bluuebunny/crossref_metadata_2025 huggingface dataset:
Notes on Some Mousterian Finds in Spain and Irak
Authors: Garrod D. A.
Published: October 2013

The following sites were discovered by Mr. and Mrs. Harry Milton and myself during the summer and autumn of 1926, while I was excavating the Devil's Tower Cave at Gibraltar.

(i) Llanos de la Horadada. This is a surface site, lying on rising ground to the west of the road from San Roque to the Rio Guadiaro, near the seventh kilometre-stone out of San Roque. The Llanos de la Horadada is a group of low hills forming a southern extension of the Sierra del Arco; it takes its name from a tunnel-like cave, the Cueva de la Horadada, which runs through an outcrop of Eocene sandstone about 1 km. to the west of the road.

In a recently-ploughed field lying immediately above the road we found a small number of flint and quartzite implements, two of which, a small disc and a chopper, were unmistakably Mousterian (Fig. II, Nos. 1 and 2). The implements and flakes were all slightly abraded, and those which were made of flint were deeply patinated, some being white and others light brown.
On an Early Palæolithic Workshop Site at Stonecross, Luton, Chatham
Authors: Turner J.
Published: October 2013

It is more than twenty years since my father, Mr. S. K. Turner discovered evidence of the presence of man in the Luton valley. Stimulated by his early successes he was led to continue his search, and the result of his labours, coupled, in more recent years with my own, has been that the collections of museums both at home and abroad have been enriched.
Palaeolithic Implements from the Cannon-shot Gravel of Norfolk
Authors: Moir J. Reid
Published: October 2013

The purpose of this paper is to describe and figure eight palæolithic flint implements discovered in the Cannon-shot gravel of Norfolk. The specimens were found during researches carried out under a grant from the Percy Sladen Trustees, to whom I am much indebted for their help. I have also to acknowledge the assistance given me by Mr. G. Maynard and Mr. J. E. Sainty, who have been intimately associated with my investigations.

The Cannon-shot gravel derives its name from its contained rounded and battered flint pebbles, symmetrically shaped like the cannon-balls in use at the time when Wood and Harmer first examined it. This gravel is well-known to geologists, and extends over large areas in Norfolk. It often occupies high ground, and can be examined in the cliff sections along the north-east coast of this county, and also in many inland pits. The gravel, wnich contains an appreciable number of foreign rocks, usually presents little evidence of stratification, though horizontal and thin layers of sand and loam are to be observed in its mass. The contained stones often rest in a vertical or inclined position in the gravel, a fact which makes it difficult to believe that water-action of the normal kind was responsible for the laying down of the deposit.
On the Clactonian Industry at Swanscombe
Authors: Chandler R. H.
Published: October 2013

The river gravels of the Boyne Hill (1st., 100 ft. and, in this district, the highest) Terrace of the Thames at Swanscombe (Kent) have yielded flint implements in thousands for many years.

As long ago as 1905 these contemporary (not the derived) implements were correlated with the St. Acheul culture in the Somme Valley, and in 1912 some excavations were undertaken by the Geological Survey and the British Museum to determine the exact horizon at which these implements occur.

These excavations showed conclusively that the level where the implements were so abundant was at the top of the middle gravel. The excavators regarded these middle gravel implements as of “Chelles” type, but recent work has caused the word “Chelles” to be used in a more restricted sense, and they may now be regarded as of St. Acheul type.

The point of the exact determination of the middle gravel implements is important, on account of its bearing upon the age of the industry which occurs in the gravel below the middle gravel.
Note on the Mammalian Remains
Authors: Hinton Martin A. C.
Published: October 2013

The remains submitted to me by Mr. R. H. Chandler represent three species, Elephas antiquus, Rhinoceros, sp., and a deer which for the moment may be determined as Cervus browni. In general character these fossils are quite like those obtained many years ago from the “Shell Pit” in the High Terrace Drift of the Thames at Ingress Vale, near Greenhithe. A full account of the older collection will, I hope, be published before long. The present small collection forms a welcome addition to the relatively scanty material from this horizon, and by the kindness of Mr. A. C. Davis it will be presented to the British Museum.
The Industries of Le Moustier
Authors: Barnes Alfred S.
Published: October 2013

The Rock Shelter situated on the Middle Terrace at Le Moustier was excavated by Lartet and Christy in 1863, and yielded a series of implements of a special culture to which de Mortillet gave the name of Le Moustier. This industry, which to the early prehistorians seemed relatively simple, with the side-scraper and point as its typical implements, has now shown itself to be complex, owing to the discovery of new sites of Le Moustier date, very widely distributed geographically, and to the careful re-examination of the classical site itself. The Abri classique on the Middle Terrace at Le Moustier has been the subject of subsequent excavations by Bourlon, Chastaing, Hauser and Peyrony. The deposits in the Lower Terrace have also been examined by Rivière and Hauser. It was here that in 1908 the latter discovered the skeleton of Neanderthal type now in the Berlin Museum. In 1910 the Rock Shelter on the Middle Terrace, together with the Lower Terrace, was purchased by the French Government, and, subsequent to this, Peyrony has carried out on the Lower Terrace the admirable series of excavations, which he has carefully described in a recent publication. The present paper deals briefly with the morphology of the implements from the various layers as determined by Peyrony, and applies the statistical methods developed by the author to the discrimination of the various layers and the correlation of the implements from the Middle and Lower Terraces.
A Late Upper Aurignacian Station in North Lincolnshire
Authors: Armstrong A. Leslie
Published: October 2013

