bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury
Authors: Cen Ling-Ping , Ng Tsz Kin , Liang Jia-Jian , Zhuang Xi , Yao Xiaowu , Yam Gary Hin-Fai , Chen Haoyu , Cheung Herman S. , Zhang Mingzhi , Pang Chi Pui
Published: February 2018

Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of βIII-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell–cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies.
Lake Sturgeon, Lake Whitefish, and Walleye Egg Deposition Patterns with Response to Fish Spawning Substrate Restoration in the St. Clair–Detroit River System
Authors: Fischer Jason L. , Pritt Jeremy J. , Roseman Edward F. , Prichard Carson G. , Craig Jaquelyn M. , Kennedy Gregory W. , Manny Bruce A.
Published: February 2018

Egg deposition and use of restored spawning substrates by lithophilic fishes (e.g., Lake SturgeonAcipenser fulvescens, Lake WhitefishCoregonus clupeaformis, and WalleyeSander vitreus) were assessed throughout the St. Clair–Detroit River system from 2005 to 2016. Bayesian models were used to quantify egg abundance and presence/absence relative to site‐specific variables (e.g., depth, velocity, and artificial spawning reef presence) and temperature to evaluate fish use of restored artificial spawning reefs and assess patterns in egg deposition. Lake Whitefish and Walleye egg abundance, probability of detection, and probability of occupancy were assessed with detection‐adjusted methods; Lake Sturgeon egg abundance and probability of occurrence were assessed using delta‐lognormal methods. The models indicated that the probability of Walleye eggs occupying a site increased with water velocity and that the rate of increase decreased with depth, whereas Lake Whitefish egg occupancy was not correlated with any of the attributes considered. Egg deposition by Lake Whitefish and Walleyes was greater at sites with high water velocities and was lower over artificial spawning reefs. Lake Sturgeon eggs were collected least frequently but were more likely to be collected over artificial spawning reefs and in greater abundances than elsewhere. Detection‐adjusted egg abundances were not greater over artificial spawning reefs, indicating that these projects may not directly benefit spawning Walleyes and Lake Whitefish. However, 98% of the Lake Sturgeon eggs observed were collected over artificial spawning reefs, supporting the hypothesis that the reefs provided spawning sites for Lake Sturgeon and could mitigate historic losses of Lake Sturgeon spawning habitat.
Natural history of neurological abnormalities in cerebrotendinous xanthomatosis
Authors: Wong Janice C. , Walsh Kailey , Hayden Douglas , Eichler Florian S.
Published: February 2018

Objectives

Cerebrotendinous xanthomatosis (CTX) is a rare inherited neurodegenerative disorder in bile acid synthesis. The natural history of neurological abnormalities in CTX is not well understood. The object of this study was to determine neurological progression in CTX.

Methods

A literature search on PubMed for “cerebrotendinous xanthomatosis” yielded 91 publications that reported cases of CTX patients. Two independent reviewers abstracted information about the presence and age of onset of neurological abnormalities in published CTX cases. For each neurological abnormality, we estimated the probability of its onset at any given age using cumulative incidence function analysis. We also present our own case series, in which five CTX patients were evaluated.

Results

The literature search yielded 194 CTX cases (ages ranging from newborn to 67 years old). The most common neurological abnormalities were corticospinal tract abnormalities including weakness, hyperreflexia, spasticity, Babinski sign (59.8%), ataxia (58.8%), cognitive decline (46.4%), and gait difficulty (38.1%); 68 (35.0%) had baseline cognitive problems. Cumulative incidence function analysis revealed that ataxia, gait difficulties, and corticospinal tract abnormalities developed throughout life, while cognitive decline tended to develop later in life. Of the less common neurological abnormalities, seizures, psychiatric changes and speech changes developed throughout life, while parkinsonism and sensory changes tended to develop later in life. Our case series corroborated this temporal pattern of neurological abnormalities.

Conclusion

We provide estimates for the neurological progression of CTX, categorizing neurological abnormalities according to time and probability of development. Our approach may be applicable to other rare disorders.
An English–Chinese termbase of neological medical terms
Authors: Sun Qingxiang , Zhang Xuhua
Published: February 2018

Rapid advances in medical sciences produce an enormous number of neologisms that are not promptly included in the dictionaries. Corpus technology and IT have furnished language researchers and lexicographers with more effective and efficient means than traditional manual efforts of extracting neologisms. Online dictionaries are gaining popularity against those in print. This paper reports a corpus-based project aimed to build an English–Chinese neological medical termbase. For this purpose, a corpus and an exclusion list have been prepared, the former containing the articles published in the top four comprehensive medical journals from 2010 to 2015 and the latter composed of entry items in a recently published bilingual medical dictionary, a general English lexicon, and all entry items in a name dictionary. Medical neologisms extracted from the corpus are being standardized and translated into Chinese, thus constituting the intended termbase. A search engine has been constructed and will be launched as the outlet of the termbase for the target users.
A socio-cognitive investigation of English medical terminology
Authors: Dahm Maria
Published: February 2018

