bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface‐Active Properties of Solvent‐Extracted Panax ginseng Saponin‐Based Surfactants
Authors: Mesgarzadeh Iraj , Akbarzadeh Ali Reza , Rahimi Rahmatollah
Published: March 2017

In this study, saponins were extracted from Panax ginseng root powder. The crude solvent‐extracted saponins containing triterpenoid glycosides and terpenes that were identified by TLC techniques. The critical micelle concentrations (CMC) of the saponins were determined by measuring the change in (a) the UV‐visible spectrum of iodine due to the micelle‐iodine complexation, (b) the absorption intensity of aqueous alpha‐lipoic acid due to the micellar solubilization of the drug, and (c) the surface tension due to the abrupt change in the air/liquid interface saturation by surfactants monomers. The development of new absorption peak due to the micelle‐iodine complexation, enhancement in the absorbance due to the micelle‐solubilized lipoic acid, and displacement of monomer‐micelle equilibrium to micelle formation in higher monomer concentration region are some of the physicochemical properties in which CMC could be determined. We found a CMC of 0.009% w/v.
Regional integration in Central Asia: From knowing-that to knowing-how
Authors: Azizov Ulugbek
Published: March 2017

The paper examines regional integration in Central Asia in the context of two types of knowledge, that is, knowing-that and knowing-how. While knowing-that prioritizes representational (i.e. “talking”) practices of actors to explain region-building processes, knowing-how focuses on non-representational (i.e. “doing”) practices. The article demonstrates that the orthodox scholars, who deal with the region of Central Asia, mostly employ knowing-that to explain region-building processes. The article criticizes knowing-that, assuming that this type of knowledge limits our understanding with regard to how regions get their boundaries and symbolism in the era of globalization and standardization of sectoral activities. Thus the article develops and introduces an alternative knowing-how framework to better understand the region-building processes in Central Asia and beyond it.
Safety of disclosing amyloid status in cognitively normal older adults
Authors: Burns Jeffrey M. , Johnson David K. , Liebmann Edward P. , Bothwell Rebecca J. , Morris Jill K. , Vidoni Eric D.
Published: March 2017

Introduction

Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk.

Methods

We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test‐related distress after disclosure.

Results

Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test‐related distress were present after disclosure and were related to greater baseline levels of anxiety and depression.

Discussion

Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre‐ and postdisclosure counseling has a low risk of psychological harm.
‘MY GARDEN IS NOT PRISTINE’: AN INTERVIEW WITH LINDA CATLIN SMITH
Authors: Höstman Anna
Published: March 2017

Linda Catlin Smith was born in 1957 and grew up in New York. She studied composition in New York and at the University of Victoria, before settling in Toronto in 1981. Linda has received Canada's prestigious Jules Léger prize for her work Garland (2005). She was the Artistic Director of Toronto's contemporary ensemble Arraymusic (1988–93), and a founding member of the interdisciplinary collective Urge (1992–2006). She currently teaches composition at Wilfrid Laurier University. I sat down with Linda in the summer of 2016 at her home in the Trinity Bellwoods neighbourhood of Toronto to ask her about her life and work.
James Wishart: Mad Songs and English Wo/men. Sixtieth Birthday Concerts, Liverpool, 5 October and 16 November 2016
Authors: Thomas Helen
Published: March 2017

Two concerts in Liverpool in autumn 2016 celebrated the sixtieth birthday year of James Wishart, the composer, pianist, conductor, writer and concert promoter who has been a major figure in musical life in the north west of England for nearly four decades. His music reflects his wide cultural and social interests and these concerts showcased three compositions that were witty, emotionally searing and sonically daring.
Screening for Cerebellopontine Angle Tumours: Conventional MRI vs T2 Fast Spin Echo MRI
Authors: Dort Joseph C. , Sadler David , Hu William , Wallace Carla , La Forge Pierre , Sevick Robert
Published: March 2017

Background:

Unilateral audiovestibular symptoms are commonly seen in clinical practice and are rarely caused by retrocochlear pathology. However, clinicians are often required to rule out potentially serious causes of these unilateral symptoms. Gadolinium enhanced magnetic resonance imaging (GdMRI) is the most accurate test for detecting small cerebellopontine angle lesions and also screens the adjacent CNS structures. Its main disadvantage is the cost of the procedure.

Methods:

We studied 100 consecutive patients with both GdMRI and a newer MRI screening study utilizing unenhanced T2-weighted fast spin echo (fse) MRI. Acquired images were randomly assessed by a panel of three neuro-radiologists.

Results:

We found that the screening (fse) MRI was as sensitive and specific when detecting cerebellopontine angle tumors.

