bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions to the Geology of Gloucestershire
Authors: Brodie P. B.
Published: March 2016

As the Lias in this county is a very bad material for economical purposes, it is not often extensively quarried; and, considering the few available sections, the number and variety of organic remains which have been, from time to time, collected, are really remarkable, and show the prolific nature of the sea of that period. Some localities in that sea, of course, would be richer than others, as is the case in the present day; but, on the whole, this formation is everywhere marked by a great abundance and diversity of fossils. The Palæontologist often looks with a longing eye at some old quarry, long since closed, which had been at one time famous for its zoological contents, and speculates upon the wonders which lie concealed beneath his feet; and he restores in thought some ancient monster of the deep, some curiously-formed shell, or some strange plant; and perhaps, if he had the power, he would dig away, in the hope of possessing some of these treasures which his imagination has conjured up before him. And yet, after all, such speculations are not so imaginative or unreal as they may at first sight appear, for the strange and extraordinary forms of extinct life, which the extended researches of scientific inquirers have brought to light, seem to justify the highest flights of fancy; and none can tell when or where some wonderful relic of the past may be found.
The Common Fossils of the British Rocks
Authors: Mackie S. J.
Published: March 2016

The divisional line of the “Bottom Rocks” is not, however, to be placed at the point at which life first appears. This great series is naturally divided by differences of mineral conditions, by order of deposition, and in reality of age, in our own country, and in other countries both of Europe and America, and apparently also, as far as our present information goes, in Asia and Africa.

In Canada, below the equivalents of our Shropshire “Bottom Rocks” and of our lower Cambrian beds, as in the Highlands of Scotland, as we have already obtained, are still more ancient beds of sedimentary origin, which have become crystalline. In Bohemia, in Finland, and in Scandinavia we have these primeval gneissic lands below the lowermost Silurian deposits; but the geologists generally of other countries, except, the Canadian, have not yet made much progress in this investigation, and it is only in very few instances that the distinctions between the older and younger gneiss have been noticed; and so little regard as to geological age has been ordinarily paid in the case of granitic rocks, that, knowing as we do the very various periods at which some of those masses were erupted, or protruded through sedimentary strata, the mere knowledge of their existence is nearly or quite valueless as evidence.
On The Lower Carboniferous Beds of the Clee Hills
Authors: Roberts George E.
Published: March 2016

Perhaps in all the physical geology of England there is nothing finer than the erupted heights of the Clee. Encircled by the typical “Old Red”—a wide-stretching tract of alternating sandy shores and gravel-beaches of that period—are the characteristic beds of the coal-measures, lying upon Millstone Grit and Mountain Limestone.

Of the causes that have elevated these deposits into the hills of Titterstone and the Brown Clee I need not speak—their basaltic summits, where the erupted rock has assumed a rude columnar form after cooling, are sufficient evidence; but I would direct especial attention to that group of beds whose strike is along the Oreton ridge, and whose chief member, the Mountain Limestone, forms its axial line. This lies midway between the two hills; its southern side slopes down the “Common,” and is composed of Millstone Grit, cut off abruptly by a long line of fault, the effect of which has been to have depressed that deposit into a valley, and to have raised the underlying “Old Red” into a nearly continuous line of cliff. The accompanying section will better describe their relative positions.

These Millstone Grits are non-fossiliferous; but the mineralogist may detect in their conglomerated structure many pebbles of a high class, jaspers and cornelians of pure quality being often met with. These beds lead up to the Mountain Limestone, which contains a fine series of organic remains, such as palatal teeth of the Cestraciont fishes. Petalodus Hastingsii and Psammodus porosus are abundant; yet, although fragments of their jaws are not uncommon, I have only met with one specimen having the teeth in their true position.
Contributions to the Geology of Gloucestershire, intended chiefly for the use of Students
Authors: Brodie P. B.
Published: March 2016

We think it may prove useful and interesting to the geological student if, from time to time, we give a brief sketch of the Geology of some of the more famous localities in England, adding directions where to go, and how to work—which, to say the least, will be a great saving of time and labour, and enable those who are anxious to visit rich and instructive fields of research to make the most of perhaps only a brief holiday—a matter of no little moment in these days of almost unceasing toil.

The lovers of nature who live in the smoky atmosphere of great towns, shut up day after day in a close counting-house, enjoy a ramble amongst new or favourite haunts all the more on this account; and it matters not whether they are naturalists, geologists, artists, or merely admirers of the picturesque—the relish for their particular hobby is more keenly felt because it can be rarely indulged in, even if many difficulties stand in the way.

