bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the Wnt signalling pathway in the development of endothelial disorders in response to hyperglycaemia
Authors: Durak-Kozica Martyna , Paszek Elżbieta , Stępień Ewa Ł
Published: December 2019

Introduction

Diabetes mellitus (DM) is the most common metabolic disease. A WHO report from 2016 indicates that 422 million people worldwide suffer from DM or hyperglycaemia because of impaired glucose metabolism. Chronic hyperglycaemia leads to micro- and macrovessel damage, which may result in life-threatening complications. The Wnt pathway regulates cell proliferation and survival by modulating the expression of genes that control cell differentiation. Three linked Wnt pathways have been discovered thus far: aβ-catenin-dependent pathway and two pathways independent ofβ-catenin – the planar cell polarity pathway and calcium-dependent pathway. The Wnt pathway regulates genes associated with inflammation, cell cycle, angiogenesis, fibrinolysis and other molecular processes.

Areas covered

This review presents the current state of knowledge regarding the contribution of the Wnt pathway to endothelial ageing under hyperglycaemic conditions and provides new insights into the molecular basis of diabetic endothelial dysfunction.

Conclusion

Theβ-catenin-dependent pathway is a potential target in the prophylaxis and treatment of early-stage diabetes-related vascular complications. However, the underlying molecular mechanisms remain largely undetermined and require further investigation.
The Contentious Politics of Resettlement Programs: Evidence from Newfoundland and Labrador, Canada
Authors: Côté Isabelle , Pottie-Sherman Yolande
Published: December 2019

Labelling resettlement programs as voluntary suggests that they cause little contention and are devoid of coercion. But is this representation accurate? Drawing on unpublished government documents and media reports, we provide a detailed case study of the Community Relocation Policy (CRP) of Newfoundland and Labrador (NL) from 2009 to the present. We show that CRP has been fraught with contention due to the nature of the voting process and the slow and uncertain nature of the community-oriented consultative process. This article highlights the ways in which coercion has emerged from within the very communities considering resettlement, in addition to any coercion that might come from government officials.
Understanding resilience from the perspective of Appalachian centenarians
Authors: Holston Ezra C. , Callen Bonnie
Published: December 2019

Centenarians worldwide are growing rapidly and thriving as they age. This growth reflects their desire to thrive beyond personal and societal obstacles, a hallmark sign of resilience. However, little research exists on centenarians’ perspectives about their lived experiences that reflect resilience. Therefore, the purpose of this secondary analysis was to capture the perspectives of Appalachian centenarians about (a) living through their childhood and early adulthood in an area known for poverty and isolation, and (b) exploring the resilient nature that emerged from their narratives. With a qualitative descriptive design, 21 community-dwelling Appalachian centenarians participated in face-to-face interviews. They resided in either their homes or assisted-living facilities. Transcripts were analysed with Neuendorf's method of content analysis. Within three themes, 11 sub-themes were identified: (a) working hard for the family, (b) loss of a loved one, (c) gender and race discrimination, (d) impact of isolation on health, (e) living a simple life, (f) using family/community support, (g) consuming and appreciating food from their farms, (h) spirituality, (i) generosity of spirit, (j) living a clean life, and (k) happy, good and loving life. Collectively, these themes and sub-themes reflected how the centenarians overcame and grew from challenges and adversities to become resilient. Consequently, these findings show that understanding resilience from centenarians’ perspectives can significantly contribute to the potential for longevity.
Coupling the normative regulation with the constitutive state management in Situated Artificial Institutions
Authors: De Brito Maiquel , Fred Hübner Jomi , Boissier Olivier
Published: December 2019

Artificial Institutions are systems where the regulation defined through norms is based on an interpretation of the concrete world where the agents are situated and interact. Such interpretation can be defined through constitutive rules. The literature proposes independent approaches for the definition and management of both norms and constitutive rules. However, they are usually either not coupled or coupled in an ad hoc and limiting solution. This paper investigates how to make such a coupling. The main contribution of this paper is a formal model basing the regulation provided by the norms on the institutional interpretation of the world provided by constitutive rules. This contribution is based on the Situated Artificial Institutions model that proposes an integrated model of constitutive rules based on status functions.
New access services in HbbTV based on a deep learning approach for media content analysis
Authors: Uribe Silvia , Belmonte Alberto , Moreno Francisco , Llorente Álvaro , López Juan Pedro , Álvarez Federico
Published: December 2019

Universal access on equal terms to audiovisual content is a key point for the full inclusion of people with disabilities in activities of daily life. As a real challenge for the current Information Society, it has been detected but not achieved in an efficient way, due to the fact that current access solutions are mainly based in the traditional television standard and other not automated high-cost solutions. The arrival of new technologies within the hybrid television environment together with the application of different artificial intelligence techniques over the content will assure the deployment of innovative solutions for enhancing the user experience for all. In this paper, a set of different tools for image enhancement based on the combination between deep learning and computer vision algorithms will be presented. These tools will provide automatic descriptive information of the media content based on face detection for magnification and character identification. The fusion of this information will be finally used to provide a customizable description of the visual information with the aim of improving the accessibility level of the content, allowing an efficient and reduced cost solution for all.
Somatosensory Processing in Gilles de la Tourette Syndrome
Authors: Kleimaker Alexander , Kleimaker Maximilian , Beste Christian , Bäumer Tobias , Münchau Alexander
Published: December 2019

