bluuebunny/crossref_metadata_2025 huggingface dataset:
The Writings of Fr. Henry Garnet, S.J. (1555–1606)
Authors: Allison A. F.
Published: February 2017

Father Garnet's works were written in England during the last decade of the sixteenth century when the persecution of priests was at its most intense and Catholic literature was systematically suppressed. They were written anonymously and those that were printed were printed secretly, without indication of place or date. The result has been that his bibliography has remained in a state of confusion to this day. The earliest printed list of his writings, in Alegambe’s Bibliotheca Scriptorum Societatis Iesu (1643), is inaccurate and incomplete, and little attempt has since been made to supplement it. Southwell’s revised edition of Alegambe (1676) reproduces the original list without alteration. Dodd, in The Church History of England (1737–42), also follows Alegambe. The first and only attempt to check Alegambe’s list in the light of original documents is to be found in Oliver’s Collections…S.J. (1845) which gives some corrections and fresh information based on the Stonyhurst MSS. Gillow combines the findings of Dodd and Oliver, adding some speculations of his own which do not stand the test of investigation. Sommervogel and D.N.B. follow Gillow. The extent to which bibliographers blindly copy one another is not always fully realized. Before any satisfactory study of Father Garnet’s life and work can be begun it is essential that his bibliography should be re-established, if possible, from documentary evidence.
Was Dr. Edward Hawarden A Missioner in Durham?
Authors: Vincent Smith W.
Published: February 2017

“It has been said that Dr. Hawarden left Douay in 1707. He then came on the Mission, and was placed at Aldcliffe, near Lancaster, where the Daltons then resided … Such, however, was the high opinion that Dr. Smith, Bishop of the North District, had of him, that, wishing to have him nearer to his own person, he placed him at Gilligate in Durham, and when he made his will in 1709 appointed him one of his trustees, and left him £10 for life on condition of his continuing to reside in the North. Soon after his arrival in England he was chosen a member of the Chapter, and in 1710 an Archdeaon, and also the Catholic Controversy Writer. On this latter account it probably was found necessary that he should reside in London in order to have an eye to the works written against us, and that he might have the convenience of books necessary to answer them. He therefore quitted Durham sometime after 1719, and repaired to London.” (Kirk. 115).
Vaux of Harrowden
Authors: G. Anstruther O.P.
Published: February 2017

The family of Vaux of Harrowden, which has kept the Faith to this day, has received less than its due in Catholic reference books. G-illow devotes six lines to Thomas, 2nd Lord Vaux, but makes no allusion to the rest. William, the 3rd Lord, was a friend of Edmund Campion, S.J., and suffered imprisonment on his behalf. His daughters, Eleanor and Anne, were the devoted friends of Henry Garnet, S.J.: his eldest son, Henry, resigned the title to become a Jesuit, but died early. His daughter-in-law, Elizabeth, was the host of John Gerard, S.J., at Harrowden. Seven members of the family suffered imprisonment for the Faith at various times. Nothing more is here attempted than a list of the members of the family with the dates (where known) of their births, marriages and deaths.
William Somers, Henry VIII’s Jester
Authors: Whatmore L.E.
Published: February 2017

Thomas Bourchier, the Franciscan martyrologist, writing of the Venerable Thomas Belchiam (d. 3 August 1537) gives the following curious fragment of information: after Belchiam’s death, he says, a congenital idiot named William Sommer went running about the court shouting “The simplicity of one mendicant breaks the pride of the King” (1). In view of Bourchier’s general unsatisfactoriness as a historian one is disposed fo regard with suspicion any of his statements which cannot be corroborated, buk in this instance there i s good reason to believe that his information i s correct, or at least founded on fact.
John Huddleston O. S. B.
Authors: Kenny Anthony
Published: February 2017

The two great moments of John Huddleston’s life have made the latter half of it stand out in high relief, while his earlier days have always been lost in obscurity. Everyone knows that he was instrumental in saving the life of Charles II after the battle of Worcester, and that he reconciled the dying King to the Faith; but concerning his childhood, College days and early priestly life the old biographers have little to say. New evidence which has come to light about his youth, and inaccuracies which are common even in the well-documented history of his dealings with the King, make it worth while to try to rewrite the story of his life.
The Husseys of Marnhull, Dorset
Authors: Scantlebury R. B.
Published: February 2017

Joseph Gillow in his “Bibliographical Dictionary of the English Catholics” gives a notice of Giles Hussey, the Artist, and refers to other members of the family only en passant. Following, no doubt, Hutchins “History of Dorset” and Burke's “Landed Gentry”, he gives Elizabeth Hussey’s maiden name as Walcot and states that she was the daughter of Charles Walcot of Waloot, Salop. This statement has been repeated many times; but Charles Walcot had no daughter named Elizabeth. An attempt is made here to set out the genealogy of the Marnhull Husseys on the basis of memoranda written in 1740 by a grandson of the George Hussey who purchased Marnhull Manor in 1651. These memoranda appeared in “Notes and Queries for Somerset and Dorset,” Vol.xv, 1916–7, pp. 220–224 (cited here as N, & Q.).
Curvature-dependent energies: a geometric and analytical approach
Authors: Acerbi Emilio , Mucci Domenico
Published: February 2017