Few persons who have a scientific turn have unlimited time and means at their disposal; and, therefore, to the majority in such a case it is of some consequence to see as much as they can, and take the shortest route to their destination. The rapid and comparatively cheap means of transit afforded by the railway is equally available both for business and pleasure; but where science is the object, it is not always easy in a new country to find out the best and most productive places, and a few hints from any one who knows them well are invaluable.
The Carboniferous System in Scotland Characterized by its Brachiopoda
Authors: Davidson Thomas
Published: March 2016

Much has been written on the geology of Scotland, and perhaps no country has given birth to a larger proportion of eminent inquirers. The names of Hutton, Playfair, Murchison, and Lyell will ever be remembered among those of the great Scotchmen, who by their acquirements, genius, and perseverance, have so materially contributed to elevate the science of Geology to the rank it now holds among all men of learning.

Much has, however, still to be achieved before the geological and palæontological details connected with our country will have been completely worked out, and many zealous inquirers must be summoned to the field; some will do much, others little; but every accurate observation is so much gain, and will tend towards the complete elucidation of the subject, as well as help to form a basis upon which great minds may found with safety their general views and appreciations. I therefore hailed with much hope and delight the foundation of a Geological Society in Glasgow, which originated in May, 1858, with about a dozen young men, who wished to gain knowledge of the geological phenomena in the neighbourhood of their great city, under the guidance of an experienced and practical geologist; and thus, owing to the active co-operation and direction of Mr. J. P. Fraser, and that of some of its founders, the Society has already done some good work, and increased its numbers to about one hundred.
Geological Localities.—No. I. Folkestone
Authors: Mackie S. J.
Published: March 2016

Slowly the calm sea ebbs. As the pulse of the great ocean beats, its glassy ribbon-waves flow swellingly along in long thin lines, and then drain rapidly away. Every now and then, with higher swelling motion, one wavelet ripples further in, leaving us doubtful for a moment of the tide's recess. But gently, surely are those slippery rocks unveiled, and on their smooth and purple flats the glittering fossils lie.

There, in their radiant iridescence in scores are pearly Ammonites. A. lautus, A. splendens, A. auritus, A. tuberculatus, and the little ribbed and everywhere bestrewn A. varicosus.

There hundreds of amber-like translucent Belemnites (B. Listen) protrude their spine-like forms from the dark blue solid clay.

Curled Hamites, small nut-shaped Nuculœ (N. pectinata and N. ovata), spiny Rostellariœ, Pterocera, and Naticæ, and black phosphatic caste of antique forms of crabs and prawns, and little stud- and cup-like corals await your gathering. Everything to your hand, resplendent as the sea has left them for you. Every here and there the smallest portion of some shell or crab reveals the untouched treasure buried underneath. Pick, trowel, knife, anything will dig into that moist yielding clay, or cut your treasure out. Patience and care are all you want.
The Common Fossils of the British Rocks
Authors: Mackie S. J.
Published: March 2016

For the Vegetable Kingdom it is impossible to give any list composed with the same degree of elaboration as has been attained in the classification of animals. Modern plants are, it is true, as well known and as correctly grouped as modern animal life-forms; but our knowledge of fossil botany is not at all equal to our knowledge of fossil animals. The most minute divisions as well as the most important of botanical classifications are dependent upon the more fully developed and most perishable parts of vegetable organisms—the flowers and the fruits or seeds. Of these the former, the most essential of all, have rarely indeed, if ever, been preserved. One or two doubtful instances have been stated; but these have been by others disputed as being only incipient buds or leaflets, or as accidental appearances, and the investigator of the extinct forms of the vegetable creations of past geological ages has, at the best, to infer from the remains of leaves, branches, or stems, usually more or less decayed, the probable class to which the originals—often, indeed generally, of very different structures and organic characters from his existing types—belong. Not uncommonly, indeed, his only guides are vague and indefinite resemblances of form. Still, however, if it be essential for the attainment of a knowledge of the exact concatenation of past events in the succession of organic life on our planet, it is equally as important to note whether plants have been progressive in their development, as to determine this point in relation to the animal-kingdom.
On the Flagstones of Forfarshire
Authors: Mitchell Hugh
Published: March 2016

There is a close resemblanoe between the fossil contents of the “Upper Ludlow Tilestones,” as described by Mr. Roberts, of Kidderminster, in the last number of The Geologist, and those of certain strata developed in this neighbourhood. The rocks of the southern districts of Forfarshire have been described by Fleming and Miller, and their fossils have attracted the attention of the scientific world. I am acquainted with sections in the north-eastern division, an account of which has not yet appeared in print, and it may be of interest to indicate their organisms.
The Common Fossils of the British Rocks
Authors: Mackie S. J.
Published: March 2016

