bluuebunny/crossref_metadata_2025 huggingface dataset:
II. The Pardon of the Clergy, 1531
Authors: Scarisbrick J.
Published: July 2016

The story of the Pardon of the Clergy in 1531 and all that it entailed has long been familiar to historians of the English Reformation; and despite the several gaps, not to say incongruities, in the accepted narrative, no writer has found difficulty in repeating the inherited version. Indeed, this most important episode in the story of Henry's overthrow of the medieval church has been distinguished by the unquestioning and brief, even peremptory, treatment which it has usually received. In the course of time, minor accretions have added to the first statement of events contained in the Chronicles. But perhaps because the Calendars are disappointingly reticent about public affairs during the winter of 1530–1, no author has seriously questioned that statement, however uneasy he may have felt about it on a priori grounds. The earliest version, therefore, compounded from Hall and Wilkins, still stands. According to it, shortly after Wolsey's death at the end of November 1530, the whole of the English clergy were indicted on a praemunire charge in the King's Bench by the Attorney General for having submitted themselves to the late cardinal's legacy. To escape from their dilemma, the two Convocations made a cash payment to Henry allowing him at the same time a new, if guarded, title of overlordship that was to prove full of consequence. Whatever the significance of the celebrated ‘saving clause’ and despite the reluctance of the clergy to concede any ground, the fact remained that Henry had won the first round with comparative ease and it was only a matter of time before he would proceed with confidence and equal success to the second.
I. The origin of the Cambridge Modern History
Authors: Clark G. N.
Published: July 2016

It will soon be half a century since the Cambridge Modern History was planned: the first entry relating to it in the minutes of the Syndics of the University Press is dated 13 March 1896. It is forty-three years since the first volume was published, and throughout that time the history has held its own as one of the indispensable books. It was the parent of all the other Cambridge Histories, of which there are eight series down to the present time. No other modern general history on anything like the same scale has been written or even projected in the English language, and this is a testimony not only to its usefulness but also to the efficiency of those who produced it. The time from the publication of the first volume to that of the last, the Atlas, was only ten years; and perhaps only those who have been concerned in similar enterprises can tell what energy and competence that implies. There were 160 contributors. Some of them, though it seems not so many as twenty, are happily still living and working; but they would probably agree that the Cambridge Modern History, taken as a whole, is a monument of a stage in English historical studies which may now be regarded not unfairly as a past stage.
V. The Principles and Methods of Lord Salisbury's Foreign Policy
Authors: Penson Lillian M.
Published: July 2016

“Ce clergyman laïque, obstiné et maladroit”, so Bismarck spoke of Salisbury to the French Ambassador in 1879, contrasting him with Beaconsfield, whom he thought a man of broader outlook; and we have Salisbury's testimony to Bismarck's “extraordinary penetration”. Yet, among the many difficulties that hamper an attempt to analyse the policy of Salisbury, perhaps the greatest is that there are few subjects on which he was consistent. He made almost a principle of inconsistency. “This country”, he said, “which is popularly governed, and cannot therefore be counted on to act on any uniform or consistent system of policy….” This was in April 1878 at the beginning of his first term at the Foreign Office. As so often happens circumstances strengthened his belief. His early tenures of the Foreign Secretaryship were short, and divided by a Liberal administration whose actions materially affected British policy. The whole period was crowded by movements abroad and at home which compelled adjustments of ideas. Twice, at any rate, he had not a free hand, in 1878–80 and again in 1886, for in the first case he had to reckon with Disraeli and in the other with a divided Cabinet.
III. Lord North and Mr Robinson, 1779
Authors: Butterfield H.
Published: July 2016

The letters of Lord North have made us familiar with the portrait and the general posture of a Minister who was in the habit of behaving like a prisoner seeking release—a man “tied to the stake”as he once said—a Minister who repeatedly urged that his continuance in office would bring certain disaster upon the nation; who cursed the futility of what he privately called that damned American war; who complained of illness, depression of mind, loss of memory and general unfitness for his post.
IV. Russia's New Policy in the near East after the Peace of Adrianople; Including the Text of the Protocol of 16 September 1829
Authors: Kerner Robert J.
Published: July 2016

General Diebitsch's victory at Kulevcha on 11 June precipitated a series of events which brought the Russian army to the gates of Constantinople and Turkey to the verge of dissolution early in September. The maintenance or the dissolution of the Ottoman Empire in Europe suddenly became the issue in St Petersburg. Was the maintenance of that empire more advantageous to Russia than its dissolution?
I. Literary Tradition and Early Greek Code-Makers
Authors: Adcock F. E.
Published: July 2016

