bluuebunny/crossref_metadata_2025 huggingface dataset:
Azilian Harpoons
Authors: Thompson M. W.
Published: February 2015

It is convenient to begin this study of Azilian harpoons by first considering the Magdalenian harpoons of northern Spain. The two Basque sites of Aitzbitarte, a few miles within the Spanish side of the frontier, and Isturitz, not many miles within the French side of the frontier, are useful in delimiting the Spanish area from the point of view of the fauna. At Aitzbitarte, Harlé (1908) found a great predominance of red deer with one or two odd fragments of reindeer antler, whereas the well-known excavations by St. Périer (1936) at Isturitz showed a great preponderance of reindeer in conformity with other sites in the Pyrenees. The other occurrences in the three east Spanish provinces agree with that at Aitzbitarte (for instance, at Valle, Lorenzo Sierra, 1908, gives the ratio of antler fragments as red deer to reindeer: 73–1). Judged by the fauna, therefore, the modern political frontier corresponds roughly to the limit of the effective penetration of the reindeer westward, and consequently to the line of demarcation between harpoon-heads made respectively from red deer and reindeer antler.

The subdivision of the Magdalenian deposits in north Spain has never been satısfactorily resolved, and they have obstinately refused to conform to the French sequence. The main difficulty has been the lack of stratified sites; only Cueto de la Mina has yielded three layers; and two or three other caves have given two layers. Nevertheless two stages, an earlier one without and a later one with harpoons have been clearly distinguished (Breuil and Obermaier, 1936, 165–70, 192–4). Although no stratigraphical division of this later stage is possible, a number of interesting points arise from a typological study of the known harpoons.
The First Waggons and Carts—from the Tigris to the Severn
Authors: Childe V. Gordon
Published: February 2015

At the end of the 12th century A.D. Henry II sent a substantial portion of the provisions and gear for his invasion of Ireland from Abingdon and Oxford to Bristol by cart. At the beginning of the 12th century B.C. a migrating horde from the north conveyed its household goods, women and children to the frontiers of Egypt in ox carts. No doubt the wide alluvial plains of Hither Asia, even before goats and charcoal-burners had stripped them of their parkland vegetation, were more congenial to the use of wheeled vehicles for long distance transport than the temperate forests of Britain and Cis-Alpine Europe. Still even in Asia, I suspect, the first economic use of wheeled vehicles was for the carriage of bulky foodstuffs from the fields, where they were grown, to the settlements, where they were stored and consumed, and of farmyard manure in the opposite direction. It was in this way by allowing a larger population to be fed at a single centre that the invention of the wheel contributed to the Urban Revolution in Mesopotamia. (In Egypt, where all cultivable land lies close to the Nile, boats took the place of carts).
Excavations at Little Woodbury
Authors: Brailsford John
Published: February 2015

While examining the pottery from Little Woodbury in 1939–40, Professor Hawkes observed that the critical pottery from the lower filling of the Ditch ‘DA’ was so sparse as to be useless for comparative purposes. On his suggestion, the Council of the Prehistoric Society decided that a substantial section of the Ditch should be cleared for the purpose of obtaining additional material from the primary filling, and in the spring of 1947 it became possible to put this project into effect. The work was superintended by Mr J. W. Brailsford and Professor Stuart Piggott and Mrs C. M. Piggott, with the assistance of Mrs M. F. Brailsford and members of the Archaeological Society of Bishop Wordsworth's School, Salisbury. The Prehistoric Society is indebted to the landowner, Mr F. H. T. Jervoise, F.S.A., for permission to carry out the excavation, and to his tenant, Mr Tilley, for the interest and cooperation which he showed throughout.

Two ten-foot lengths of the Ditch ‘DA’ were cleared, in the northern sector, Pl. XXIV lower (inset). Significant finds of pottery and other objects were recovered from all levels of the filling, though it was confirmed that layers ‘A’ to ‘C’ were very poor in archaeological material. The pottery is included with that from the pre-war excavation in the Pottery Report, and the small finds are described in the general report on small finds (Part V).

Reports on the animal bones by Dr F. C. Fraser, of the Dept. of Zoology, British Museum (Natural History), and on the non-marine mollusca by Mr A. E. Ellis of Epsom College are appended to this note.
The Levalloisian Industries of Egypt
Authors: Caton-Thompson Gertrude
Published: February 2015

Within the past few years the multiplication in the Egyptian Nile Valley and adjoining desert of stone industries with Levalloisian technical characters or affinities, has suggested to me that a review of the evidence about them—geological, chronological and typological—might be of some momentary value pending the resumption in a post-war world of field-work in palaeolithic studies.