The site forming the subject of this communication is an open-air station of Upper Palæolithic date, situated near the northern extremity of the Lincolnshire Cliff range, and previously unrecorded. The cultural horizon of the site closely corresponds with that of the upper levels of the rock-shelter known as ‘Mother Grundy's Parlour,’ Creswell Crags, Derbyshire, excavated by the writer in 1924, under the auspices of the British Association Research Committee for the Exploration of Caves in Derbyshire. Those excavations revealed, for the first time, the gradual development of our English phase of the Upper Aurignacian, and established the fact that this was of a distinctive character, and had been evolved practically free from Magdalenian influences. Excavations in the Mendip caves by the University of Bristol Spelæological Society, and elsewhere, have since confirmed these conclusions; and it is now recognised tlhat the culture is essentially an English expression of Upper Aurignacian, which is typical of the Upper Palæolithic in this country.
Notes on the Beaker Pottery of the Ipswich Museum
Authors: Clark J. G. D.
Published: October 2013

There are in Ipswich Museum some 18 beakers, more or less complete, together with fragments of at least four more. As these pots are all from a restricted area of south-east Suffolk, and have, with one exception, never before been described, I have undertaken, with the consent and help of the Secretary, to make a few observations upon them. With tine exception of a group from Brantham, and a single example from Wherstead, all the beakers were recovered loose ın gravel digging or cliff-falls. Near Brantham Hall, near the point where the Stour broadens out into its estuary, three beakers were found by Mr. G. Maynard together in the grave of a woman buried with a child; the pots were discovered near the flexed shin bones of the woman. Just south of this grave, was found another one containing a single beaker. Near these graves, which were discovered in gravel-digging, was a disc barrow, from the central part of which Mr. Maynard recovered 16 fragments of a single beaker, while from the trench, the late Mr. E. T. Lingwood succeeded in obtaining a fragment of a second beaker. Of the group from the woman's grave (Figs. 3, 4, 5, Pl. XXVIII.), Fig 3 has a smooth outline with an everted lip, is decorated over its whole area by seventeen horizontal lines coarsely incised, and has a maximum height of 4.9 inches; Fig. 4 is a crudely formed pot standing no more than 3½ inches high, poorly decorated with faint finger-nail impressions; Fig. 5, standing 6 inches high, is of fine paste with the smooth outline typical of Abercromby's type B, decorated with horizontal lines and linear chevrons arranged over the whole surface.
Bronze Age Settlements in Norfolk
Authors: Apling Harry
Published: October 2013

In 1922 Miss N. F. Layard gave as her presidential address an account of some prehistoric cooking-places, which she had discovered near a stream at Buckenham Tofts, Norfolk (Proc., P.S.E.A., Vol. III., Part IV.). One of the hearths excavated consisted of a triangular mass of calcined flints, up to two feet in depth, and covering an area of over 100 square yards. This was on one end of a mound rising about ten feet above the general level of the swamp bordering the stream. Amongst this material were found several flint implements, including knives typical of the Bronze Age. There were also found two sherds of pottery corresponding closely to a known Bronze Age type, though this also continued into the Early Iron Age.

Knowing nothing of Miss Layard's discoveries, in 1927 I came across similar deposits of pot-boilers, etc., at Hoe, near East Dereham. These are on either side of a small stream, which eventually runs into the River Wensum. Mr. Sainty and Mr. Newnham were good enough to come over and examine them, and Mr. Newnham subsequently gave a short account of them at the December meeting that year (Proc., P.S.E.A., Vol. V., Part III. page 311).

I was able to revisit the site in June this year (1931), and at one place where, however, there was hardly a mound at all, a layer of pot-boilers, 6 ins. deep, was found under about 6 ins. of turf and soil. Excavation of an area 12 feet by 8 feet produced nearly a pailful of pottery fragments, three dozen scrapers, and an implement of the bone-breaker type, besides numbers of flakes and cores.
Prehistoric Man Round Bombay
Authors: Todd K. R. U.
Published: October 2013

The purpose of this paper is to put on record the discovery of various sites, containing traces of prehistoric man, in the neighbourhood of Bombay.

