factors, country and cultural factors, and the cognitive and affective characteristics of caregivers and children. Results of the conference and a subsequent writing workshop include a synthesis of core questions and key considerations for the field of research on the HME. Findings highlight the need for the field at large to use multi-method measurement approaches to capture nuances in the HME, and to do so with increased international and interdisciplinary collaboration, open science practices, and communication among scholars.

The home learning environment includes what parents do to stimulate children's literacy and numeracy skills at home and their overall beliefs and attitudes about children's learning. The home literacy and numeracy environments are two of the most widely discussed aspects of the home learning environment, and past studies have identified how socioeconomic status and parents' own abilities and interest in these domains also play a part in shaping children's learning experiences. However, these studies are mostly from the West, and there has been little focus on the situation of homes in Asia, which captures a large geographical area and a wide diversity of social, ethnic, and linguistic groups. Therefore, this paper aims to review extant studies on the home literacy and numeracy environments that have been conducted in different parts of Asia, such as China, the Philippines, India, Iran, Turkey, and the United Arab Emirates. Specifically, we explore how parents in these places perceive their roles in children's early literacy and numeracy development, the methods they regard as effective for promoting young children's literacy and numeracy learning, and the frequency with which they engage their young children in different types of home literacy and numeracy activities. We also examine studies on the relationship of the home literacy and numeracy environment with young children's developmental outcomes, and the effectiveness of parent training programs to improve the home literacy and numeracy environments in these contexts. By examining potential trends in findings obtained in different geographical areas, we can initially determine whether there are characteristics that are potentially unique to contexts in Asia. We propose future research directions that acknowledge the role of cultural values and social factors in shaping the home learning environment, and, by extension, in facilitating children's early literacy and numeracy development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheung, Dulay, Yang, Mohseni and McBride.)

Aim: This communication reviews results and toxicity of image-guided high-dose-rate endorectal brachytherapy (HDREBT) boost after external beam radiotherapy (ERT) in medically inoperable patients with rectal cancer., Materials and Methods: A total of 18 patients with rectal cancer and clinical stage T2-4N0‑2 treated with HDREBT boost after ERT were retrospectively reviewed., Results: Following treatment with a median total dose (EQD2, α/β = 10) of 66 Gy (range 48-92 Gy), the incidence of early and late rectal grade 3 toxicity was 11% and 19%, respectively. There was no correlation between the occurrence of acute and late toxicity., Conclusion: With proper technique, a combined approach using EBRT and HDREBT was associated with acceptable toxicity in medically inoperable rectal cancer patients.