In one of my last papers on the “Bottom-rocks” I appended a coloured map to a portion of the first dry-land of our mother-earth, a portion of the first division of the land from those waters “which covered the globe,” a fraction of one of those primeval cracks or ridges which then remotely shadowed out our present continents and oceans; and in the little green patches I gave all the traces known of the first beaches and sands which spread around those low and barren tracts in the great region of North America which I selected for an illustration. To this map I hope soon to add, as supplements, others of South America and of Europe. Africa must be left yet a long while ere one dare make the like attempt. To these maps, from time to time, I shall add colour after colour to show the successive deposition of those great rock-formations in which the animals and plants of the successive life-creations of our planet have been entombed; and I hope also to be able to give charts of the teeming oceans during each of those past wonderful ages severally characterised as the stages of progress and development of organic beings.
Gems from Private Collections. III.–Phacops Caudatus; from the Dudley Limestone
Authors: Tennant J.
Published: March 2016

The beautiful specimen of Phacops caudatus, which we figure in Plate V., has long been in the private collection of Professor Tennant. It is from the Upper Silurian limestone of Dudley, and would be a perfect example but for the exception only of its having the segments of the body somewhat bent inwards, and slightly distorted from their natural positions by pressure. The lateral edges and their segments are unfortunately obscured by being embedded in the matrix, so that they cannot be accurately delineated.

This characteristic species of Trilobite was first noticed by Brunnich, in 1781, under the name of Trilobus caudatus. It was subsequently termed Asaphus caudatus by Brongniart, Dalman, Dr. Buckland, and other writers. Burmeister, however, in his valuable work on the “Organization of Trilobites,” called it Phacops caudatus, which generic determination modern palæontologists have followed.
The Carboniferous System in Scotland Characterized by its Brachiopoda
Authors: Davidson Thomas
Published: March 2016

This species appears to vary somewhat in appearance, but is usually transversely semi-cylindrical, the hinge-line being at the same time the widest portion of the shell. The ventral valve is very much vaulted, and usually longitudinally divided by a median depression or sinus of variable depth. The beak is small, and does not overlie the hinge-line, while the ears are of moderate dimensions and clearly defined. Exteriorly the surface is ornamented with numerous longitudinal ribs, which increase in number by means of occasional intercalations; certain ribs will also disappear before having attained the margin; while again two will sometimes unite, so as to constitute but a single rib. The costæ are very often of unequal width, rounded, or flattened, and sometimes will rapidly increase in width as they extend towards the margin: concentric wrinkles are also observable upon the auriculate portions of the valve, and a row of long tubular spines may be seen close to the cardinal edge, as well as upon the lateral portions of the beak; spines of smaller proportions project likewise here and there from the ribs themselves, while the longitudinal costæ are closely intersected or decussated to some distance from the extremity of the beak by numerous undulating concentric lines.
The Geology of the Sea
Authors: Mackie S. J.
Published: March 2016

No man is right at all times, says the common proverb, and Geologists are not always exceptions to the rule. Granite has been looked upon as the “back-bone” of the earth's crust, and fire or deeply-seated internal heat has been supposed to have fused an ancient unknown kind of rock into its present compact and crystalline state, while although now scarcely anything more than, at most, hot water will be allowed as an agent in the structural change. The older geologists invoked on all occasions when great effects were to be produced most terrible commotions and catastrophes, just as melodramatists bring in blue fire and demons. Nature is, however, a most methodical business personage. Sedate and steady, she takes quietly and methodically everything with which she has to do, and keeps her accounts properly by double entry. If you draw on her on the one hand, immediately she pays into her bankers on the other. Nothing goes down on the one side of her accounts but instantly she makes some entry on the other.
Geological Localities.—No. I. Folkestone
Authors: Mackie S. J.
Published: March 2016

Crossing the railway to the harbour, a footpath brings us to some old white-washed cottages, “The Folly Houses,” as they are called (but why I know not), where a young dealer (Griffiths) lives, of whom some good specimens may often be got. Continuing the footpath to the edge of the cliff, we descend by rugged green-sand steps again to the favourite collecting ground, Eastwear Bay.

