Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of physiological phenotypes of dentate gyrus synapses of PDZ1/2 domain‐deficient PSD‐95‐knockin mice

The hippocampal formation is involved in several important brain functions of animals, such as memory formation and pattern separation, and the synapses in the dentate gyrus (DG) play critical roles as the first step in the hippocampal circuit. Previous studies have reported that mice with genetic modifications of the PDZ1/2 domains of postsynaptic density (PSD)‐95 exhibit altered synaptic properties in the DG and impaired hippocampus‐dependent behaviors. Based on the involvement of the DG in the regulation of behaviors, these data suggest that the abnormal behavior of these knockin (KI) mice is due partly to altered DG function. Precise understanding of the phenotypes of these mutant mice requires characterization of the synaptic properties of the DG, and here we provide detailed studies of DG synapses. We have demonstrated global changes in the PSD membrane‐associated guanylate kinase expression pattern in the DG of mutant mice, and DG synapses in these mice exhibited increased long‐term potentiation under a wide range of stimulus intensities, although the N‐methyl‐d‐aspartic acid receptor dependence of the long‐term potentiation was unchanged. Furthermore, our data also indicate increased silent synapses in the DG of the KI mice. These findings suggest that abnormal protein expression and physiological properties disrupt the function of DG neurons in these KI mice.
Problem-Based Learning in Teacher Education : Trajectories of Change

Teaching is a complex enterprise that requires solving intricate problems and issues in numerous facets of learning and teaching. Problem-based learning (PBL) provides generative contexts for prospective and certified teachers to work together in smallcollaborative groups. Together, they analyze problems, discuss options, and make informed decisions to solve problems based on authentic teaching situations with real, multifaceted challenges. Given the increasing number of classroom implementations of PBL studies, it is timely to extend this body of work to include research that is aimed at teacher education. New and experienced teachers are facing educational reform that requires themto meet the demands of an arduous profession. The discussion in this paper shows that PBL can be instrumental in equipping teachers to meet these demands. Frameworks for implementing PBL that move away from the traditional medical models and better respond to the demands of teacher education are discussed.
Evolving European guidance on the medical management of neovascular age related macular degeneration

Background: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)—thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. Methods: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. Results: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size ⩽4 Macular Photocoagulation Study (MPS) disc areas (DA). The new classes of anti-angiogenic agents—namely, pegaptanib sodium and ranibizumab (the latter when peer reviewed phase III data become available) are recommended for subfoveal lesions with any proportion of classic CNV or occult with no classic CNV. For juxtafoveal classic CNV, PDT-V or anti-angiogenic therapy should be considered if the new vessels are so close to the fovea that laser photocoagulation would almost certainly extend under the centre of the foveal avascular zone. For all other well demarcated juxtafoveal lesions and for extrafoveal classic lesions, laser photocoagulation remains the standard treatment. Therapy should be undertaken within 1 week of the fluorescein angiogram on which the clinical decision to treat is based. At each follow up, fluorescein angiography should be performed and best corrected visual acuity measured as a minimum requirement. Conclusions: These recommendations provide evidence based guidance for the choice and use of non-surgical therapies for the management of neovascular AMD. Revisions of the recommendations may be required as new data become available.
Glial Cells Generate Neurons—Master Control within CNS Regions: Developmental Perspectives on Neural Stem Cells

A common problem in neural stem cell research is the poor generation of neuronal or oligodendroglial descendants. The author takes a developmental perspective to propose solutions to this problem. After a general overview of the recent progress in developmental neurobiology, she highlights the necessity of the sequential and hierarchical specification of CNS precursors toward the generation of specific cell types, for example, neurons. In the developing as well as the adult CNS, multipotent stem cells do not directly generate neurons but give rise to precursors that are specified and restricted toward the generation of neurons. Some molecular determinants of this fate restriction have been identified during recent years and reveal that progression via this fate-restricted state is a necessary step of neurogenesis. These discoveries also demonstrate that neuronal fate specification is inseparably linked at the molecular level to regionalization of the developing CNS. These fate determinants and their specific action in distinct region-specific con-texts are essential to direct the progeny of stem cells more efficiently toward the generation of the desired cell types. Recent data are discussed that demonstrate the common identity of precursors and stem cells in the developing and adult nervous system as radial glia, astroglia, or non-myelinating glia. A novel line-age model is proposed that incorporates these new views and explains why the default pathway of stem cells is astroglia. These new insights into the cellular and molecular mechanisms of neurogenesis help to design novel approaches for reconstitutive therapy of neurodegenerative diseases.
Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy.