Even without the perhaps beneficial interruption to them of the past six years, it was already, I think, becoming apparent before the war that the periodic stock-taking of world prehistory of rather a drastic kind was again due. It may make a clearance of several current doctrines and give others a rest. Among the latter I should myself like to number the overworked conception of culture-contact to account for modifications and new introductions within a given stone industry. Culture-contact may, I concede, have occasionally occurred in rare geographical passage-areas—Palestine is perhaps one of them, the Iberian peninsula another. But I doubt in general if, on the simple level of the Old Stone Age, we are justified in readily assuming that the industrial culture of one group was perceptibly affected by another until late in palaeolithic prehistory.
The Bronze Age Round Barrows of Wessex
Authors: Grinsell L. V.
Published: February 2015

The area covered by this survey, which epitomizes the writer's work on Wessex barrows since 1929, is limited on the west by a line drawn from Weston-super-Mare to Bridport, on the east by a line drawn from Dorking to Arundel, on the north roughly by the northern limit of the chalk downs south of the Thames, and on the south by the sea. It encloses the great majority of bell, disc, and saucer barrows, all of which appear to be expressions of Piggott's Wessex Bronze Age culture. It should be noted however that elements of this culture are found outside the area dealt with, notably at various places to the north-east. Nearly all of these are so close to the Icknield Way as to make it certain that this was the means of communication linking the one with the other. Another, though less important, extension of the Wessex Bronze Age culture is represented by a few sites, some of them doubtful, within a short distance of the course of the Upper Thames, and it is probable that the river was the means of communication used.

Here it is well to point out the respects in which the boundaries of Bronze Age Wessex, as determined by my own distribution-maps of barrows, differ from those adopted in the O.S. Map of Neolithic Wessex, and by Mr Stuart Piggott in his recent paper, ‘The Early Bronze Age in Wessex.’
The Upper Palaeolithic in the Light of Recent Discovery
Authors: Garrod D. A. E.
Published: February 2015

The last twelve years have seen a new impetus given to prehistoric studies by the multiplication of researches outside Europe. Excavations in Africa, the Near East, Asiatic Russia and China have opened up a new field for speculation, and at the same time have revealed the unsuspected complexity of many problems which to De Mortillet and other pioneers seemed relatively simple. Gone for ever is the straightforward succession of Palaeolithic cultures from Chellian to Magdalenian as laid down in the Musée Préhistorique. Even as early as 1912, when Breuil produced his classic paper on the subdivisions of the Upper Palaeolithic its foundations were sapped, and the discoveries of the last decade have merely completed its demolition as a system of world-wide application.

I need not insist that De Mortillet's scheme, as corrected by Breuil, who first pointed out the true position of the Aurignacian in western Europe, was the best that could be devised given the very incomplete information, relating to a very limited area, possessed by workers at that date. The fault of De Mortillet's disciples lay in their canonisation of a system which could only be applied locally, and which in any case contained enormous gaps.
The Antler Maceheads Dating Project
Authors: Loveday R. , Gibson A. , Marshall P. D. , Bayliss A. , Ramsey C. Bronk , van der Plicht H.
Published: February 2015

This paper reports the first examples of direct radiocarbon measurements from antler maceheads, demonstrating that both the middle Thames specimens and those from northern Britain date to the second half of the 4th millennium cal BC. This suggests a degree of contemporaneity between riverine activity in the south and ‘prestige’ burial in the north, although the possibility that this is a function of the radiocarbon calibration curve cannot be discounted. The possibility that lattice decorated maceheads can be regarded as prototypes for the Maesmore series of fine stone maceheads is considered but the failure of two out of three decorated examples to produce radiocarbon determinations means that the debate cannot yet be settled.
Resource Dependence and Human Capital Investment in China
Authors: Zhan Jing Vivian , Duan Haiyan , Zeng Ming
Published: February 2015

Countries endowed with rich natural resources such as fuels and minerals often fall behind in human development. Does resource endowment hamper human capital development in China, a country that hosts rich resources in many of its regions? Through cross-regional and longitudinal statistical analysis and field research in selected mining areas, this study finds that resource dependence reduces government expenditure on human capital-enhancing public goods including education and health care. The local economic structure and reduced demand for labour, the shifting of government responsibilities onto mining enterprises, and the myopia of local residents and officials all discourage the local governments in resource-rich regions from investing in human capital.
Seed dormancy is a dynamic state: variable responses to pre- and post-shedding environmental signals in seeds of contrastingArabidopsisecotypes
Authors: Huang Ziyue , Ölçer-Footitt Hulya , Footitt Steven , Finch-Savage William E.
Published: February 2015