Abstract. In Tourette syndrome, premonitory urges preceding tics play a prominent role, e. g., as an urge to perform a certain action, but also as a cold or warm feeling, the feeling of a mounting tension in the muscles involved in tics or other unpleasant perceptions. The execution of tics results in a temporary reduction of these feelings. Additionally, there is a hypersensitivity to external stimuli and a high level of distractibility. In corroboration of these findings, adolescent Tourette patients show a thinning of the primary somatosensory cortex and secondary somatosensory areas. Also, reduced prepulse inhibition and reductions of short afferent inhibition provide further evidence for deficient inhibitory and gating functions in Tourette patients.
Offset Channels May Not Accurately Record Strike‐Slip Fault Displacement: Evidence From Landscape Evolution Models
Authors: Reitman Nadine G. , Mueller Karl J. , Tucker Gregory E. , Gold Ryan D. , Briggs Richard W. , Barnhart Katherine R.
Published: December 2019

Slip distribution, slip rate, and slip per event for strike‐slip faults are commonly determined by correlating offset stream channels—under the assumption that they record seismic slip—but offset channels are formed by the interplay of tectonic and geomorphic processes. To constrain offset channel development under known tectonic and geomorphic conditions, we use numerical landscape evolution simulations along a theoretical strike‐slip fault with uniform and steady uplift, erosion, and diffusion. We investigate the influence of four tectonic parameters (fault zone width, earthquake recurrence interval, variance of the recurrence interval, and total slip relative to channel spacing) on offset channel development through multiple earthquake cycles. Analysis of >3,000 automatically measured offsets from >135 simulations suggests ~30% variability in individual measurements, but modeled displacement is recovered by averaging multiple measurements. However, the average of multiple offset measurements systematically underestimates modeled slip except when the fault zone is less than ~5 m wide, total slip is less than channel spacing, and offsets are measured shortly after an earthquake. In these simulations, postearthquake landscape evolution widens the geomorphic expression of the fault zone and modifies apparent channel offsets. We distinguish this “geomorphic fault zone” from the tectonic fault zone (zone of coseismic distributed deformation). This study highlights the capability of landscape evolution models to explore a range of conditions not easily defined in natural examples and the importance of averaging multiple measurements. Our results verify that paleoseismic studies must consider how geomorphic change has modified offset markers and use caution interpreting slip histories with multiple earthquakes.
Ofatumumab maintenance prolongs progression-free survival in relapsed chronic lymphocytic leukemia: final analysis of the PROLONG study
Authors: van Oers Marinus , Smolej Lukas , Petrini Mario , Offner Fritz , Grosicki Sebastian , Levin Mark-David , Davis Jaclyn , Banerjee Hiya , Stefanelli Tommaso , Hoever Petra , Geisler Christian
Published: December 2019

We report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300 mg first week, followed by 1000 mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43–0.70]; P < 0.0001). Median time to next treatment for ofatumumab and observation arms, respectively, was 37.4 and 27.6 months (0.72 [0.57–0.91]; P = 0.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72–1.37]). Grade ≥ 3 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.
First-time postmenopausal bleeding as a clinical marker of long-term cancer risk: A Danish Nationwide Cohort Study
Authors: Bengtsen Maria B. , Veres Katalin , Nørgaard Mette
Published: December 2019

Background

Data on long-term risk of cancer after a postmenopausal bleeding diagnosis are sparse.

Methods

We used Danish medical registries to conduct a population-based cohort study of women with a first hospital-diagnosed postmenopausal bleeding during 1995–2013. We computed the absolute risk of cancer and the standardised incidence ratio (SIR) comparing the observed cancer incidence with that expected in the general population.

Results

Among 43,756 women with postmenopausal bleeding, the absolute 1- and 5-year risk of endometrial cancer were 4.66% and 5.18%, respectively. The SIR of endometrial cancer was elevated during 0–3 months (SIR = 330.36 (95% CI: 315.43–345.81)), 3–12 months (SIR = 11.39 (95% CI: 9.79–13.17)), 1–5 years (SIR = 2.55 (95% CI: 2.19–2.94)) and >5 years of follow-up (SIR = 1.63 (95% CI: 1.40–1.90)). All selected gynaecological and urological, gastrointestinal and haematological cancers had elevated 0–3 months SIRs. Beyond 1 year of follow-up the SIRs of ovarian and bladder cancer remained elevated with a 1–5-year SIR of 2.15 (95% CI: 1.71–2.65) and 1.45 (95% CI: 1.14–1.80), respectively.