The literary tradition about the makers of early written codes in Greece presents so many contradictions and inconsistencies that it is natural to take refuge in complete scepticism. But if the tradition is analysed, it appears that there are two strata, the first reasonably consistent, matter-of-fact and credible, the second progressively vitiated by influences which can be isolated and explained. The division between the two strata lies about the year 300 B.C. and the primary tradition is not necessarily less credible because of the existence of the secondary tradition, which proves not that the primary tradition was false, but that truth itself could not prevail against the pseudo-history which set in after Aristotle. The primary tradition about the personalities of the early makers of codes cannot be lightly rejected; the content of their codes, as far as it is given in the primary tradition, is not inconsistent with the general character of early Greek lawgiving as it can be reconstructed from other evidence.
III. The Cardinal of Lorraine and the Colloquy of Poissy
Authors: Evennett H. O.
Published: July 2016

Of the many sixteenth-century conferences which sought to bridge the gulf between Catholicism and those who had broken away from the Church, the Colloquy of Poissy was perhaps the most spectacularly staged. It was, however, remarkable more as a spectacle than as a serious theological discussion, and its true importance lies rather in the movement which brought it into being, and the particular aspirations, both political and religious, which were bound up in it, than in the actual tenor of the debates. Its real significance lay in this, that it represented a local attempt made by those Catholics who were opposed to the continuation of the suspended Council of Trent, to deal on their own initiative with the religious situation and to put into action their own eirenic ideas of church reform. They counselled concessions in ceremonial and discipline and the largest possible doctrinal lenience, in the hope, if not actually of effecting reunion with the Protestants, at least of removing some of the most powerful incentives to schism. The realization that the Council of Trent, if resumed, would neither favour this policy nor commend itself to Protestant support impelled them to resist the papal wishes and to call for a new council of Catholics and Protestants at which reunion should be the principal objective. These views spread wherever the growth of large bodies of heretics, organized and defying persecution, had caused serious embarrassment to the state by weakening the country's unity, imperilling the general administration, and presenting altogether a political problem that demanded urgent solution. But although to a large extent inspired by the exigencies of government the programme of the moderates was not based entirely on considerations of political expediency. The party did not lack theologians: Zasius, Gienger, Staphylus, in the Emperor's entourage, and liberal Catholics like George Cassander, were all men on whom some shreds of the mantle of Contarini and his followers may not unjustly be said to have fallen.
III. The End of the Napoleonic Senate
Authors: Bury J. P. T.
Published: July 2016

In none of the critical years 1830, 1848, 1870 and 1940 did the French Second Chamber as a body play an independent part in effecting or hindering a change of regime. But in 1814 there is one of the most striking occurrences in the history of the French legislature. The Conservative Senate takes a lead in bringing about a change of government, while the Lower House, so much more to the fore in later crises, obediently confirms the acts of the Upper. The story, often told as an episode in the fall of the Empire or the beginning of the Restoration, may bear a brief re-examination as an episode also in the history of the French Second Chamber.
V. A ‘Petty’ Professor of Modern History: William Smyth (1765–1849)
Authors: Butler K. T. B.
Published: July 2016

In 1807 William Smyth, tutor of Peterhouse, was appointed Regius Professor of Modern History at Cambridge through the good offices of Lord Henry Petty, later third Marquis of Lansdowne and then still liberal M.P. for the University. Two years later, not long after Smyth had delivered his first course of lectures, there appeared the caricature of him reproduced as a frontispiece to this paper and bearing the same title. It represents him in profile lecturing to a drowsy and yawning audience of undergraduates and elderly bewigged Fellows.
IV. British West India Commerce as a Factor in the Napoleonic War
Authors: Rose J. Holland
Published: July 2016

The decline in prosperity of the British West Indies after 1815 was so rapid as to obscure their importance during the Napoleonic War; but of their commercial pre-eminence among British colonies at that time there are many proofs. Thus, on 12 September 1804, while watching Toulon, Nelson, who knew them well, wrote in a lately published letter, “…I think the French will some day send their fleets to sea, and that the West Indies … is (sic) more likely for them to hurt us in than this country. We have but few troops to defend our islands and recent conquests; 10 or 12,000 French troops would injure us more there than in any other part of the world.” Herein he agreed with Dundas, who in August 1796 stated to Earl Spencer, First Lord of the Admiralty, that far more harm would result to our commerce and credit from a French invasion of Jamaica than of Great Britain or Ireland. As is well known, Nelson in April 1805 acted on his conviction recorded above, and, despite the perilously scanty news as to the course of the Franco-Spanish fleet, he chased it to the West Indies because of his conviction of the immense importance of those colonies. Lord Barham, now First Lord, approved his action; for he himself had come to the conclusion from the French moves against those colonies, “that depredation and the destruction of our trade is their grand object,” and that the invasion of England was now a secondary object. This view was for the present somewhat exaggerated; for Napoleon, who overworked his admirals even more than his generals, expected Villeneuve and Gravina first to devastate our Leeward Islands (with Tobago thrown in) and then to fly back, along with Ganteaume's fleet, to cover the invasion of England.
II. Crusaders' Castles of the Twelfth Century
Authors: Smail R. C.
Published: July 2016