Seeds have evolved to be highly efficient environmental sensors that respond not only to their prevailing environment, but also their environmental history, to regulate dormancy and the initiation of germination. In the present work we investigate the combined impact of a number of environmental signals (temperature, nitrate, light) during seed development on the mother plant, during post-shedding imbibition and during prolonged post-shedding exposure in both dry and imbibed states, simulating time in the soil seed bank. The differing response to these environments was observed in contrasting winter (Cvi, Ler) and summer (Bur) annualArabidopsisecotypes. Results presented show that environmental signals both pre- and post-shedding determine the depth of physiological dormancy and therefore the germination response to the ambient environment. The ecotype differences in seed response to ambient germination conditions are greatly enhanced by seed maturation in different environments. Further variation in response develops following shedding when seeds do not receive the full complement of environmental signals required for germination and enter the soil seed bank in either dry or imbibed states. Species seed dormancy characteristics cannot therefore be easily defined, as seed dormancy is a dynamic state subject to within-species adaptation to local environments.
IMPLICATIONS OF MACHLUP’S INTERPRETATION OF MISES’S EPISTEMOLOGY
Authors: Zanotti Gabriel J. , Cachanosky Nicolás
Published: February 2015

We argue that Fritz Machlup’s (1995) interpretation of Mises’s epistemology is at least as, if not more, plausible than Murray N. Rothbard’s (1957) interpretation. The implications of Machlup’s interpretation of Mises and of Austrian epistemology affect Austrians and non-Austrians in their academic interaction. Machlup’s interpretation shows that Austrian epistemology is well grounded in post-Popperian epistemology and that most criticisms of Austrian economics based on its aprioristic character are misplaced. Furthermore, Machlup’s interpretation provides us with a setting to rebuild the academic interaction between Austrians and non-Austrians that was characteristic of the early twentieth century.
Effects of Metabolic Syndrome on Language Functions in Aging
Authors: Cahana-Amitay Dalia , Spiro Avron , Cohen Jason A. , Oveis Abigail C. , Ojo Emmanuel A. , Sayers Jesse T. , Obler Loraine K. , Albert Martin L.
Published: February 2015

This study explored effects of the metabolic syndrome (MetS) on language in aging. MetS is a constellation of five vascular and metabolic risk factors associated with the development of chronic diseases and increased risk of mortality, as well as brain and cognitive impairments. We tested 281 English-speaking older adults aged 55–84, free of stroke and dementia. Presence of MetS was based on the harmonized criteria (Alberti et al., 2009). Language performance was assessed by measures of accuracy and reaction time on two tasks of lexical retrieval and two tasks of sentence processing. Regression analyses, adjusted for age, education, gender, diabetes, hypertension, and heart disease, demonstrated that participants with MetS had significantly lower accuracy on measures of lexical retrieval (action naming) and sentence processing (embedded sentences, both subject and object relative clauses). Reaction time was slightly faster on the test of embedded sentences among those with MetS. MetS adversely affects the language performance of older adults, impairing accuracy of both lexical retrieval and sentence processing. This finding reinforces and extends results of earlier research documenting the negative influence of potentially treatable medical conditions (diabetes, hypertension) on language performance in aging. The unanticipated finding that persons with MetS were faster in processing embedded sentences may represent an impairment of timing functions among older individuals with MetS. (JINS, 2015, 21, 116–125)
Legalizing physician-assisted suicide and/or euthanasia: Pragmatic implications
Authors: Hudson Peter , Hudson Rosalie , Philip Jennifer , Boughey Mark , Kelly Brian , Hertogh Cees
Published: February 2015

Objective:

Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated—particularly around ethical and legal issues—and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community.

Method:

We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized.

Results:

We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered.

Significance of Results:

Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.
Applying neuroimaging to detect neuroanatomical dysconnectivity in psychosis
Authors: O'Donoghue S. , Cannon D. M. , Perlini C. , Brambilla P. , McDonald C.
Published: February 2015

This editorial discusses the application of a novel brain imaging analysis technique in the assessment of neuroanatomical dysconnectivity in psychotic illnesses. There has long been a clinical interest in psychosis as a disconnection syndrome. In recent years graph theory metrics have been applied to functional and structural imaging datasets to derive measures of brain connectivity, which represent the efficiency of brain networks. These metrics can be derived from structural neuroimaging datasets acquired using diffusion imaging whereby cortical structures are parcellated into nodes and white matter tracts represent edges connecting these nodes. Furthermore neuroanatomical measures of connectivity may be decoupled from measures of physiological connectivity as assessed using functional imaging, underpinning the need for multi-modal imaging approaches to probe brain networks. Studies to date have reported a number of structural brain connectivity abnormalities associated with schizophrenia that carry potential as illness biomarkers. Structural connectivity abnormalities have also been reported in well patients with bipolar disorder and in unaffected relatives of patients with schizophrenia. Such connectivity metrics may represent clinically relevant biomarkers in studies employing a longitudinal design of illness course in psychosis.
Aktuelles zur Niereninsuffizienz bei Diabetikern
Authors: Lindenmeyer Maja
Published: February 2015