Slowly the bright green tide is quitting the flat shore, and leaving again exposed the dark blue clay, dotted with black phosphatic nodes and glittering iridescent shells, washed clean and bright. Daily may you pick up hundreds of these ancient inhabitants of the sea; gather the crop as clean as you will, there will be another harvest for you when the next tide falls. Here are Inocerami, or “fibre-shells,” in abundance. Two species, the Inoceramus sulcatus and Inoceramus concentricus—the furrowed and concentric are particularly characteristic of the gault.
Geological Localities.—No. I. Folkestone
Authors: Mackie S. J.
Published: March 2016

Of all the Gault fossils, the Ammonites take precedence both for beauty and number; and, holding as the Cephalopods do the highest rank of molluscous animals, we cannot but view their extraordinary variety in this deposit with singular interest. If, therefore, we dwell here somewhat at length on their general classification, we could scarcely choose a more fitting occasion.

As ordinarily seen in collections, the Gault Ammonites appear to be all more or less of diminutive size. Few exceed two inches in diameter; many are little more than an inch; while one of three inches would be looked upon as a fine individual.

These specimens are, however, for the most part only the central whirls solidified or hardened by interior walls, or in-fillings of iron-pyrites. In the Gault itself Ammonite-shells of far larger size—commonly of six or seven inches across, sometimes more than a foot—are not merely frequent, but extremely abundant, although, from the fragile state of the main mass, they are commonly cleft to pieces in breaking out the central pyritous cores without attracting observation.
Notes on the Metalliferous Saddles, or Orebearing Beds in the Contorted Strata of the Lower Carboniferous Rocks of Certain Parts of Derbyshire and North Staffordshire
Authors: Watson Joseph J. W.
Published: March 2016

The inferior division of the Carboniferous series in Derbyshire and North Staffordshire, composed of calcareous rocks and shales, and forming the Mountain Limestone group of those counties, presents, particularly about the neighbourhood of Alstonfield, some very interesting and remarkable associations of metallic minerals with certain mechanical disturbances of the strata; moreover, these associations are not to be indiscriminately classed with the general phenomena of the mineral veins of the districts in question, but must be considered as special facts requiring a separate consideration and explanation. Their existence is no new discovery, since they have been recognized from the earliest times that mines have been worked in the places where they occur, and where also they are at most times regarded as valuable features, inasmuch as the richest deposits of ore have been found in connection with them; indeed, so decidedly has this been the case, that, in working the mines, much of the future success has been calculated by the amount of probability of any particular vein intersecting the disturbed beds; such unions having, in nearly all cases, been attended with most important results, both as respects the quantity, as well as the kind of ore met with. Nevertheless, I am not aware of their having ever received any particular attention from geologists, nor of their having been anywhere described, circumstances which may probably arise from the fact of these beds only being visible below the surface, and usually in deep mines; or they may have remained unnoticed, from the really small amount of scientific observation which in this country has been brought to bear on the facts connected with metalliferous deposits, compared with what has been done, and is still doing, in other branches of physical geology. The present article is drawn from memoranda made during several careful surveys of mines which are notable, in North Staffordshire, for exhibiting the phenomena of the saddles in great force.
American Politics and Political Science in an Era of Growing Racial Diversity and Economic Disparity
Authors: Hero Rodney E.
Published: March 2016

Political science should play a larger role in grappling with the political roots, meanings, and implications of the various levels and unique configurations of class inequality and racial diversity that have characterized the last several decades of U.S. history. I offer some observations about the discipline’s research, or lack thereof, and indicate suggestions about how we might think about and do more in these respects.

I will come at these concerns by noting some developments that influenced the present in social and political terms and other events in political science; identifying intellectual guideposts that may help how we think about research issues of our day; considering why race and class are not studied (more); acknowledging how the questions have been studied, as well as noting some reservations about these; and providing several examples from the research in which I have been involved, both directly and indirectly, that suggest how we might or can study these questions.
Narratives of Fear in Syria
Authors: Pearlman Wendy
Published: March 2016

Scholarship on Syria has traditionally been limited by researchers' difficulty in accessing the reflections of ordinary citizens due to their reluctance to speak about politics. The 2011 revolt opened exciting opportunities by producing an outpouring of new forms of self-expression, as well as encouraging millions to tell their stories for the first time. I explore what we can learn from greater attention to such data, based on thick descriptive analysis of original interviews with 200 Syrian refugees. I find that individuals' narratives coalesce into a collective narrative emphasizing shifts in political fear. Before the uprising, fear was a pillar of the state's coercive authority. Popular demonstrations generated a new experience of fear as a personal barrier to be surmounted. As rebellion militarized into war, fear became a semi-normalized way of life. Finally, protracted violence has produced nebulous fears of an uncertain future. Study of these testimonials aids understanding of Syria and other cases of destabilized authoritarianism by elucidating lived experiences obscured during a repressive past, providing a fresh window into the construction and evolution of national identity, and demonstrating how the act of narration is an exercise in meaning making within a revolution and itself a revolutionary practice.
How to Get Away with Cholera: The UN, Haiti, and International Law
Authors: Pillinger Mara , Hurd Ian , Barnett Michael N.
Published: March 2016