Although the castle is regarded as a distinguishing feature of feudal society in medieval Europe, its functions in that society have been less adequately studied than its architecture. The variety and importance of those functions arose principally from the role of the castle in government. Any ruler needs organized force at his disposal as a final sanction for his authority. It is required both against the external enemy and to preserve internal order; it has both a military and a police function.
IV. The Hudson's Bay Company and the Treaty of Utrecht
Authors: Rich E. E.
Published: July 2016

The military triumphs and the political eclipse of Marlborough epitomize much of the history of the Treaty of Utrecht. He was, as even Bolingbroke acknowledged, the great successor to William, keeping the Grand Alliance together and imparting to it a rapid and vigorous motion in sharp contrast to the delays of William's ‘languishing out disastrous campaigns’. As ‘the greatest general, and as the greatest minister, that our country or perhaps any other has produced’ (to quote Bolingbroke again), he was deeply involved in the prolonged negotiations leading to the peace. But Marlborough and the Whigs were discredited and ousted from office in the course of the negotiations, and the peace was the work of a Tory ministry which claimed that the terms showed a reaction from the impracticable proposals of the Whigs to the more sound, statesmanlike and feasible, concepts of William III.
V. Afghanistan in Anglo-Russian Diplomacy, 1869–1873
Authors: Thornton A. P.
Published: July 2016

The strides made by the Russians into Central Asia between 1864 and 1869 were greater than any they took thereafter in that area. In 1865 they captured Tashkend. In 1866 they occupied Khojend and broke the power of the Khanate of Khokand. In 1867 they invaded the Khanate of Bokhara, and established fortified posts far to the south of the Jaxartes River; they also established the new Province of Turkestan, erecting it into a separate Viceroyalty with its capital at Tashkend. In 1868 they captured the city of Samarkand, capital of Bokhara, and made it clear that the Amir of Bokhara lived henceforth as a subservient client.
III. The Earl of Sunderland and the Revolution of 1688
Authors: Kenyon J. P.
Published: July 2016

A Study of the historiography of the Revolution of 1688—the Revolution considered not only as an event in space and time but also in the minds of men—is long overdue. Although such a study would far transgress the decent limits of this paper, it is possible to isolate here a single phenomenon in the historiography of 1688; to examine the posthumous reputation of one of the central figures in that Revolution, to uncover the sources from which it rose, and assess the validity of the evidence upon which it is based.
I. The Earlier Growth of Papal Jurisdiction and Leo the Great
Authors: Whitney J. P.
Published: July 2016

THE PAPACY of Leo the Great gives us a good halting place in papal history; it closes one period and leaves another to begin. The Bishop of Imperial Rome could never be a mere ecclesiastical official of the greatest city; while it had been the home of Emperors he had been often enough a trusted adviser to them; when it ceased to be their dwelling-place fresh responsibilities and new opportunities came to him. There is hardly need even to mention the change due to the foundation of a new Rome in the East, with its fresh magnificence, so largely brought from the Western capital, and with its political outlook on the richest and most important provinces. Moreover the wealth of the Roman Church had long been great and it was matched by its Christian generosity; its influence in this way had passed into a tradition, which grew steadily from the time of St Ignatius onward. In all the cities where a church had been founded there was Christian organisation, and the Roman episcopate could not but profit by the business-like methods of the imperial and civic governments. Roman ecclesiastics were naturally distinguished for the same characteristics as were the civilians. The gravitas Romana could be noted even in the eleventh century, and its mere existence would have given peculiar weight to the decisions of Roman bishops and the decrees of Roman councils. Everywhere throughout the provinces local churches and local municipalities had almost alone stood the shock of the barbarian hordes; these inheritances from the past were naturally much greater in Rome itself than elsewhere, and owing to the turns of history advantage from them fell mainly to the papacy. And for the most part the papacy did not fail the Western world; it faced its dangers and its duties boldly.
I. The Legal Status of Markets
Authors: Salzman L. F.
Published: July 2016