Patients and doctors can differ in their ideas about what constitutes ‘a medical term’ and what a particular term might mean. Differences in the understanding of medical terminology in doctor–patient communication can impact patient health outcomes. The field of terminology has moved away from the notion of univocity (one term permanently assigned by scholars to describe one concept). Novel, more applied approaches to terminology study have provided evidence for the dynamic variety of meanings associated with specialist terms. One of these, the socio-cognitive approach to terminology aims to explore how the understanding of terms is influenced by the interplay between different cultural, linguistics and knowledge backgrounds. However, most studies in doctor–patient communication have previously neglected to include non-native English speaking doctors or patient in studies focused on the impact of medical terminology in medical encounters. This mixed methods study aims to contribute the new era of descriptive and applied terminology studies by exploring the perception, and understanding of medical terminology among native and non-native English speaking patients and doctors in Australia. In this way, this study adds to the growing evidence base that challenges the ideal of univocity in a global world where monolingual and multilingual individuals from different cultural and knowledge backgrounds commonly use (medical) terminology in specific (medical) contexts.
Etiology and clinical characteristics of pediatric acute pancreatitis in Saudi Arabia
Authors: Alabdulkareem Abdulrahman , Almahmoud Tameem , Al-Tahan Husam , Javad Sundas , Al Hatlani Maher
Published: February 2018

Background:

Cases of acute pancreatitis (AP) have increased among pediatric populations worldwide; however, the natural course of this condition in Saudi Arabia was unknown.

Aim:

To report the characteristics as well as outcomes of pediatric AP.

Patients and methods:

A retrospective chart review study was conducted to include acute pancreatitis in patients < 19 years. The period was from 1994 until 2015. Demographic, clinical, laboratory, imaging and outcome data were collected and analyzed.

Results:

50 patients (n = 26; 52% males vs. n = 24; 48% females) were included. The mean age at diagnosis was 11.6 years. The mean length of hospital stay was 10.5 days. 9 (18%) patients had a recurrence of AP and 4 (8%) had complications. Idiopathic AP was the most frequent etiology (n = 21; 42%), followed by cholelithiasis (n = 11; 22%). 2 patients (4%) had drug-induced AP, where one was taking isoniazid and the other had taken a large amount of erythromycin, amoxicillin and ibuprofen. 2 choledochal cysts complicated by AP (4%). Pancreaticobiliary diseases, as a complete entity, accounted for 34% (n = 17). Clinically, abdominal pain (n = 47; 94%) and vomiting (n = 38; 76%) were most commonly encountered. KUB was non-diagnostic in all patients. No patient died during their admission.

Conclusion:

Although still relatively uncommon in Saudi Arabia, there are on average 2–3 cases of pediatric AP diagnosed annually in our institution. Idiopathic AP was the most common cause. Isoniazid and choledochal cysts are rare causes of AP and were reported in the study.
Powder forging in PSRSPU
Authors: Dorofeyev Yury , Dorofeyev Vladimir
Published: February 2018

The technology of powder forging (PF) gained significant development after the Second World War. In 1990, almost simultaneously, two monographs were published, which examined the scientific and practical aspects of PF [1 , 2] . Kuhn and Ferguson gave a review of the studies on obtaining parts for structural purposes by PF, which were performed in North America and Europe by that time. The monograph by Kuhn and Ferguson published in English is available to a wide circle of specialists in the field of powder metallurgy (PM). Monograph by Dorofeyev Yu. G. et al. was published in Russian, which had limited readership. In this monograph experience in developing PF technology on the territory of the former Soviet Union was extended. For a variety of historical circumstances, the most significant volume of scientific and practical developments of PF was held at the Department of Materials Science and Problematic research laboratory of dynamic hot pressing of the Platov South-Russian State Polytechnic University (PSRSPU). Previously, the University was named the Novocherkassk Polytechnic Institute. Part of the works was performed in collaboration with the Institute for Problems of Materials Science (Kiev, Ukraine) [3] .
Sums of Quadratic Endomorphisms of an Infinite-Dimensional Vector Space
Authors: de Seguins Pazzis Clément
Published: February 2018

We prove that every endomorphism of an infinite-dimensional vector space over a field splits into the sum of four idempotents and into the sum of four square-zero endomorphisms, a result that is optimal in general.
Day hospital mentalization-based treatment v. specialist treatment as usual in patients with borderline personality disorder: randomized controlled trial
Authors: Laurenssen Elisabeth M. P. , Luyten Patrick , Kikkert Martijn J. , Westra Dieuwertje , Peen Jaap , Soons Mirjam B. J. , van Dam Anne-Marie , van Broekhuyzen Anna J. , Blankers Matthijs , Busschbach Jan J. V. , Dekker Jack J. M.
Published: February 2018

Background

Day hospital mentalization-based treatment (MBT-DH) is a promising treatment for borderline personality disorder (BPD) but its evidence base is still limited. This multi-site randomized trial compared the efficacy of MBT-DH delivered by a newly set-up service v. specialist treatment as usual (S-TAU) tailored to the individual needs of patients, and offered by a well-established treatment service.