The Risk Assessment and Management Program (RAMP) has successfully demonstrated a reduction of blood pressure (BP) and cardiovascular (CVD) risk of patients with hypertension. This study aimed to compare the blood pressure control rate of participants after attended RAMP group, with those attended RAMP individual from usual care. A prospective open cluster-randomized controlled trial was performed in five public primary care clinics. Patients with uncontrolled hypertension were recruited. RAMP group consisted of multi-disciplinary group education on knowledge of hypertension, lifestyle modification, and hands-on home blood pressure monitoring (HBPM) training. Each participant was given a branchial HBPM device. An individual face-to-face nurse follow-up was arranged 6 weeks later. Participants' office BP and clinical parameters were assessed at 6, 12, and 18 months. Three RAMP group and two RAMP-individual clusters recruited 152 and 139 participants, respectively. The mean age was 67.0 (SD 9.9) year. After 18 months of treatment, there was a significantly higher BP control rate in the RAMP-group participants than the RAMP-individual participants (78.9% vs 36.5%, P < .001). The systolic BP was reduced by 19.7 mm Hg (95% CI -22.03, -17.40, P < .001) and diastolic BP by 8.1 mm Hg (95% CI -9.66, -6.61, P < .001) in RAMP group while the RAMP individual demonstrated 9.3 mm Hg (95% CI -12.1, -6.4, P < .001) reduction in systolic BP without any significant difference in diastolic BP. The RAMP-group participants' body weight (BW) and body mass index(BMI) had no significant changes, while the RAMP-individual participants had a significant increase in BW and BMI. No adverse effect was reported., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The home numeracy environment is often assumed to play a role in early numeracy development. This study aimed to provide a comprehensive picture of the home numeracy environment of children living in low- to middle-income communities in the Philippines. Moreover, it examined the relations among various parents' characteristics, the home numeracy environment parents created, and their young children's numeracy skills. Data were collected from 290 families through parental questionnaires, numeracy tests for children, and numeracy tests for parents. Results of structural equation modeling showed that parents' education level, calculation fluency, own reported math activities, home numeracy resources and home numeracy activities all had direct associations with children's numeracy skills. Parents' calculation fluency and own math activities also had indirect links with children's numeracy skills through home numeracy resources and home numeracy activities. These findings provide insights into the question of which children are at risk for poor numeracy development and how to support children's early numeracy learning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pretreatment dual-tracer ( 18 F-fluorodeoxyglucose and 11 C-acetate) PET/computed tomography (CT) has potential to predict treatment response for 90 Y microsphere radioembolization (RE) in patients with inoperable hepatocellular carcinoma (HCC). Patients with 11 C-acetate-avid HCC have a better response to 90 Y microsphere RE, and possibly better survival. Pretreatment dual-tracer PET/CT has a significant theranostic value on 90 Y microsphere RE in determining target tumor dose for HCCs with different cellular differentiation, metabolic tumor volume, and functioning liver volume, and can be used to prescribe individual injected activity of 90 Y microspheres., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We examined the joint role of parental word reading skills and conventional home literacy environment measures among 320 Filipino low- to middle-income families in Cebu City, Philippines with children aged 5-8 years old. A ranking of parent-reported ratings of their frequency of engaging in home literacy activities and adult literacy practices revealed that book-related behaviors were less frequently practiced relative to other behaviors, and mean ratings on the home literacy resources scale suggested a relatively print-poor environment. Nevertheless, scale items about book reading and direct literacy instruction at home correlated with child's language and literacy skills. Structural equation modeling showed that parent's education and frequency of engaging in home literacy activities uniquely accounted for variance in child's oral language and print knowledge skills. In a second model, parent's word reading skills were significantly related to child's skills, but did not eliminate or attenuate influences from parent's education and home literacy activities. Results are important in relation to theories on the intergenerational transmission of literacy skills and the generalizability of findings from developed countries to developing country contexts., (© 2019 John Wiley & Sons Ltd.)

Mathematical word problem solving (MWPS) involves multiple steps, including comprehending the problem statements, determining the arithmetic operations that have to be performed, and finding the answers. This study investigated the relative contributions of different cognitive and affective variables to children's MWPS. To achieve this goal, 116 third-grade Chinese children were tested. Results showed that after controlling for age and non-verbal intelligence, the abilities to solve direct and indirect mathematical word problems were positively correlated with the working memory component of executive function, reading comprehension ability, math fact fluency and math anxiety. Moreover, math anxiety was found to fully mediate the relationships between reading anxiety and MWPS. Implications of the findings on how to promote children's MWPS skills were discussed.