We consider the total curvature of graphs of curves in high-codimension Euclidean space. We introduce the corresponding relaxed energy functional and prove an explicit representation formula. In the case of continuous Cartesian curves, i.e. of graphs cu of continuous functions u on an interval, we show that the relaxed energy is finite if and only if the curve cu has bounded variation and finite total curvature. In this case, moreover, the total curvature does not depend on the Cantor part of the derivative of u. We treat the wider class of graphs of one-dimensional functions of bounded variation, and we prove that the relaxed energy is given by the sum of the length and total curvature of the new curve obtained by closing the holes in cu generated by jumps of u with vertical segments.
Application of convex optimization to identification of atomic species from diffraction patterns
Authors: Oishi-Tomiyasu Ryoko
Published: February 2017

Computational methods and a program to obtain crystal structures that have the perfectly identical diffraction patterns, i.e. structure factors with the same absolute values and the same lattice symmetry are discussed. This is directly related to the uniqueness of solutions in crystal structure determination of single-crystal/powder-crystal samples from diffraction data. In order to solve the problem, it is necessary to solve a system of quadratic equations. The framework of positive-semidefinite programming is used herein to solve the system efficiently.
A doctrinal approach to modal/temporal Heyting logic and non-determinism in processes
Authors: BOTTONI PAOLO , GORLA DANIELE , KASANGIAN STEFANO , LABELLA ANNA
Published: February 2017

The study of algebraic modelling of labelled non-deterministic concurrent processes leads us to consider a categoryLB, obtained from a complete meet-semilatticeBand fromB-valued equivalence relations. We prove that, ifBhas enough properties, thenLBpresents a two-fold internal logical structure, induced by two doctrines definable on it: one related to its families of subobjects and one to its families of regular subobjects. The first doctrine is Heyting and makesLBa Heyting category, the second one is Boolean. We will see that the difference between these two logical structures, namely the different behaviour of the negation operator, can be interpreted in terms of a distinction between non-deterministic and deterministic behaviours of agents able to perform computations in the context of the same process. Moreover, the sorted first-order logic naturally associated withLBcan be extended to a modal/temporal logic, again using the doctrinal setting. Relations are also drawn to other computational models.
Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson’s disease: a systematic review and metaanalysis
Authors: Elgebaly Ahmed , Elfil Mohamed , Attia Attia , Magdy Mayar , Negida Ahmed
Published: February 2017

Background

Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson’s disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS.

Methods

A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows).

Results

Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=–0.31,p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading:SMD=–0.21,p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward:SMD=0.08,p=0.47; Trail Making Test Part A:SMD=–0.05,p=0.65; WAIS–R digit symbol:SMD=–0.16,p=0.29; Trail Making Test Part B:SMD=–0.14,p=0.23; Stroop color–word interference:SMD=–0.16,p=0.18; phonemic verbal fluency: bilateral DBSSMD=–0.04,p=0.73, and unilateral DBSSMD=–0.05,p=0.83; semantic verbal fluency: bilateral DBSSMD=–0.09,p=0.37, and unilateral DBSSMD=–0.29,p=0.22; Boston Naming Test:SMD=–0.11,p=0.33; Beck Depression Inventory: bilateral DBSSMD=0.15,p=0.31, and unilateral DBSSMD=0.36,p=0.11).

Conclusions

There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.
Pressure to Progress: Severe Traumatic Brain Injury and Slow Recovery in the Current Health Care Environment
Authors: Foster Michele , Tilse Cheryl , Fleming Jennifer
Published: February 2017

This paper discusses issues arising from a study of referral from acute care following traumatic brain injury (TBI) in Queensland, in which aged care facilities were relied upon for the discharge of those with slow recovery after severe TBI. The discussion considers: (1) recovery following severe TBI; (2) the current policy context; (3) approaches to care beyond acute care; and (4) implications for policy and practice. In the current health care environment, with increasing pressure on scarce resources, it is critical that practitioners advocate for the dignity and care of people who sustain severe TBI and who are slow to recover.
The Nature of Social Support Available to People Living with Spinal Cord Injury
Authors: Reilly Sian , Murphy Gregory
Published: February 2017

This study examined the nature of the social support received by persons following spinal cord injury (SCI). Social support was assessed through use of an abridged version of the ISEL scale (Cohen et al., 1985), a self-report measure of perceived support. Seventy persons who had been living in the community at least one year post discharge from hospital provided information about four types of support received — instrumental, emotional, informational, and appraisal social support. The aim of this study was to identify whether there were any significant differences in the perceived availability of the four types of social support. Analyses revealed that overall there were significant (p < .05) perceived differences in the average availability of the four separate types of support, with Instrumental support being seen as the most available. Taken together, these findings support the usefulness of measuring separately the different types of social support perceived to be available to individuals, and thus hold important implications for the rehabilitation effort following SCI.
Are Perfectionist Therapists Perfect? The Relationship between Therapist Perfectionism and Client Outcomes in Cognitive Behavioural Therapy
Authors: Presley Vickie L. , Jones Christopher A. , Newton Elizabeth K.
Published: February 2017