Methods

Two mental healthcare institutes in The Netherlands participated in the study. Patients who met DSM-IV criteria for BPD and had a score of ⩾20 on the borderline personality disorder severity index (BPDSI) were randomly allocated to MBT-DH (N = 54) or S-TAU (N = 41). The primary outcome variable was the total score on the BPDSI. Secondary outcome variables included symptom severity, quality of life, and interpersonal functioning. Data were collected at baseline and every 6 months until 18-month follow-up, and were analyzed using multilevel analyses based on intention-to-treat principles.

Results

Both treatments were associated with significant improvements in all outcome variables. MBT-DH was not superior to S-TAU on any outcome variable. MBT-DH was associated with higher acceptability in BPD patients compared v. S-TAU, reflected in significantly higher early drop-out rates in S-TAU (34%) v. MBT-DH (9%).

Conclusions

MBT-DH delivered by a newly set-up service is as effective as specialist TAU in The Netherlands in the treatment of BPD at 18-month follow-up. Further research is needed to investigate treatment outcomes in the longer term and the cost-effectiveness of these treatments.
Avian species–area relationships indicate that towns are not different from natural areas
Authors: FATTORINI SIMONE , LIN GIULIA , MANTONI CRISTINA
Published: February 2018

Urban areas host many bird species, and urban species richness can be compared with that in natural areas using species–area relationships (SARs). We used a multimodel selection approach to investigate the influence of area, human population, elevation and climatic variables on species richness of breeding birds from 34 towns and 54 nature reserves in Italy. Using the linearized power function, area was identified as the most important correlate of avian species richness in both urban and natural areas. The SARs did not differ significantly between towns and reserves, although human density had a negative effect on bird richness. These findings underline the possible importance of urban areas in biodiversity conservation, but also stress that human density is a factor reducing species richness. However, species richness alone cannot inform conservation priorities because it does not take into account the different conservation values of species.
The Prosecution of Rape in Wartime: Evidence from the Mau Mau Rebellion, Kenya 1952–60
Authors: Anderson David M. , Weis Julianne
Published: February 2018

In July 2012, a landmark hearing before the High Court in London found that the British government had a case to answer concerning human rights abuses, including torture and rapes, allegedly perpetrated by British colonialists in Kenya, during the Mau Mau counterinsurgency of the 1950s. Among the four elderly Kenyan claimants in court that day was a Kikuyu woman, Jane Mara, whose testimony related the sexual abuses she had suffered. Jane had been only 15 years of age, in 1954, when she was accused of being a Mau Mau sympathizer, and along with other villagers, she was taken for interrogation. The experience Jane Mara recounted was horrific. Beaten repeatedly by her inquisitors, she was then pinned to the floor by four African guards who held her thighs apart, while another guard forced a glass bottle into her vagina, using the sole of his boot to direct the bottle deeply into her. The pain was excruciating, and Jane realized that the bottle had been heated. When this ordeal came to an end, she was compelled to sit and watch as the three other young women were subjected to the same torture.
INTERNATIONAL OUTPUT AND INFLATION UNCERTAINTY AND THEIR IMPACT ON COUNTRIES' MACROECONOMIC PERFORMANCE. EVIDENCE FROM A DYNAMIC FACTOR GARCH-IN-MEAN MODEL
Authors: Berger Tino , Grabert Sibylle
Published: February 2018

We identify international output and inflation uncertainty and analyze their impact on individual countries' macroeconomic performance. Output and inflation uncertainty on an international level is measured through the conditional variances of common factors in inflation and output growth, estimated from a bivariate dynamic factor model with GARCH errors. The impact of international and country-specific uncertainty is analyzed by including the conditional variances as regressors. We find increases in uncertainty during the first and second oil crisis, the 1980s and 1990s recessions as well as the recent Great Recession to be confined to the international level. The effect of international uncertainty results to be highly significant and unambiguously negative on countries' output growth and inflation rates whereas the impact of country-specific uncertainty is very mixed.
A change of paradigm for the insurance industry
Authors: Dacorogna Michel
Published: February 2018

In this paper, we review changes in the insurance industry due to new risk-based regulations such as Solvency 2 and Swiss Solvency Test. The move from corporate management based on cash-flow to risk-based management is described and discussed through its consequences on capital management, economic valuation and the internal model. We discuss the limits and difficulties of enterprise risk management and its effect on the organisation of companies and the role of actuaries in insurance. The risk/return relation is becoming a central element of the company’s management slowly supplanting the traditional accounting view.
An analysis of power law distributions and tipping points during the global financial crisis
Authors: Li Yifei , Shi Lei , Allan Neil , Evans John
Published: February 2018