The area of greatest importance is that of Worli. It is a cotton milling suburb of Bombay, distant some 4 miles from the Fort, and is situated on low lying marshy ground and bounded to the West by a low steep hill having a maximum height of 100 ft. O.D., and consisting of igneous basalt overlying amygdaloidal trap with a dyke of F.W. strata between. This dyke contains fossils of marsh tortoises, frogs and plants resembling bulrushes. The basalt is capped with red earth which is decomposing trap, and contains nodules of agate and blocks of chert. West of the hill is the Arabian Sea. The northern extremity of this hill ends in a spur which juts out into the sea, and here is the fishing village of Koliwada, consisting of mud huts.
Modes of Prehension of some forms of Upper Palaeolithic Implements
Authors: Barnes Alfred S.
Published: October 2013

Common sense and simple experiment have already indicated certain ways in which some of the more common forms of Upper Palaeolithic implements may have been held. Thus for example, there is a general consensus of opinion that knife blades were held either by the butt end only, or by the butt with the index finger extended along the back of the tool. When however, we come to consider other types of tools, such as the scrapers, we find that there are a number of possible ways in which such tools may be held. The actual way or ways in which these tools were held becomes therefore, largely a matter of conjecture unless we can fortify our opinion by relevant facts relating to some particular mode or modes of prehension.

To guide us in selecting the particular way in which a tool was held from the many possible ways in which it could be held, we have the following factors:—

(i) The general shape of the tool.

(ii) The character of the traces of wear on the cutting edge due to use.

(iii) The situation and character of any special trimming which may have been made to facilitate prehension.

(iv) The degree of comfort or freedom from constraint with which a tool may be used in a given position.

(v) The frequency of occurrence of tools of certain lengths and widths which are comparable with the average dimensions of the human hand when gripping an object in certain ways.

(vi) The mode of prehension of stone tools adopted by existing primitive races.
The Percy Sladen Trust Excavations, Grime's Graves, Norfolk. Interim Report 1927–1932
Authors: Armstrong A. Leslie
Published: October 2013

Since the publication of the 1926 Report on these excavations much important work has been accomplished, four pits, all of the intermediate mining phase, have been completely excavated and a fifth, (Pit No. 12) commenced. In addition, 32 sections have been dug, chiefly in the West Field, which have confirmed the evidence already published and provided further important evidence as to the extent and nature of the mining activities in general.
Prehistoric Archaeology in Wales Since 1925
Authors: Grimes W. F.
Published: October 2013

In this paper I shall endeavour to outline the progress which has been made recently in archaeological studies in the prehistoric periods in Wales. In the last number of the Proceedings (1931, 383–4), I contributed at the request of the Secretary a number of notes on this subject, taking as my starting point the publication of Dr. R. E. M. Wheeler's book, Prehistoric and Roman Wales, in 1925. In the present instance I propose to give a more detailed, as well as a more general account, demonstrating how recent research and discoveries have advanced our knowledge, clarifying the position in relation both to Wales herself and to the connexions of Wales with other external influences.

The publication of Prehistoric and Roman Wales in 1925 may truly be said to mark the end of one era and the beginning of a new. Drawing together the scattered threads of what had been done before, Wheeler has given them meaning and set forth the results of many years of unorganised, frequently ill-considered, work in tangible form. In so doing, he has exposed the gaps in our knowledge and suggested, specifically or by implication, a policy in the form of a series of problems the elucidation of which will lead ultimately to a more complete picture of the early cultures of Wales, and hence of Britain as a whole. Wheeler's survey therefore forms a natural and admirable jumping-off place, and the subject will be treated in the following pages in its natural chronological sequence.
Some Norfolk Palaeolithic Discoveries: With an Appendix on Implementiferous Gravels in East Anglia
Authors: Sainty J. E. , Solomon J. D.
Published: October 2013

In June, 1927, Mr. H. H. Halls noticed that the footpath beside the main Cambridge line of the L.N.E.R. had been made up with gravel. With the then recent discovery of implementiferous gravels at Whitlingham fresh in his mind he scrutinised the gravel carefully and soon found definite flakes. With some difficulty the gravel was traced to its source, and proved to come from Messrs. J. &. J Colman's Carrow works, where to extensive alterations were in progress. By the courtesy of the Directors, Mr. Halls was enabled to visit the site and examine the sections exposed. No flakes were seen in situ, but the workmen were instructed what to look for, and he arranged that any find of apparent interest should be preserved for his inspection. Throughout the rest of the year Mr. Halls regularly visited the site and a number of flakes were recovered, and fragments of bone, too decayed for identification, were seen.

Early in 1928 the Rev. T. C. Rae found the end of a broken hand-axe—a promise of future discoveries—and in February a good hand-axe was recovered from a sand layer 12 feet below the top of the section. The same deposit also yielded a worked flake of Chellean type, evidently derived from an older deposit, as well as some fresh-looking flakes with prominent bulbs. Finds of coarse scrapers and worked flakes continued steadily, and early in July a mammoth tooth, too disintegrated for preservation, prepared us for the discovery of a large portion of tusk, over three feet long.
Mesolithic Sites of the North East Coast of England
Authors: Raistrick A.
Published: October 2013