The legalization of world politics is often celebrated for reducing impunity for those who contribute to humanitarian crises. This may sometimes be true but the opposite is also true. In 2010, United Nations peacekeepers unwittingly brought cholera to Haiti and sparked an epidemic. Nearly a million people were made sick and 8,500 died. Legal activists have sought to hold the UN responsible for the harms it caused and win compensation for the cholera victims. However, these efforts have been stymied by the structures of public international law—particularly UN immunity—which effectively insulate the organization from accountability. In short, the UN is empowered, and the cholera victims disempowered, by legalization. The Haiti case powerfully illustrates the dangers of legalism, which have been largely overlooked in discussions of international law, and suggests that law alone is an inadequate arbiter of responsibility in international politics.
Finnish Twin Research in the 1930s: Contributions of Arvo Lehtovaara and His Mentor, Eino Kaila
Authors: Pulkkinen Lea , Latvala Antti , Rose Richard J.
Published: March 2016

We offer a brief sketch of an overlooked early twin researcher, Arvo Johannes Lehtovaara (1905–1985), Professor of Psychology at the University of Jyväskylä, 1939–1952, and the University of Helsinki, 1952–1970, with background notes on his mentor, Eino Kaila.
Morphodynamics of submarine channel inception revealed by new experimental approach
Authors: de Leeuw Jan , Eggenhuisen Joris T. , Cartigny Matthieu J. B.
Published: March 2016

Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor.
Exciton localization in solution-processed organolead trihalide perovskites
Authors: He Haiping , Yu Qianqian , Li Hui , Li Jing , Si Junjie , Jin Yizheng , Wang Nana , Wang Jianpu , He Jingwen , Wang Xinke , Zhang Yan , Ye Zhizhen
Published: March 2016

Organolead trihalide perovskites have attracted great attention due to the stunning advances in both photovoltaic and light-emitting devices. However, the photophysical properties, especially the recombination dynamics of photogenerated carriers, of this class of materials are controversial. Here we report that under an excitation level close to the working regime of solar cells, the recombination of photogenerated carriers in solution-processed methylammonium–lead–halide films is dominated by excitons weakly localized in band tail states. This scenario is evidenced by experiments of spectral-dependent luminescence decay, excitation density-dependent luminescence and frequency-dependent terahertz photoconductivity. The exciton localization effect is found to be general for several solution-processed hybrid perovskite films prepared by different methods. Our results provide insights into the charge transport and recombination mechanism in perovskite films and help to unravel their potential for high-performance optoelectronic devices.
Erratum: φXANES: In vivo imaging of metal-protein coordination environments
Authors: James Simon A. , Hare Dominic J. , Jenkins Nicole L. , de Jonge Martin D. , Bush Ashley I. , McColl Gawain
Published: March 2016

Scientific Reports 6: Article number: 20350; published online: 10 February 2016; updated: 21 March 2016 In this Article, the online methods were omitted. The online methods should read: Strains Wild type C. elegans (strain N2) were obtained from the Caenorhabditis Genetics Center (University of Minnesota), and ftn-2(ok404) and the ferritin null ftn-2(ok404); ftn-1(ok3625) (strain GMC005) have been previously described 1 .
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes
Authors: Chindera Kantaraja , Mahato Manohar , Kumar Sharma Ashwani , Horsley Harry , Kloc-Muniak Klaudia , Kamaruzzaman Nor Fadhilah , Kumar Satish , McFarlane Alexander , Stach Jem , Bentin Thomas , Good Liam
Published: March 2016

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.
A p-i-n junction diode based on locally doped carbon nanotube network
Authors: Liu Xiaodong , Chen Changxin , Wei Liangming , Hu Nantao , Song Chuanjuan , Liao Chenghao , He Rong , Dong Xusheng , Wang Ying , Liu Qinran , Zhang Yafei
Published: March 2016

A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~104), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm.
Quantification of HER2 heterogeneity in breast cancer–implications for identification of sub-dominant clones for personalised treatment
Authors: Buckley Niamh E. , Forde Claire , McArt Darragh G. , Boyle David P. , Mullan Paul B. , James Jacqueline A. , Maxwell Perry , McQuaid Stephen , Salto-Tellez Manuel
Published: March 2016