Conclusions:

We conclude that T2-weighted fse MRI is a safe and cost-effective alternative to GdMRI and offers better diagnostic utility when compared to auditory brain stem response (ABR) and CT scans.
A Founder Mutation in French-Canadian Families with X-linked Hereditary Neuropathy
Authors: Dupré Nicolas , Cossette Louise , Hand Collette K. , Bouchard Jean-Pierre , Rouleau Guy A , Puymirat Jack
Published: March 2017

Background:

The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX).

Methods:

Molecular analysis was performed by nonisotopic single strand conformation polymorphism (SSCP) analysis and sequencing. Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium.

Results:

In one family, the mutation Arg142Trp was located in the transmembrane domain III whereas, in four other families we identified a novel mutation (Ser26Trp) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demyelination.

Conclusion:

Our study suggests that the Ser26Trp mutation may cause a primary demyelinating neuropathy that is not associated with a specific clinical phenotype. We also find evidence that the majority of kindreds share a common ancestor.
Treatment Costs for Glioblastoma Multiforme in Nova Scotia
Authors: Mendez Ivar , Jacobs Philip , MacDougall Andrea , Schultz Margarita
Published: March 2017

Background:

Glioblastoma Multiforme (GBM) is the most common and malignant brain tumor in adults. The median survival in patients harboring this neoplasm is 12 months irrespective of any form of therapy. Health care costs of illnesses with high mortality rates, such as GBM, are of particular interest in times of constrained health care resources. No information regarding costs for the treatment of patients with GBM is available in Canada. The aim of this study was to conduct an analysis of the costs of treatment of GBM in Nova Scotia.

Methods:

Patients with histologically proven GBM during a three year period (1996-1998) in Nova Scotia were included in the study. Analysis was based on hospital costs supplemented by data on additional medical services received following discharge for the primary intervention.

Results:

The mean cost of medical care per patient from the time of diagnosis to death was $ 17,149. The highest costs were related to hospitalization with ward costs alone accounting for 48% of all costs. Radiotherapy costs were 25%, surgery costs were 16% and chemotherapy costs were 7% of all costs. Costs for diagnostic procedures were 6% of the total costs.

Conclusion:

Our data reflect the costs and practice pattern in the treatment of GBM in Nova Scotia and may be of value as an initial attempt to analyze costs of treatment of GBM in Canada.
The Spectrum of Electrophysiological Abnormalities in Bell's Palsy
Authors: Hill Michael D. , Midroni Gyl , Goldstein Warren C. , Deeks Shelley L. , Low Donald E. , Morris Andrew M.
Published: March 2017

Background:

As part of an investigation of a suspected "outbreak" of Bell's palsy in the Greater Toronto Area, a population-based sample of patients with Bell's palsy was investigated electrophysiologically to help understand the spectrum of abnormalities that can be seen in this setting.

Methods:

Two hundred and twenty-four patients were surveyed, of whom 91 underwent formal neurological assessment. Of the latter, 44 were studied electrophysiologically using standard techniques. Thirty-two of the 44 patients fulfilled clinical criteria for Bell's palsy.

Results:

A wide range of electrophysiological changes was observed. Blink responses were the most useful test showing diagnostic sensitivity of 81% and specificity of 94% compared to the contralateral control side. Needle electromyography was additionally helpful in only one patient of six with normal conduction studies.

Conclusions:

There is a wide spectrum of electrophysiological abnormalities in Bell's palsy. Blink reflex latencies may be under-utilized in the assessment of the facial nerve in Bell's palsy. Facial EMG is not generally useful in routine assessment.
Effect of Corticosteroid Therapy on Serum and CSF Malondialdehyde and Antioxidant Proteins in Multiple Sclerosis
Authors: Keles M.S. , Taysi S. , Sen N. , Aksoy H. , Akçay F.
Published: March 2017

Objective:

Multiple sclerosis (MS) is a disease characterised by perivascular infiltrates and demyelination of the white matter in the central nervous system. Although the precise cause of MS remains unknown, some investigations have been carried out on antioxidant mechanisms in these patients.

Methods:

In this study, malondialdehyde (MDA), as a lipid peroxidation marker, and ceruloplasmin (Cp) and transferrin (Trf), as antioxidant proteins, levels were determined in cerebrospinal fluid (CSF) and serum of 30 MS patients before and after corticosteroid therapy and in 20 control subjects. Transferrin and Cp levels were measured by the nephelometric method and MDAwas measured spectrophotometrically.

Results:

Mean MDAserumand MDACSFlevels were found to be highest in the pretreatment group and lowest in the control group. Although there was no significant difference in terms of serum Trf level, serum Cp was found higher in pre- and posttreatment groups than in the control groups. Ceruloplasmin and Trf levels of CSF were not detectable using the nephelometric method. A significant correlation was found between MDACSFand MDAserumin the pretreatment group (r=0.58).