For a distance of four miles north of Newbiggin-on-Sea, Northumberland, the coast presents a stretch of low cliffs and headlands of sandstone, alternating with shallow bays flanked by sand-dunes, the dunes usually resting visibly on a low boulder clay cliff, not usually rising more than 20 ft. above high tide level. The river Lyne reaches the coast now about two miles north of Newbiggin, at Lyne Sands, but in preglacial and early post-glacial time, entered the sea at Newbiggin bay. The old course of the river is occupied by the “Carrs,” a strip of swampy peat, proved at several places by boring, to reach a depth of over twenty feet and to be underlain by river gravel on boulder clay. The basal layers of the peat are proved by pollen analysis to be of latest Boreal age. Between this old channel and the sea, lies Newbiggin Moor, between 30 ft. and 50 ft. OD. a wide stretch of sandstone covered by thin soil, and occasional peat and blown sand. In early Boreal time this would be a headland prolonged southward between the sea on the east and the river Lyne on the west. At a subsequent period the Lyne has broken through its present course to the sea, north of Lyne Sands. The foreshore is made up by a wide stretch of sandstone, flats and skerries overlain by boulder clay, making the low cliff in the southern part, with sand dunes resting directly on the clay. Northward the sandstone gradually rises and towards Cresswell Point makes the whole cliff, with only a thin boulder clay cover on top.
Evidence of Human Sacrifice in Seacliff Cave, Scotland
Authors: Layard Nina Frances
Published: October 2013

It is perhaps rather late in the day to be describing an experience of twenty-nine years ago, but unless it is done now, possibly a unique relic of the past, though still in existence, may remain unknown to a large majority of antiquaries.

It was on the 15th of April, 1905, that accompanied by Miss Outram, I started from North Berwick, in East Lothian, Scotland, on a voyage of discovery along the picturesque coast. Our goal was a cave opened out rather more than a hundred years ago by Mr. George Sligo, on his property of Seacliff, in the county of Haddington. According to tradition there was incontestable evidence that on this spot human sacrifices had been offered in the remote past. Fired by these dramatic accounts, we decided to seek out the cave for ourselves, and if possible, to test the accuracy of these statements.

A short drive took us to Seacliff House, marked by a cross on fig. 1. In the foreground stands Tantallon Castle, the ruined stronghold of the Douglases, and in the cliff beyond the promontory on which the Castle stands is Seacliff Cave below the arrow (fig. 1).

As we turned the corner in the winding descent from the cliff, it was an arresting scene which held us for amoment spell-bound. At the mouth of a cave, hollowed out in the red sandstone cliff, stood a large pear-shaped stone, with every appearance of an altar, raised upon an artificial mound (fig. 3). Its surface, which was approximately flat, was covered with a small blood-red plant, which had crept over it, and hanging down, seemed to drip over the edge, conjuring up with startling effect, the scene of some gruesome Pagan sacrifice. It was with feelings almost akin to awe that we entered the cave, where other remains were equally suggestive both of occupation and worship.
The problem of raptor electrocution in Asia: case studies from Mongolia and China
Authors: DIXON ANDREW , MAMING ROLLER , GUNGA AMARKHUU , PUREV-OCHIR GANKHUYAG , BATBAYAR NYAMBAYAR
Published: October 2013

We report a large number of raptors electrocuted on recently erected electricity distribution lines in the open landscapes of the Mongolian steppe and Qinghai-Tibetan plateau, China. Upland BuzzardsButeo hemilasiusand Saker FalconsFalco cherrug, characteristic raptors of these bioregions, were among those found to be electrocuted. Raptor electrocution was a consequence of poorly designed hardware configurations on anchor poles along surveyed lines on the Qinghai-Tibetan Plateau and, additionally, on line poles in the Mongolian steppe. The design flaws were upright pin-insulators on earthed crossarms and the use of jump wires that passed over crossarms via pin insulators on anchor poles. Targeted mitigation of anchor poles could significantly reduce the incidence of electrocution on the lines surveyed on the Qinghai-Tibetan Plateau, whilst all poles on the lines surveyed in the Mongolian steppe require remediation to make them safe for raptors. The Mongolian steppe and the Qinghai-Tibetan Plateau are bioregions that hold the largest breeding and wintering populations of the globally threatened Saker Falcon. The existing and growing network of dangerous electricity distribution lines in these regions may potentially impact the Saker Falcon population, thus we suggest that preventative and/or mitigation measures are implemented.
Bacterial evolution of antibiotic hypersensitivity
Authors: Lázár Viktória , Pal Singh Gajinder , Spohn Réka , Nagy István , Horváth Balázs , Hrtyan Mónika , Busa‐Fekete Róbert , Bogos Balázs , Méhi Orsolya , Csörgő Bálint , Pósfai György , Fekete Gergely , Szappanos Balázs , Kégl Balázs , Papp Balázs , Pál Csaba
Published: October 2013

The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large‐scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole‐genome sequencing of laboratory‐evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton‐motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF‐dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade‐offs under antibiotic selection.
Exceptional gravimetric and volumetric hydrogen storage for densified zeolite templated carbons with high mechanical stability
Authors: Masika Eric , Mokaya Robert
Published: October 2013

Densification of zeolite templated carbons increases their volumetric hydrogen uptake from ca. 31 g l−1 to >50 g l−1 at 20 bar and −196 °C.
Growth of Finiteness in the Third Year of Life: Replication and Predictive Validity
Authors: Hadley Pamela A. , Rispoli Matthew , Holt Janet K. , Fitzgerald Colleen , Bahnsen Alison
Published: October 2013

Purpose

The authors of this study investigated the validity of tense and agreement productivity (TAP) scoring in diverse sentence frames obtained during conversational language sampling as an alternative measure of finiteness for use with young children.