Purpose: The aim of this study was to establish an algorithm for the prescription of 90 Y glass microsphere radioembolization ( 90 Y-GMRE) of HCC in individual patients based on the relationship between tumour dose (TD) and response validated by 90 Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters., Methods: The study group comprised 62 HCC patients prospectively recruited for 90 Y-GMRE who underwent pretreatment dual-tracer ( 11 C-acetate and 18 F-FDG) PET/CT as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to-nontumour ratio on 99m Tc-MAA SPECT/CT (T/NT MAA ) was correlated with posttreatment 90 Y PET/CT T/NT 90Y after quantification validation. The TD-response relationship for HCC of different tracer groups was assessed on follow-up PET/CT 2 months after treatment., Results: 90 Y PET/CT was accurate in the measurement of recovery of injected 90 Y activity (81.9-99.9%, median 94.8%). Pretreatment SPECT/CT T/NT MAA was strongly correlated with posttreatment 90 Y PET/CT T/NT 90Y (5.6 ± 3.2 versus 5.9 ± 3.5, T/NT 90Y 1.01 × T/NT MAA  + 0.161, r = 0.918, P < 0.05). The response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well, moderately and poorly differentiated HCC, respectively. The cut-off TD for a good response was significantly different between poorly differentiated and well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2% sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the T/NT MAA thresholds for predicting a good response in poorly differentiated and well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity (70.3%) and specificity (76%)., Conclusion: 90 Y PET/CT can provide accurate dosimetry for 90 Y-GMRE. Pretreatment T/NT MAA predicts posttreatment T/NT 90Y . The TD thresholds for a good response are tracer-dependent, with a strong correlation between HCC radiosensitivity and cellular differentiation and other PET-based parameters. These cytokinetic factors improve treatment efficacy while minimizing organ damage for the prescription of personalized 90 Y-GMRE.

Children's early numeracy outcomes set the foundation for mathematics learning in their future school years. This study examined how different family and individual variables were associated with the numeracy interest and competence of disadvantaged young children in the Philippines. The numeracy and literacy skills of 673 children living in low-middle income communities were tested. Their parents were also asked to complete a questionnaire on demographics, their home numeracy practices, attitudes about numeracy learning, and children's numeracy interest. Structural equation modelling analyses showed that children's numeracy interest was linked with their parents' practices and attitudes. Children's numeracy competence, on the other hand, was related to their gender, age, socioeconomic status, and literacy abilities. These findings suggest that family and individual variables might play different roles in disadvantaged children's early numeracy development. Moreover, parents can be encouraged to make effective use of home numeracy experiences to promote their children's numeracy competence. Statement of contribution What is already known on this subject? In developed countries, home environment is occasionally found to link with early numeracy development. Some individual variables are also found to play significant roles in early numeracy development. What does this study add? Among young Filipino children from disadvantaged backgrounds, home environment is related to numeracy interest. Family socioeconomic status plays a significant role in early numeracy competence. Early literacy and numeracy skills are interrelated with each other., (© 2017 The British Psychological Society.)

Background: The present study investigated the role of early language abilities in the development of math skills among Chinese K-3 students. About 2000 children in China, who were on average aged 6 years, were assessed for both informal math (e.g., basic number concepts such as counting objects) and formal math (calculations including addition and subtraction) skills, language abilities and nonverbal intelligence., Methodology: Correlation analysis showed that language abilities were more strongly associated with informal than formal math skills, and regression analyses revealed that children's language abilities could uniquely predict both informal and formal math skills with age, gender, and nonverbal intelligence controlled. Mediation analyses demonstrated that the relationship between children's language abilities and formal math skills was partially mediated by informal math skills., Results: The current findings indicate 1) Children's language abilities are of strong predictive values for both informal and formal math skills; 2) Language abilities impacts formal math skills partially through the mediation of informal math skills.

Feeding decisions are highly plastic and bidirectionally regulated by neurons that either promote or inhibit feeding. In Drosophila melanogaster, recent studies have identified four GABAergic interneurons that act as critical brakes to prevent incessant feeding. These GABAergic neurons may inhibit target neurons that drive consumption. Here, we tested this hypothesis by examining GABA receptors and neurons that promote consumption. We find that Resistance to dieldrin (RDL), a GABAA type receptor, is required for proper control of ingestion. Knockdown of Rdl in a subset of neurons causes overconsumption of tastants. Acute activation of these neurons is sufficient to drive consumption of appetitive substances and non-appetitive substances and acute silencing of these neurons decreases consumption. Taken together, these studies identify GABAA receptor-expressing neurons that promote Drosophila ingestive behavior and provide insight into feeding regulation.