Conclusions:

These data revealed that lipid peroxidation was increased in serum and particulary in CSF of MS patients and was reduced with corticosteroid therapy.
Sarcoidosis Presenting as an Intramedullary Spinal Cord Lesion
Authors: Maroun F.B. , O'Dea F.J. , Mathieson G. , Fox G. , Murray G. , Jacob J.C. , Reddy R. , Avery R.
Published: March 2017

Objectives:

Meige syndrome is a movement disorder that includes blepharospasm and oromandibular dystonias. Its etiology may be idiopathic (primary) or it may arise secondary to focal brain injury. Acute respiratory distress as a feature of such dystonias occurs infrequently. A review of the literature on Meige syndrome and the relationship between dystonias and respiratory compromise is presented.

Methods:

A 60-year-old woman suffered a cerebral anoxic event secondary to manual strangulation. She developed progressive blepharospasm combined with oromandibular and cervical dystonias. Neuroimaging demonstrated bilateral damage localized to the globus pallidus. Years later, she presented to the emergency department in intermittent respiratory distress associated with facial and cervical muscle spasms.

Results and conclusions:

Increasing frequency and severity of the disorder was noted over years. The acute onset of respiratory involvement required intubation and eventual tracheotomy. A partial therapeutic benefit of tetrabenazine was demonstrated.
Meige Syndrome Secondary to Basal Ganglia Injury: A Potential Cause of Acute Respiratory Distress
Authors: Kirton C. Adam , Riopelle Richard J.
Published: March 2017

Background:

Meige syndrome is a movement disorder that includes blepharospasm and oromandibular dystonias. Its etiology may be idiopathic (primary) or it may arise secondary to focal brain injury. Acute respiratory distress as a feature of such dystonias occurs infrequently. A review of the literature on Meige syndrome and the relationship between dystonias and respiratory compromise is presented.

Methods:

A 60-year-old woman suffered a cerebral anoxic event secondary to manual strangulation. She developed progressive blepharospasm combined with oromandibular and cervical dystonias. Neuroimaging demonstrated bilateral damage localized to the globus pallidus. Years later, she presented to the emergency department in intermittent respiratory distress associated with facial and cervical muscle spasms.

Results:

Increasing frequency and severity of the disorder was noted over years. The acute onset of respiratory involvement required intubation and eventual tracheotomy. A partial therapeutic benefit of tetrabenazine was demonstrated.

Conclusions:

This case highlights two interesting aspects of Meige's syndrome: (1) Focal bilateral basal ganglia lesions appear to be responsible for this patient's movement disorder which is consistent with relative overactivity of the direct pathway from striatum to globus pallidus internal and substantia nigra pars reticularis; (2) Respiratory involvement in a primarily craniofacial dystonia to the point of acute airway compromise.
The impact of poor asthma control among asthma patients treated with inhaled corticosteroids plus long-acting β2-agonists in the United Kingdom: a cross-sectional analysis
Authors: Pavord Ian D. , Mathieson Nicola , Scowcroft Anna , Pedersini Riccardo , Isherwood Gina , Price David
Published: March 2017

There are several new treatment options for patients whose asthma remains uncontrolled on free-dose and fixed-dose combinations of inhaled corticosteroids plus long-acting β2-agonists (ICS+LABA). In order to evaluate the likely impact of these treatments, we assessed the effect of uncontrolled asthma on healthcare and patient burden within the UK among adult patients treated with ICS+LABA. Data obtained from 2010–2011 UK National Health and Wellness Surveys identified 701 patients treated with ICS+LABA. Patients with not well-controlled asthma (Asthma Control Test™ score <20) were compared with well-controlled asthma (score ≥ 20) patients on multiple measures. Cost burden was calculated using healthcare resource utilisation models and work productivity and impairment questionnaire. Overall, 452 and 249 patients reported not well-controlled and well-controlled asthma, respectively. A greater proportion of not well-controlled patients visited the accident & emergency department (21 vs. 14%, P = 0.016), were hospitalised (13 vs. 8%, P = 0.022) and had lower mental and physical health-related quality of life (P < 0.001) and impaired work productivity and activity scores: presenteeism (23 vs. 11%, P < 0.001), work impairment (29 vs. 17%, P < 0.001) and activity impairment (46 vs. 24%, P < 0.001). Calculated direct and indirect yearly costs/person doubled among not well-controlled compared to well-controlled asthma patients (£6592 vs. £3220). Total cost to society was estimated at £6172 million/year (direct costs, £1307 million; indirect costs, £4865 million). In conclusion, not well-controlled asthma is common among UK adults treated with ICS+LABA, resulting in impairments across a number of important health outcomes and represents a significant unmet need and resource burden.
Raising awareness of bronchiectasis in primary care: overview of diagnosis and management strategies in adults
Authors: Chalmers James D. , Sethi Sanjay
Published: March 2017