Method

Longitudinal language samples were used to model TAP growth from 21 to 30 months of age for 37 typically developing toddlers. Empirical Bayes (EB) linear and quadratic growth coefficients and child sex were then used to predict elicited grammar composite scores on the Test of Early Grammatical Impairment (TEGI; Rice & Wexler, 2001) at 36 months.

Results

A random-effects quadratic model with no intercept best characterized TAP growth, replicating the findings of Rispoli, Hadley, and Holt (2009). The combined regression model was significant, with the 3 variables accounting for 55.5% of the variance in the TEGI composite scores.

Conclusion

These findings establish TAP growth as a valid metric of finiteness in the 3rd year of life. Developmental and theoretical implications are discussed.
High-speed laser microsurgery of alert fruit flies for fluorescence imaging of neural activity
Authors: Sinha Supriyo , Liang Liang , Ho Eric T. W. , Urbanek Karel E. , Luo Liqun , Baer Thomas M. , Schnitzer Mark J.
Published: October 2013

Significance

Microscopy and neurophysiology experiments in live animals commonly involve complex surgical preparations, which are often time-consuming, demand considerable manual dexterity, and can sharply limit experimental throughput. Here we present a spatially precise laser microsurgical technique using a pulsed UV laser. Our approach reduces surgical time by up to two orders of magnitude while substantially improving reproducibility. Using the fruit fly as a model, we show that laser microsurgery leaves complex behaviors intact and allows us to visualize brain activity in live flies for up to 18 h, more than four times longer than reported previously using hand dissection. We also demonstrate laser microsurgery on nematodes, ants, and the mouse cranium, illustrating broad potential utility for both optical and electrophysiological studies.
Enduring legacy of a toxic fan via episodic redistribution of California gold mining debris
Authors: Singer Michael Bliss , Aalto Rolf , James L. Allan , Kilham Nina E. , Higson John L. , Ghoshal Subhajit
Published: October 2013

Significance

This paper is of fundamental interest to the millions of residents living at the downstream end of this and other global river basins beset by industrial metals mining. Sediment-bound Hg has contaminated food webs of the San Francisco Bay-Delta, but the dominant geographical sources of Hg to downstream ecosystems in this and similar river basins are debated. Likewise, the processes by which Hg is delivered to lowlands and the patterns of its floodplain deposition are poorly understood. This research addresses a gap in generic theory of postmining fan evolution that enables anticipation, prediction, and management of contamination risk to food webs.
Hypermutability and error catastrophe due to defects in ribonucleotide reductase
Authors: Ahluwalia Deepti , Schaaper Roel M.
Published: October 2013

Significance

The accuracy by which cells are able to replicate their chromosomal DNA is critical for the rate by which they produce mutations. To keep the mutation rate low, cells have developed several mechanisms including accurate base selection by DNA polymerase, exonucleolytic proofreading that can excise incorrectly inserted bases, and postreplicative DNA mismatch repair. Also important are the concentrations of the deoxynucleoside-5′-triphosphates (dNTPs) that serve as direct substrates for the DNA synthesis reaction. Here, we describe a case in which certain changes in the relative levels of the four dNTPs (dATP, dTTP, dGTP, dCTP) can profoundly disturb the overall replication fidelity by impairing the efficiency of each of the three main fidelity systems, leading to a case of extreme hypermutability.
Conformational selection and adaptation to ligand binding in T4 lysozyme cavity mutants
Authors: López Carlos J. , Yang Zhongyu , Altenbach Christian , Hubbell Wayne L.
Published: October 2013

Significance

Analysis of protein packing reveals the prevalence of cavities, some of which are evolutionarily conserved. Despite the fact that these packing defects are generally destabilizing, they can play important roles in facilitating functionally important protein motions and in the evolution of protein function. In this study, we used site-directed spin-labeling with electron paramagnetic resonance spectroscopy to investigate the structural and dynamical response of an enzyme to engineered ligand-binding cavities. The results show that the engineered cavities introduce conformational fluctuations between a native-like state and a new state. Ligand binding shifts the equilibrium toward the native-like state, suggesting binding via conformational selection, although additional structural adaptation is observed for one mutant. The results underscore the potential role of cavities in modulating molecular flexibility.
Fast protein fragment similarity scoring using a Binet–Cauchy kernel
Authors: Guyon Frédéric , Tufféry Pierre
Published: October 2013

Motivation: Meaningful scores to assess protein structure similarity are essential to decipher protein structure and sequence evolution. The mining of the increasing number of protein structures requires fast and accurate similarity measures with statistical significance. Whereas numerous approaches have been proposed for protein domains as a whole, the focus is progressively moving to a more local level of structure analysis for which similarity measurement still remains without any satisfactory answer.