Heavy-tailed distributions have been observed for various financial risks and papers have observed that these heavy-tailed distributions are power law distributions. The breakdown of a power law distribution is also seen as an indicator of a tipping point being reached and a system then moves from stability through instability to a new equilibrium. In this paper, we analyse the distribution of operational risk losses in US banks, credit defaults in US corporates and market risk events in the US during the global financial crisis (GFC). We conclude that market risk and credit risk do not follow a power law distribution, and even though operational risk follows a power law distribution, there is a better distribution fit for operational risk. We also conclude that whilst there is evidence that credit defaults and market risks did reach a tipping point, operational risk losses did not. We conclude that the government intervention in the banking system during the GFC was a possible cause of banks avoiding a tipping point.
Prävalenz grenzüberschreitender Verhaltensweisen in romantischen Beziehungen unter Jugendlichen (Teen-Dating-Violence)
Authors: Kliem Sören , Baier Dirk , Bergmann Marie Christine
Published: February 2018

Zusammenfassung. Teen-Dating-Violence (TDV) erscheint als gesellschaftliches Problemfeld mit ausgeprägter Prävalenz und Reichweite. Im Rahmen der vorliegenden Untersuchung wird anhand einer repräsentativen Schülerbefragung für das Bundesland Niedersachsen eine 12-Monats-Prävalenz für verschiedene TDV Dimensionen vorgelegt. Etwa 62 % der befragten Mädchen sowie etwa 49 % der befragten Jungen gaben an (Stichprobe unter Risiko), in den letzten 12 Monaten mindestens eine TDV Erfahrung gemacht zu haben. Besonders häufig wurde von Jugendlichen beider Geschlechter das Erleben emotionaler Gewalt angeführt (Mädchen: 56.9 %; Jungen: 42.6 %), gefolgt von relationaler Gewalt (Mädchen: 17.9 %; Jungen: 14.4 %), körperlicher Gewalt (Mädchen: 10.5 %; Jungen: 8.2 %), Drohungen (Mädchen: 8.0 %; Jungen: 5.4 %) und sexueller Gewalt (Mädchen: 9.0 %; Jungen: 3.5 %). Erhöhte Raten von Suizidalität, Depressivität und Substanzkonsum der Betroffenen deuten auf einen ausgeprägten, mit dem Phänomen verbundenen Leidensdruck hin.
Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles
Authors: Churchman Adam H. , Mico Victoria , de Pablo Julia Gala , Peyman Sally A. , Freear Steven , Evans Stephen D.
Published: February 2018

Lipid and polymer stabilized microbubbles are used in medicine as contrast agents for ultrasound imaging and are being developed for the delivery of water soluble drugs to diseased areas of the body. However, many new therapeutics exhibit poor water solubility or stability, which has led to the requirement for the development of effective hydrophobic drug delivery systems. This study presents a new method to produce microbubbles coated with an oil layer capable of encapsulating hydrophobic drugs and suitable for targeted, triggered drug release. This new method utilizes highly controllable flow-focusing microfluidics with lipid oil nanodroplets self-assembling and spreading at gas–aqueous interfaces. Oil layer inside microbubbles were produced with diameters of 2.4±0.3 μm (s.d., 1.6 μm) and at concentrations up to 106 bubbles per milliliter. The mechanism of oil layer inside microbubble assembly and stability were characterized using methods including contact angle measurements, quartz crystal microbalance with dissipation monitoring and fluorescence resonance energy transfer imaging.
Zinc oxide nano-enabled microfluidic reactor for water purification and its applicability to volatile organic compounds
Authors: Azzouz Imadeddine , Habba Yamina Ghozlane , Capochichi-Gnambodoe Martine , Marty Frédéric , Vial Jérôme , Leprince-Wang Yamin , Bourouina Tarik
Published: February 2018

This paper reports fast and efficient chemical decontamination of water within a tree-branched centimeter-scale microfluidic reactor. The microreactor integrates Zinc oxide nanowires (ZnO NWs) in situ grown acting as an efficient photocatalytic nanomaterial layer. Direct growth of ZnO NWs within the microfluidic chamber brings this photocatalytic medium at the very close vicinity of the water flow path, hence minimizing the required interaction time to produce efficient purification performance. We demonstrate a degradation efficiency of 95% in <5 s of residence time in one-pass only. According to our estimates, it becomes attainable using microfluidic reactors to produce decontamination of merely 1 l of water per day, typical of the human daily drinking water needs. To conduct our experiments, we have chosen a laboratory-scale case study as a seed for addressing the health concern of water contamination by volatile organic compounds (VOCs), which remain difficult to remove using alternative decontamination techniques, especially those involving water evaporation. The contaminated water sample contains mixture of five pollutants: Benzene; Toluene; Ethylbenzene; m–p Xylenes; and o-Xylene (BTEX) diluted in water at 10 p.p.m. concentration of each. Degradation was analytically monitored in a selective manner until it falls below 1 p.p.m. for each of the five pollutants, corresponding to the maximum contaminant level (MCL) established by the US Environmental Protection Agency (EPA). We also report on a preliminary study, investigating the nature of the chemical by-products after the photocatalytic VOCs degradation process.
RANKL deletion in periodontal ligament and bone lining cells blocks orthodontic tooth movement
Authors: Yang Chia-Ying , Jeon Hyeran Helen , Alshabab Ahmed , Lee Yu Jin , Chung Chun-Hsi , Graves Dana T.
Published: February 2018