OBJECTIVE This study compared the potency of a somatostatin receptor (sstr)2-sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide. MATERIALS AND METHODS The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations. RESULTS In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels+/-s.e.m. 0.4+/-0.1, 5.3+/-1.9 and 2.0+/-0.4 copy/copy beta-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30+/-3%) and BIM-23244 (28+/-3%) was greater than that produced by octreotide (23+/-3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal suppression of GH secretion than octreotide (33+/-5, 38+/-2 and 41+/-2 vs 24+/-2%). Their EC(50) values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41+/-2 vs 32+/-4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62+/-8 to 74+/-5 vs 46+/-11%). CONCLUSIONS Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC50 1-10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.
Texture Segmentation by Genetic Programming

This paper describes a texture segmentation method using genetic programming (GP), which is one of the most powerful evolutionary computation algorithms. By choosing an appropriate representation texture, classifiers can be evolved without computing texture features. Due to the absence of time-consuming feature extraction, the evolved classifiers enable the development of the proposed texture segmentation algorithm. This GP based method can achieve a segmentation speed that is significantly higher than that of conventional methods. This method does not require a human expert to manually construct models for texture feature extraction. In an analysis of the evolved classifiers, it can be seen that these GP classifiers are not arbitrary. Certain textural regularities are captured by these classifiers to discriminate different textures. GP has been shown in this study as a feasible and a powerful approach for texture classification and segmentation, which are generally considered as complex vision tasks.
Partial molar volumes of polypeptides and their constituent groups in aqueous solution over a broad temperature range

The partial molar volumes of various compounds that model protein constituent groups, such as tripeptides (Gly‐X‐Gly, where X = Gly, Ala, Val, Leu, Ile, Pro, Met, His, Ser), homopeptides (Glyn, n = 3, 4, 5), and simple organic analogues of amino acid side chains (methanol, acetamide, propanamide, acetic acid, propanoic acid, n‐butanamine, n‐butanamine nitrate, n‐propylguanidine nitrate, 4‐methylphenol), have been determined in aqueous solution with a vibrational densimeter in the temperature range of 5–85°C. The partial molar volumes of amino acid side chains and the peptide unit were estimated from the data obtained. Assuming additivity of component groups, the partial molar volumes of polypeptide chains of several proteins over a broad temperature range were calculated. The partial molar volume functions of four proteins (myoglobin, cytochrome C, ribonuclease A, lysozyme) were compared with those determined experimentally for the unfolded and native forms of these proteins. It has been shown that the average deviation of the calculated functions from the experimental ones does not exceed 3% over the temperature range studied.
Strategy Transformation Under Technological Convergence: Evidence from the Printed Electronics Industry

Radical technological innovations have transformed competition in high-tech markets. One result of innovation is technological convergence, whereby different technologies are integrated and businesses become more complex, thus blurring industry boundaries. We examine the evolution of firms' strategic positions under technological convergence. Specifically, we analyse the printed electronics industry using patent-centric network indexes and reveal technological intensity using firm-based networks of patent citations. We labelled firms that own core-functional (ink) technology core functional leaders in the patent network of the printed electronics industry. Additionally, we labelled firms that own control-related (device) technology technology integrators and those involved in application-related (electronics) technology application pioneers. Furthermore, we constructed a strategic quadrant framework that categorises firms according to their strategic positioning and
A systematic review of factors influencing human papillomavirus vaccination among immigrant parents in the United States