Conclusions

In the Danish population, women with a first hospital-diagnosed postmenopausal bleeding have an increased 0–3 months risk of gynaecological, urological, gastrointestinal and haematological cancers. The SIR of endometrial, ovarian and bladder cancer remained elevated for several years.
Renewed proliferation in adult mouse cochlea and regeneration of hair cells
Authors: Shu Yilai , Li Wenyan , Huang Mingqian , Quan Yi-Zhou , Scheffer Deborah , Tian Chunjie , Tao Yong , Liu Xuezhong , Hochedlinger Konrad , Indzhykulian Artur A. , Wang Zhengmin , Li Huawei , Chen Zheng-Yi
Published: December 2019

The adult mammalian inner ear lacks the capacity to divide or regenerate. Damage to inner ear generally leads to permanent hearing loss in humans. Here, we present that reprogramming of the adult inner ear induces renewed proliferation and regeneration of inner ear cell types. Co-activation of cell cycle activator Myc and inner ear progenitor gene Notch1 induces robust proliferation of diverse adult cochlear sensory epithelial cell types. Transient MYC and NOTCH activities enable adult supporting cells to respond to transcription factor Atoh1 and efficiently transdifferentiate into hair cell-like cells. Furthermore, we uncover that mTOR pathway participates in MYC/NOTCH-mediated proliferation and regeneration. These regenerated hair cell-like cells take up the styryl dye FM1-43 and are likely to form connections with adult spiral ganglion neurons, supporting that Myc and Notch1 co-activation is sufficient to reprogram fully mature supporting cells to proliferate and regenerate hair cell-like cells in adult mammalian auditory organs.
Carbon-nanotube reinforcement of DNA-silica nanocomposites yields programmable and cell-instructive biocoatings
Authors: Hu Yong , Domínguez Carmen M. , Bauer Jens , Weigel Simone , Schipperges Alessa , Oelschlaeger Claude , Willenbacher Norbert , Keppler Stephan , Bastmeyer Martin , Heißler Stefan , Wöll Christof , Scharnweber Tim , Rabe Kersten S. , Niemeyer Christof M.
Published: December 2019

Biomedical applications require substrata that allow for the grafting, colonization and control of eukaryotic cells. Currently available materials are often limited by insufficient possibilities for the integration of biological functions and means for tuning the mechanical properties. We report on tailorable nanocomposite materials in which silica nanoparticles are interwoven with carbon nanotubes by DNA polymerization. The modular, well controllable and scalable synthesis yields materials whose composition can be gradually adjusted to produce synergistic, non-linear mechanical stiffness and viscosity properties. The materials were exploited as substrata that outperform conventional culture surfaces in the ability to control cellular adhesion, proliferation and transmigration through the hydrogel matrix. The composite materials also enable the construction of layered cell architectures, the expansion of embryonic stem cells by simplified cultivation methods and the on-demand release of uniformly sized stem cell spheroids.
Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys
Authors: Luo Xin , He Yaoxi , Zhang Chao , He Xiechao , Yan Lanzhen , Li Min , Hu Ting , Hu Yan , Jiang Jin , Meng Xiaoyu , Ji Weizhi , Zhao Xudong , Zheng Ping , Xu Shuhua , Su Bing
Published: December 2019

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect and on-target complex mutations remain a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, to our knowledge no comprehensive in vivo off-target and on-target assessment has been conducted in NHPs. Here, we perform whole genome trio sequencing of Cas9-treated rhesus monkeys. We only find a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected off-target mutations (OTMs) were detected. Furthermore, the long-read sequencing data does not detect large structural variants in the target region.
Self-organized twist-heterostructures via aligned van der Waals epitaxy and solid-state transformations
Authors: Sutter Peter , Ibragimova Rina , Komsa Hannu-Pekka , Parkinson Bruce A. , Sutter Eli
Published: December 2019

Vertical van der Waals (vdW) heterostructures of 2D crystals with defined interlayer twist are of interest for band-structure engineering via twist moiré superlattice potentials. To date, twist-heterostructures have been realized by micromechanical stacking. Direct synthesis is hindered by the tendency toward equilibrium stacking without interlayer twist. Here, we demonstrate that growing a 2D crystal with fixed azimuthal alignment to the substrate followed by transformation of this intermediate enables a potentially scalable synthesis of twisted heterostructures. Microscopy during growth of ultrathin orthorhombic SnS on trigonal SnS2 shows that vdW epitaxy yields azimuthal order even for non-isotypic 2D crystals. Excess sulfur drives a spontaneous transformation of the few-layer SnS to SnS2, whose orientation – rotated 30° against the underlying SnS2 crystal – is defined by the SnS intermediate rather than the substrate. Preferential nucleation of additional SnS on such twisted domains repeats the process, promising the realization of complex twisted stacks by bottom-up synthesis.
Synthetic chimeric nucleases function for efficient genome editing
Authors: Liu R. M. , Liang L. L. , Freed E. , Chang H. , Oh E. , Liu Z. Y. , Garst A. , Eckert C. A. , Gill R. T.
Published: December 2019