The bone remodeling process in response to orthodontic forces requires the activity of osteoclasts to allow teeth to move in the direction of the force applied. Receptor activator of nuclear factor-κB ligand (RANKL) is essential for this process although its cellular source in response to orthodontic forces has not been determined. Orthodontic tooth movement is considered to be an aseptic inflammatory process that is stimulated by leukocytes including T and B lymphocytes which are presumed to stimulate bone resorption. We determined whether periodontal ligament and bone lining cells were an essential source of RANKL by tamoxifen induced deletion of RANKL in which Cre recombinase was driven by a 3.2 kb reporter element of the Col1α1 gene in experimental mice (Col1α1.CreERTM+.RANKLf/f) and compared results with littermate controls (Col1α1.CreERTM−.RANKLf/f). By examination of Col1α1.CreERTM+.ROSA26 reporter mice we showed tissue specificity of tamoxifen induced Cre recombinase predominantly in the periodontal ligament and bone lining cells. Surprisingly we found that most of the orthodontic tooth movement and formation of osteoclasts was blocked in the experimental mice, which also had a reduced periodontal ligament space. Thus, we demonstrate for the first time that RANKL produced by periodontal ligament and bone lining cells provide the major driving force for tooth movement and osteoclastogenesis in response to orthodontic forces.
Nanoporous membrane device for ultra high heat flux thermal management
Authors: Hanks Daniel F. , Lu Zhengmao , Sircar Jay , Salamon Todd R. , Antao Dion S. , Bagnall Kevin R. , Barabadi Banafsheh , Wang Evelyn N.
Published: February 2018

High power density electronics are severely limited by current thermal management solutions which are unable to dissipate the necessary heat flux while maintaining safe junction temperatures for reliable operation. We designed, fabricated, and experimentally characterized a microfluidic device for ultra-high heat flux dissipation using evaporation from a nanoporous silicon membrane. With ~100 nm diameter pores, the membrane can generate high capillary pressure even with low surface tension fluids such as pentane and R245fa. The suspended ultra-thin membrane structure facilitates efficient liquid transport with minimal viscous pressure losses. We fabricated the membrane in silicon using interference lithography and reactive ion etching and then bonded it to a high permeability silicon microchannel array to create a biporous wick which achieves high capillary pressure with enhanced permeability. The back side consisted of a thin film platinum heater and resistive temperature sensors to emulate the heat dissipation in transistors and measure the temperature, respectively. We experimentally characterized the devices in pure vapor-ambient conditions in an environmental chamber. Accordingly, we demonstrated heat fluxes of 665 ± 74 W/cm2 using pentane over an area of 0.172 mm × 10 mm with a temperature rise of 28.5 ± 1.8 K from the heated substrate to ambient vapor. This heat flux, which is normalized by the evaporation area, is the highest reported to date in the pure evaporation regime, that is, without nucleate boiling. The experimental results are in good agreement with a high fidelity model which captures heat conduction in the suspended membrane structure as well as non-equilibrium and sub-continuum effects at the liquid–vapor interface. This work suggests that evaporative membrane-based approaches can be promising towards realizing an efficient, high flux thermal management strategy over large areas for high-performance electronics.
Engineering 3D approaches to model the dynamic microenvironments of cancer bone metastasis
Authors: Qiao Han , Tang Tingting
Published: February 2018

Cancer metastasis to bone is a three-dimensional (3D), multistep, dynamic process that requires the sequential involvement of three microenvironments, namely, the primary tumour microenvironment, the circulation microenvironment and the bone microenvironment. Engineered 3D approaches allow for a vivid recapitulation of in vivo cancerous microenvironments in vitro, in which the biological behaviours of cancer cells can be assessed under different metastatic conditions. Therefore, modelling bone metastasis microenvironments with 3D cultures is imperative for advancing cancer research and anti-cancer treatment strategies. In this review, multicellular tumour spheroids and bioreactors, tissue engineering constructs and scaffolds, microfluidic systems and 3D bioprinting technology are discussed to explore the progression of the 3D engineering approaches used to model the three microenvironments of bone metastasis. We aim to provide new insights into cancer biology and advance the translation of new therapies for bone metastasis.
A light carbon isotope composition for the Sun
Authors: Lyons James R. , Gharib-Nezhad Ehsan , Ayres Thomas R.
Published: February 2018

Measurements by the Genesis mission have shown that solar wind oxygen is depleted in the rare isotopes, 17O and 18O, by approximately 80 and 100‰, respectively, relative to Earth’s oceans, with inferred photospheric values of about −60‰ for both isotopes. Direct astronomical measurements of CO absorption lines in the solar photosphere have previously yielded a wide range of O isotope ratios. Here, we reanalyze the line strengths for high-temperature rovibrational transitions in photospheric CO from ATMOS FTS data, and obtain an 18O depletion of δ18O = −50 ± 11‰ (1σ). From the same analysis we find a carbon isotope ratio of δ13C = −48 ± 7‰ (1σ) for the photosphere. This implies that the primary reservoirs of carbon on the terrestrial planets are enriched in 13C relative to the bulk material from which the solar system formed, possibly as a result of CO self-shielding or inheritance from the parent cloud.
Item-level analyses reveal genetic heterogeneity in neuroticism
Authors: Nagel Mats , Watanabe Kyoko , Stringer Sven , Posthuma Danielle , van der Sluis Sophie
Published: February 2018