ABSTRACT To critically appraise factors influencing human papillomavirus (HPV) vaccination among immigrant parents in the United States, a comprehensive search of electronic databases and reference lists was conducted. The findings from 22 articles were ordered based on a socioecological model. About 30% of children initiated and 14% completed a three-dose series. Correlates of HPV vaccine initiation rates included lack of information, concerns about vaccine safety and promiscuity, providers' recommendations, school mandates, financial issues, immigration laws, and living in disadvantaged neighborhoods. Upstream initiatives embracing cultural descriptors could facilitate HPV vaccination, reducing HPV-related disparities in cancer among immigrants in the US.
Childhood maltreatment is associated with altered frontolimbic neurobiological activity during wakefulness in adulthood

Abstract Childhood maltreatment can disturb brain development and subsequently lead to adverse socioemotional and mental health problems across the life span. The long-term association between childhood maltreatment and resting–wake brain activity during adulthood is unknown and was examined in the current study. Forty-one medically stable and medication-free military veterans (M = 29.31 ± 6.01 years, 78% male) completed a battery of clinical assessments and had [18F]-fluorodeoxyglucose positron emission tomography neuroimaging scans during quiet wakefulness. After statistically adjusting for later-life trauma and mental health problems, childhood maltreatment was negatively associated with brain activity within a priori defined regions that included the left orbital frontal cortex and left hippocampus. Childhood maltreatment was significantly associated with increased and decreased brain activity within six additional whole-brain clusters that included the frontal, parietal–temporal, cerebellar, limbic, and midbrain regions. Childhood maltreatment is associated with altered neural activity in adulthood within regions that are involved in executive functioning and cognitive control, socioemotional processes, autonomic functions, and sleep/wake regulation. This study provides support for taking a life span developmental approach to understanding the effects of early-life maltreatment on later-life neurobiology, socioemotional functioning, and mental health.
Spectrum of SMPD1 mutations in Asian‐Indian patients with acid sphingomyelinase (ASM)‐deficient Niemann–Pick disease

Acid sphingomyelinase (ASM)‐deficient Niemann–Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM‐deficient NPD world‐wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM‐deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM‐deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen‐2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS‐MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM‐deficient Niemann–Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc.
Particle Inhalability at Low Wind Speeds

Accurate quantification of the dose delivered by aerosol exposures is essential for estimating the risk of potential adverse health effects. The fraction of airborne particles that can enter the nose or mouth during inhalation is referred to as the inspirable particulate mass fraction. This inhalable fraction is equivalent to delivered dose for particles greater than approximately 25 μm (aerodynamic particle diameter, dae), which deposit completely and almost exclusively in the extrathoracic airways. Particle inhalability at high wind speeds (1–9 m/s) has been well characterized. However, there is a paucity of data describing the inhalability of particles at low wind speeds (≤0.3 m/s), which are typical of indoor environments. High-wind-speed criteria poorly describe inhalability at low wind speeds. Based on the aspiration efficiencies of blunt and sharp-edged inlets, a function was developed for oral inhalability, P(IO), of particles at low wind speeds. This function predicts a slow decline in P(IO) from 0.95 at dae= 8 μ m, to 0.5 at dae = 74 μ m, and 0.1 at dae= 175 μm. Data available from the literature for inhalability at relatively low wind speeds during oral breathing are well described by this logistic function (r2= 0.69).
Iron deficiency anemia in infants aged 12-15 months in Ahwaz, Iran.