In his study ofLes Droits des Marchés et des Foires, M. Huvelin discusses the question whether markets owed their origin to grants made by the king, direct or through authority delegated to a lord, or to grants made by a lord and confirmed by the king. His decision that they were entirely of royal origin would have met with the approval of Edward I, whose attorneys during theQuo Warantoinquest constantly asserted that, “to no one in the realm is it permitted to have a market without the licence and goodwill of the lord king or his predecessors.” In the delegated regality of the Palatinate of Durham it had been definitely stated in 1228 that, “no one has toll save the Bishop, because no one has market or fair in the Haliwarifolc save he alone.” Yet it is legitimate to wonder how this particular apple got into the royal dumpling. The majority of theregaliaare obviously such by nature; but there are some about which we feel that, while we hear much of baronial usurpations from the king, we might well hear something of royal encroachments upon domanial rights. If a market is regarded simply as a regularly recurrent assembly for the sale of local products, it is surely a matter that concerns the local community or its lord rather than the king. A phrase in the so-called “Laws of William the Conqueror”—“There shall not be any market or fair save in cities of our realm and in boroughs enclosed by a wall and in castles and very safe places, where the customs of our realm and our common right and the royalties of our crown … may not be defrauded”—sounds more like an attempt to bring an existing, independent market system under the control of the Crown than the assertion of an acknowledged regality; and it may be noted that a previous attempt, made by Athelstan in 925, to confine markets to towns had had to be abandoned.
III. Recent Works on Medieval, Turkish and Modern Greece
Authors: Miller William
Published: July 2016

I propose in the present article to mention the additions which have been made during recent years to our knowledge of the medieval, Turkish and modern periods of Greek history, especially by the Greeks themselves. In the fifth edition of Paparregopoulos' standardHistory of the Greek Nation, edited and continued by Professor P. Karolides, we have an account of the whole history of the Greeks from prehistoric times down to the annexation of Thessaly and Arta in 1881. The editor, who sat in the Turkish parliament and is particularly strong in all that regards the Moslem world, has, by large additions to the text and by footnotes, brought the classic masterpiece of his author up to date, while for the first time this work is illustrated and indexed. In the general field of medieval Greek history theAnnual of the Society of Byzantine Studies, which first appeared in 1924, has published a number of articles by Greek specialists, while theByzantinisch-Neugriechische Jahrbücherof Professor Nikos A. Bees, started at Berlin in 1920, has been published since 1926 in Athens, where a similar periodical,Helleniká, edited by Professors Amantos and Kougeas, is announced. The local medieval and modern history of Epeiros is being collected in theEpeirote Chronicles, of which two volumes and a biographical supplement have appeared; that of Thrace in the similar periodical,Thrakiká, of which one complete volume has been issued. Dr Franz Dölger has produced two instalments of theCorpus der griechischen Urkunden des Mittelalters und der neueren Zeit, planned by Krumbacher, and giving German summaries of documents from 565 to 1204, andBeiträge zur Geschichte der byzantinischen Finanzverwaltung besonders des10.und11.Fahrhunderts. Messrs A. E. R. Boak and James E. Dunlap have contributedTwo Studies in Later Roman and Byzantine Administrationon “The Master of the Offices” and “The Office of the Grand Chamberlain” respectively toThe University of Michigan Studies, Humanistic Series(vol. XIV, New York, 1924).
II. The Receipt of the Exchequer, 1413–32
Authors: Steel Anthony
Published: July 2016

The object of this article is to carry one stage further an analysis which was begun elsewhere of the late medieval receipt rolls of the English exchequer. The technique of this analysis is essentially comparative; thus the first time it was used the two halves of Richard II's reign were compared with each other and with the whole of Henry IV's, while on the present occasion Henry V's reign of nine and a half years, producing nineteen complete rolls, will be compared with the first ten years and nineteen rolls of Henry VI. That is to say, two approximately equal periods are being studied instead of three, but in order to preserve continuity some reference will also be made to Henry IV's reign of thirteen and a half years with its twenty-one complete and four fragmentary rolls. It has been thought that the rough approximation to equality of evidence over these three periods will still justify, as in the former article, the frequent use of absolute totals instead of averages, but it will have to be borne in mind that 1413–22 and 1422–32 are both slightly under-estimated in relation to 1399–1413 wherever absolute totals and not averages are used.
Some are More Equal than Others: the Decision of the Court of Justice in Grant v. South-West Trains
Authors: Barnard Catherine
Published: July 2016

InPv.Sthe Court of Justice sent out a strong message that it was keen to protect the rights of minorities. Ruling that the Equal Treatment Directive 76/207 applies to the gender reassignment of the person concerned, the Court gave protection to P, a male to female transsexual. To justify its decision the Court said “[to] tolerate such discrimination [against transsexuals] would be tantamount, as regards such a person, to a failure to respect the dignity and freedom to which he or she is entitled, and which the Court has a duty to safeguard”. Its genuine commitment to safeguarding such rights was put to the test inGrant, when faced by the claim of a lesbian for concessionary rail travel for her partner under Article 141 (Article 119) EC on equal pay.
On the Application of European Law in (Not Only) the Courts of the New Member States: ‘Don’t Do as I Say’?
Authors: Bobek Michal
Published: July 2016