Breast cancer is a heterogeneous disease, at both an inter- and intra-tumoural level. Appreciating heterogeneity through the application of biomarkers and molecular signatures adds complexity to tumour taxonomy but is key to personalising diagnosis, treatment and prognosis. The extent to which heterogeneity exists and its interpretation remains a challenge to pathologists. Using HER2 as an exemplar, we have developed a simple reproducible heterogeneity index. Cell-to-cell HER2 heterogeneity was extensive in a proportion of both reported ‘amplified’ and ‘non-amplified’ cases. The highest levels of heterogeneity objectively identified occurred in borderline categories and higher ratio non-amplified cases. A case with particularly striking heterogeneity was analysed further with an array of biomarkers in order to assign a molecular diagnosis. Broad biological complexity was evident. In essence, interpretation, depending on the area of tumour sampled, could have been one of three distinct phenotypes, each of which would infer different therapeutic interventions. Therefore, we recommend that heterogeneity is assessed and taken into account when determining treatment options.
Autonomous pump against concentration gradient
Authors: Xu Zhi-cheng , Zheng Dong-qin , Ai Bao-quan , Zhong Wei-rong
Published: March 2016

Using non-equilibrium molecular dynamics and Monte Carlo methods, we have studied the molecular transport in asymmetric nanochannels. The efficiency of the molecular pump depends on the angle and apertures of the asymmetric channel, the environmental temperature and average concentration of the particles. The pumping effect can be explained as the competition between the molecular force field and the thermal disturbance. Our results provide a green approach for pumping fluid particles against the concentration gradient through asymmetric nanoscale thin films without any external forces. It indicates that pumping vacuum can be a spontaneous process.
Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia
Authors: Wood Thomas , Osredkar Damjan , Puchades Maja , Maes Elke , Falck Mari , Flatebø Torun , Walløe Lars , Sabir Hemmen , Thoresen Marianne
Published: March 2016

Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was investigated after either moderate or severe injury. At postnatal-day seven, rat pups underwent moderate or severe HI followed by 5 h at normothermia (37 °C), or one of five HT temperatures: 33.5 °C, 32 °C, 30 °C, 26 °C, and 18 °C. One week after treatment, neuropathological analysis of hemispheric and hippocampal area loss, and CA1 hippocampal pyramidal neuron count, was performed. After moderate injury, a significant reduction in hemispheric and hippocampal loss on the injured side, and preservation of CA1 pyramidal neurons, was seen in the 33.5 °C, 32 °C, and 30 °C groups. Cooling below 33.5 °C did not provide additional neuroprotection. Regardless of treatment temperature, HT was not neuroprotective in the severe HI model. Based on these findings, and previous experience translating preclinical studies into clinical application, we propose that milder cooling should be considered for future clinical trials.
Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis
Authors: Sharma Raman , Jayoussi Ghaith Al , Tyrer Hayley E. , Gamble Joanne , Hayward Laura , Guimaraes Ana F. , Davies Jill , Waterhouse David , Cook Darren A. N. , Myhill Laura J. , Clare Rachel H. , Cassidy Andrew , Steven Andrew , Johnston Kelly L. , Ford Louise , Turner Joseph D. , Ward Stephen A. , Taylor Mark J.
Published: March 2016

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.
Tracking of STAT3 signaling for anticancer drug-discovery based on localized surface plasmon resonance
Authors: Song Sojin , Nguyen Anh H. , Lee Jong Uk , Cha Misun , Sim Sang Jun
Published: March 2016

The label-free sensor, based on the LSPR shift response by tracking of the STAT3 signaling pathways, is an ultrasensitive for drug screening of anticancer therapy.
The ultrafast reactions in the photochromic cycle of water-soluble fulgimide photoswitches
Authors: Slavov C. , Boumrifak C. , Hammer C. A. , Trojanowski P. , Chen X. , Lees W. J. , Wachtveitl J. , Braun M.
Published: March 2016

High polarity and protic nature of the solvent strongly influence the reaction dynamics of a photochromic water-soluble indolylfulgimide.
Homopolar dihydrogen bonding in ligand stabilized diberyllium hydride complexes, Be2(CH3)2H2L2(L = H−, CO, N-heterocyclic carbene and CN−)
Authors: Nijesh Karikkeeriyil , De Susmita , Parameswaran Pattiyil
Published: March 2016