CRISPR–Cas systems have revolutionized genome editing across a broad range of biotechnological endeavors. Many CRISPR-Cas nucleases have been identified and engineered for improved capabilities. Given the modular structure of such enzymes, we hypothesized that engineering chimeric sequences would generate non-natural variants that span the kinetic parameter landscape, and thus provide for the rapid selection of nucleases fit for a particular editing system. Here, we design a chimeric Cas12a-type library with approximately 560 synthetic chimeras, and select several functional variants. We demonstrate that certain nuclease domains can be recombined across distantly related nuclease templates to produce variants that function in bacteria, yeast, and human cell lines. We further characterize selected chimeric nucleases and find that they have different protospacer adjacent motif (PAM) preferences and the M44 chimera has higher specificity relative to wild-type (WT) sequences. This demonstration opens up the possibility of generating nuclease sequences with implications across biotechnology.
Author Correction: Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases
Authors: An Jiyuan , Gharahkhani Puya , Law Matthew H. , Ong Jue-Sheng , Han Xikun , Olsen Catherine M. , Neale Rachel E. , Lai John , Vaughan Tom L. , Gockel Ines , Thieme René , Böhmer Anne C. , Jankowski Janusz , Fitzgerald Rebecca C. , Schumacher Johannes , Palles Claire ,   BEACON, Gammon Marilie D. , Corley Douglas A. , Shaheen Nicholas J. , Bird Nigel C. , Hardie Laura J. , Murray Liam J. , Reid Brian J. , Chow Wong-Ho , Risch Harvey A. , Ye Weimin , Liu Geoffrey , Romero Yvonne , Bernstein Leslie , Wu Anna H. ,   23andMe Research Team, Agee M. , Alipanahi B. , Auton A. , Bell R. K. , Bryc K. , Elson S. L. , Fontanillas P. , Furlotte N. A. , Hinds D. A. , Huber K. E. , Kleinman A. , Litterman N. K. , McIntyre M. H. , Mountain J. L. , Noblin E. S. , Northover C. A. M. , Pitts S. J. , Sathirapongsasuti J. Fah , Sazonova O. V. , Shelton J. F. , Shringarpure S. , Tian C. , Tung J. Y. , Vacic V. , Wilson C. H. , Whiteman David C. , MacGregor Stuart
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Individual face- and house-related eye movement patterns distinctively activate FFA and PPA
Authors: Wang Lihui , Baumgartner Florian , Kaule Falko R. , Hanke Michael , Pollmann Stefan
Published: December 2019

We investigated if the fusiform face area (FFA) and the parahippocampal place area (PPA) contain a representation of fixation sequences that are typically used when looking at faces or houses. Here, we instructed observers to follow a dot presented on a uniform background. The dot’s movements represented gaze paths acquired separately from observers looking at face or house pictures. Even when gaze dispersion differences were controlled, face- and house-associated gaze patterns could be discriminated by fMRI multivariate pattern analysis in FFA and PPA, more so for the current observer’s own gazes than for another observer’s gaze. The discrimination of the observer’s own gaze patterns was not observed in early visual areas (V1 – V4) or superior parietal lobule and frontal eye fields. These findings indicate a link between perception and action—the complex gaze patterns that are used to explore faces and houses—in the FFA and PPA.
Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter
Authors: Retzer Katarzyna , Akhmanova Maria , Konstantinova Nataliia , Malínská Kateřina , Leitner Johannes , Petrášek Jan , Luschnig Christian
Published: December 2019

Arabidopsis PIN2 protein directs transport of the phytohormone auxin from the root tip into the root elongation zone. Variation in hormone transport, which depends on a delicate interplay between PIN2 sorting to and from polar plasma membrane domains, determines root growth. By employing a constitutively degraded version of PIN2, we identify brassinolides as antagonists of PIN2 endocytosis. This response does not require de novo protein synthesis, but involves early events in canonical brassinolide signaling. Brassinolide-controlled adjustments in PIN2 sorting and intracellular distribution governs formation of a lateral PIN2 gradient in gravistimulated roots, coinciding with adjustments in auxin signaling and directional root growth. Strikingly, simulations indicate that PIN2 gradient formation is no prerequisite for root bending but rather dampens asymmetric auxin flow and signaling. Crosstalk between brassinolide signaling and endocytic PIN2 sorting, thus, appears essential for determining the rate of gravity-induced root curvature via attenuation of differential cell elongation.
Author Correction: A tool for functional brain imaging with lifespan compliance
Authors: Hill Ryan M. , Boto Elena , Holmes Niall , Hartley Caroline , Seedat Zelekha A. , Leggett James , Roberts Gillian , Shah Vishal , Tierney Tim M. , Woolrich Mark W. , Stagg Charlotte J. , Barnes Gareth R. , Bowtell Richard , Slater Rebeccah , Brookes Matthew J.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Shell potentials for microgravity Bose–Einstein condensates
Authors: Lundblad N. , Carollo R. A. , Lannert C. , Gold M. J. , Jiang X. , Paseltiner D. , Sergay N. , Aveline D. C.
Published: December 2019