Results: We introduce a new score based on Binet–Cauchy kernel. It is normalized and bounded between 1—maximal similarity that implies exactly the same conformations for protein fragments—and −1—mirror image conformations, the unrelated conformations having a null mean score. This allows for the search of both similar and mirror conformations. In addition, such score addresses two major issue of the widely used root mean square deviation (RMSD). First, it achieves length independent statistics even for short fragments. Second, it shows better performance in the discrimination of medium range RMSD values. Being simpler and faster to compute than the RMSD, it also provides the means for large-scale mining of protein structures.

Availability and implementation: The computer software implementing the score is available at http://bioserv.rpbs.univ-paris-diderot.fr/BCscore/

Contact: frederic.guyon@univ-paris-diderot.fr

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Daptomycin‐Loaded Polymethylmethacrylate Bone Cement for Joint Arthroplasty Surgery
Authors: Hsu Yuan‐Ming , Liao Chun‐Hsing , Wei Yu‐Hong , Fang Hsu‐Wei , Hou Hsiang‐Huan , Chen Chia‐Chun , Chang Chih‐Hung
Published: October 2013

Antibiotic‐loaded acrylic bone cement has been frequently used as an infection prophylaxis or antibiotic‐loaded spacer in infected arthroplasty. In addition, daptomycin has been used recently against broad spectrum Gram‐positive organisms. The goal of this in vitro study is to investigate the bacteriacidal and mechanical properties of daptomycin‐incorporated polymethylmethacrylate (PMMA) bone cement and evaluate its feasibility for clinical use. Daptomycin (0.5, 1, or 2 g) was premixed with 40 g of PMMA bone cement powder before curing. The mechanical properties of the daptomycin‐loaded acrylic bone cement (DLABC) were estimated following standard guidance, and the release profile and kinetics of daptomycin from PMMA were analyzed. The antimicrobial efficacy of DLABC was determined with a zone of inhibition (ZOI) assay against Staphylococcus aureus, Staphylococcus epidermis, Enterococcus faecalis, and Enterococcus faecium, respectively. The results showed that the compressive strength, of PMMA bone cement, which was higher than 100 MPa in all groups, was sufficient according to ISO 5833 after incorporation of daptomycin. The encapsulated daptomycin was released for 2 weeks with a 9.59 ± 0.85%, 15.25 ± 0.69%, and 20.64 ± 20.33% released percentage on the first day in the low, mid, and high groups, respectively. According to the calculated release kinetics, incorporated daptomycin should be 3.3 times the original dose to double its release. Although all recipes of DLABC had a microbial inhibitory effect, the effect with a higher encapsulated amount of daptomycin was more significant. Therefore, we believe that daptomycin can be locally delivered from PMMA bone cement at the surgical site as a prophylactic or treatment for osteomyelitis against Gram‐positive organisms with intact cement function.
Paediatric pharmacokinetics: key considerations
Authors: Batchelor Hannah Katharine , Marriott John Francis
Published: October 2013

A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.
Induction of apoptosis and G2/M cell cycle arrest by Scrophularia striata in a human leukaemia cell line
Authors: Azadmehr A. , Hajiaghaee R. , Mazandarani M.
Published: October 2013

Objectives

Scrophularia striata Boiss (Scrophulariaceae) is a plant that grows in northeastern Iran; it has been used traditionally to treat various inflammatory disorders. This study was designed to investigate cytotoxic effects of S. striata extract, on the Jurkat human leukaemia cell line (T‐cell leukaemia).

Materials and methods

Phytochemical assay by thin layer chromatography and 2, 2 diphenyl‐1‐picryl‐hydrazyl were used to evaluate main compounds and antioxidant capacity of the plant extract, respectively. Its inhibitory effect on Jurkat cells was evaluated by MTT assay. In addition, cell cycle distribution and apoptotic cell death were evaluated by propidium iodide and annexin V‐FITC/ propidium iodide staining.

Results

These showed that the main components present in S. striata extract included flavonoids, phenolic compounds and phenyl propanoids. Treatment with extract was significantly cytotoxic to the tumour cell line. In addition, flow cytometry analysis indicated that S. striata extract induced cell cycle arrest in G2/M phase and apoptosis of tumour cells.