Genome-wide association studies (GWAS) of psychological traits are generally conducted on (dichotomized) sums of items or symptoms (e.g., case-control status), and not on the individual items or symptoms themselves. We conduct large-scale GWAS on 12 neuroticism items and observe notable and replicable variation in genetic signal between items. Within samples, genetic correlations among the items range between 0.38 and 0.91 (mean rg = .63), indicating genetic heterogeneity in the full item set. Meta-analyzing the two samples, we identify 255 genome-wide significant independent genomic regions, of which 138 are item-specific. Genetic analyses and genetic correlations with 33 external traits support genetic differences between the items. Hierarchical clustering analysis identifies two genetically homogeneous item clusters denoted depressed affect and worry. We conclude that the items used to measure neuroticism are genetically heterogeneous, and that biological understanding can be gained by studying them in genetically more homogeneous clusters.
Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells
Authors: Xu Yan , Ikeda Satoshi , Sumida Kentaro , Yamamoto Ryusuke , Tanaka Hiroki , Minato Nagahiro
Published: February 2018

Chronic myelogenous leukemia (CML) caused by hematopoietic stem cells expressing the Bcr-Abl fusion gene may be controlled by Bcr-Abl tyrosine kinase inhibitors (TKIs). However, CML-initiating cells are resistant to TKIs and may persist as minimal residual disease. We demonstrate that mice deficient in Sipa1, which encodes Rap1 GTPase-activating protein, rarely develop CML upon transfer of primary hematopoietic progenitor cells (HPCs) expressing Bcr-Abl, which cause lethal CML disease in wild-type mice. Resistance requires both T cells and nonhematopoietic cells. Sipa1−/− mesenchymal stroma cells (MSCs) show enhanced activation and directed migration to Bcr-Abl+ cells in tumor tissue and preferentially produce Cxcl9, which in turn recruits Sipa1−/− memory T cells that have markedly augmented chemotactic activity. Thus, Sipa1 deficiency uncovers a host immune mechanism potentially capable of eradicating Bcr-Abl+ HPCs via coordinated interplay between MSCs and immune T cells, which may provide a clue for radical control of human CML.
Studying light-harvesting models with superconducting circuits
Authors: Potočnik Anton , Bargerbos Arno , Schröder Florian A. Y. N. , Khan Saeed A. , Collodo Michele C. , Gasparinetti Simone , Salathé Yves , Creatore Celestino , Eichler Christopher , Türeci Hakan E. , Chin Alex W. , Wallraff Andreas
Published: February 2018

The process of photosynthesis, the main source of energy in the living world, converts sunlight into chemical energy. The high efficiency of this process is believed to be enabled by an interplay between the quantum nature of molecular structures in photosynthetic complexes and their interaction with the environment. Investigating these effects in biological samples is challenging due to their complex and disordered structure. Here we experimentally demonstrate a technique for studying photosynthetic models based on superconducting quantum circuits, which complements existing experimental, theoretical, and computational approaches. We demonstrate a high degree of freedom in design and experimental control of our approach based on a simplified three-site model of a pigment protein complex with realistic parameters scaled down in energy by a factor of 105. We show that the excitation transport between quantum-coherent sites disordered in energy can be enabled through the interaction with environmental noise. We also show that the efficiency of the process is maximized for structured noise resembling intramolecular phononic environments found in photosynthetic complexes.
Strong selection during the last millennium for African ancestry in the admixed population of Madagascar
Authors: Pierron Denis , Heiske Margit , Razafindrazaka Harilanto , Pereda-loth Veronica , Sanchez Jazmin , Alva Omar , Arachiche Amal , Boland Anne , Olaso Robert , Deleuze Jean-Francois , Ricaut Francois-Xavier , Rakotoarisoa Jean-Aimé , Radimilahy Chantal , Stoneking Mark , Letellier Thierry
Published: February 2018

While admixed populations offer a unique opportunity to detect selection, the admixture in most of the studied populations occurred too recently to produce conclusive signals. By contrast, Malagasy populations originate from admixture between Asian and African populations that occurred ~27 generations ago, providing power to detect selection. We analyze local ancestry across the genomes of 700 Malagasy and identify a strong signal of recent positive selection, with an estimated selection coefficient >0.2. The selection is for African ancestry and affects 25% of chromosome 1, including the Duffy blood group gene. The null allele at this gene provides resistance to Plasmodium vivax malaria, and previous studies have suggested positive selection for this allele in the Malagasy population. This selection event also influences numerous other genes implicated in immunity, cardiovascular diseases, and asthma and decreases the Asian ancestry genome-wide by 10%, illustrating the role played by selection in recent human history.
Carboxylic acid-modified metal oxide catalyst for selectivity-tunable aerobic ammoxidation
Authors: Jia Xiuquan , Ma Jiping , Xia Fei , Xu Yongming , Gao Jin , Xu Jie
Published: February 2018