Extending the understanding of Bose–Einstein condensate (BEC) physics to new geometries and topologies has a long and varied history in ultracold atomic physics. One such new geometry is that of a bubble, where a condensate would be confined to the surface of an ellipsoidal shell. Study of this geometry would give insight into new collective modes, self-interference effects, topology-dependent vortex behavior, dimensionality crossovers from thick to thin shells, and the properties of condensates pushed into the ultradilute limit. Here we propose to implement a realistic experimental framework for generating shell-geometry BEC using radiofrequency dressing of magnetically trapped samples. Such a tantalizing state of matter is inaccessible terrestrially due to the distorting effect of gravity on experimentally feasible shell potentials. The debut of an orbital BEC machine (NASA Cold Atom Laboratory, aboard the International Space Station) has enabled the operation of quantum-gas experiments in a regime of perpetual freefall, and thus has permitted the planning of microgravity shell-geometry BEC experiments. We discuss specific experimental configurations, applicable inhomogeneities and other experimental challenges, and outline potential experiments.
Development and implementation of a nurse-led allergy clinic model in primary care: feasibility trial protocol
Authors: Kelman Margaret , Hammersley Victoria , Kendall Marilyn , Mukherjee Mome , Morrice Lynn , Harley Susan , Schwarze Jürgen , Sheikh Aziz
Published: December 2019

In the United Kingdom, there are acknowledged short comings in allergy care provision for patients seen in primary care. There is a lack of allergy training for healthcare professionals and this leads to inappropriate referrals to the limited number of allergy specialists. The primary aims of this study are to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and quality of life. This is a single arm feasibility trial in which up to 250 participants referred to the nurse-led allergy clinic will receive the intervention and complete 6–12 weeks follow-up before being referred back to their usual care. Primary outcomes for this study will be establishment of clinics, recruitment and retention rates, and estimates of change in disease-specific quality of life measures. Secondary outcomes will be acceptability of the new service to participants/carers and healthcare professionals. A sample of participants and professional stakeholders will take part in more in-depth semi-structured qualitative interviews. Data from this feasibility trial will be used to inform plans for a pilot randomised controlled trial of nurse-led allergy clinics.
A reference library for Canadian invertebrates with 1.5 million barcodes, voucher specimens, and DNA samples
Authors: deWaard Jeremy R. , Ratnasingham Sujeevan , Zakharov Evgeny V. , Borisenko Alex V. , Steinke Dirk , Telfer Angela C. , Perez Kate H. J. , Sones Jayme E. , Young Monica R. , Levesque-Beaudin Valerie , Sobel Crystal N. , Abrahamyan Arusyak , Bessonov Kyrylo , Blagoev Gergin , deWaard Stephanie L. , Ho Chris , Ivanova Natalia V. , Layton Kara K. S. , Lu Liuqiong , Manjunath Ramya , McKeown Jaclyn T. A. , Milton Megan A. , Miskie Renee , Monkhouse Norm , Naik Suresh , Nikolova Nadya , Pentinsaari Mikko , Prosser Sean W. J. , Radulovici Adriana E. , Steinke Claudia , Warne Connor P. , Hebert Paul D. N.
Published: December 2019

The reliable taxonomic identification of organisms through DNA sequence data requires a well parameterized library of curated reference sequences. However, it is estimated that just 15% of described animal species are represented in public sequence repositories. To begin to address this deficiency, we provide DNA barcodes for 1,500,003 animal specimens collected from 23 terrestrial and aquatic ecozones at sites across Canada, a nation that comprises 7% of the planet’s land surface. In total, 14 phyla, 43 classes, 163 orders, 1123 families, 6186 genera, and 64,264 Barcode Index Numbers (BINs; a proxy for species) are represented. Species-level taxonomy was available for 38% of the specimens, but higher proportions were assigned to a genus (69.5%) and a family (99.9%). Voucher specimens and DNA extracts are archived at the Centre for Biodiversity Genomics where they are available for further research. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, and the Global Genome Biodiversity Network Data Portal.
Hybrid Organic/Inorganic Nano-I-Beam for Structural Nano-mechanics
Authors: Elmoselhy Salah A. M.
Published: December 2019