Background: The psychological literature suggests that therapist perfectionism is common and potentially detrimental to client recovery. Little is known about the relationship between therapist perfectionism and client outcomes. Aims: This study aimed to measure perfectionism in High Intensity Cognitive Behavioural therapists, and establish any relationships between dimensions of therapist perfectionism, client outcomes and drop-out rates in treatment. Method: Thirty-six therapists took part in the study; levels of perfectionism were measured using a self-report questionnaire and these were analysed in relation to the clinical outcomes from a sample of their clients. Results: The results indicated that therapist perfectionism may be less common than previously suggested. Overall, a number of significant negative associations were observed between aspects of therapist perfectionism (e.g. having high standards for others), treatment efficacy and client retention in treatment. Conclusions: Therapist perfectionism is associated with CBT treatment outcomes; tentative recommendations for therapists managing their own schema as part of their clinical practice have been made, although further investigation is required.
The Potential for Co-production in Developing Violence against Women Services in Wales
Authors: McCarry Melanie , Larkins Cath , Berry Vashti , Radford Lorraine , Stanley Nicky
Published: February 2017

The UK Conservative government has committed to increasing funding for domestic violence and abuse (DVA) services in England but this has not been extended to Wales. Wales has however made clear commitments to developing these services, through the Violence against Women, Domestic Abuse and Sexual Violence (Wales) Act 2015. This article draws on focus groups and interviews with fifty-three service users and thirty-one purposively selected service providers to explore their perspectives on Violence Against Women (VAW) service provision in Wales. There are clear shared priorities and some tensions between service user and provider perspectives on appropriate services. Drawing on the long history of intermediate co-production in VAW services, the article argues that co-production at the strategic level is now needed. This would provide an arena for resolving tensions, setting standards and developing funding criteria to enable co-produced VAW policy and build resistance to funding cuts.
Strip-tillage reduces productivity in organically managed grain and forage cropping systems in the Upper Midwest, USA
Authors: Weyers Sharon L. , Archer David W. , Forcella Frank , Gesch Russ , Johnson Jane M.F.
Published: February 2017

Tillage is decreasing globally due to recognized benefits of fuel savings and improved soil health in the absence of disturbance. However, a perceived inability to control weeds effectively and economically hinders no-till adoption in organic production systems in the Upper Midwest, USA. A strip-tillage (ST) strategy was explored as an intermediate approach to reducing fuel use and soil disturbance, and still controlling weeds. An 8-year comparison was made between two tillage approaches, one primarily using ST the other using a combination of conventional plow, disk and chisel tillage [conventional tillage (CT)]. Additionally, two rotation schemes were explored within each tillage system: a 2-year rotation (2y) of corn (Zea mays L.), and soybean (Glycine max [L.] Merr.) with a winter rye (Secale cereale L.) cover crop; and a 4-year rotation (4y) of corn, soybean, spring wheat (Triticum aestivum L.) underseeded with alfalfa (Medicago sativa L.), and a second year of alfalfa. These treatments resulted in comparison of four main management systems CT-2y, CT-4y, ST-2y and ST-4y, which also were managed under fertilized and non-fertilized conditions. Yields, whole system productivity (evaluated with potential gross returns), and weed seed densities (first 4 years) were measured. Across years, yields of corn, soybean and wheat were greater by 34% or more under CT than ST but alfalfa yields were the same. Within tillage strategies, corn yields were the same in 2y and 4y rotations, but soybean yields, only under ST, were 29% lower in the fertilized 4y than 2 yr rotation. In the ST-4y system yields of corn and soybean were the same in fertilized and non-fertilized treatments. Over the entire rotation, system productivity was highest in the fertilized CT-2y system, but the same among fertilized ST-4y, and non-fertilized ST-2y, ST-4y, and CT-4y systems. Over the first 4 years, total weed seed density increased comparatively more under ST than CT, and was negatively correlated to corn yields in fertilized CT systems and soybean yields in the fertilized ST-2y system. These results indicated ST compromised productivity, in part due to insufficient weed control, but also due to reduced nutrient availability. ST and diverse rotations may yet be viable options given that overall productivity of fertilized ST-2y and CT-4y systems was within 70% of that in the fertilized CT-2y system. Closing the yield gap between ST and CT would benefit from future research focused on organic weed and nutrient management, particularly for corn.
How has China formed its conception of the rule of law? A contextual analysis of legal instrumentalism in ROC and PRC law-making
Authors: Wu Qianlan
Published: February 2017