Die diabetische Nierenerkrankung (DN) ist die häufigste Ursache einer chronischen Niereninsuffizienz. Neuere Untersuchungen zeigen, dass bei einigen Diabetikern die Ursache einer Niereninsuffizienz vielfältiger und häufig Folge einer anderen Nierenerkrankung ist, sodass gerade untypische klinische Verläufe einer genauen Abklärung bedürfen. Neben einer optimierten Blutzuckereinstellung stellt eine gute Blutdruckkontrolle einen wichtigen Therapieeckpfeiler dar. Obwohl sich die Prognose der DN in den letzten Jahren sichtlich gebessert hat, ist es auch mit neuen Therapieansätzen bisher nicht möglich, die Entwicklung einer DN zu verhindern. Es bleibt zu hoffen, dass mit einem verbesserten Verständnis der Pathophysiologie, intensiveren präklinischen und gut definierten klinischen Studien neue nephroprotektive Therapien in den nächsten Jahren verfügbar sein werden.
Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition
Authors: Nowak-Sliwinska P , Weiss A , van Beijnum J R , Wong T J , Kilarski W W , Szewczyk G , Verheul H M W , Sarna T , van den Bergh H , Griffioen A W
Published: February 2015

The angiogenesis inhibitor sunitinib is a tyrosine kinase inhibitor that acts mainly on the VEGF and PDGF pathways. We have previously shown that sunitinib is sequestered in the lysosomes of exposed tumor and endothelial cells. This phenomenon is part of the drug-induced resistance observed in the clinic. Here, we demonstrate that when exposed to light, sequestered sunitinib causes immediate destruction of the lysosomes, resulting in the release of sunitinib and cell death. We hypothesized that this photoactivation of sunitinib could be used as a vaso-occlusive vascular-targeting approach to treating cancer. Spectral properties of sunitinib and its lysosomal accumulation were measured in vitro. The human A2780 ovarian carcinoma transplanted onto the chicken chorioallantoic membrane (CAM) and the Colo-26 colorectal carcinoma model in Balb/c mice were used to test the effects of administrating sunitinib and subsequently exposing tumor tissue to light. Tumors were subsequently resected and subject to immunohistochemical analysis. In A2780 ovarian carcinoma tumors, treatment with sunitinib+light resulted in immediate specific angio-occlusion, leading to a necrotic tumor mass 24 h after treatment. Tumor growth was inhibited by 70% as compared with the control group (**P<0.0001). Similar observations were made in the Colo-26 colorectal carcinoma, where light exposure of the sunitinib-treated mice inhibited tumor growth by 50% as compared with the control and by 25% as compared with sunitinib-only-treated tumors (N≥4; P=0.0002). Histology revealed that photoactivation of sunitinib resulted in a change in tumor vessel architecture. The current results suggest that the spectral properties of sunitinib can be exploited for application against certain cancer indications.
Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death
Authors: Carriba P , Jimenez S , Navarro V , Moreno-Gonzalez I , Barneda-Zahonero B , Moubarak R S , Lopez-Soriano J , Gutierrez A , Vitorica J , Comella J X
Published: February 2015

The brains of patients with Alzheimer’s disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1M146LxAPP751sl) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells.
Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex
Authors: Iordanova Bistra , Vazquez Alberto L , Poplawsky Alexander J , Fukuda Mitsuhiro , Kim Seong-Gi
Published: February 2015

Introducing optogenetics into neurovascular research can provide novel insights into the cell-specific control of the hemodynamic response. To generalize findings from molecular approaches, it is crucial to determine whether light-activated circuits have the same effect on the vasculature as sensory-activated ones. For that purpose, rats expressing channelrhodopsin (ChR2) specific to excitatory glutamatergic neurons were used to measure neural activity, blood flow, hemoglobin-based optical intrinsic signal, and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during optogenetic and sensory stimulation. The magnitude of the evoked hemodynamic responses was monotonically correlated with optogenetic stimulus strength. The BOLD hemodynamic response function was consistent for optogenetic and sensory stimuli. The relationship between electrical activities and hemodynamic responses was comparable for optogenetic and sensory stimuli, and better explained by the local field potential (LFP) than the firing rate. The LFP was well correlated with cerebral blood flow, moderately with cerebral blood volume, and less with deoxyhemoglobin (dHb) level. The presynaptic firing rate had little impact on evoking vascular response. Contribution of the postsynaptic LFP to the blood flow response induced by optogenetic stimulus was further confirmed by the application of glutamate receptor antagonists. Overall, neurovascular coupling during optogenetic control of glutamatergic neurons largely conforms to that of a sensory stimulus.
Tat-NR2B9c Prevents Excitotoxic Neuronal Superoxide Production
Authors: Chen Yanting , Brennan-Minnella Angela M , Sheth Sunil , El-Benna Jamel , Swanson Raymond A
Published: February 2015