A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation. Advanced prostate cancer may require investigation for pathological neuroendocrine transformation, although PSA may suggest improvement.

Purpose: This study was designed to compare waste anesthetic gas (WAG) concentrations within patients' breathing zones after removal of the patient's airway device in the postanesthesia care unit (PACU) vs in the operating room (OR)., Methods: Following Research Ethics Board approval and patient consent, we recruited patients undergoing surgery who received volatile anesthesia via an endotracheal tube or supraglottic airway. Patients had their airway device removed in the OR or in the PACU depending on the attending anesthesiologist's preference. Upon the patient's arrival in the PACU, concentrations of exhaled sevoflurane and desflurane were measured at their breathing zone (i.e., 15 cm from the patient's mouth and nose) using a single-beam infrared spectrophotometer., Results: Seventy patients were recruited during the five-month study period. The median [interquartile range] WAG levels in the patients' breathing zones were higher when their airway devices were removed in the PACU vs in the OR. The WAG levels for sevoflurane were 0.7 [0.4-1.1] parts per million (ppm) vs 0.5 [0.4-0.7] ppm, respectively; median difference, 0.3; 95% confidence interval (CI), 0.1 to 0.6; P = 0.04. The WAG levels for desflurane were 2.4 [1.2-3.4] ppm vs 4.1 [2.5-5.2] ppm, respectively; median difference, 1.5; 95% CI, 0.3 to 2.7; P = 0.04., Conclusions: After a volatile-based anesthetic, our results suggest that removal of the airway device in the PACU vs in the OR increases the amount of waste anesthetic gas in a patient's breathing zone and thus potentially in the PACU nurse's working zone.

The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.

The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored. We found that these long-range inhibitory projections enhance the specificity of contextual and object memory encoding. At the circuit level, these γ-aminobutyric acid (GABA)-releasing projections target hippocampal inhibitory neurons and thus act as a disinhibitory gate that transiently promotes the excitation of hippocampal CA1 pyramidal neurons by suppressing feedforward inhibition. This enhances the ability of CA1 pyramidal neurons to fire synaptically evoked dendritic spikes and to generate a temporally precise form of heterosynaptic plasticity. Long-range inhibition from entorhinal cortex may thus increase the precision of hippocampal-based long-term memory associations by assessing the salience of mnemonormation to the immediate sensory input., (Copyright © 2016, American Association for the Advancement of Science.)

Background: In Hong Kong, people aged 50-64 years were added as a recommended priority group (recommended group) for influenza vaccination by the Department of Health (DH) starting from 2011/12 onwards. The coverage rate of influenza vaccination for this age group was suboptimal at 8.5 % in 2012/13. This study investigates the factors associated with the uptake of influenza vaccination among adults in Hong Kong aged 50-64 years., Methods: A case-control study was conducted in communities by street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50-64 years who had received the influenza vaccine in 2011/12 or 2012/13, while controls were the same as the cases, except they had not received the influenza vaccine in 2011/12 or 2012/13. Multiple logistic regression analysis was performed on the data to explore the associations between vaccination status and the variables., Results: Six hundred and four respondents in total were interviewed and included in the analysis. There were 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The following were strongly associated with vaccination compared to other factors: 'eligible for free government vaccine' (OR6.38, 95 % CI, 3.43-11.87, p < 0.001); 'willing to receive flu vaccination for free' (OR4.84, 95 % CI, 2.13-11.03, p < 0.001); 'perceived having severe or moderate symptoms when contracting flu' (OR2.90, 95 % CI, 1.21-6.97, p = 0.02), and 'convenient to reach a vaccination location' (OR2.87, 95 % CI, 1.06-7.74, p = 0.04). The majority of the cases (80.8 %) and controls (93.9 %) were not aware that they belonged to a recommended group for influenza vaccination and most (>80 %) were willing to be vaccinated if it was free., Conclusions: Factors related to free and convenient vaccination, the perception of the severity of symptoms when contracting influenza had a comparatively strong association with influenza vaccination uptake amongst 50-64 year olds, compared to other factors.