Diberyllium hydride complex – not a diborane analogue: the diberyllium hydrides Be2(CH3)2H2L2(L = H−, CO, NHC and CN−) are isostructural to diborane but differ in the nature of the bonding interaction at the bridging H-atoms.
Recent advances in the synthesis of hierarchically porous silica materials on the basis of porous glasses
Authors: Inayat Alexandra , Reinhardt Björn , Herwig Jan , Küster Christian , Uhlig Hans , Krenkel Sharon , Raedlein Edda , Enke Dirk
Published: March 2016

The methods for integrating an additional pore system in glass-based monoliths are reviewed with an emphasis on sintering and pseudomorphic transformation routes.
A neutralization charge detection method for detecting ions under ambient and liquid-phase conditions
Authors: Chang Ko-Keng , Cai Yi-Hong , Chen Chung-Hsuan , Wang Yi-Sheng
Published: March 2016

A novel neutralization charge detection method enabling the fast and sensitive detection of ions under ambient and liquid phases.
Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53–Mdm4
Authors: Hoppmann Christian , Wang Lei
Published: March 2016

A new method for developing macromolecular covalent drugs by designing an unnatural amino acid to target a nearby natural residue.
Design of a confined environment using protein cages and crystals for the development of biohybrid materials
Authors: Abe Satoshi , Maity Basudev , Ueno Takafumi
Published: March 2016

This feature article reviews the recent development of protein cages and in vivo and in vitro engineering of protein crystals with functional properties.
Acid-mediated topological control in a functionalized foldamer
Authors: Knipe Peter C. , Thompson Sam , Hamilton Andrew D.
Published: March 2016

Protonation mediates the transition between linear and helical foldamer topologies giving rise to a dynamic, functionalized molecular surface.
Rational synthesis of an exceptionally stable Zn(ii) metal–organic framework for the highly selective and sensitive detection of picric acid
Authors: Hu Yingli , Ding Meili , Liu Xiao-Qin , Sun Lin-Bing , Jiang Hai-Long
Published: March 2016

An exceptionally stable Zn(ii) metal–organic framework has been rationally synthesized and behaves as a fluorescence chemosensor for the highly selective and sensitive detection of picric acid.
In situ recrystallization of lanthanide coordination polymers: from 1D ladder chains to 1D linear chains
Authors: Sun Jing-Wen , Li Shang-Ju , Yan Peng-Fei , Yao Xu , Li Guang-Ming
Published: March 2016

A rare SCSC transformation for lanthanide coordination polymers is triggered by solvent-mediated isomerization.
Temperature dependence of the photoluminescence from ZnO microrods prepared by a float zone method
Authors: Guo Xingyuan , Tripp Carl P. , Chen Changfeng , Wang Yan , Yin Shengyan , Qin Weiping
Published: March 2016

ZnO microrods were grown with a high c-axis orientation. The PL spectra of the ZnO microrods at temperatures between 15 and 150 K were monitored to verify the peak assignments.
Three steps to gold: mechanism of protein adsorption revealed by Brownian and molecular dynamics simulations
Authors: Ozboyaci M. , Kokh D. B. , Wade R. C.
Published: March 2016

Complete adsorption of a model protein to a gold surface takes place in three distinct steps.
Analytical gradients for excitation energies from frozen-density embedding
Authors: Kovyrshin Arseny , Neugebauer Johannes
Published: March 2016

Analytical excitation-energy gradients from frozen-density embedding–time-dependent density functional theory are derived and implemented, which are important for photochemistry in complex systems.
Synthesis, characterization and magnetic properties of hollow Co2FeAl nanoparticles: the effects of heating rate
Authors: Almasi-Kashi Mohammad , Ramazani Abdolali , Alikhanzadeh-Arani Sima , Pezeshki-Nejad Zahra , Hassan Montazer Amir
Published: March 2016

Magnetic properties of hollow Co2FeAl nanoparticles, synthesized in the presence of polyethylene glycol, were characterized by the first-order reversal curve (FORC) analysis.
Application of magnetic lamotrigine-imprinted polymer nanoparticles as an electrochemical sensor for trace determination of lamotrigine in biological samples
Authors: Bojdi Majid Kalate , Behbahani Mohammad , Hesam Ghasem , Mashhadizadeh Mohammad Hosein
Published: March 2016

A magnet contain carbon paste electrode based on for magnetic molecularly imprinted polymer nanoparticles have been synthesized for the preconcentration and selective trace determination of lamotrigine (LTG) in urine and plasma samples.
Evaluation of peristaltic micromixers for highly integrated microfluidic systems
Authors: Kim Duckjong , Rho Hoon Suk , Jambovane Sachin , Shin Soojeong , Hong Jong Wook
Published: March 2016