The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c is designed to prevent nitric oxide (NO) production by preventing postsynaptic density protein 95 (PSD-95) binding to N-methyl- D-aspartate (NMDA) receptors and neuronal nitric oxide synthase; however, PSD-95 is a scaffolding protein that also couples NMDA receptors to other downstream effects. Here, using neuronal cultures, we show that Tat-NR2B9c also prevents NMDA-induced activation of neuronal NADPH oxidase, thereby blocking superoxide production. Given that both superoxide and NO are required for excitotoxic injury, the neuroprotective effect of Tat-NR2B9c may alternatively be attributable to uncoupling neuronal NADPH oxidase from NMDA receptor activation.
Glucagon-Like Receptor 1 Agonists and DPP-4 Inhibitors: Potential Therapies for the Treatment of Stroke
Authors: Darsalia Vladimer , Larsson Martin , Nathanson David , Klein Thomas , Nyström Thomas , Patrone Cesare
Published: February 2015

During the past decades, candidate drugs that have shown neuroprotective efficacy in the preclinical setting have failed in clinical stroke trials. As a result, no treatment for stroke based on neuroprotection is available today. The activation of the glucagon-like peptide 1 receptor (GLP-1) for reducing stroke damage is a relatively novel concept that has shown neuroprotective effects in animal models. In addition, clinical studies are currently ongoing. Herein, we review this emerging research field and discuss the next milestones to be achieved to develop a novel antistroke therapy.
Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-[11C]Verapamil PET Study
Authors: Bauer Martin , Karch Rudolf , Zeitlinger Markus , Philippe Cécile , Römermann Kerstin , Stanek Johann , Maier-Salamon Alexandra , Wadsak Wolfgang , Jäger Walter , Hacker Marcus , Müller Markus , Langer Oliver
Published: February 2015

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate ( R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( VT) of ( R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.
Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG
Authors: Fischer Nicolas , Elson Greg , Magistrelli Giovanni , Dheilly Elie , Fouque Nicolas , Laurendon Amélie , Gueneau Franck , Ravn Ulla , Depoisier Jean-François , Moine Valery , Raimondi Sylvain , Malinge Pauline , Di Grazia Laura , Rousseau François , Poitevin Yves , Calloud Sébastien , Cayatte Pierre-Alexis , Alcoz Mathias , Pontini Guillemette , Fagète Séverine , Broyer Lucile , Corbier Marie , Schrag Delphine , Didelot Gérard , Bosson Nicolas , Costes Nessie , Cons Laura , Buatois Vanessa , Johnson Zoe , Ferlin Walter , Masternak Krzysztof , Kosco-Vilbois Marie
Published: February 2015

Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies.
Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway
Authors: Xing Mengtan , Yang Mingrui , Huo Wei , Feng Feng , Wei Leizhen , Jiang Wenxia , Ning Shaokai , Yan Zhenxin , Li Wen , Wang Qingsong , Hou Mei , Dong Chunxia , Guo Rong , Gao Ge , Ji Jianguo , Zha Shan , Lan Li , Liang Huanhuan , Xu Dongyi
Published: February 2015

Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct interactor of Ku. The crystal structure of PAXX is similar to those of XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive to DSB-causing agents. Moreover, epistasis analysis demonstrates that PAXX functions together with XLF in response to ionizing radiation-induced complex DSBs, whereas they function redundantly in response to Topo2 inhibitor-induced simple DSBs. Consistently, PAXX and XLF coordinately promote the ligation of complex but not simple DNA ends in vitro. Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends.
Crystal structure of VmoLac, a tentative quorum quenching lactonase from the extremophilic crenarchaeon Vulcanisaeta moutnovskia
Authors: Hiblot Julien , Bzdrenga Janek , Champion Charlotte , Chabriere Eric , Elias Mikael
Published: February 2015

A new representative of the Phosphotriesterase-Like Lactonases (PLLs) family from the hyperthermophilic crenarchaeon Vulcanisaeta moutnovskia has been characterized and crystallized. VmoLac is a native, proficient lactonase with promiscuous, low phosphotriesterase activity. VmoLac therefore represents an interesting candidate for engineering studies, with the aim of developing an efficient bacterial quorum-quenching agent. Here, we provide an extensive biochemical and kinetic characterization of VmoLac and describe the X-ray structures of the enzyme bound to a fatty acid and to its cognate substrate 3-oxo-C10 AHL (Acyl-Homoserine Lactone). The structures highlight possible structural determinants that may be involved in its extreme thermal stability (Tm = 128°C). Moreover, the structure reveals that the substrate binding mode of VmoLac significantly differs from those of its close homologues, possibly explaining the substrate specificity of the enzyme. Finally, we describe the specific interactions between the enzyme and its substrate and discuss the possible lactone hydrolysis mechanism of VmoLac.
Emergence of topological and topological crystalline phases in TlBiS2 and TlSbS2
Authors: Zhang Qingyun , Cheng Yingchun , Schwingenschlögl Udo
Published: February 2015