Bronchiectasis is a chronic lung disease characterised by recurrent infection, inflammation, persistent cough and sputum production. The disease is increasing in prevalence, requiring a greater awareness of the disease across primary and secondary care. Mild and moderate cases of bronchiectasis in adults can often be managed by primary care clinicians. Initial assessments and long-term treatment plans that include both pharmacological and non-pharmacological treatments, however, should be undertaken in collaboration with a secondary care team that includes physiotherapists and specialists in respiratory medicine. Bronchiectasis is often identified in patients with other lung diseases, such as chronic obstructive pulmonary disease, asthma, and in a lesser but not insignificant number of patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Overall goals of therapy are to prevent exacerbations, improve symptoms, improve quality of life and preserve lung function. Prompt treatment of exacerbations with antibiotic therapy is important to limit the impact of exacerbations on quality of life and lung function decline. Patient education and cooperation with health-care providers to implement treatment plans are key to successful disease management. It is important for the primary care provider to work with secondary care providers to develop an individualised treatment plan to optimise care with the goal to delay disease progression. Here, we review the diagnosis and treatment of bronchiectasis with a focus on practical considerations that will be useful to primary care.
Environmental filtering structures tree functional traits combination and lineages across space in tropical tree assemblages
Authors: Asefa Mengesha , Cao Min , Zhang Guocheng , Ci Xiuqin , Li Jie , Yang Jie
Published: March 2017

Environmental filtering consistently shapes the functional and phylogenetic structure of species across space within diverse forests. However, poor descriptions of community functional and lineage distributions across space hamper the accurate understanding of coexistence mechanisms. We combined environmental variables and geographic space to explore how traits and lineages are filtered by environmental factors using extended RLQ and fourth-corner analyses across different spatial scales. The dispersion patterns of traits and lineages were also examined in a 20-ha tropical rainforest dynamics plot in southwest China. We found that environmental filtering was detected across all spatial scales except the largest scale (100 × 100 m). Generally, the associations between functional traits and environmental variables were more or less consistent across spatial scales. Species with high resource acquisition-related traits were associated with the resource-rich part of the plot across the different spatial scales, whereas resource-conserving functional traits were distributed in limited-resource environments. Furthermore, we found phylogenetic and functional clustering at all spatial scales. Similar functional strategies were also detected among distantly related species, suggesting that phylogenetic distance is not necessarily a proxy for functional distance. In summary, environmental filtering considerably structured the trait and lineage assemblages in this species-rich tropical rainforest.
Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy
Authors: Huang Bao-tian , Huang Rui-hong , Zhang Wu-zhe , Lin Wen , Guo Long-jia , Xu Liang-yu , Lin Pei-xian , Chen Jian-zhou , Li De-rui , Chen Chuang-zhen
Published: March 2017

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESOwhole); ESOwhole within the treatment field (ESOinfield); ESOinfield, excluding the tumor (ESOinfield-tumor) and ESOwhole, excluding the tumor (ESOwhole-tumor). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESOwhole, ESOinfield, ESOinfield-tumor and ESOwhole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10−2% and 1.5 × 10−3%. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.
miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer
Authors: Yang Dong , Zhan Ming , Chen Tao , Chen Wei , Zhang Yunhe , Xu Sunwang , Yan Jinchun , Huang Qihong , Wang Jian
Published: March 2017

Gallbladder cancer represents the most common malignancy of the biliary tract and is highly lethal with less than 5% overall 5-year survival rate. Chemotherapy remains the major treatment for late-stage patients. However, insensitivity to these chemotherapeutic agents including cisplatin is common. MicroRNAs (miRNAs) have been shown as modulators of drug resistance in many cancer types. We used genome-wide gene expression analysis in clinical samples to identify miR-125b-5p down-regulated in gallbladder cancer. miR-125b-5p up-regulation promoted cell death in gallbladder cancer cells in the presence of cisplatin. In contrast, knockdown of miR-125b-5p reduced cell death in gallbladder cancer cells treated with cisplatin. Up-regulation of miR-125b-5p significantly decreased tumor growth in combination with cisplatin in a mouse model. We identified Bcl2 as a direct target of miR-125b-5p which mediates the function of miR-125b-5p in gallbladder cancer. In clinical samples, miR-125b-5p was down-regulated in gallbladder cancer whereas Bcl2 was up-regulated and their expression was inversely correlated. Moreover, low miR-125b-5p expression or high expression of Bcl2 is correlated with poor prognosis in gallbladder cancer. Taken together, our findings indicate that miR-125b-5p is a potent chemotherapy sensitizer and may function as a new biomarker for the prognosis of gallbladder cancer patients.
Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death
Authors: Bussi Claudio , Peralta Ramos Javier Maria , Arroyo Daniela S. , Gaviglio Emilia A. , Gallea Jose Ignacio , Wang Ji Ming , Celej Maria Soledad , Iribarren Pablo
Published: March 2017

Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells. We observed that both trehalose and rapamycin activate autophagy in BV2 microglial cells and down-regulate the production of pro-inflammatory cytokines and nitric oxide (NO), in response to LPS and alpha-synuclein. Autophagy also modulated the phosphorylation of p38 and ERK1/2 MAPKs in BV2 cells, which was required for NO production. These actions of autophagy modified the impact of microglial activation on neuronal cells, leading to suppression of neurotoxicity. Our results demonstrate a novel role for autophagy in the regulation of microglial cell activation and pro-inflammatory molecule secretion, which may be important for the control of inflammatory responses in the CNS and neurotoxicity.
Production of the medaka derived from vitrified whole testes by germ cell transplantation
Authors: Seki Shinsuke , Kusano Kazunari , Lee Seungki , Iwasaki Yoshiko , Yagisawa Masaru , Ishida Mariko , Hiratsuka Tadashi , Sasado Takao , Naruse Kiyoshi , Yoshizaki Goro
Published: March 2017

The medaka (Oryzias latipes) is a teleost model distinguished from other model organisms by the presence of inbred strains, wild stocks, and related species. Cryopreservation guarantees preservation of these unique biological resources. However, because of their large size, cryopreservation techniques for their eggs and embryos have not been established. In the present study, we established a methodology to produce functional gametes from cryopreserved testicular cells (TCs). Whole testes taken from medaka were cryopreserved by vitrification. After thawing, the cells dissociated from cryopreserved testicular tissues were intraperitoneally transplanted into sterile triploid hatchlings. Some cells, presumably spermatogonial stem cells, migrated into the genital ridges of recipients and resulted in the production of eggs or sperm, based on sex of the recipient. Mating of recipients resulted in successful production of cryopreserved TC-derived offspring. We successfully produced individuals from the Kaga inbred line, an endangered wild population in Tokyo, and a sub-fertile mutant (wnt4b−/−) from cryopreserved their TCs. This methodology facilitates semi-permanent preservation of various medaka strains.
Limitations and challenges of genetic barcode quantification
Authors: Thielecke Lars , Aranyossy Tim , Dahl Andreas , Tiwari Rajiv , Roeder Ingo , Geiger Hartmut , Fehse Boris , Glauche Ingmar , Cornils Kerstin
Published: March 2017

Genetic barcodes are increasingly used to track individual cells and to quantitatively assess their clonal contributions over time. Although barcode quantification relies entirely on counting sequencing reads, detailed studies about the method’s accuracy are still limited. We report on a systematic investigation of the relation between barcode abundance and resulting read counts after amplification and sequencing using cell-mixtures that contain barcodes with known frequencies (“miniBulks”). We evaluated the influence of protocol modifications to identify potential sources of error and elucidate possible limitations of the quantification approach. Based on these findings we designed an advanced barcode construct (BC32) to improved barcode calling and quantification, and to ensure a sensitive detection of even highly diluted barcodes. Our results emphasize the importance of using curated barcode libraries to obtain interpretable quantitative data and underline the need for rigorous analyses of any utilized barcode library in terms of reliability and reproducibility.
Multistability of the Brain Network for Self-other Processing
Authors: Chen Yi-An , Huang Tsung-Ren
Published: March 2017

Early fMRI studies suggested that brain areas processing self-related and other-related information were highly overlapping. Hypothesising functional localisation of the cortex, researchers have tried to locate “self-specific” and “other-specific” regions within these overlapping areas by subtracting suspected confounding signals in task-based fMRI experiments. Inspired by recent advances in whole-brain dynamic modelling, we instead explored an alternative hypothesis that similar spatial activation patterns could be associated with different processing modes in the form of different synchronisation patterns. Combining an automated synthesis of fMRI data with a presumption-free diffusion spectrum image (DSI) fibre-tracking algorithm, we isolated a network putatively composed of brain areas and white matter tracts involved in self-other processing. We sampled synchronisation patterns from the dynamical systems of this network using various combinations of physiological parameters. Our results showed that the self-other processing network, with simulated gamma-band activity, tended to stabilise at a number of distinct synchronisation patterns. This phenomenon, termed “multistability,” could serve as an alternative model in theorising the mechanism of processing self-other information.
An association between time-varying serum alkaline phosphatase concentrations and mortality rate in patients undergoing peritoneal dialysis: a five-year cohort study
Authors: Liu Ying , Zhu Jin-Gang , Cheng Ben-Chung , Liao Shang-Chih , Lee Chih-Hsiung , Chang Wen Xiu , Chen Jin-Bor
Published: March 2017