Controlling the reaction selectivity of a heterobifunctional molecule is a fundamental challenge in many catalytic processes. Recent efforts to design chemoselective catalysts have focused on modifying the surface of metal nanoparticle materials having tunable properties. However, precise control over the surface properties of base-metal oxide catalysts remains a challenge. Here, we show that green modification of the surface with carboxylates can be used to tune the ammoxidation selectivity toward the desired products during the reaction of hydroxyaldehyde on manganese oxide catalysts. These modifications improve the selectivity for hydroxynitrile from 0 to 92% under identical reaction conditions. The product distribution of dinitrile and hydroxynitrile can be continuously tuned by adjusting the amount of carboxylate modifier. This property was attributed to the selective decrease in the hydroxyl adsorption affinity of the manganese oxides by the adsorbed carboxylate groups. The selectivity enhancement is not affected by the tail structure of the carboxylic acid.
Ambient nitrate switches the ammonium consumption pathway in the euphotic ocean
Authors: Wan Xianhui Sean , Sheng Hua-Xia , Dai Minhan , Zhang Yao , Shi Dalin , Trull Thomas W. , Zhu Yifan , Lomas Michael W. , Kao Shuh-Ji
Published: February 2018

Phytoplankton assimilation and microbial oxidation of ammonium are two critical conversion pathways in the marine nitrogen cycle. The underlying regulatory mechanisms of these two competing processes remain unclear. Here we show that ambient nitrate acts as a key variable to bifurcate ammonium flow through assimilation or oxidation, and the depth of the nitracline represents a robust spatial boundary between ammonium assimilators and oxidizers in the stratified ocean. Profiles of ammonium utilization show that phytoplankton assemblages in nitrate-depleted regimes have higher ammonium affinity than nitrifiers. In nitrate replete conditions, by contrast, phytoplankton reduce their ammonium reliance and thus enhance the success of nitrifiers. This finding helps to explain existing discrepancies in the understanding of light inhibition of surface nitrification in the global ocean, and provides further insights into the spatial linkages between oceanic nitrification and new production.
Measurement of the Berry curvature of solids using high-harmonic spectroscopy
Authors: Luu Tran Trung , Wörner Hans Jakob
Published: February 2018

Berry phase and Berry curvature have become ubiquitous concepts in physics, relevant to a variety of phenomena, such as polarization, various Hall effects, etc. Studies of these phenomena call for characterization of Berry phase or curvature which is largely limited to theory, and a few measurements in optical lattices. In this work, we report polarimetry of high-harmonic emission from solids and exploit this novel capability to directly retrieve the Berry curvature of α-quartz. We show that the two manifestations of broken inversion symmetry in solids lead to perpendicular or parallel polarization of even harmonics with respect to the driving field. Using semiclassical transport theory, we retrieve the Berry curvature from spectra measured in perpendicular polarization, the results being supported by ab initio calculation. Our work demonstrates an approach for the direct measurement of Berry curvature in solids, which could serve as a benchmark for theoretical studies.
Three-dimensional localization of nanoscale battery reactions using soft X-ray tomography
Authors: Yu Young-Sang , Farmand Maryam , Kim Chunjoong , Liu Yijin , Grey Clare P. , Strobridge Fiona C. , Tyliszczak Tolek , Celestre Rich , Denes Peter , Joseph John , Krishnan Harinarayan , Maia Filipe R. N. C. , Kilcoyne A. L. David , Marchesini Stefano , Leite Talita Perciano Costa , Warwick Tony , Padmore Howard , Cabana Jordi , Shapiro David A.
Published: February 2018

Battery function is determined by the efficiency and reversibility of the electrochemical phase transformations at solid electrodes. The microscopic tools available to study the chemical states of matter with the required spatial resolution and chemical specificity are intrinsically limited when studying complex architectures by their reliance on two-dimensional projections of thick material. Here, we report the development of soft X-ray ptychographic tomography, which resolves chemical states in three dimensions at 11 nm spatial resolution. We study an ensemble of nano-plates of lithium iron phosphate extracted from a battery electrode at 50% state of charge. Using a set of nanoscale tomograms, we quantify the electrochemical state and resolve phase boundaries throughout the volume of individual nanoparticles. These observations reveal multiple reaction points, intra-particle heterogeneity, and size effects that highlight the importance of multi-dimensional analytical tools in providing novel insight to the design of the next generation of high-performance devices.
Spontaneous imbibition in fractal tortuous micro-nano pores considering dynamic contact angle and slip effect: phase portrait analysis and analytical solutions
Authors: Li Caoxiong , Shen Yinghao , Ge Hongkui , Zhang Yanjun , Liu Tao
Published: February 2018