In the classical narratives of the story called European integration, national judges are said to have a ‘mandate’ under European law: they are ‘empowered’ by EC law or, in the less thrilling versions of the story, they simply become ‘Community judges’. Not only are national judges obliged to apply substantive EC law, they are also requested to apply it in the way required by the Court of Justice. How, precisely, national judges are asked to apply EC law in domestic courts has traditionally been portrayed through the case law of the Court of Justice; not much attention has been paid to the reality in national courts. Over the years, the case law of the Court of Justice has created an image of a veritable European judicial Hercules: a judge who reads in many of the official languages of the European Union; who knows not only all the relevant national and European law, which he or she appliesex officio, but also engages in comparative interpretation of the law; who identifies him- or herself with the Europeanteloswhich he or she is applying on the national level; and so on.
Situating International Human Rights Law in an Age of Counter-Terrorism
Authors: Gearty Conor
Published: July 2016

Youssef nada is a 77-year-old man, who lives in the tiny commune of Campione in Switzerland. He is not allowed to leave this commune. Nor can he access his financial accounts, despite being a senior figure in the world of banking. The problem Mr Nada faces is that his bank, the Al Taqwa bank, is associated with the Moslem Brotherhood and that Mr Nada—an Egyptian by birth—is also connected with this organisation. Among his adversaries is the Egyptian Government of Hosni Mubarak, which desires to get him back to Cairo, where it is clear his safety could by no means be guaranteed. After the attacks of 11 September 2001, Mr Nada also incurred the enmity of the US Government. He found himself placed on a UN sanctions black-list—hence the restrictions on his movement and financial dealings.
The Domestic Reach of General Principles of Law: First City Trading Revisited
Authors: Grief Nick
Published: July 2016

This is a critical analysis—in the light of the Lisbon Treaty, the Charter of Fundamental Rights and recent European Court of Justice (ECJ) case law—of the judgment inR v MAFF, ex p First City Trading, or at least of that part of the judgment concerning the domestic reach of general principles of law. Laws J held that the legal status of the general principles ‘made’ by the ECJ is inferior to that of the principles enshrined in the Treaty, and that therefore the domestic reach of the former is narrower than that of the latter. In the years since the judgment was delivered, however, it does not appear to have been considered by the ECJ and there seems to have been little academic evaluation of its cogency and implications. One commentator considered that the distinction drawn by the judge seemed correct. Another was critical, asserting that ‘the distinction between principles based on Treaty provisions and general principles of law cannot be deduced from the case law of the Court of Justice’. The possible entry into force of the Treaty of Lisbon, which recognises that the Charter of Fundamental Rights of the European Union (and thus presumably the rights, freedoms and principles within it) has ‘the same legal value as the Treaties’, makes it appropriate to revisit the judgment and consider whether Laws J’s approach was correct.
The EU under Public International Law: Challenging Prospects
Authors: Szabó Marcel
Published: July 2016

The aim of this chapter is to analyse whether the EU order has the potential to exert a beneficial influence on the future development of international law. While the work strongly argues in favour of this aim, it is nevertheless sensitive to the difficulties in the relationship between these two legal orders and examines these issues in some detail. The article accordingly pursues its aim by exploring the history of that relationship, as one that has not always been easy, but, which, in the future, may prove fruitful.
Human Rights in the Twenty-First Century
Authors: Straw Jack
Published: July 2016

If you read certain newspapers you might be forgiven for thinking that human rights were an alien imposition foisted upon us by ‘the other’. It is a misconception that has regrettably taken root. A central theme of my lecture this evening is to explode this myth, and to demonstrate how far from being some ‘European’ imposition, Britain has been at the forefront of the political and legal development of human rights across Europe and across the world.
The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis
Authors: Coppo Maddalena , Chinenov Yurii , Sacta Maria A. , Rogatsky Inez
Published: July 2016

Diet-induced obesity causes chronic macrophage-driven inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT macrophages, however, differ in their origin, gene expression and activities: unlike infiltrating monocyte-derived inflammatory macrophages, WAT-resident macrophages counteract inflammation and insulin resistance, yet, the mechanisms underlying their transcriptional programming remain poorly understood. We recently reported that a nuclear receptor cofactor—glucocorticoid receptor (GR)-interacting protein (GRIP)1—cooperates with GR to repress inflammatory genes. Here, we show that GRIP1 facilitates macrophage programming in response to IL4 via a GR-independent pathway by serving as a coactivator for Kruppel-like factor (KLF)4—a driver of tissue-resident macrophage differentiation. Moreover, obese mice conditionally lacking GRIP1 in macrophages develop massive macrophage infiltration and inflammation in metabolic tissues, fatty livers, hyperglycaemia and insulin resistance recapitulating metabolic disease. Thus, GRIP1 is a critical regulator of immunometabolism, which engages distinct transcriptional mechanisms to coordinate the balance between macrophage populations and ultimately promote metabolic homeostasis.
M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma
Authors: Shen Long , Li Honghao , Shi Yuzhi , Wang Dekun , Gong Junbo , Xun Jing , Zhou Sifan , Xiang Rong , Tan Xiaoyue
Published: July 2016

Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain and therefore play an active role in the progression of DLBCL.
Reinforcement of integrin-mediated T-Lymphocyte adhesion by TNF-induced Inside-out Signaling
Authors: Li Qian , Huth Steven , Adam Dieter , Selhuber-Unkel Christine
Published: July 2016

Integrin-mediated leukocyte adhesion to endothelial cells is a crucial step in immunity against pathogens. Whereas the outside-in signaling pathway in response to the pro-inflammatory cytokine tumour necrosis factor (TNF) has already been studied in detail, little knowledge exists about a supposed TNF-mediated inside-out signaling pathway. In contrast to the outside-in signaling pathway, which relies on the TNF-induced upregulation of surface molecules on endothelium, inside-out signaling should also be present in an endothelium-free environment. Using single-cell force spectroscopy, we show here that stimulating Jurkat cells with TNF significantly reinforces their adhesion to fibronectin in a biomimetic in vitro assay for cell-surface contact times of about 1.5 seconds, whereas for larger contact times the effect disappears. Analysis of single-molecule ruptures further demonstrates that TNF strengthens sub-cellular single rupture events at short cell-surface contact times. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte initial adhesion machinery.
Real time and label free profiling of clinically relevant exosomes
Authors: Sina Abu Ali Ibn , Vaidyanathan Ramanathan , Dey Shuvashis , Carrascosa Laura G. , Shiddiky Muhammad J. A. , Trau Matt
Published: July 2016

Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(−) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14–35% of their bulk population express HER2.
Swarm dynamics may give rise to Lévy flights
Authors: Reynolds Andrew M. , Ouellette Nicholas T.
Published: July 2016

“Continuous-time correlated random walks” are now gaining traction as models of scale-finite animal movement patterns because they overcome inherent shortcomings with the prevailing paradigm - discrete random walk models. Continuous-time correlated random walk models are founded on the classic Langevin equation that is driven by purely additive noise. The Langevin equation is, however, changed fundamentally by the smallest of multiplicative noises. The inclusion of such noises gives rise to Lévy flights, a popular but controversial model of scale-free movement patterns. Multiplicative noises have not featured prominently in the literature on biological Lévy flights, being seen, perhaps, as no more than a mathematical contrivance. Here we show how Langevin equations driven by multiplicative noises and incumbent Lévy flights arise naturally in the modelling of swarms. Model predictions find some support in three-dimensional, time-resolved measurements of the positions of individual insects in laboratory swarms of the midgeChironomus riparius.We hereby provide a new window on Lévy flights as models of movement pattern data, linking patterns to generative processes.
Discovery of midgut genes for the RNA interference control of corn rootworm
Authors: Hu Xu , Richtman Nina M. , Zhao Jian-Zhou , Duncan Keith E. , Niu Xiping , Procyk Lisa A. , Oneal Meghan A. , Kernodle Bliss M. , Steimel Joseph P. , Crane Virginia C. , Sandahl Gary , Ritland Julie L. , Howard Richard J. , Presnail James K. , Lu Albert L. , Wu Gusui
Published: July 2016

RNA interference (RNAi) is a promising new technology for corn rootworm control. This paper presents the discovery of new gene targets - dvssj1 and dvssj2, in western corn rootworm (WCR). Dvssj1 and dvssj2 are orthologs of the Drosophila genes snakeskin (ssk) and mesh, respectively. These genes encode membrane proteins associated with smooth septate junctions (SSJ) which are required for intestinal barrier function. Based on bioinformatics analysis, dvssj1 appears to be an arthropod-specific gene. Diet based insect feeding assays using double-stranded RNA (dsRNA) targeting dvssj1 and dvssj2 demonstrate targeted mRNA suppression, larval growth inhibition, and mortality. In RNAi treated WCR, injury to the midgut was manifested by “blebbing” of the midgut epithelium into the gut lumen. Ultrastructural examination of midgut epithelial cells revealed apoptosis and regenerative activities. Transgenic plants expressing dsRNA targeting dvssj1 show insecticidal activity and significant plant protection from WCR damage. The data indicate that dvssj1 and dvssj2 are effective gene targets for the control of WCR using RNAi technology, by apparent suppression of production of their respective smooth septate junction membrane proteins located within the intestinal lining, leading to growth inhibition and mortality.
Physical activity, body composition and lipids changes in adolescents: analysis from the MyHeART Study
Authors: Majid Hazreen Abdul , Amiri Mohammadreza , Mohd Azmi Nahar , Su Tin Tin , Jalaludin Muhammad Yazid , Al-Sadat Nabilla
Published: July 2016