The relationship between serum alkaline phosphatase (ALP) concentrations and mortality in peritoneal dialysis (PD) patients is rarely reported. We enrolled 667 PD patients in one PD centre in Taiwan to retrospectively examine the association between three ALP concentrations (baseline, time-averaged, time-dependent) and mortality over a 5-year period (2011–2015). Baseline data collection included demographics, clinical, and laboratory parameters. Multivariable-adjusted Cox models were used to analyse the association. Four ALP quartiles were defined at the baseline: ≤62, 63–82, 83–118, and ≥119 U/L. Of 667 patients, 65 patients died, of which 8 patients died due to cardiovascular disease. Females were predominant in the higher ALP quartiles, and 24-h urine volume was significantly proportionately decreased in the higher ALP quartiles. ALP quartiles expressed by the three models were not associated with all-cause or cardiovascular mortalities after adjusting for demographics, liver function, bone metabolism, mortality, hemoglobin, and 24-h urine volume. In conclusion, ALP concentrations were not associated with death risk in PD patients over the 5-year period.
An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system
Authors: Choi Kwangmin , Komurov Kakajan , Fletcher Jonathan S. , Jousma Edwin , Cancelas Jose A. , Wu Jianqiang , Ratner Nancy
Published: March 2017

Neurofibromas are benign peripheral nerve tumors driven by NF1 loss in Schwann cells (SCs). Macrophages are abundant in neurofibromas, and macrophage targeted interventions may have therapeutic potential in these tumors. We generated gene expression data from fluorescence-activated cell sorted (FACS) SCs and macrophages from wild-type and mutant nerve and neurofibroma to identify candidate pathways involved in SC-macrophage cross-talk. While in 1-month-old Nf1 mutant nerve neither SCs nor macrophages significantly differed from their normal counterparts, both macrophages and SCs showed significantly altered cytokine gene expression in neurofibromas. Computationally reconstructed SC-macrophage molecular networks were enriched for inflammation-associated pathways. We verified that neurofibroma SC conditioned medium contains macrophage chemo-attractants including colony stimulation factor 1 (CSF1). Network analysis confirmed previously implicated pathways and predict novel paracrine and autocrine loops involving cytokines, chemokines, and growth factors. Network analysis also predicted a central role for decreased type-I interferon signaling. We validated type-I interferon expression in neurofibroma by protein profiling, and show that treatment of neurofibroma-bearing mice with polyethylene glycolyated (PEGylated) type-I interferon-α2b reduces the expression of many cytokines overexpressed in neurofibroma. These studies reveal numerous potential targetable interactions between Nf1 mutant SCs and macrophages for further analyses.
Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy
Authors: Allen Micah , Frank Darya , Glen James C. , Fardo Francesca , Callaghan Martina F. , Rees Geraint
Published: March 2017

Empathy is a key component of our ability to engage and interact with others. In recent years, the neural mechanisms underlying affective and cognitive empathy have garnered intense interest. This work demonstrates that empathy for others depends upon a distributed network of regions such as the insula, parietal cortex, and somatosensory areas, which are also activated when we ourselves experience an empathized-with emotion (e.g., pain). Individuals vary markedly in their ability to empathize with others, which predicts the tendency to help others and relates to individual differences in the neuroanatomy of these areas. Here, we use a newly developed, high-resolution (800 μm isotropic), quantitative MRI technique to better elucidate the neuroanatomical underpinnings of individual differences in empathy. Our findings extend previous studies of the neuroanatomical correlates of cognitive and affective empathy. In particular, individual differences in cognitive empathy were associated with markers of myeloarchitectural integrity of the insular cortex, while affective empathy was predicted by a marker of iron content in second somatosensory cortex. These results indicate potential novel biomarkers of trait empathy, suggesting that microstructural features of an empathy and body-related network are crucial for understanding the mental and emotional states of others.
Antimicrobial efficacy against Pseudomonas aeruginosa biofilm formation in a three-dimensional lung epithelial model and the influence of fetal bovine serum
Authors: Crabbé Aurélie , Liu Yulong , Matthijs Nele , Rigole Petra , De La Fuente-Nùñez César , Davis Richard , Ledesma Maria A. , Sarker Shameema , Van Houdt Rob , Hancock Robert E. W. , Coenye Tom , Nickerson Cheryl A.
Published: March 2017