BACKGROUND Iron deficiency anemia (IDA) is one of the most common nutritional problems in the world, especially in developing countries. Infants aged between 4 and 24 months are among the population groups that are most affected by iron deficiency (ID). The aim of this study was to investigate the prevalence of ID and IDA in infants aged 12-15 months, living in Ahwaz, southwest of Iran. MATERIALS AND METHODS One hundred and twenty-six infants participated in the study. The mean corpuscular volume and hemoglobin (Hb), serum ferritin and hematocrit levels were measured. Anemia was defined when Hb < 11 g/dL and ID when ferritin < 12 microg/mL. RESULTS The prevalence of ID and IDA was 31.7 and 26.2%, respectively. The tendency to have IDA in infants fed with cow's milk and infants who did not receive ferrous sulfate was higher than in the other subjects. CONCLUSION ID and IDA are common among infants aged 12-15 months living in Ahwaz, Iran. Maintenance of exclusive breastfeeding up to the 4-6th month of life and iron supplementation for the target group is needed.
Sustainable Development: How Social Entrepreneurs Make it Happen

This paper demonstrates that entrepreneurs who have created innovative organizations and service provision models are contributing to sustainable development. The processes, structures and outcomes of their initiatives are contrasted with more traditional efforts. World leaders have recently renewed the momentum for 'buying' sustainable development through massive allocation of development funds. The authors argue that such traditional approaches have repeatedly failed in the past and are unlikely to overcome the more fundamental hurdles to create development. Building on the findings of a three-year research project, the paper presents case studies which demonstrate how so-called 'social entrepreneurs' succeed in creating social and economic development in a poor country context. The process of discovery and creation from the ground up, in contrast to traditional design-driven development processes and strategies, is illustrated. The cases show how social entrepreneurs cater to various levels of needs: the basic needs of individuals, the institutional needs of communities, and the needs of future generations. The impact of social entrepreneurial activity on sustainable development measures such as the Millennium Development Goals is demonstrated. The findings suggest that social innovation may change the very structures and systems that recreate the circumstances for poverty and that development processes need to consider the link between social and economic development.
Microsatellite signature of ecological selection for salt tolerance in a wild sunflower hybrid species, Helianthus paradoxus

The hybrid sunflower species Helianthus paradoxus inhabits sporadic salt marshes in New Mexico and southwest Texas, USA, whereas its parental species, Helianthus annuus and Helianthus petiolaris, are salt sensitive. Previous studies identified three genomic regions — survivorship quantitative trait loci (QTLs) — that were under strong selection in experimental hybrids transplanted into the natural habitat of H. paradoxus. Here we ask whether these same genomic regions experienced significant selection during the origin and evolution of the natural hybrid, H. paradoxus. This was accomplished by comparing the variability of microsatellites linked to the three survivorship QTLs with those from genomic regions that were neutral in the experimental hybrids. As predicted if one or more selective sweeps had occurred in these regions, microsatellites linked to the survivorship QTLs exhibited a significant reduction in diversity in populations of the natural hybrid species. In contrast, no difference in diversity levels was observed between the two microsatellite classes in parental populations.
Selective loss of B‐cell phenotype in lymphocyte predominant Hodgkin lymphoma

The neoplastic Reed–Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B‐cell origin but they almost always show striking loss of a range of B‐cell‐associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL‐6 expression, ‘ongoing’ Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down‐regulation of a number of markers associated with the B‐cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down‐regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
SiGe:C HBT architecture with epitaxial external base

We present a novel double-polysilicon (DP) HBT technology with a SiGe:C base fabricated by selective epitaxial growth (SEG), in which the external base is formed by in-situ doped epitaxy completely after the internal base. This approach aims to achieve a lower parasitic base resistance compared to our previously reported DP-SEG technology [8], while keeping a low capacitive lateral base link arrangement. We demonstrate fT/fmax of 310GHz/480GHz, as well as a CML gate delay of 1.9ps, achieving the lowest value reported so far.
Characterizing Deleted Tweets and Their Authors

This paper provides a detailed characterization of tweets posted and then later deleted by their authors, in the Twitter microblogging platform. Our characterization shows significant personality differences between users who delete their tweets and those who do not. We find that users who delete their tweets are more likely to be extroverted and neurotic while being less conscientious. Further, although deleted tweets contain more negative sentiment and swear words, they also show significant signs of being thoughtfully constructed.