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in humans; however, there is no accurate and fast quantitative test to detect UTI. Dipstick urinalysis is semi-quantitative with a limited diagnostic accuracy, while urine culture is accurate but takes time. We described a quantitative biochemical method for the diagnosis of bacteriuria using a single marker., Methods: We compared the urine metabolomes from 88 patients with bacterial UTI and 61 controls using (1)H NMR spectroscopy followed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The biomarker identified was subsequently validated using independent samples., Results: The urine acetic acid/creatinine (mmol/mmol) level was determined to be the most discriminatory marker for bacterial UTI with an area-under-receiver operating characteristic curve=0.97, sensitivity=91% and specificity=95% at the optimal cutoff 0.03 mmol/mmol. For validation, 60 samples were recruited prospectively. Using the optimal cutoff for acetic acid/creatinine, this method showed sensitivity=96%, specificity=94%, positive predictive value=92%, negative predictive value=97% and an overall accuracy=95%. The diagnostic performance was superior to dipstick urinalysis or microscopy. In addition, we also observed an increase of urinary trimethylamine (TMA) in patients with Escherichia coli-associated UTI. TMA is a mammalian-microbial co-metabolite and the high level of TMA generated is related to the bacterial enzyme, trimethylamine N-oxide (TMAO) reductase which reduces TMAO to TMA., Conclusions: Urine acetic acid is a neglected metabolite that can be used for rapid diagnosis of UTI and TMA can be used for etiologic diagnosis of UTI. With the introduction of NMR-based clinical analyzers to clinical laboratories, NMR-based urinalysis can be translated for clinical use., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The apical dendrites of many neurons contain proximal and distal compartments that receive synaptic inputs from different brain regions. These compartments also contain distinct complements of ion channels that enable the differential processing of their respective synaptic inputs, making them functionally distinct. At present, the molecular mechanisms that specify dendritic compartments are not well understood. Here, we report that the extracellular matrix protein Reelin, acting through its downstream, intracellular Dab1 and Src family tyrosine kinase signaling cascade, is essential for establishing and maintaining the molecular identity of the distal dendritic compartment of cortical pyramidal neurons. We find that Reelin signaling is required for the striking enrichment of HCN1 and GIRK1 channels in the distal tuft dendrites of both hippocampal CA1 and neocortical layer 5 pyramidal neurons, where the channels actively filter inputs targeted to these dendritic domains., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Feeding is dynamically regulated by the palatability of the food source and the physiological needs of the animal. How consumption is controlled by external sensory cues and internal metabolic state remains under intense investigation. Here, we identify four GABAergic interneurons in the Drosophila brain that establish a central feeding threshold which is required to inhibit consumption. Inactivation of these cells results in indiscriminate and excessive intake of all compounds, independent of taste quality or nutritional state. Conversely, acute activation of these neurons suppresses consumption of water and nutrients. The output from these neurons is required to gate activity in motor neurons that control meal initiation and consumption. Thus, our study reveals a layer of inhibitory control in feeding circuits that is required to suppress a latent state of unrestricted and nonselective consumption., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Trauma care systems aim to reduce both death and disability, yet there is little data on post-trauma health status and functional outcome., Objectives: To evaluate baseline, discharge, six month and 12 month post-trauma quality of life, functional outcome and predictors of quality of life in Hong Kong., Methods: Multicentre, prospective cohort study using data from the trauma registries of three regional trauma centres in Hong Kong. Trauma patients with an ISS≥9 and aged≥18 years were included. The main outcome measures were the physical component summary (PCS) score and mental component summary (MCS) scores of the Short-Form 36 (SF36) for health status, and the extended Glasgow Outcome Scale (GOSE) for functional outcome., Results: Between 1 January 2010 and 31 September 2010, 400 patients (mean age 53.3 years; range 18-106; 69.5% male) were recruited to the study. There were no statistically significant differences in baseline characteristics between responders (N=177) and surviving non-responders (N=163). However, there were significant differences between these groups and the group of patients who died (N=60). Only 16/400 (4%) cases reported a GOSE≥7. 62/400 (15.5%) responders reached the HK population norm for PCS. 125/400 (31%) responders reached the HK population norm for MCS. If non-responders had similar outcomes to responders, then the percentages for GOSE≥7 would rise from 4% to 8%, for PCS from 15.5% to 30%, and for MCS from 31% to 60%. Univariate analysis showed that 12-month poor quality of life was significantly associated with age>65 years (OR 4.77), male gender (OR 0.44), pre-injury health problems (OR 2.30), admission to ICU (OR 2.15), ISS score 26-40 (OR 3.72), baseline PCS (OR 0.89), one-month PCS (OR 0.89), one-month MCS (OR 0.97), 6-month PCS (OR 0.76) and 6-month MCS (OR 0.97)., Conclusion: For patients sustaining moderate or major trauma in Hong Kong at 12 months after injury<1 in 10 patients had an excellent recovery, ≤3 in 10 reached a physical health status score≥Hong Kong norm, although as many as 6 in 10 patients had a mental health status score which is≥Hong Kong norm., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Intracranial hemangiopericytoma (IHPC) is a rare tumor representing less than 1% of all CNS tumors and is often indistinguishable from meningioma on structural imaging alone. Unlike meningioma, IHPC is an aggressive tumor with the propensity for early locoregional recurrence and distant metastases. Hence, its management strategies differ greatly from that of meningioma. Some investigators have reported the potential role of multitracers (F-FDG, C-methionine, and O-H2O) PET imaging in distinguishing IHPC from meningioma. We described the findings of dual-tracer (C-acetate and F-FDG) PET/CT imaging in a histopathologically proven case of IHPC with extensive extracranial osseous metastases that showed significantly greater C-acetate avidity.