In vitro models that mimic in vivo host-pathogen interactions are needed to evaluate candidate drugs that inhibit bacterial virulence traits. We established a new approach to study Pseudomonas aeruginosa biofilm susceptibility on biotic surfaces, using a three-dimensional (3-D) lung epithelial cell model. P. aeruginosa formed antibiotic resistant biofilms on 3-D cells without affecting cell viability. The biofilm-inhibitory activity of antibiotics and/or the anti-biofilm peptide DJK-5 were evaluated on 3-D cells compared to a plastic surface, in medium with and without fetal bovine serum (FBS). In both media, aminoglycosides were more efficacious in the 3-D cell model. In serum-free medium, most antibiotics (except polymyxins) showed enhanced efficacy when 3-D cells were present. In medium with FBS, colistin was less efficacious in the 3-D cell model. DJK-5 exerted potent inhibition of P. aeruginosa association with both substrates, only in serum-free medium. DJK-5 showed stronger inhibitory activity against P. aeruginosa associated with plastic compared to 3-D cells. The combined addition of tobramycin and DJK-5 exhibited more potent ability to inhibit P. aeruginosa association with both substrates. In conclusion, lung epithelial cells influence the efficacy of most antimicrobials against P. aeruginosa biofilm formation, which in turn depends on the presence or absence of FBS.
Terahertz metamaterials and systems based on rolled-up 3D elements: designs, technological approaches, and properties
Authors: Prinz Victor Ya. , Naumova Elena V. , Golod Sergey V. , Seleznev Vladimir A. , Bocharov Andrey A. , Kubarev Vitaliy V.
Published: March 2017

Electromagnetic metamaterials opened the way to extraordinary manipulation of radiation. Terahertz (THz) and optical metamaterials are usually fabricated by traditional planar-patterning approaches, while the majority of practical applications require metamaterials with 3D resonators. Making arrays of precise 3D micro- and nanoresonators is still a challenging problem. Here we present a versatile set of approaches to fabrication of metamaterials with 3D resonators rolled-up from strained films, demonstrate novel THz metamaterials/systems, and show giant polarization rotation by several chiral metamaterials/systems. The polarization spectra of chiral metamaterials on semiconductor substrates exhibit ultrasharp quasiperiodic peaks. Application of 3D printing allowed assembling more complex systems, including the bianisotropic system with optimal microhelices, which showed an extreme polarization azimuth rotation of 85° with drop by 150° at a frequency shift of 0.4%. We refer the quasiperiodic peaks in the polarization spectra of metamaterial systems to the interplay of different resonances, including peculiar chiral waveguide resonance. Formed metamaterials cannot be made by any other presently available technology. All steps of presented fabrication approaches are parallel, IC-compatible and allow mass fabrication with scaling of rolled-up resonators up to visible frequencies. We anticipate that the rolled-up meta-atoms will be ideal building blocks for future generations of commercial metamaterials, devices and systems on their basis.
Recovering the quantum formalism from physically realist axioms
Authors: Auffèves Alexia , Grangier Philippe
Published: March 2017

We present a heuristic derivation of Born’s rule and unitary transforms in Quantum Mechanics, from a simple set of axioms built upon a physical phenomenology of quantization. This approach naturally leads to the usual quantum formalism, within a new realistic conceptual framework that is discussed in details. Physically, the structure of Quantum Mechanics appears as a result of the interplay between the quantized number of “modalities” accessible to a quantum system, and the continuum of “contexts” that are required to define these modalities. Mathematically, the Hilbert space structure appears as a consequence of a specific “extra-contextuality” of modalities, closely related to the hypothesis of Gleason’s theorem, and consistent with its conclusions.
Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation
Authors: Maria M. Sneha , Rakesh P. E. , Chandra T. S. , Sen A. K.
Published: March 2017

We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a ‘self-built-in filter’ and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour’s model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from <10 μl whole blood) in 15 min with a purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks.
Insights into the sonochemical synthesis and properties of salt-free intrinsic plutonium colloids
Authors: Dalodière Elodie , Virot Matthieu , Morosini Vincent , Chave Tony , Dumas Thomas , Hennig Christoph , Wiss Thierry , Dieste Blanco Oliver , Shuh David K. , Tyliszcak Tolek , Venault Laurent , Moisy Philippe , Nikitenko Sergey I.
Published: March 2017