Insufficient physical activity and growing obesity levels among Malaysian adolescents are becoming a public health concern. Our study is to identify the trends of self-reported physical activity (PA) levels, blood lipid profiles, and body composition (BC) indices from a cohort of 820 adolescents. The self-reported PA was assessed using a validated Malay version of the PA Questionnaire for Older Children (PAQ-C). Fasting blood samples were collected to investigate their lipid profiles. Height, weight, waist and hip circumferences as well as body fat percentage were measured. The baseline and the first follow-up were conducted in 2012 and 2014, respectively. A downward trend in the PA level was seen in all categories with a significant reduction among all rural adolescents (P = 0.013) and more specifically, PA among girls residing in rural areas dropped significantly (P = 0.006). Either a significant reduction in high-density lipoprotein (HDL) or a significant increment in BC indices (i.e., body mass index [BMI], waist circumference [WC], hip circumference, and body fat percentage [BF %]) were seen in this group. Female adolescents experienced more body fat increment with the reduction of physical activity. If not intervened early, adolescents from rural areas may increase their risk of developing cardiovascular diseases earlier.
A Fossilized Energy Distribution of Lightning
Authors: Pasek Matthew A. , Hurst Marc
Published: July 2016

When lightning strikes soil, it may generate a cylindrical tube of glass known as a fulgurite. The morphology of a fulgurite is ultimately a consequence of the energy of the lightning strike that formed it and hence fulgurites may be useful in elucidating the energy distribution frequency of cloud-to-ground lightning. Fulgurites from sand mines in Polk County, Florida, USA were collected and analyzed to determine morphologic properties. Here we show that the energy per unit length of lightning strikes within quartz sand has a geometric mean of ~1.0 MJ/m and that the distribution is lognormal with respect to energy per length and frequency. Energy per length is determined from fulgurites as a function of diameter and frequency is determined both by cumulative number and by cumulative length. This distribution parallels those determined for a number of lightning parameters measured in actual atmospheric discharge events, such as charge transferred, voltage and action integral. This methodology suggests a potential useful pathway for elucidating lightning energy and damage potential of strikes.
Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients
Authors: Kehlet S. N. , Sanz-Pamplona R. , Brix S. , Leeming D. J. , Karsdal M. A. , Moreno V.
Published: July 2016

During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer.
Growth of epitaxial silicon nanowires on a Si substrate by a metal-catalyst-free process
Authors: Ishiyama Takeshi , Nakagawa Shuhei , Wakamatsu Toshiki
Published: July 2016

The growth of epitaxial Si nanowires by a metal-catalyst-free process has been investigated as an alternative to the more common metal-catalyzed vapor–liquid–solid process. The well-aligned Si nanowires are successfully grown on a (111)-oriented Si substrate without any metal catalysts by a thermal treatment using silicon sulfide as a Si source at approximately 1200 °C. The needle-shaped Si nanowires, which have a core–shell structure that consists of a single-crystalline Si core along the <111> direction consistent with the substrate direction and a surface coating of silicon oxide, are grown by a metal-catalyst-free process. In this process, the silicon sulfide in the liquid phase facilitates the nucleation and nanowire growth. In contrast, oxygen-rich nanowires that consist of crystalline Si at the tip and lumpy silicon oxide on the body are observed in a sample grown at 1300 °C, which disturbs the epitaxial growth of Si nanowires.
Cooperative effect of silicon and other alloying elements on creep resistance of titanium alloys: insight from first-principles calculations
Authors: Li Yang , Chen Yue , Liu Jian-Rong , Hu Qing-Miao , Yang Rui
Published: July 2016

Creep resistance is one of the key properties of titanium (Ti) alloys for high temperature applications such as in aero engines and gas turbines. It has been widely recognized that moderate addition of Si, especially when added together with some other elements (X), e.g., Mo, significantly improves the creep resistance of Ti alloys. To provide some fundamental understandings on such a cooperative effect, the interactions between Si and X in both hexagonal close-packed α and body-centered cubic β phases are systematically investigated by using a first-principles method. We show that the transition metal (TM) atoms with the number of d electrons (Nd) from 3 to 7 are attractive to Si in α phase whereas those with Nd > 8 and simple metal (SM) alloying atoms are repulsive to Si. All the alloying atoms repel Si in the β phase except for the ones with fewer d electrons than Ti. The electronic structure origin underlying the Si-X interaction is discussed based on the calculated electronic density of states and Bader charge. Our calculations suggest that the beneficial X-Si cooperative effect on the creep resistance is attributable to the strong X-Si attraction.
DNA-free two-gene knockout in Chlamydomonas reinhardtii via CRISPR-Cas9 ribonucleoproteins
Authors: Baek Kwangryul , Kim Duk Hyoung , Jeong Jooyeon , Sim Sang Jun , Melis Anastasios , Kim Jin-Soo , Jin EonSeon , Bae Sangsu
Published: July 2016