Conclusions

Results of the study indicated that S. striata extract could inhibit leukaemia cell proliferation by inducing G2/M phase arrest and apoptosis.
Use of Groundwater Levels with the PULSE Analytical Model
Authors: Rutledge Albert T.
Published: October 2013

The PULSE analytical model, which calculates daily groundwater discharge on the basis of user‐specified recharge, was originally developed for calibration using streamflow data. This article describes a model application in which groundwater level data constitute the primary control on model input. As a test case, data were analyzed from a small basin in central Pennsylvania in which extensive groundwater level data are available. The timing and intensity of daily water‐level rises are used to ascertain temporal distribution of recharge, and the simulated groundwater discharge hydrograph has shape features that are similar to the streamflow hydrograph. This article does not include details about calibration, but some steps are illustrated and general procedures are described for calibration in specific hydrologic studies. The PULSE model can be used to assess results of fully automated base flow methods and can be used to define groundwater recharge and discharge at a relatively small time scale.
The Multitarget Drug Approach in Migraine Treatment: The New Challenge to Conquer
Authors: González‐Hernández Abimael , Condés‐Lara Miguel
Published: October 2013

Migraine is a complex neurovascular disorder where a complex and interrelated neuronal spinal, supraspinal and central mechanisms are involved. Although we have greatly advanced in the knowledge of the main pathways involved in this disorder, the current drugs used are not effective in all patients, suggesting that the key mechanism related to headache relief remains elusive. In this context, the multi‐target drug approach or network pharmacology emerges as a new step in the development of innovative migraine pharmacotherapy. The design, discovery, and development of new drugs that reach several (instead of unique) specific targets (functional selectivity) involved in the migraine pathophysiology is essential to progress in the migraine treatment and open a new field of study about the main pathways and targets that could synergistically improve the migraine management.
Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon
Authors: Marrouche Nadine , Kurban Mazen , Kibbi Abdul‐Ghani , Abbas Ossama
Published: October 2013

Background

Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous disorder of unknown etiology. Studies on this condition from our region are lacking.

Methods

To describe the clinical and histopathological findings as well as response to treatment of all patients diagnosed with PRP at the American University of Beirut Medical Center between 1995 and 2010 and compare our findings with those published in the literature.

Results

Pityriasis rubra pilaris was diagnosed in 32 patients (16 males, 16 females). Age of onset ranged between 2.5 and 70 years. The majority of patients (n = 15) were classified as type I (47%) followed by type III (n = 9, 28%) and type IV (n = 6, 19%). Based on treatment responses, retinoids appear to be very effective in our population as all patients treated with isotretinoin or acitretin had excellent response. In addition to checkerboard alternating orthokeratosis/parakeratosis, which was observed in 31 cases, interesting features, including the presence of follicular plugging in all 21 cases in which follicles were available for examination, eosinophils in 12 cases, and focal acantholysis in three cases were observed.

Conclusions

Features of patients with PRP in our study are generally comparable to those published in the literature, with minor differences. Microscopically follicular plugging, in addition to checkerboard alternating orthokeratosis/parakeratosis, may serve as clues to PRP diagnosis. The presence of eosinophils and focal acantholysis, observed in a few cases, should not exclude PRP diagnosis.
Communication, Excess Comovement and Factor Structures
Authors: Yang Baozhong
Published: October 2013

This paper develops a model in which investors communicate before trading in a general equilibrium. Investors repeatedly communicate in a social network but have limited knowledge of the network structure and thus do not fully realize the consequences of their communication and belief updating. As a result, asset returns contain excess comovement and more concentrated factor structures than fundamental values do. The model generates testable empirical predictions that are consistent with the empirical literature on excess comovement in asset returns.
A single amino acid residue controls ROS production in the respiratory Complex I from Escherichia coli
Authors: Knuuti Juho , Belevich Galina , Sharma Vivek , Bloch Dmitry A. , Verkhovskaya Marina
Published: October 2013

Reactive oxygen species (ROS) production by respiratory Complex I from Escherichia coli was studied in bacterial membrane fragments and in the isolated and purified enzyme, either solubilized or incorporated in proteoliposomes. We found that the replacement of a single amino acid residue in close proximity to the nicotinamide adenine dinucleotide (NADH)‐binding catalytic site (E95 in the NuoF subunit) dramatically increases the reactivity of Complex I towards dioxygen (O2). In the E95Q variant short‐chain ubiquinones exhibit strong artificial one‐electron reduction at the catalytic site, also leading to a stronger increase in ROS production. Two mechanisms can contribute to the observed kinetic effects: (a) a change in the reactivity of flavin mononucleotide (FMN) towards dioxygen at the catalytic site, and (b) a change in the population of the ROS‐generating state. We propose the existence of two (closed and open) states of the NAD+‐bound enzyme as one feature of the substrate‐binding site of Complex I. The analysis of the kinetic model of ROS production allowed us to propose that the population of Complex I with reduced FMN is always low in the wild‐type enzyme even at low ambient redox potentials, minimizing the rate of reaction with O2 in contrast to E95Q variant.
Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes
Authors: Rudshteyn Benjamin , Castillo Álvaro , Ghogare Ashwini A. , Liebman Joel F. , Greer Alexander
Published: October 2013