For years Carbon nano-tube has shown merits in industrial applications including high structural strength-to-weight ratio. However, from structural mechanics perspective the tube geometrical cross-section is less favored for providing high structural stiffness and strength. Hybrid Organic/Inorganic Nano-I-Beam is thus introduced for improved Structural Nano-mechanics. It has been found that both Wide Flange Nano-I-Beam and Equal Flange & Web Nano-I-beam provide higher structural stiffness and less induced stress and thus longer service life than Nano-Tube. It has been also found that Wide Flange Nano-I-Beam provides higher structural stiffness and less induced stress and thus longer service life than Equal Flange & Web Nano-I-beam. A thermodynamic model of the growth of nano-tubes accounting for vibrational entropy is presented. The results have cost-effectively potential benefit in applications such as nano-heat engines & sensors.
Lithium alters expression of RNAs in a type-specific manner in differentiated human neuroblastoma neuronal cultures, including specific genes involved in Alzheimer’s disease
Authors: Maloney Bryan , Balaraman Yokesh , Liu Yunlong , Chopra Nipun , Edenberg Howard J. , Kelsoe John , Nurnberger John I. , Lahiri Debomoy K.
Published: December 2019

Lithium (Li) is a medication long-used to treat bipolar disorder. It is currently under investigation for multiple nervous system disorders, including Alzheimer’s disease (AD). While perturbation of RNA levels by Li has been previously reported, its effects on the whole transcriptome has been given little attention. We, therefore, sought to determine comprehensive effects of Li treatment on RNA levels. We cultured and differentiated human neuroblastoma (SK-N-SH) cells to neuronal cells with all-transretinoic acid (ATRA). We exposed cultures for one week to lithium chloride or distilled water, extracted total RNA, depleted ribosomal RNA and performed whole-transcriptome RT-sequencing. We analyzed results by RNA length and type. We further analyzed expression and protein interaction networks between selected Li-altered protein-coding RNAs and common AD-associated gene products. Lithium changed expression of RNAs in both non-specific (inverse to sequence length) and specific (according to RNA type) fashions. The non-coding small nucleolar RNAs (snoRNAs) were subject to the greatest length-adjusted Li influence. When RNA length effects were taken into account, microRNAs as a group were significantly less likely to have had levels altered by Li treatment. Notably, several Li-influenced protein-coding RNAs were co-expressed or produced proteins that interacted with several common AD-associated genes and proteins. Lithium’s modification of RNA levels depends on both RNA length and type. Li activity on snoRNA levels may pertain to bipolar disorders while Li modification of protein coding RNAs may be relevant to AD.
Deterministic networks for probabilistic computing
Authors: Jordan Jakob , Petrovici Mihai A. , Breitwieser Oliver , Schemmel Johannes , Meier Karlheinz , Diesmann Markus , Tetzlaff Tom
Published: December 2019

Neuronal network models of high-level brain functions such as memory recall and reasoning often rely on the presence of some form of noise. The majority of these models assumes that each neuron in the functional network is equipped with its own private source of randomness, often in the form of uncorrelated external noise. In vivo, synaptic background input has been suggested to serve as the main source of noise in biological neuronal networks. However, the finiteness of the number of such noise sources constitutes a challenge to this idea. Here, we show that shared-noise correlations resulting from a finite number of independent noise sources can substantially impair the performance of stochastic network models. We demonstrate that this problem is naturally overcome by replacing the ensemble of independent noise sources by a deterministic recurrent neuronal network. By virtue of inhibitory feedback, such networks can generate small residual spatial correlations in their activity which, counter to intuition, suppress the detrimental effect of shared input. We exploit this mechanism to show that a single recurrent network of a few hundred neurons can serve as a natural noise source for a large ensemble of functional networks performing probabilistic computations, each comprising thousands of units.
DeepSynth: Three-dimensional nuclear segmentation of biological images using neural networks trained with synthetic data
Authors: Dunn Kenneth W. , Fu Chichen , Ho David Joon , Lee Soonam , Han Shuo , Salama Paul , Delp Edward J.
Published: December 2019

The scale of biological microscopy has increased dramatically over the past ten years, with the development of new modalities supporting collection of high-resolution fluorescence image volumes spanning hundreds of microns if not millimeters. The size and complexity of these volumes is such that quantitative analysis requires automated methods of image processing to identify and characterize individual cells. For many workflows, this process starts with segmentation of nuclei that, due to their ubiquity, ease-of-labeling and relatively simple structure, make them appealing targets for automated detection of individual cells. However, in the context of large, three-dimensional image volumes, nuclei present many challenges to automated segmentation, such that conventional approaches are seldom effective and/or robust. Techniques based upon deep-learning have shown great promise, but enthusiasm for applying these techniques is tempered by the need to generate training data, an arduous task, particularly in three dimensions. Here we present results of a new technique of nuclear segmentation using neural networks trained on synthetic data. Comparisons with results obtained using commonly-used image processing packages demonstrate that DeepSynth provides the superior results associated with deep-learning techniques without the need for manual annotation.
Fire and brief human occupations in Iberia during MIS 4: Evidence from Abric del Pastor (Alcoy, Spain)
Authors: Mallol Carolina , Hernández Cristo , Mercier Norbert , Falguères Christophe , Carrancho Ángel , Cabanes Dan , Vidal-Matutano Paloma , Connolly Rory , Pérez Leopoldo , Mayor Alejandro , Ben Arous Eslem , Galván Bertila
Published: December 2019