Unlabelled: We prospectively compared (11)C-acetate with (18)F-FDG in a PET/CT evaluation of multiple myeloma (MM), specifically on diagnostic accuracy, identification of high-risk patients, and monitoring of treatment response., Methods: Dual-tracer PET/CT was performed on 35 pathologically and clinically confirmed and untreated patients (26 with symptomatic MM, 5 with smoldering MM, and 4 with monoclonal gammopathy of unknown significance) and 20 individuals with normal marrow., Results: (11)C-acetate showed significant incremental value over (18)F-FDG (84.6% vs. 57.7%) for positively identifying patients with diffuse and focal symptomatic MM, and was negative in patients with indolent smoldering MM and monoclonal gammopathy of unknown significance. Three functional parameters-number of (11)C-acetate-avid and (18)F-FDG-avid focal bone lesions and (11)C-acetate general marrow activity-strongly correlated with β-2-microglobulin as surrogate imaging markers of tumor burden. After induction chemotherapy, the metabolic change in (11)C-acetate general marrow activity correlated with clinical response., Conclusion: Metabolic characterization of MM in diagnosis, risk stratification, and treatment monitoring can be done more accurately by assessing lipid metabolism with (11)C-acetate than by assessing glucose metabolism with (18)F-FDG.

Coxiella burnetii is an obligate intracellular gram-negative bacterium uniquely evolved to thrive in the inhospitable phagolysosome of macrophage. C. burnetii causes Q fever in humans and animals, which is emerging as a global public health concern. It is highly infectious and designated as a category B biowarfare agent because of its ubiquitous nature, abundant natural reservoirs, high resistance to environmental conditions, ease of transmission and low infectious dose. The lack of knowledge and awareness of C. burnetii leads to under-reporting and under-diagnosing of Q fever cases. Therefore, further understanding of the interactions between the infected host and the bacteria is necessary. C. burnetii macrophage infectivity potentiator (cb-Mip) is a secreted protein of 230 amino acids involving in intracellular survival of the pathogen. cb-Mip belongs to the family of FK506 binding protein, which possesses peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a PPIase, Mip protein homolog has been identified as virulence factor of many intracellular pathogenic microorganisms. In the present study, we report the near complete resonance assignments of the PPIase domain-containing region of Mip protein of C. burnetii. Secondary structure prediction based on chemical shift index analysis indicates that the protein adopts a predominately beta-strand structure, which is consistent with the crystal structure of homologous Mip protein in Legionella pneumophila.

Alzheimer's disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

How does coordinated activity between distinct brain regions implement a set of learning rules to sculpt information processing in a given neural circuit? Using interneuron cell-type-specific optical activation and pharmacogenetic silencing in vitro, we show that temporally precise pairing of direct entorhinal perforant path (PP) and hippocampal Schaffer collateral (SC) inputs to CA1 pyramidal cells selectively suppresses SC-associated perisomatic inhibition from cholecystokinin (CCK)-expressing interneurons. The CCK interneurons provide a surprisingly strong feedforward inhibitory drive to effectively control the coincident