Photobiologic and synthetic versatility of hydrazones has not yet been established with 1O2 as a route to commonly encountered nitrosamines. Thus, to determine whether the “parent” reaction of formalhydrazone and 1O2 leads to facile C=N bond cleavage and resulting nitrosamine formation, we have carried out CCSD(T)//DFT calculations and analyzed the energetics of the oxidation pathways. A [2 + 2] pathway occurs via diradicals and formation of 3‐amino‐1,2,3‐dioxazetidine in a 16 kcal/mol−1 process. Reversible addition or physical quenching of 1O2 occurs either on the formalhydrazone carbon for triplet diradicals at 2–3 kcal mol−1, or on the nitrogen (N(3)) atom forming zwitterions at ~15 kcal/mol−1, although the quenching channel by charge‐transfer interaction was not computed. The computations also predict a facile conversion of formalhydrazone and 1O2 to hydroperoxymethyl diazene in a low‐barrier ‘ene’ process, but no 2‐amino‐oxaziridine‐O‐oxide (perepoxide‐like) intermediate was found. A Benson‐like analysis (group increment calculations) on the closed‐shell species are in accord with the quantum chemical results.
Intergenerational transmission of neighbourhood poverty: an analysis of neighbourhood histories of individuals
Authors: van Ham Maarten , Hedman Lina , Manley David , Coulter Rory , Östh John
Published: October 2013

The extent to which socioeconomic (dis)advantage is transmitted between generations is receiving increasing attention from academics and policymakers. However, few studies have investigated whether there is a spatial dimension to this intergenerational transmission of (dis)advantage. Drawing on the concept of neighbourhood biographies, this study contends that there are links between the places individuals live with their parents and their subsequent neighbourhood experiences as independent adults. Using individual‐level register data tracking the whole Stockholm population from 1990 to 2008, and bespoke neighbourhoods, this study is the first to use sequencing techniques to construct individual neighbourhood histories. Through visualisation methods and ordered logit models, we demonstrate that the socioeconomic composition of the neighbourhood children lived in before they left the parental home is strongly related to the status of the neighbourhood they live in 5, 12 and 18 years later. Children living with their parents in high poverty concentration neighbourhoods are very likely to end up in similar neighbourhoods much later in life. The parental neighbourhood is also important in predicting the cumulative exposure to poverty concentration neighbourhoods over a long period of early adulthood. Ethnic minorities were found to have the longest cumulative exposure to poverty concentration neighbourhoods. These findings imply that for some groups, disadvantage is both inherited and highly persistent.
Workflow For Creating a Simulation Ready Virtual Population For Finite Element Modeling
Authors: Genc Kerim O. , Segars Paul , Cockram Steve , Thompson Dane , Horner Marc , Cotton Ross , Young Philippe
Published: October 2013

Three dimensional image-based meshing of multipart structures from medical scan data continues to reveal exciting new possibilities for the application of simulation techniques to a wide range of biomedical problems. However, significant challenges to creating a population of simulation compatible models still exist. These include: 1) dataset availability—due to privacy rules and cost, very few readily available dataset repositories of human phantoms exist; 2) segmentation difficulty—segmentation of scan datasets is extremely man-hour intensive. Effort is often measured by months to years for a single model; 3) clean CAD model extraction—the faceted volumetric meshes and CAD geometry must contain conformal face mapping between touching objects. Since traditional part-by-part meshing approaches risk gaps or overlap between adjacent parts, manual and time consuming repair may be required. This paper demonstrates a potential solution to these challenges through a fast and efficient workflow that begins with newly available anatomical geometries, and culminates in a solved multi-object computational simulation. Using the new series of 4D extended cardiac-torso (XCAT) phantoms created by Segars et al., we use ScanIP (Simpleware Ltd., Exeter, UK) to convert these datasets into multi-object simulation ready geometry files that are imported into HFSS (ANSYS Inc., Canonsburg, PA) for EM simulation and analysis.
Low but Sufficient Anidulafungin Exposure in Critically Ill Patients
Authors: van Wanrooy Marjolijn J. P. , Rodgers Michael G. G. , Uges Donald R. A. , Arends Jan P. , Zijlstra Jan G. , van der Werf Tjip S. , Kosterink Jos G. W. , Alffenaar Jan-Willem C.
Published: October 2013

The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive
Candida
infection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of the
Candida
species were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (
C
max
), and minimum concentration of drug in plasma (
C
min
) were 69.8 ± 24.1 mg · h/liter, 4.7 ± 1.4 mg/liter, and 2.2 ± 0.8 mg/liter, respectively. The MIC values of all cultured
Candida
species were below the EUCAST MIC breakpoints. The exposure to anidulafungin in relation to the MIC that was determined appeared sufficient in all patients. The anidulafungin exposure was low in our critically ill patients. However, combined with the low MICs of the isolated
Candida
strains, the lower exposure observed in comparison to the exposure in the general patient population resulted in favorable AUC/MIC ratios, based on EUCAST data. No correlation was observed between anidulafungin exposure and disease severity or plasma protein concentrations. In patients with less-susceptible
Candida albicans
or
glabrata
strains, we recommend considering determining the anidulafungin exposure to ensure adequate exposure. (This trial has been registered at ClinicalTrials.gov under registration no. NCT01047267.)