Microalgae are versatile organisms capable of converting CO2, H2O and sunlight into fuel and chemicals for domestic and industrial consumption. Thus, genetic modifications of microalgae for enhancing photosynthetic productivity and biomass and bio-products generation are crucial for both academic and industrial applications. However, targeted mutagenesis in microalgae with CRISPR-Cas9 is limited. Here we report, a one-step transformation of Chlamydomonas reinhardtii by the DNA-free CRISPR-Cas9 method rather than plasmids that encode Cas9 and guide RNAs. Outcome was the sequential CpFTSY and ZEP two-gene knockout and the generation of a strain constitutively producing zeaxanthin and showing improved photosynthetic productivity.
Light-induced negative differential resistance in graphene/Si-quantum-dot tunneling diodes
Authors: Lee Kyeong Won , Jang Chan Wook , Shin Dong Hee , Kim Jong Min , Kang Soo Seok , Lee Dae Hun , Kim Sung , Choi Suk-Ho , Hwang Euyheon
Published: July 2016

One of the interesing tunneling phenomena is negative differential resistance (NDR), the basic principle of resonant-tunneling diodes. NDR has been utilized in various semiconductor devices such as frequency multipliers, oscillators, relfection amplifiers, logic switches, and memories. The NDR in graphene has been also reported theoretically as well as experimentally, but should be further studied to fully understand its mechanism, useful for practical device applications. Especially, there has been no observation about light-induced NDR (LNDR) in graphene-related structures despite very few reports on the LNDR in GaAs-based heterostructures. Here, we report first observation of LNDR in graphene/Si quantum dots-embedded SiO2 (SQDs:SiO2) multilayers (MLs) tunneling diodes. The LNDR strongly depends on temperature (T) as well as on SQD size, and the T dependence is consistent with photocurrent (PC)-decay behaviors. With increasing light power, the PC-voltage curves are more structured with peak-to-valley ratios over 2 at room temperature. The physical mechanism of the LNDR, governed by resonant tunneling of charge carriers through the minibands formed across the graphene/SQDs:SiO2 MLs and by their nonresonant phonon-assisted tunneling, is discussed based on theoretical considerations.
Thermophysical properties of imidazolium tricyanomethanide ionic liquids: experiments and molecular simulation
Authors: Zubeir Lawien F. , Rocha Marisa A. A. , Vergadou Niki , Weggemans Wilko M. A. , Peristeras Loukas D. , Schulz Peter S. , Economou Ioannis G. , Kroon Maaike C.
Published: July 2016

The low-viscous tricyanomethanide ([TCM]−)-based ionic liquids (ILs) are gaining increasing interest as attractive fluids for a variety of industrial applications.
Bioactive gold(i) complexes with 4-mercaptoproline derivatives
Authors: Gutiérrez Alejandro , Cativiela Carlos , Laguna Antonio , Gimeno M. Concepción
Published: July 2016

Unprecedented gold(i) bioconjugates bearing non-proteinogenic amino acid 4-mercaptoproline species as bioorganic ligands have been prepared. The complexes displayed excellent cytotoxic activity with IC50 values in the low μM range and even in the nM range.
Absorption and disposition of naringenin and quercetin after simultaneous administration via intestinal perfusion in mice
Authors: Orrego-Lagarón Naiara , Martínez-Huélamo Miriam , Quifer-Rada Paola , Lamuela-Raventos Rosa M. , Escribano-Ferrer Elvira
Published: July 2016

As common constituents of vegetables, naringenin and quercetin are ingested together; for a clearer understanding of their bioavailability it is insightful to study them together.
Humidity responsive self-healing based on intermolecular hydrogen bonding and metal–ligand coordination
Authors: Zhu Yanxi , Xuan Hongyun , Ren Jiaoyu , Liu Xuefan , Zhao Bo , Zhang Jianhao , Ge Liqin
Published: July 2016

Self-healing process occurring when a self-healing Co–CS/PAA PEM film is integrated (I), damaged (II), self-healing (III), and self-healed (IV).
Facile synthesis of NiS/CdS nanocomposites for photocatalytic degradation of quinoline under visible-light irradiation
Authors: Wu Deyong , Wang Fei , Tan Yuanbin , Li Caolong
Published: July 2016

NiS/CdS nanocomposites with good visible-light-induced photocatalytic activity were successfully prepared via a facile two-step process.