The rule of law as a globally recognised concept is multi-faceted (Chesterman, 2008). In the common-law tradition, it is conceived through a formal and substantive framework. In essence, it centres on the supremacy of the law over the arbitrary exercise of power and the formal legality of the law (Tamanaha, 2004, p. 115; Cotterrell, 1992, p. 157). The rule-of-law concept has been criticised as being of unique European origin, where plural social organisation and universal natural law constitute its two preconditions (Unger, 1977, pp. 80–110). It has, however, been advocated around the world as one essential principle leading to modernity, where the legitimacy of the law based on the formal and substantive rule of law serves as a strong symbol for a modern society (Deflem, 1996, p. 5).
Do shared values promote social cohesion? If so, which? Evidence from Denmark
Authors: Breidahl Karen N. , Holtug Nils , Kongshøj Kristian
Published: February 2017

Social scientists and political theorists often claim that shared values are conducive to social cohesion, and trust and solidarity in particular. Furthermore, this idea is at the heart of what has been labeled the ‘national identity argument’, according to which religious and/or cultural diversity is a threat to the shared (national) values underpinning social cohesion and redistributive justice. However, there is no consensus among political theorists about what values we need to share to foster social cohesion and indeed, for example, nationalists, liberals, and multiculturalists provide different answers to this question. On the basis of a survey conducted in Denmark in 2014, this study empirically investigates the relation between, on the one hand, commitments to the community values of respectively conservative nationalism, liberal nationalism, liberal citizenship, and multiculturalism, and on the other, trust and solidarity. First, we investigate in what ways commitments to these four sets of values are correlated to trust and solidarity at the individual level and, then, whether the belief that others share one’s values is correlated to these aspects of social cohesion for individuals committed to these four sets of values. We find that conservative and liberal nationalism are negatively correlated to our different measures of trust and solidarity, whereas liberal citizenship and (in particular) multiculturalism are positively correlated. In broad terms, this picture remains when we control for a number of socio-economic factors and ideology (on a left-right scale). Finally, individuals who believe that others share their values do not, in general, have higher levels of trust and solidarity. Rather, this belief works in different ways when associated with different sets of community values.
The Weighting is the Hardest Part: On the Behavior of the Likelihood Ratio Test and the Score Test Under a Data-Driven Weighting Scheme in Sequenced Samples
Authors: Minică Camelia C. , Genovese Giulio , Hultman Christina M. , Pool René , Vink Jacqueline M. , Neale Michael C. , Dolan Conor V. , Neale Benjamin M.
Published: February 2017

Sequence-based association studies are at a critical inflexion point with the increasing availability of exome-sequencing data. A popular test of association is the sequence kernel association test (SKAT). Weights are embedded within SKAT to reflect the hypothesized contribution of the variants to the trait variance. Because the true weights are generally unknown, and so are subject to misspecification, we examined the efficiency of a data-driven weighting scheme. We propose the use of a set of theoretically defensible weighting schemes, of which, we assume, the one that gives the largest test statistic is likely to capture best the allele frequency–functional effect relationship. We show that the use of alternative weights obviates the need to impose arbitrary frequency thresholds. As both the score test and the likelihood ratio test (LRT) may be used in this context, and may differ in power, we characterize the behavior of both tests. The two tests have equal power, if the weights in the set included weights resembling the correct ones. However, if the weights are badly specified, the LRT shows superior power (due to its robustness to misspecification). With this data-driven weighting procedure the LRT detected significant signal in genes located in regions already confirmed as associated with schizophrenia — thePRRC2A(p= 1.020e-06) and theVARS2(p= 2.383e-06) — in the Swedish schizophrenia case-control cohort of 11,040 individuals with exome-sequencing data. The score test is currently preferred for its computational efficiency and power. Indeed, assuming correct specification, in some circumstances, the score test is the most powerful test. However, LRT has the advantageous properties of being generally more robust and more powerful under weight misspecification. This is an important result given that, arguably, misspecified models are likely to be the rule rather than the exception in weighting-based approaches.
Mesenchymal stem cells in alleviating sepsis-induced mice cardiac dysfunction via inhibition of mTORC1-p70S6K signal pathway
Authors: Huang Wei , Fan Wensi , Wang Yabin , Han Dong , Li Xiujuan , Li Shuang , Li Congye , Xu Bin , Huang Yuesheng , Fu Xiaobin , Cao Feng
Published: February 2017