Shales have abundant micro-nano pores. Meanwhile, a considerable amount of fracturing liquid is imbibed spontaneously in the hydraulic fracturing process. The spontaneous imbibition in tortuous micro-nano pores is special to shale, and dynamic contact angle and slippage are two important characteristics. In this work, we mainly investigate spontaneous imbibition considering dynamic contact angle and slip effect in fractal tortuous capillaries. We introduce phase portrait analysis to analyse the dynamic state and stability of imbibition. Moreover, analytical solutions to the imbibition equation are derived under special situations, and the solutions are verified by published data. Finally, we discuss the influences of slip length, dynamic contact angle and gravity on spontaneous imbibition. The analysis shows that phase portrait is an ideal tool for analysing spontaneous imbibition because it can evaluate the process without solving the complex governing ordinary differential equations. Moreover, dynamic contact angle and slip effect play an important role in fluid imbibition in fractal tortuous capillaries. Neglecting slip effect in micro-nano pores apparently underestimates imbibition capability, and ignoring variations in contact angle causes inaccuracy in predicting imbibition speed at the initial stage of the process. Finally, gravity is one of the factors that control the stabilisation of the imbibition process.
Author Correction: Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
Authors: Moro Massimo , Bertolini Giulia , Caserini Roberto , Borzi Cristina , Boeri Mattia , Fabbri Alessandra , Leone Giorgia , Gasparini Patrizia , Galeone Carlotta , Pelosi Giuseppe , Roz Luca , Sozzi Gabriella , Pastorino Ugo
Published: February 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3
Authors: Li Guorui , Huang Jinguang , Yang Jun , He Dan , Wang Chao , Qi Xiaoxuan , Taylor Ian A. , Liu Junfeng , Peng You-Liang
Published: February 2018

Magnaporthe oryzae is a model fungal plant pathogen employed for studying plant-fungi interactions. Whole genome sequencing and bioinformatics analyses revealed that this fungal pathogen has more than 12,000 protein-coding genes with 65% of the genes remaining functionally un-annotated. Here, we determine the structure of the hypothetical protein, MGG_01005 and show that it is the Magnaporthe oryzae Dynein light chain Tctex-type 1 (dynlt1/3), demonstrated by its structural similarity to other orthologous dynlt1 proteins and its conserved interaction with the N-terminus of the Magnaporthe oryzae dynein intermediate chain, MoDyn1I2. In addition, we present the structure of the MGG_01005-MoDyn1I2 complex together with mutagenesis studies that reveals a di-histidine motif interaction with a glutamate residue in the dynein intermediate chain within a conserved molecular interface. These results demonstrate the utility of structure-based annotation and validate it as a viable approach for the molecular assignment of hypothetic proteins from phyto-pathogenic fungi.
Observation of microwave absorption and emission from incoherent electron tunneling through a normal-metal–insulator–superconductor junction
Authors: Masuda Shumpei , Tan Kuan Y. , Partanen Matti , Lake Russell E. , Govenius Joonas , Silveri Matti , Grabert Hermann , Möttönen Mikko
Published: February 2018

We experimentally study nanoscale normal-metal–insulator–superconductor junctions coupled to a superconducting microwave resonator. We observe that bias-voltage-controllable single-electron tunneling through the junctions gives rise to a direct conversion between the electrostatic energy and that of microwave photons. The measured power spectral density of the microwave radiation emitted by the resonator exceeds at high bias voltages that of an equivalent single-mode radiation source at 2.5 K although the phonon and electron reservoirs are at subkelvin temperatures. Measurements of the generated power quantitatively agree with a theoretical model in a wide range of bias voltages. Thus, we have developed a microwave source which is compatible with low-temperature electronics and offers convenient in-situ electrical control of the incoherent photon emission rate with a predetermined frequency, without relying on intrinsic voltage fluctuations of heated normal-metal components or suffering from unwanted losses in room temperature cables. Importantly, our observation of negative generated power at relatively low bias voltages provides a novel type of verification of the working principles of the recently discovered quantum-circuit refrigerator.
Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate
Authors: Sarig Udi , Sarig Hadar , Gora Aleksander , Krishnamoorthi Muthu Kumar , Au-Yeung Gigi Chi Ting , de-Berardinis Elio , Chaw Su Yin , Mhaisalkar Priyadarshini , Bogireddi Hanumakumar , Ramakrishna Seeram , Boey Freddy Yin Chiang , Venkatraman Subbu S. , Machluf Marcelle
Published: February 2018

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)—as representative natural soft-tissue biomaterial—to study a spectrum of common cell–niche interactions. Model monocultures and 1:1 co-cultures on the pcECM of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were mechano-biologically characterized using macro- (Instron), and micro- (AFM) mechanical testing, histology, SEM and molecular biology aspects using RT-PCR arrays. The obtained data was analyzed using developed statistics, principal component and gene-set analyses tools. Our results indicated biomechanical cell-type dependency, bi-modal elasticity distributions at the micron cell-ECM interaction level, and corresponding differing gene expression profiles. We further show that hMSCs remodel the ECM, HUVECs enable ECM tissue-specific recognition, and their co-cultures synergistically contribute to tissue integration—mimicking conserved developmental pathways. We also suggest novel quantifiable measures as indicators of tissue assembly and integration. This work may benefit basic and translational research in materials science, developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.