Fundamental knowledge on intrinsic plutonium colloids is important for the prediction of plutonium behaviour in the geosphere and in engineered systems. The first synthetic route to obtain salt-free intrinsic plutonium colloids by ultrasonic treatment of PuO2 suspensions in pure water is reported. Kinetics showed that both chemical and mechanical effects of ultrasound contribute to the mechanism of Pu colloid formation. In the first stage, fragmentation of initial PuO2 particles provides larger surface contact between cavitation bubbles and solids. Furthermore, hydrogen formed during sonochemical water splitting enables reduction of Pu(IV) to more soluble Pu(III), which then re-oxidizes yielding Pu(IV) colloid. A comparative study of nanostructured PuO2 and Pu colloids produced by sonochemical and hydrolytic methods, has been conducted using HRTEM, Pu LIII-edge XAS, and O K-edge NEXAFS/STXM. Characterization of Pu colloids revealed a correlation between the number of Pu-O and Pu-Pu contacts and the atomic surface-to-volume ratio of the PuO2 nanoparticles. NEXAFS indicated that oxygen state in hydrolytic Pu colloid is influenced by hydrolysed Pu(IV) species to a greater extent than in sonochemical PuO2 nanoparticles. In general, hydrolytic and sonochemical Pu colloids can be described as core-shell nanoparticles composed of quasi-stoichiometric PuO2 cores and hydrolyzed Pu(IV) moieties at the surface shell.
Thermographic Microstructure Monitoring in Electron Beam Additive Manufacturing
Authors: Raplee J. , Plotkowski A. , Kirka M. M. , Dinwiddie R. , Okello A. , Dehoff R. R. , Babu S. S.
Published: March 2017

To reduce the uncertainty of build performance in metal additive manufacturing, robust process monitoring systems that can detect imperfections and improve repeatability are desired. One of the most promising methods for in situ monitoring is thermographic imaging. However, there is a challenge in using this technology due to the difference in surface emittance between the metal powder and solidified part being observed that affects the accuracy of the temperature data collected. The purpose of the present study was to develop a method for properly calibrating temperature profiles from thermographic data to account for this emittance change and to determine important characteristics of the build through additional processing. The thermographic data was analyzed to identify the transition of material from metal powder to a solid as-printed part. A corrected temperature profile was then assembled for each point using calibrations for these surface conditions. Using this data, the thermal gradient and solid-liquid interface velocity were approximated and correlated to experimentally observed microstructural variation within the part. This work shows that by using a method of process monitoring, repeatability of a build could be monitored specifically in relation to microstructure control.
Transcriptional and post-transcriptional regulation of the ionizing radiation response by ATM and p53
Authors: Venkata Narayanan Ishwarya , Paulsen Michelle T. , Bedi Karan , Berg Nathan , Ljungman Emily A. , Francia Sofia , Veloso Artur , Magnuson Brian , di Fagagna Fabrizio d’Adda , Wilson Thomas E. , Ljungman Mats
Published: March 2017

In response to ionizing radiation (IR), cells activate a DNA damage response (DDR) pathway to re-program gene expression. Previous studies using total cellular RNA analyses have shown that the stress kinase ATM and the transcription factor p53 are integral components required for induction of IR-induced gene expression. These studies did not distinguish between changes in RNA synthesis and RNA turnover and did not address the role of enhancer elements in DDR-mediated transcriptional regulation. To determine the contribution of synthesis and degradation of RNA and monitor the activity of enhancer elements following exposure to IR, we used the recently developed Bru-seq, BruChase-seq and BruUV-seq techniques. Our results show that ATM and p53 regulate both RNA synthesis and stability as well as enhancer element activity following exposure to IR. Importantly, many genes in the p53-signaling pathway were coordinately up-regulated by both increased synthesis and RNA stability while down-regulated genes were suppressed either by reduced synthesis or stability. Our study is the first of its kind that independently assessed the effects of ionizing radiation on transcription and post-transcriptional regulation in normal human cells.
A Core Regulatory Circuit in Glioblastoma Stem Cells Links MAPK Activation to a Transcriptional Program of Neural Stem Cell Identity
Authors: Riddick Gregory , Kotliarova Svetlana , Rodriguez Virginia , Kim H. S. , Linkous Amanda , Storaska Andrew J. , Ahn Susie , Walling Jennifer , Belova Galina , Fine Howard A.
Published: March 2017

Glioblastoma, the most common primary malignant brain tumor, harbors a small population of tumor initiating cells (glioblastoma stem cells) that have many properties similar to neural stem cells. To investigate common regulatory networks in both neural and glioblastoma stem cells, we subjected both cell types to in-vitro differentiation conditions and measured global gene-expression changes using gene expression microarrays. Analysis of enriched transcription factor DNA-binding sites in the promoters of differentially expressed genes was used to reconstruct regulatory networks involved in differentiation. Computational predictions, which were biochemically validated, show an extensive overlap of regulatory circuitry between cell types including a network centered on the transcription factor KLF4. We further demonstrate that EGR1, a transcription factor previously shown to be downstream of the MAPK pathway, regulates KLF4 expression and that KLF4 in turn transcriptionally activates NOTCH as well as SOX2. These results demonstrate how known genomic alterations in glioma that induce constitutive activation of MAPK are transcriptionally linked to master regulators essential for neural stem cell identify.