Sepsis-induced cardiac dysfunction remains a major cause of morbidity and mortality in patients suffered from severe trauma. Mesenchymal stem cells (MSCs) -based treatment has been verified as a promising approach to mitigate the sepsis-induced cardiac dysfunction, but the mechanism is still ambiguous. Thus, our study was designed to explore the potential role of MSCs in sepsis-induced cardiac dysfunction. In vivo bioluminescence imaging revealed 80% acute donor cell death of bone marrow-derived MSCs (BM-MSCs) within 3 days after transplantation. However, echocardiography demonstrated that systolic function in wild-type mice group were reduced after sepsis, while the cardiac function was relatively well persevered in cardiac-conditional deletion of Raptor (component of mTORC1 complex) mice group. Raptor KO group treated with BM-MSCs appeared better cardiac function than other groups (P<0.05). In vitro cell study revealed that co-culture of H9C2 (Raptor-Knock down) and BM-MSC could attenuate the level of proinflammatory cytokines and promote the expression of anti-inflammatory cytokine accompanied by mTORC2-Akt activation (P<0.05). In contrast, co-culture H9C2 (Raptor-O.E) and BM-MSC could aggravate the inflammatory response accompanied by the activation of mTORC1-p70S6K and inhibition of mTORC2-Akt (P<0.05). The immunomodulatory property of MSC is related to the inhibition of mTORC1-p70S6K and activation of mTORC2-Akt signaling pathway. mTORC1-p70S6K and mTORC2-Akt pathways were involved in the therapeutic adjuncts of MSC. The possible mechanism due to MSC`s immunomodulatory property through activation of mTORC2-Akt and inhibition of mTORC1-p70S6K signal pathways which may lead to modulate the expression of inflammation cytokines.
Controllable alignment of elongated microorganisms in 3D microspace using electrofluidic devices manufactured by hybrid femtosecond laser microfabrication
Authors: Xu Jian , Kawano Hiroyuki , Liu Weiwei , Hanada Yasutaka , Lu Peixiang , Miyawaki Atsushi , Midorikawa Katsumi , Sugioka Koji
Published: February 2017

This paper presents a simple technique to fabricate new electrofluidic devices for the three-dimensional (3D) manipulation of microorganisms by hybrid subtractive and additive femtosecond (fs) laser microfabrication (fs laser-assisted wet etching of glass followed by water-assisted fs laser modification combined with electroless metal plating). The technique enables the formation of patterned metal electrodes in arbitrary regions in closed glass microfluidic channels, which can spatially and temporally control the direction of electric fields in 3D microfluidic environments. The fabricated electrofluidic devices were applied to nanoaquariums to demonstrate the 3D electro-orientation of Euglena gracilis (an elongated unicellular microorganism) in microfluidics with high controllability and reliability. In particular, swimming Euglena cells can be oriented along the z-direction (perpendicular to the device surface) using electrodes with square outlines formed at the top and bottom of the channel, which is quite useful for observing the motions of cells parallel to their swimming directions. Specifically, z-directional electric field control ensured efficient observation of manipulated cells on the front side (45 cells were captured in a minute in an imaging area of ~160×120 μm), resulting in a reduction of the average time required to capture the images of five Euglena cells swimming continuously along the z-direction by a factor of ~43 compared with the case of no electric field. In addition, the combination of the electrofluidic devices and dynamic imaging enabled observation of the flagella of Euglena cells, revealing that the swimming direction of each Euglena cell under the electric field application was determined by the initial body angle.
Synergy of ammonium chloride and moisture on perovskite crystallization for efficient printable mesoscopic solar cells
Authors: Rong Yaoguang , Hou Xiaomeng , Hu Yue , Mei Anyi , Liu Linfeng , Wang Ping , Han Hongwei
Published: February 2017

Organometal lead halide perovskites have been widely used as the light harvester for high-performance solar cells. However, typical perovskites of methylammonium lead halides (CH3NH3PbX3, X=Cl, Br, I) are usually sensitive to moisture in ambient air, and thus require an inert atmosphere to process. Here we demonstrate a moisture-induced transformation of perovskite crystals in a triple-layer scaffold of TiO2/ZrO2/Carbon to fabricate printable mesoscopic solar cells. An additive of ammonium chloride (NH4Cl) is employed to assist the crystallization of perovskite, wherein the formation and transition of intermediate CH3NH3X·NH4PbX3(H2O)2 (X=I or Cl) enables high-quality perovskite CH3NH3PbI3 crystals with preferential growth orientation. Correspondingly, the intrinsic perovskite devices based on CH3NH3PbI3 achieve an efficiency of 15.6% and a lifetime of over 130 days in ambient condition with 30% relative humidity. This ambient-processed printable perovskite solar cell provides a promising prospect for mass production, and will promote the development of perovskite-based photovoltaics.
Erratum: Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals
Authors: Kimura Tetsuya , Nada Shigeyuki , Takegahara Noriko , Okuno Tatsusada , Nojima Satoshi , Kang Sujin , Ito Daisuke , Morimoto Keiko , Hosokawa Takashi , Hayama Yoshitomo , Mitsui Yuichi , Sakurai Natsuki , Sarashina-Kida Hana , Nishide Masayuki , Maeda Yohei , Takamatsu Hyota , Okuzaki Daisuke , Yamada Masaki , Okada Masato , Kumanogoh Atsushi
Published: February 2017

Nature Communications 7 Article number: 13130 (2016); Published 12 October 2016; Updated 27 February 2017 In this Article, there are errors in the labelling of the x axis in Fig. 5g,h that were introduced during the production process. The second label on the x axis of each graph in Fig. 5g should have been ‘ΦWT’ instead of ‘ΦKO’.
Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
Authors: Schofield Deborah , Alam Khurshid , Douglas Lyndal , Shrestha Rupendra , MacArthur Daniel G. , Davis Mark , Laing Nigel G. , Clarke Nigel F. , Burns Joshua , Cooper Sandra T. , North Kathryn N. , Sandaradura Sarah A. , O’Grady Gina L.
Published: February 2017