excitation of CA1 pyramidal neurons by convergent inputs. Thus, in-phase cortico-hippocampal activity provides a powerful heterosynaptic learning rule for long-term gating of information flow through the hippocampal excitatory macrocircuit by the silencing of the CCK inhibitory microcircuit., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A novel member of the genus Amycolatopsis was isolated from soil collected from the banks of the Umgeni River, KwaZulu Natal province, South Africa. The strain, designated UM16(T), grouped with the type strains of Amycolatopsis alba, Amycolatopsis coloradensis and Amycolatopsis thailandensis by 16S rRNA gene based phylogeny. Genetic distance values, based on the gyrB and recN genes, between strain UM16(T) and its closest relatives were all above the threshold values of 0.02 and 0.04, respectively, that have been proposed to distinguish Amycolatopsis type strains. DNA-DNA hybridisation experiments confirmed that strain UM16(T) represents a unique genomic species, sharing 18.4 ± 5.1, 16.2 ± 1.8 and 45.8 ± 8.9 % DNA relatedness to the type strains of A. alba, A. coloradensis and A. thailandensis, respectively. The physiological, phylogenetic and DNA-relatedness data support the description of strain UM16(T) as the type strain of a novel species, for which the name Amycolatopsis umgeniensis sp. nov. is proposed (= DSM 45272(T) = NRRL B-24724(T)).

Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH-keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.

Staphylococcus aureus can be distinguished from similar coagulase-positive staphylococci by its absence of β-galactosidase activity. This is commonly tested using o-nitrophenyl-β-D-galactopyranoside (ONPG) as the substrate. Unexpectedly, 111 and 58 of 123 isolates displayed apparent β-galactosidase activity in the ONPG assay and on the Vitek 2 system, respectively. Compositional analysis showed that the yellow coloration of the positive ONPG assay resulted from production of 2-aminophenoxazin-3-one. Alternative β-galactosidase substrates like X-Gal (5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside) should be used for testing staphylococci.

Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate, and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and coexpress multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms, including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast cancer subtypes. Our results reveal links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis, and therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the anaphase-promoting complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood., Results: Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20's C box. Cdc20 turnover by this intramolecular mechanism is cell cycle regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination., Conclusion: We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We report a first-principles study of static transport of localized waves in quasi-one-dimensional open media. We find that such transport, dominated by disorder-induced resonant transmissions, displays novel diffusive behavior. Our analytical predictions are entirely confirmed by numerical simulations. We show that the prevailing self-consistent localization theory [B. A. van Tiggelen, Phys. Rev. Lett. 84, 4333 (2000)] is valid only if disorder-induced resonant transmissions are negligible. Our findings open a new direction in the study of Anderson localization in open media.