There is a relatively low amount of Middle Paleolithic sites in Europe dating to MIS 4. Of the few that exist, several of them lack evidence for anthropogenic fire, raising the question of how this period of global cooling may have affected the Neanderthal population. The Iberian Peninsula is a key area to explore this issue, as it has been considered as a glacial refugium during critical periods of the Neanderthal timeline and might therefore yield archaeological contexts in which we can explore possible changes in the behaviour and settlement patterns of Neanderthal groups during MIS 4. Here we report recent data from Abric del Pastor, a small rock shelter in Alcoy (Alicante, Spain) with a stratified deposit containing Middle Palaeolithic remains. We present absolute dates that frame the sequence within MIS 4 and multi-proxy geoarchaeological evidence of in situ anthropogenic fire, including microscopic evidence of in situ combustion residues and thermally altered sediment. We also present archaeostratigraphic evidence of recurrent, functionally diverse, brief human occupation of the rock shelter. Our results suggest that Neanderthals occupied the Central Mediterranean coast of the Iberian Peninsula during MIS 4, that these Neanderthals were not undergoing climatic stress and they were habitual fire users.
Randomised trial on clinical performances and biocompatibility of four high-flux hemodialyzers in two mode treatments: hemodialysis vs post dilution hemodiafiltration
Authors: Morena Marion , Creput Caroline , Bouzernidj Mouloud , Rodriguez Annie , Chalabi Lotfi , Seigneuric Bruno , Lauret Céline , Bargnoux Anne-Sophie , Dupuy Anne-Marie , Cristol Jean-Paul
Published: December 2019

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was β2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total ‘TDC’ vs partial ‘PDC’ collection of dialysate). Significant increases in removal rates of β2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), β-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except β2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.
Determinants of Brain Rhythm Burst Statistics
Authors: Powanwe Arthur S. , Longtin André
Published: December 2019

Brain rhythms recorded in vivo, such as gamma oscillations, are notoriously variable both in amplitude and frequency. They are characterized by transient epochs of higher amplitude known as bursts. It has been suggested that, despite their short-life and random occurrence, bursts in gamma and other rhythms can efficiently contribute to working memory or communication tasks. Abnormalities in bursts have also been associated with e.g. motor and psychiatric disorders. It is thus crucial to understand how single cell and connectivity parameters influence burst statistics and the corresponding brain states. To address this problem, we consider a generic stochastic recurrent network of Pyramidal Interneuron Network Gamma (PING) type. Using the stochastic averaging method, we derive dynamics for the phase and envelope of the amplitude process, and find that they depend on only two meta-parameters that combine all the model parameters. This allows us to identify an optimal parameter regime of healthy variability with similar statistics to those seen in vivo; in this regime, oscillations and bursts are supported by synaptic noise. The probability density for the rhythm’s envelope as well as the mean burst duration are then derived using first passage time analysis. Our analysis enables us to link burst attributes, such as duration and frequency content, to system parameters. Our general approach can be extended to different frequency bands, network topologies and extra populations. It provides the much needed insight into the biophysical determinants of rhythm burst statistics, and into what needs to be changed to correct rhythms with pathological statistics.
Epidermal biopolysaccharides from plant seeds enable biodegradable turbulent drag reduction
Authors: Rajappan Anoop , McKinley Gareth H.
Published: December 2019

The high cost of synthetic polymers has been a key impediment limiting the widespread adoption of polymer drag reduction techniques in large-scale engineering applications, such as marine drag reduction. To address consumable cost constraints, we investigate the use of high molar mass biopolysaccharides, present in the mucilaginous epidermis of plant seeds, as inexpensive drag reducers in large Reynolds number turbulent flows. Specifically, we study the aqueous mucilage extracted from flax seeds (Linum usitatissimum) and compare its drag reduction efficacy to that of poly(ethylene oxide) or PEO, a common synthetic polymer widely used as a drag reducing agent in aqueous flows. Macromolecular and rheological characterisation confirm the presence of high molar mass (≥2 MDa) polysaccharides in the extracted mucilage, with an acidic fraction comprising negatively charged chains. Frictional drag measurements, performed inside a bespoke Taylor-Couette apparatus, show that the as-extracted mucilage has comparable drag reduction performance under turbulent flow conditions as aqueous PEO solutions, while concurrently offering advantages in terms of raw material cost, availability, and bio-compatibility. Our results indicate that plant-sourced mucilage can potentially serve as a cost-effective and eco-friendly substitute for synthetic drag reducing polymers in large scale turbulent flow applications.
Nanoparticle-Mediated Cavitation via CO2 Laser Impacting on Water: Concentration Effect, Temperature Visualization, and Core-Shell Structures
Authors: Hu Man , Wang Feng , Huo Peng , Pan Xueqin , Johnson Steven G. , Fink Yoel , Deng Daosheng
Published: December 2019