Using first-principles calculations, we investigate the band structure evolution and topological phase transitions in TlBiS2 and TlSbS2 under hydrostatic pressure as well as uniaxial and biaxial strain. The phase transitions are identified by parity analysis and by calculating the surface states. Zero, one and four Dirac cones are found for the (111) surfaces of both TlBiS2 and TlSbS2 when the pressure grows, which confirms trivial-nontrivial-trivial phase transitions. The Dirac cones at the "Equation missing" points are anisotropic with large out-of-plane component. TlBiS2 shows normal, topological and topological crystalline insulator phases under hydrostatic pressure, thus being the first compound to exhibit a phase transition from a topological to a topological crystalline insulator.
Ethanol extract of Remotiflori radix induces endoplasmic reticulum stress-mediated cell death through AMPK/mTOR signaling in human prostate cancer cells
Authors: Kim Aeyung , Im Minju , Ma Jin Yeul
Published: February 2015

Remotiflori radix is the root of Mosidae, which has long been used as a traditional medicine to treat chills, fever and phlegm discharge. The ethanol extract of Mosidae leaves (MLE) possesses strong antioxidant and chemopreventive activities. However, the anti-cancer effects of the Remotiflori radix have not been examined. We used the ethanol extract of Remotiflori radix (ERR) and the PC-3 and DU145 prostate cancer cell lines in this study. We found that > 100 μg/mL ERR caused dose- and time-dependent cell death. Autophagic and apoptotic cell numbers increased in a dose-dependent manner as incubation time was prolonged and LC3 punctuation, YO-PRO-1 uptake, DNA fragmentation, activation of caspases and PARP cleavage were induced. Phosphorylation of AMPK, ULK and p38 was increased after ERR treatment and the level of the ER stress marker CHOP was also elevated. AMPK knockdown dramatically blocked ERR-mediated CHOP expression and cell death, suggesting that AMPK activation and ER stress play a critical role in ERR-induced cell death. Furthermore, oral administration of ERR at 50 mg/kg efficiently suppressed tumorigenic growth of PC-3 cells with no adverse effects. These results suggest that the ERR can be used as a safe and potent alternative therapy for patients with prostate cancer.
Multi-barrier field-emission behavior in PBTTT thin films at low temperatures
Authors: Kang Evan S. H. , Kim Eunseong
Published: February 2015

We investigated the low-temperature transport mechanism for poly[2,5-bis(3-alkylthiophen-2-yl)thieno(3,2-b)thiophene] (PBTTT). The temperature-dependent transport behavior was studied by varying the drain–source electric field and gate bias. The results suggest that low-temperature charge transport is dominated by direct tunneling at low electric fields, while field emission is prevailing for high electric fields with high carrier densities. However, the obtained barrier heights are remarkably greater than expected in a conventional field emission. We propose a simplified model of field emission through quasi-one-dimensional path with multiple barriers which shows good agreement with the results more clearly. Field emission across the domain boundaries may assist in overcoming the transport barriers induced by the interchain disorder, which results in the weak temperature dependence of conductivities and nonlinear current–voltage relation at low temperatures.
Dependence of structure and temperature for lithium-rich layered-spinel microspheres cathode material of lithium ion batteries
Authors: Wang Di , Yu Ruizhi , Wang Xianyou , Ge Long , Yang Xiukang
Published: February 2015

Homogeneous lithium-rich layered-spinel 0.5Li2MnO3·0.5LiMn1/3Ni1/3Co1/3O2 microspheres (~1 μm) are successfully prepared by a solvothermal method and subsequent high-temperature calcinations process. The effects of temperature on the structure and performance of the as-prepared cathode material are systemically studied by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), galvanostatical charge/discharge and electrochemical impedance spectra. The results show that a spinel Li4Mn5O12 component can be controllably introduced into the lithium-rich layered material at 750°C. Besides, it has been found that the obtained layered-spinel cathode material represents excellent electrochemical characteristics. For example, it can deliver a high initial discharge capacity of 289.6 mAh g−1 between 2.0 V and 4.6 V at a rate of 0.1 C at room temperature and a discharge capacity of 144.9 mAh g−1 at 5 C and 122.8 mAh g−1 even at 10 C. In addition, the retention of the capacity is still as high as 88% after 200 cycles, while only 79.9% for the single-phase layered material. The excellent electrochemical performance of the as-prepared cathode material can probably be attributed to the hybrid structures combining a fast Li-ion diffusion rate of 3D spinel Li4Mn5O12 phase and a high capacity of the layered Li-Mn-Ni-Co-O component.
Worldwide variations in artificial skyglow
Authors: Kyba Christopher C. M. , Tong Kai Pong , Bennie Jonathan , Birriel Ignacio , Birriel Jennifer J. , Cool Andrew , Danielsen Arne , Davies Thomas W. , Outer Peter N. den , Edwards William , Ehlert Rainer , Falchi Fabio , Fischer Jürgen , Giacomelli Andrea , Giubbilini Francesco , Haaima Marty , Hesse Claudia , Heygster Georg , Hölker Franz , Inger Richard , Jensen Linsey J. , Kuechly Helga U. , Kuehn John , Langill Phil , Lolkema Dorien E. , Nagy Matthew , Nievas Miguel , Ochi Nobuaki , Popow Emil , Posch Thomas , Puschnig Johannes , Ruhtz Thomas , Schmidt Wim , Schwarz Robert , Schwope Axel , Spoelstra Henk , Tekatch Anthony , Trueblood Mark , Walker Constance E. , Weber Michael , Welch Douglas L. , Zamorano Jaime , Gaston Kevin J.
Published: February 2015