Childhood-onset muscle disorders are genetically heterogeneous. Diagnostic workup has traditionally included muscle biopsy, protein-based studies of muscle specimens, and candidate gene sequencing. High throughput or massively parallel sequencing is transforming the approach to diagnosis of rare diseases; however, evidence for cost-effectiveness is lacking. Patients presenting with suspected congenital muscular dystrophy or nemaline myopathy were ascertained over a 15-year period. Patients were investigated using traditional diagnostic approaches. Undiagnosed patients were investigated using either massively parallel sequencing of a panel of neuromuscular disease genes panel, or whole exome sequencing. Cost data were collected for all diagnostic investigations. The diagnostic yield and cost effectiveness of a molecular approach to diagnosis, prior to muscle biopsy, were compared with the traditional approach. Fifty-six patients were analysed. Compared with the traditional invasive muscle biopsy approach, both the neuromuscular disease panel and whole exome sequencing had significantly increased diagnostic yields (from 46 to 75% for the neuromuscular disease panel, and 79% for whole exome sequencing), and reduced the cost per diagnosis from USD$16,495 (95% CI: $12,413–$22,994) to USD$3706 (95% CI: $3086–$4453) for the neuromuscular disease panel and USD$5646 (95% CI: $4501–$7078) for whole exome sequencing. The neuromuscular disease panel was the most cost-effective, saving USD$17,075 (95% CI: $10,654–$30,064) per additional diagnosis, over the traditional diagnostic pathway. Whole exome sequencing saved USD$10,024 (95% CI: $5795–$17,135) per additional diagnosis. This study demonstrates the cost-effectiveness of investigation using massively parallel sequencing technologies in paediatric muscle disease. The findings emphasise the value of implementing these technologies in clinical practice, with particular application for diagnosis of Mendelian diseases, and provide evidence crucial for government subsidy and equitable access.
Differences in place of death between lung cancer and COPD patients: a 14-country study using death certificate data
Authors: Cohen Joachim , Beernaert Kim , Van den Block Lieve , Morin Lucas , Hunt Katherine , Miccinesi Guido , Cardenas-Turanzas Marylou , Onwuteaka-Philipsen Bregje , MacLeod Rod , Ruiz-Ramos Miguel , Wilson Donna M , Loucka Martin , Csikos Agnes , Rhee Yong-Joo , Teno Joan , Ko Winne , Deliens Luc , Houttekier Dirk
Published: February 2017

Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life. Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before. We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information. We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death. Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease. Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France. In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea. Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries. Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home. This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.
Realizing universal quantum gates with topological bases in quantum-simulated superconducting chains
Authors: Hu Yong , Zhao Y. X. , Xue Zheng-Yuan , Wang Z. D.
Published: February 2017

One-dimensional time-reversal invariant topological superconducting wires of the symmetry class DIII exhibit exotic physics which can be exploited to realize the set of universal operations in topological quantum computing. However, the verification of DIII-class physics in conventional condensed matter materials is highly nontrivial due to realistic constraints. Here we propose a symmetry-protected hard-core boson simulator of the one-dimensional DIII topological superconductor. By using the developed dispersive dynamic modulation approach, not only the faithful simulation of this new type of spinful superconducting chains is achieved, but also a set of universal quantum gates can be realized with the computational basis formed by the degenerate ground states that are topologically protected against random local perturbations. Physical implementation of our scheme based on a Josephson quantum circuit is presented, where our detailed analysis pinpoints that this scheme is experimentally feasible with the state-of-the-art technology.
A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy
Authors: Bot Ilze , Ortiz Zacarías Natalia V. , de Witte Wilhelmus E. A. , de Vries Henk , van Santbrink Peter J. , van der Velden Daniël , Kröner Mara J. , van der Berg Dirk-Jan , Stamos Dean , de Lange Elizabeth C. M. , Kuiper Johan , IJzerman Adriaan P. , Heitman Laura H.
Published: February 2017

CC Chemokine Receptor 2 (CCR2) and its endogenous ligand CCL2 are involved in a number of diseases, including atherosclerosis. Several CCR2 antagonists have been developed as potential therapeutic agents, however their in vivo clinical efficacy was limited. In this report, we aimed to determine whether 15a, an antagonist with a long residence time on the human CCR2, is effective in inhibiting the development of atherosclerosis in a mouse disease model. First, radioligand binding assays were performed to determine affinity and binding kinetics of 15a on murine CCR2. To assess the in vivo efficacy, western-type diet fed apoE−/− mice were treated daily with 15a or vehicle as control. Treatment with 15a reduced the amount of circulating CCR2+ monocytes and the size of the atherosclerotic plaques in both the carotid artery and the aortic root. We then showed that the long pharmacokinetic half-life of 15a combined with the high drug concentrations ensured prolonged CCR2 occupancy. These data render 15a a promising compound for drug development and confirms high receptor occupancy as a key parameter when targeting chemokine receptors.
Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue
Authors: Addis L. , Virdee J. K. , Vidler L. R. , Collier D. A. , Pal D. K. , Ursu D.
Published: February 2017

Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic and patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays and patch clamp recordings of transiently transfected HEK-293 cells for electrophysiological characterization, and Western blotting and confocal imaging to assay expression and surface trafficking. Mutations P79R, C231Y, G483R and M705V caused a significant reduction in glutamate and glycine agonist potency, whilst D731N was non-responsive. These mutants, along with E714K, also showed significantly decreased total protein levels and trafficking to the cell surface, whilst C436R was not trafficked at all. Crucially this reduced surface expression did not cause the reduced agonist response. We were able to rescue the phenotype of P79R, C231Y, G483R and M705V after treatment with a GluN2A-selective positive allosteric modulator. With our methodology we were not able to identify any functional deficits in mutations I814T, D933N and N976S located between the glutamate-binding domain and C-terminus. We show GRIN2A mutations affect the expression and function of the receptor in different ways. Careful molecular profiling of patients will be essential for future effective personalised treatment options.
Rapid adaptation to microgravity in mammalian macrophage cells
Authors: Thiel Cora S. , de Zélicourt Diane , Tauber Svantje , Adrian Astrid , Franz Markus , Simmet Dana M. , Schoppmann Kathrin , Hauschild Swantje , Krammer Sonja , Christen Miriam , Bradacs Gesine , Paulsen Katrin , Wolf Susanne A. , Braun Markus , Hatton Jason , Kurtcuoglu Vartan , Franke Stefanie , Tanner Samuel , Cristoforetti Samantha , Sick Beate , Hock Bertold , Ullrich Oliver
Published: February 2017

Despite the observed severe effects of microgravity on mammalian cells, many astronauts have completed long term stays in space without suffering from severe health problems. This raises questions about the cellular capacity for adaptation to a new gravitational environment. The International Space Station (ISS) experiment TRIPLE LUX A, performed in the BIOLAB laboratory of the ISS COLUMBUS module, allowed for the first time the direct measurement of a cellular function in real time and on orbit. We measured the oxidative burst reaction in mammalian macrophages (NR8383 rat alveolar macrophages) exposed to a centrifuge regime of internal 0 g and 1 g controls and step-wise increase or decrease of the gravitational force in four independent experiments. Surprisingly, we found that these macrophages adapted to microgravity in an ultra-fast manner within seconds, after an immediate inhibitory effect on the oxidative burst reaction. For the first time, we provided direct evidence of cellular sensitivity to gravity, through real-time on orbit measurements and by using an experimental system, in which all factors except gravity were constant. The surprisingly ultra-fast adaptation to microgravity indicates that mammalian macrophages are equipped with a highly efficient adaptation potential to a low gravity environment. This opens new avenues for the exploration of adaptation of mammalian cells to gravitational changes.
Evolution of the functionally conserved DCC gene in birds
Authors: Patthey Cedric , Tong Yong Guang , Tait Christine Mary , Wilson Sara Ivy
Published: February 2017

Understanding the loss of conserved genes is critical for determining how phenotypic diversity is generated. Here we focus on the evolution of DCC, a gene that encodes a highly conserved neural guidance receptor. Disruption of DCC in animal models and humans results in major neurodevelopmental defects including commissural axon defects. Here we examine DCC evolution in birds, which is of particular interest as a major model system in neurodevelopmental research. We found the DCC containing locus was disrupted several times during evolution, resulting in both gene losses and faster evolution rate of salvaged genes. These data suggest that DCC had been lost independently twice during bird evolution, including in chicken and zebra finch, whereas it was preserved in many other closely related bird species, including ducks. Strikingly, we observed that commissural axon trajectory appeared similar regardless of whether DCC could be detected or not. We conclude that the DCC locus is susceptible to genomic instability leading to independent disruptions in different branches of birds and a significant influence on evolution rate. Overall, the phenomenon of loss or molecular evolution of a highly conserved gene without apparent phenotype change is of conceptual importance for understanding molecular evolution of key biological processes.
Correction: Corrigendum: Calpains are involved in asexual and sexual development, cell wall integrity and pathogenicity of the rice blast fungus
Authors: Liu Xiao-Hong , Ning Guo-Ao , Huang Lu-Yao , Zhao Ya-Hui , Dong Bo , Lu Jian-Ping , Lin Fu-Cheng
Published: February 2017