By taking advantage of seeded polymer nanoparticles and strong photo energy absorption, we report CO2 laser impacting on water to produce cavitation at the air/water interface. Using a high-speed camera, three regimes (no cavitation, cavitation, and pseudo-cavitation) are identified within a broad range of nanoparticles concentration and size. The underlying correlation among cavitation, nanoparticles and temperature is revealed by the direct observation of spatiotemporal evolution of temperature using a thermal cameral. These findings indicate that nanoparticles not only act as preexisted nuclei to promote nucleation for cavitation, but also likely affect temperature to change the nucleation rate as well. Moreover, by exploiting a compound hexane/water interface, a novel core-shell cavitation is demonstrated. This approach might be utilized to attain and control cavitations by choosing nanoparticles and designing interfaces while operating at a lower laser intensity, for versatile technological applications in material science and medical surgery.
Cross-Modal Coordination of Face-Directed Gaze and Emotional Speech Production in School-Aged Children and Adolescents with ASD
Authors: Sorensen Tanner , Zane Emily , Feng Tiantian , Narayanan Shrikanth , Grossman Ruth
Published: December 2019

Autism spectrum disorder involves persistent difficulties in social communication. Although these difficulties affect both verbal and nonverbal communication, there are no quantitative behavioral studies to date investigating the cross-modal coordination of verbal and nonverbal communication in autism. The objective of the present study was to characterize the dynamic relation between speech production and facial expression in children with autism and to establish how face-directed gaze modulates this cross-modal coordination. In a dynamic mimicry task, experiment participants watched and repeated neutral and emotional spoken sentences with accompanying facial expressions. Analysis of audio and motion capture data quantified cross-modal coordination between simultaneous speech production and facial expression. Whereas neurotypical children produced emotional sentences with strong cross-modal coordination and produced neutral sentences with weak cross-modal coordination, autistic children produced similar levels of cross-modal coordination for both neutral and emotional sentences. An eyetracking analysis revealed that cross-modal coordination of speech production and facial expression was greater when the neurotypical child spent more time looking at the face, but weaker when the autistic child spent more time looking at the face. In sum, social communication difficulties in autism spectrum disorder may involve deficits in cross-modal coordination. This finding may inform how autistic individuals are perceived in their daily conversations.
3D Smith charts scattering parameters frequency-dependent orientation analysis and complex-scalar multi-parameter characterization applied to Peano reconfigurable vanadium dioxide inductors
Authors: Muller Andrei A. , Moldoveanu Alin , Asavei Victor , Khadar Riyaz A. , Sanabria-Codesal Esther , Krammer Anna , Fernandez-Bolaños Montserrat , Cavalieri Matteo , Zhang Junrui , Casu Emanuele , Schuler Andreas , Ionescu Adrian M.
Published: December 2019

Recently, the field of Metal-Insulator-Transition (MIT) materials has emerged as an unconventional solution for novel energy efficient electronic functions, such as steep slope subthermionic switches, neuromorphic hardware, reconfigurable radiofrequency functions, new types of sensors, terahertz and optoelectronic devices. Employing radiofrequency (RF) electronic circuits with a MIT material like vanadium Dioxide, VO2, requires appropriate characterization tools and fabrication processes. In this work, we develop and use 3D Smith charts for devices and circuits having complex frequency dependences, like the ones resulting using MIT materials. The novel foundation of a 3D Smith chart involves here the geometrical fundamental notions of oriented curvature and variable homothety in order to clarify first theoretical inconsistencies in Foster and Non Foster circuits, where the driving point impedances exhibit mixed clockwise and counter-clockwise frequency dependent (oriented) paths on the Smith chart as frequency increases. We show here the unique visualization capability of a 3D Smith chart, which allows to quantify orientation over variable frequency. The new 3D Smith chart is applied as a joint complex-scalar 3D multi-parameter modelling and characterization environment for reconfigurable RF design exploiting Metal-Insulator-Transition (MIT) materials. We report fabricated inductors with record quality factors using VO2 phase transition to program multiple tuning states, operating in the range 4 GHz to 10 GHz.
Formaldehyde quantification using ampicillin is not selective
Authors: Reinbold Raphael , John Tobias , Spingardi Paolo , Kawamura Akane , Thompson Amber L. , Schofield Christopher J. , Hopkinson Richard J.
Published: December 2019

Formaldehyde (HCHO) is a simple and highly reactive human metabolite but its biochemistry is poorly defined. A limiting factor in HCHO research is lack of validated quantification methods for HCHO relevant to biological samples. We describe spectroscopic studies on a reported fluorescence-based HCHO detection method involving its reaction with ampicillin. The results validate the structure and fluorescence properties of the HCHO-ampicillin reaction product. However, the same adduct is observed after reaction of ampicillin with glyoxylate. Related fluorophores were formed with other biologically relevant carbonyl compounds. Overall, our studies suggest the ampicillin method is not reliable for selective detection and quantification of HCHO in biological samples.