Despite constituting a widespread and significant environmental change, understanding of artificial nighttime skyglow is extremely limited. Until now, published monitoring studies have been local or regional in scope and typically of short duration. In this first major international compilation of monitoring data we answer several key questions about skyglow properties. Skyglow is observed to vary over four orders of magnitude, a range hundreds of times larger than was the case before artificial light. Nearly all of the study sites were polluted by artificial light. A non-linear relationship is observed between the sky brightness on clear and overcast nights, with a change in behavior near the rural to urban landuse transition. Overcast skies ranged from a third darker to almost 18 times brighter than clear. Clear sky radiances estimated by the World Atlas of Artificial Night Sky Brightness were found to be overestimated by ~25%; our dataset will play an important role in the calibration and ground truthing of future skyglow models. Most of the brightly lit sites darkened as the night progressed, typically by ~5% per hour. The great variation in skyglow radiance observed from site-to-site and with changing meteorological conditions underlines the need for a long-term international monitoring program.
A proof-of-principle study of multi-site real-time functional imaging at 3T and 7T: Implementation and validation
Authors: Baecke Sebastian , Lützkendorf Ralf , Mallow Johannes , Luchtmann Michael , Tempelmann Claus , Stadler Jörg , Bernarding Johannes
Published: February 2015

Real-time functional Magnetic Resonance Imaging (rtfMRI) is used mainly for neurofeedback or for brain-computer interfaces (BCI). But multi-site rtfMRI could in fact help in the application of new interactive paradigms such as the monitoring of mutual information flow or the controlling of objects in shared virtual environments. For that reason, a previously developed framework that provided an integrated control and data analysis of rtfMRI experiments was extended to enable multi-site rtfMRI. Important new components included a data exchange platform for analyzing the data of both MR scanners independently and/or jointly. Information related to brain activation can be displayed separately or in a shared view. However, a signal calibration procedure had to be developed and integrated in order to permit the connecting of sites that had different hardware and to account for different inter-individual brain activation levels. The framework was successfully validated in a proof-of-principle study with twelve volunteers. Thus the overall concept, the calibration of grossly differing signals and BCI functionality on each site proved to work as required. To model interactions between brains in real-time, more complex rules utilizing mutual activation patterns could easily be implemented to allow for new kinds of social fMRI experiments.
From Polysaccharides to Starbons®
Authors: Budarin Vitaliy L. , Shuttleworth Peter S. , White Robin J. , Clark James H.
Published: February 2015

Many commercially employed carbon materials are typically hydrophobic, chemically inert and microporous. Therefore, with an eye to the future, there is a need to develop new, carbon-based porous materials, the properties of which can be easily tuned to address the catalytic and separation challenges of future energy and chemical provision schemes (e.g. the Methanol Economy or Biorefinery schemes). In this regard, the synthesis of such materials must be conducted in as sustainable a manner as possible, ideally providing a flexible platform upon which to tailor properties such as functionality, porosity at different length scales (e.g. micro-, meso-, and macroporosity), hydrophilic character and macrophology (e.g. monoliths, particulates, etc.) amongst others. This chapter therefore aims to introduce one top-down synthetic approach to this end, the Starbon® materials concept. An accompanying material development history will be provided followed by a review of the variety of interesting functionally rich, highly mesoporous, high surface area (e.g. > 0.5 cm3 g–1; > 200 m2 g–1) carbonaceous materials that are accessible via the development of porous polysaccharide-derived materials and their subsequent carbonaceous derivatives. The chapter intends to provide the reader with an overview of the exciting opportunities that are open to the carbon materials chemist based on the discussed synthetic approach.
Porosity Characterisation of Carbon Materials
Authors: Weber Jens
Published: February 2015

Porous carbons have a tremendously high importance in a number of applications, ranging from adsorption technology to energy storage. It is necessary to understand the porosity characteristics of carbons in order to analyse their performance in any technology that relies on the presence of pores. The chapter will present a definition of porosity and related parameters such as specific surface area, pore volume and pore-size distribution. Basic methods of porosity characterisation (e.g. gas adsorption/desorption, scattering methods, microscopy) are discussed and introduced to the reader in the context of carbon-based materials. Additional and emerging techniques that are useful in the characterisation of such materials are also introduced in the context of providing new structural insights.
Application of scanning angle Raman spectroscopy for determining the location of buried polymer interfaces with tens of nanometer precision
Authors: Damin Craig A. , Nguyen Vy H. T. , Niyibizi Auguste S. , Smith Emily A.
Published: February 2015