Scientific Reports 6: Article number: 31204; published online: 09 August 2016; updated: 27 February 2017. This Article contains typographical errors in the legend of Figure 4. ‘(B) The semithin sections of perithecia. 1, ΔMocapn14; 2, ΔMocapn7; 3, ΔMocapn9; 4, ΔMocapn4; 5, ΔMocapn7; 6, ΔMocapn4ΔMocapn7; 7, ΔMocapn9ΔMocapn7’.
Simple and Large Scale Construction of MoS2-g-C3N4 Heterostructures Using Mechanochemistry for High Performance Electrochemical Supercapacitor and Visible Light Photocatalytic Applications
Authors: Ansari Sajid Ali , Cho Moo Hwan
Published: February 2017

The design of heterojunctions for efficient electrochemical energy storage and environmental remediation are promising for future energy and environment applications. In this study, a molybdenum disulfide-graphitic carbon nitride (MoS2-g-C3N4) heterojunction was designed by applying simple mechanochemistry, which can be scaled up for mass production. The physical-chemical and photophysical properties of the as-prepared MoS2-g-C3N4 heterojunction were analyzed using a range of characterization techniques. The supercapacitance performance was determined by electrochemical half-cell measurements, and visible light-induced photoelectrochemical and photocatalytic performance was studied using photocurrent and model organic pollutant degradation experiments. The resulting MoS2-g-C3N4 under the optimized experimental conditions showed significantly higher photocatalytic activity and photoelectrochemical performance under similar visible photoirradiation conditions compared to the bare materials. The resulting heterostructure electrode delivered a higher capacitance of 240.85 F/g than the bare material (48.77 F/g) with good capacitance retention. The superior performance was attributed mainly to the robust light harvesting ability, improved charge separation, high surface area, increased mass transfer, and capacitive and conductive behavior. The convenient and mass production of heterojunctions using a simple and cost-effective method will provide a good example for the efficient design of visible light active photocatalysts and capacitor electrode materials for environmental remediation and energy storage device applications.
SMAD3 and SMAD4 have a more dominant role than SMAD2 in TGFβ-induced chondrogenic differentiation of bone marrow-derived mesenchymal stem cells
Authors: de Kroon Laurie M. G. , Narcisi Roberto , van den Akker Guus G. H. , Vitters Elly L. , Blaney Davidson Esmeralda N. , van Osch Gerjo J. V. M. , van der Kraan Peter M.
Published: February 2017

To improve cartilage formation by bone marrow-derived mesenchymal stem cells (BMSCs), the signaling mechanism governing chondrogenic differentiation requires better understanding. We previously showed that the transforming growth factor-β (TGFβ) receptor ALK5 is crucial for chondrogenesis induced by TGFβ. ALK5 phosphorylates SMAD2 and SMAD3 proteins, which then form complexes with SMAD4 to regulate gene transcription. By modulating the expression of SMAD2, SMAD3 and SMAD4 in human BMSCs, we investigated their role in TGFβ-induced chondrogenesis. Activation of TGFβ signaling, represented by SMAD2 phosphorylation, was decreased by SMAD2 knockdown and highly increased by SMAD2 overexpression. Moreover, TGFβ signaling via the alternative SMAD1/5/9 pathway was strongly decreased by SMAD4 knockdown. TGFβ-induced chondrogenesis of human BMSCs was strongly inhibited by SMAD4 knockdown and only mildly inhibited by SMAD2 knockdown. Remarkably, both knockdown and overexpression of SMAD3 blocked chondrogenic differentiation. Chondrogenesis appears to rely on a delicate balance in the amount of SMAD3 and SMAD4 as it was not enhanced by SMAD4 overexpression and was inhibited by SMAD3 overexpression. Furthermore, this study reveals that TGFβ-activated phosphorylation of SMAD2 and SMAD1/5/9 depends on the abundance of SMAD4. Overall, our findings suggest a more dominant role for SMAD3 and SMAD4 than SMAD2 in TGFβ-induced chondrogenesis of human BMSCs.
Intraspecific variation among Tetranychid mites for ability to detoxify and to induce plant defenses
Authors: Ozawa Rika , Endo Hiroki , Iijima Mei , Sugimoto Koichi , Takabayashi Junji , Gotoh Tetsuo , Arimura Gen-ichiro
Published: February 2017

Two genotypes coexist among Kanzawa spider mites, one of which causes red scars and the other of which causes white scars on leaves, and they elicit different defense responses in host plants. Based on RNA-Seq analysis, we revealed here that the expression levels of genes involved in the detoxification system were higher in Red strains than White strains. The corresponding enzyme activities as well as performances for acaricide resistance and host adaptation toward Laminaceae were also higher in Red strains than White strains, indicating that Red strains were superior in trait(s) of the detox system. In subsequent generations of strains that had survived exposure to fenpyroximate, both strains showed similar resistance to this acaricide, as well as similar detoxification activities. The endogenous levels of salicylic acid and jasmonic acid were increased similarly in bean leaves damaged by original Red strains and their subsequent generations that inherited high detox activity. Jasmonic acid levels were increased in leaves damaged by original White strains, but not by their subsequent generations that inherited high detox activity. Together, these data suggest the existence of intraspecific variation - at least within White strains - with respect to their capacity to withstand acaricides and host plant defenses.