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip.
Single-molecule electronics: Cooling individual vibrational modes by the tunneling current
Authors: Lykkebo Jacob , Romano Giuseppe , Gagliardi Alessio , Pecchia Alessandro , Solomon Gemma C.
Published: March 2016

Electronic devices composed of single molecules constitute the ultimate limit in the continued downscaling of electronic components. A key challenge for single-molecule electronics is to control the temperature of these junctions. Controlling heating and cooling effects in individual vibrational modes can, in principle, be utilized to increase stability of single-molecule junctions under bias, to pump energy into particular vibrational modes to perform current-induced reactions, or to increase the resolution in inelastic electron tunneling spectroscopy by controlling the life-times of phonons in a molecule by suppressing absorption and external dissipation processes. Under bias the current and the molecule exchange energy, which typically results in heating of the molecule. However, the opposite process is also possible, where energy is extracted from the molecule by the tunneling current. Designing a molecular “heat sink” where a particular vibrational mode funnels heat out of the molecule and into the leads would be very desirable. It is even possible to imagine how the vibrational energy of the other vibrational modes could be funneled into the “cooling mode,” given the right molecular design. Previous efforts to understand heating and cooling mechanisms in single molecule junctions have primarily been concerned with small models, where it is unclear which molecular systems they correspond to. In this paper, our focus is on suppressing heating and obtaining current-induced cooling in certain vibrational modes. Strategies for cooling vibrational modes in single-molecule junctions are presented, together with atomistic calculations based on those strategies. Cooling and reduced heating are observed for two different cooling schemes in calculations of atomistic single-molecule junctions.
Five ab initio potential energy and dipole moment surfaces for hydrated NaCl and NaF. I. Two-body interactions
Authors: Wang Yimin , Bowman Joel M. , Kamarchik Eugene
Published: March 2016

We report full-dimensional, ab initio-based potentials and dipole moment surfaces for NaCl, NaF, Na+H2O, F−H2O, and Cl−H2O. The NaCl and NaF potentials are diabatic ones that dissociate to ions. These are obtained using spline fits to CCSD(T)/aug-cc-pV5Z energies. In addition, non-linear least square fits using the Born-Mayer-Huggins potential are presented, providing accurate parameters based strictly on the current ab initio energies. The long-range behavior of the NaCl and NaF potentials is shown to go, as expected, accurately to the point-charge Coulomb interaction. The three ion-H2O potentials are permutationally invariant fits to roughly 20 000 coupled cluster CCSD(T) energies (awCVTZ basis for Na+ and aVTZ basis for Cl− and F−), over a large range of distances and H2O intramolecular configurations. These potentials are switched accurately in the long range to the analytical ion-dipole interactions, to improve computational efficiency. Dipole moment surfaces are fits to MP2 data; for the ion-ion cases, these are well described in the intermediate- and long-range by the simple point-charge expression. The performance of these new fits is examined by direct comparison to additional ab initio energies and dipole moments along various cuts. Equilibrium structures, harmonic frequencies, and electronic dissociation energies are also reported and compared to direct ab initio results. These indicate the high fidelity of the new PESs.
Hysteresis and mode transitions in plasma sheath collapse due to secondary electron emission
Authors: Langendorf Samuel , Walker Mitchell
Published: March 2016

In this experiment, hysteresis is observed in the floating potential of wall material samples immersed in a low-temperature plasma as the energy of a prevalent non-thermal electron population is varied from 30–180 eV. It is indicated that the hysteresis is due to secondary electron emission from the wall material surface. Measurements are performed in a filament discharge in argon gas pressure 10−4 Torr of order 107 cm−3 plasma number density. The primary ionizing electrons from the discharge filament make up 1%–10% of the overall plasma number density, depending on discharge voltage. Immersed LaB6-coated steel and roughened boron nitride (BN) wall material samples are mounted on the face of a radiative heater, and the wall temperature is controlled from 50–400 °C such that thermionic emission from the LaB6-coated sample is not significant. The energy of the primary plasma electrons from the discharge filament is varied and the floating potentials of the material samples are monitored. The floating potentials are observed to transition to a “collapsed” state as the primary electron energy is increased above 110 and 130 eV for the LaB6 and rough BN, respectively. As primary electron energy is subsequently decreased, the floating potentials do not “un-collapse” until lower energies of 80 and 100 eV, respectively. The hysteresis behavior agrees with a kinetic model. The results may help explain observations of global hysteresis and mode transitions in bounded plasma devices with dielectric walls, significant secondary electron emission, and departures of electron energy distribution function from a thermal Maxwellian.