Application of near-infrared scanning angle Raman spectroscopy for determinations of total thickness and buried interface location for thin, bilayer films of polystyrene and polycarbonate.
Rapid separation of hexabromocyclododecane diastereomers using a novel method combining convergence chromatography and tandem mass spectrometry
Authors: Mullin Lauren , Burgess Jennifer A. , Jogsten Ingrid Ericson , Geng Dawei , Aubin Andy , van Bavel Bert
Published: February 2015

Analysis of the brominated flame retardant hexabromocyclododecane (HBCDD) is characterized by the separation of its three predominant diastereomers.
Construction of anti-parallel G-quadruplexes through sequential templated click
Authors: Bonnet Romaric , Lavergne Thomas , Gennaro Béatrice , Spinelli Nicolas , Defrancq Eric
Published: February 2015

Biologically relevant anti-parallel DNA G-quadruplexes were constrained and stabilised onto addressable cyclopeptide scaffolds through sequential oxime and CuAAc reactions.
A high-temperature supramolecular-based switchable dielectric material with electrical bistability between high and low dielectric states
Authors: Chen Cheng , Wang Fang-Fang , Zhang Yi , Ye Qiong , Ye Heng-Yun , Fu Da-Wei
Published: February 2015

One new hybrid supramolecular-based phase transition compound TAPC containing macrocycle stator with electrical bistability between high and low dielectric states has been prepared.
Tailoring the optical properties of lanthanide phosphors: prediction and characterization of the luminescence of Pr3+-doped LiYF4
Authors: Ramanantoanina Harry , Urland Werner , Herden Benjamin , Cimpoesu Fanica , Daul Claude
Published: February 2015

We present the first principle modelling of the luminescence spectra of LiYF4:Pr3+, complementing the insight with data that are not available by experimental line.
Capacitive charging and desalination dynamics of a packed-bed reactor
Authors: Li Mengying , Hu Howard H. , Bau Haim H.
Published: February 2015

We study theoretically the charging dynamics of a packed-bed reactor comprising percolating granular porous aggregates with finite electric conductivities.
Oxygen-assisted water partial dissociation on copper: a model study
Authors: Wang Ying-Qi , Yan Li-Fen , Wang Gui-Chang
Published: February 2015

The strong acid–base interaction, corresponding to the high activity in water dissociation.
Tailored interface and enhanced elastic modulus in epoxy-based composites in presence of branched poly(ethyleneimine) grafted multiwall carbon nanotubes
Authors: Rohini Rani , Bose Suryasarathi
Published: February 2015

Tailored interface and enhanced elastic modulus in epoxy based composites in the presence of branched poly(ethyleneimine) grafted multiwall carbon nanotubes.
Lead-free antiferroelectric: xCaZrO3-(1 − x)NaNbO3 system (0 ≤ x ≤ 0.10)
Authors: Shimizu Hiroyuki , Guo Hanzheng , Reyes-Lillo Sebastian E. , Mizuno Youichi , Rabe Karin M. , Randall Clive A.
Published: February 2015

Crystal chemistry modification stabilized antiferroelectricity in NaNbO3-based polycrystalline ceramics.
Energy-efficient desalination by forward osmosis using responsive ionic liquid draw solutes
Authors: Cai Yufeng , Shen Wenming , Wei Jing , Chong Tzyy Haur , Wang Rong , Krantz William B. , Fane Anthony G. , Hu Xiao
Published: February 2015

New thermally responsive ionic liquid draw solutes generate high flux against seawater with substantially reduced electrical energy consumption.
Differential proteome–metabolome profiling of YCA1-knock-out and wild type cells reveals novel metabolic pathways and cellular processes dependent on the yeast metacaspase
Authors: Ždralević Maša , Longo Valentina , Guaragnella Nicoletta , Giannattasio Sergio , Timperio Anna Maria , Zolla Lello
Published: February 2015

A combined proteomic and metabolomic approach revealed new non-apoptotic roles of the metacaspaseYCA1gene inSaccharomyces cerevisiae, highlighting its involvement in the cell metabolism and stress response.
Selective chemosensing of spermidine based on fluorescent organic nanoparticles in aqueous media via a Fe3+displacement assay
Authors: Chopra Shweta , Singh Jasminder , Kaur Harpreet , Singh Harpreet , Singh Narinder , Kaur Navneet
Published: February 2015

An organic–inorganic nanohybrid complex of a tripodal complex was used for the selective determination of spermidine and its use in real sample analysis.
The improved electrochemical performance of cross-linked 3D graphene nanoribbon monolith electrodes
Authors: Vineesh Thazhe Veettil , Alwarappan Subbiah , Narayanan Tharangattu N.
Published: February 2015

A novel 3D electrode using graphene nanoribbons (GNRs) is constructed using chemical cross-linking of 2D GNRs. The 3D electrode developed in this work outperformed its 2D counterpart in all the electrochemical reactions.