bluuebunny/crossref_metadata_2025 huggingface dataset:
“Amphibious Power”: The Law of Wreck, Maritime Customs, and Sovereignty in Richelieu's France
Authors: Trivellato Francesca
Published: October 2015

The precise length of territorial waters, the swath of sea along the coast over which a state extended sovereign control, remained an object of debate during the seventeenth century. Some authors still adhered to the 100-mile boundary established by medieval glossators, whereas others embraced the so-called cannon-shot rule that set the limit to the reach of a shot fired from the land. But no one disputed the existence of territorial waters. Even Hugo Grotius (1583–1645), then Europe's greatest champion of the freedom of the sea, followed Roman law in conceding that a state could exert its sovereignty over littoral waters or inlets in a shoreline (diverticula maris). This rare point of agreement between theorists ofmare liberum(the free sea) and defenders ofmare clausum(the closed sea) did not eliminate all controversies concerning the governance of coastal waters. Particularly contentious were domestic and international disputes over the property rights on the cargo of sunken ships. What sources of law governed the assignment of ownership of salvaged wreckages? Who was entitled to compensation for assisting in the recovery efforts? And how did legal claims square with political maneuvering in domestic and interstate disputes over wreckages?
Resource convertibility and ordered commutative monoids
Authors: FRITZ TOBIAS
Published: October 2015

Resources and their use and consumption form a central part of our life. Many branches of science and engineering are concerned with the question of which given resource objects can be converted into which target resource objects. For example, information theory studies the conversion of a noisy communication channel instance into an exchange of information. Inspired by work in quantum information theory, we develop a general mathematical toolbox for this type of question. The convertibility of resources into other ones and the possibility of combining resources is accurately captured by the mathematics of ordered commutative monoids. As an intuitive example, we consider chemistry, where chemical reaction equations such as\mathrm{2H_2 + O_2} \lra \mathrm{2H_2O,}are concerned both with a convertibility relation ‘→’ and a combination operation ‘+.’ We study ordered commutative monoids from an algebraic and functional-analytic perspective and derive a wealth of results which should have applications to concrete resource theories, such as a formula for rates of conversion. As a running example showing that ordered commutative monoids are also of purely mathematical interest without the resource-theoretic interpretation, we exemplify our results with the ordered commutative monoid of graphs.

While closely related to both Girard's linear logic and to Deutsch's constructor theory, our framework also produces results very reminiscent of the utility theorem of von Neumann and Morgenstern in decision theory and of a theorem of Lieb and Yngvason on the foundations of thermodynamics.

Concerning pure algebra, our observation is that some pieces of algebra can be developed in a context in which equality is not necessarily symmetric, i.e. in which the equality relation is replaced by an ordering relation. For example, notions like cancellativity or torsion-freeness are still sensible and very natural concepts in our ordered setting.
Characteristics and safety of interventions and procedures performed during catheterisation of patients with congenital heart disease: early report from the national cardiovascular data registry
Authors: Holzer Ralf , Beekman Robert , Benson Lee , Bergersen Lisa , Jayaram Natalie , Jenkins Kathy , Kennedy Kevin , Moore John , Ringel Richard , Rome Jonathan , Vincent Robert , Martin Gerard R.
Published: October 2015

Objectives

The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry.

Background

The IMproving Paediatric and Adult Congenital Treatment– registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013.

Methods

Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the ‘core’ IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis.

Results

During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types – isolated or in combination with other procedures – were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory.

Conclusions

The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.
Architecture of the longue durée: Vittorio Gregotti’s reading of the territory of architecture
Authors: Vujicic Lejla
Published: October 2015

In the post-Second World War period, Italian architects opened up a debate on the role of history and time in architectural discourse that resulted in multiple interpretations of historical time in their work. Vittorio Gregotti, one of the main protagonists of the discussion, offered an interpretation of time based on an assemblage of intellectual tendencies, from phenomenology to structuralism and the history of the longue durée. This paper traces ideas that Gregotti developed in his less known and as-yet un-translated texts such as Il territiorio dell’architettura from 1966 as well as in his project for the University of Calabria from 1972. In these, Gregotti makes an original contribution to the problem of history in relationship to urban and natural environments.
Large Area Cryo-Planing of Vitrified Samples Using Broad-Beam Ion Milling
Authors: Chang Irene Y. T. , Joester Derk
Published: October 2015

On account of its excellent resolution and high throughput, cryoSEM imaging has recently seen resurgence. In this work, we report on the development of cryogenic triple ion gun milling (CryoTIGM™), a broad ion beam milling technique for cryo-planing of vitrified, “frozen-hydrated” specimens. We find that sections prepared with CryoTIGM™ are smooth over exceptionally large areas (~700,000 µm2), and reveal ultrastructural details in similar or better quality than freeze-fractured samples.
Wideband dipole antenna using multi-mode resonance concept
Authors: Lu Wen-Jun , Zhu Lei , Tam Kam Weng , Zhu Hong-Bo
Published: October 2015

Wideband dipole antennas are proposed using the multi-mode resonance concept. By symmetrically introducing one-pair or two-pair of stubs at the nulls of current distribution of the second odd-order mode, two radiation modes are excited in a single, center-fed dipole resonator. Using these stubs, the second odd-order mode gradually moves down to its first counterpart, resulting to achieve a wideband radiation with two resonances. Prototype antennas are then fabricated to experimentally validate the design approach. Compared with a reference dipole with a bandwidth of 17%, the proposed dipole's bandwidth can be effectively increased to 49.7%.
Biodegradable magnesium/iron batteries with polycaprolactone encapsulation: A microfabricated power source for transient implantable devices
Authors: Tsang Melissa , Armutlulu Andac , Martinez Adam W. , Allen Sue Ann Bidstrup , Allen Mark G.
Published: October 2015

This study presents the design, fabrication, and testing of biodegradable magnesium/iron batteries featuring polycaprolactone (PCL) as a packaging and functional material. The use of PCL encapsulation minimized the electrochemical cell volume and supported longer discharge lifetimes and higher discharge rates than state-of-the-art biodegradable batteries. Specifically, the electrodes were separated and insulated by a 5 µm-thick PCL layer that served as both a battery packaging material and a permeable coating for physiological solution to penetrate and activate the battery. A systematic investigation of the electrode size, discharge rates, electrolyte selection, and polymeric coating revealed the critical reactions and phenomena governing the performance of the Mg-based biodegradable batteries. Comparison with previous reports on biodegradable batteries and medical-grade non-degradable lithium-ion batteries demonstrated the superior performance of PCL-coated Mg/Fe batteries at these size scales, which exhibited an energy density of 694 Wh kg−1 and a total volume of 0.02 cm3.
Wall mechanics and exocytosis define the shape of growth domains in fission yeast
Authors: Abenza Juan F. , Couturier Etienne , Dodgson James , Dickmann Johanna , Chessel Anatole , Dumais Jacques , Salas Rafael E. Carazo
Published: October 2015

The amazing structural variety of cells is matched only by their functional diversity, and reflects the complex interplay between biochemical and mechanical regulation. How both regulatory layers generate specifically shaped cellular domains is not fully understood. Here, we report how cell growth domains are shaped in fission yeast. Based on quantitative analysis of cell wall expansion and elasticity, we develop a model for how mechanics and cell wall assembly interact and use it to look for factors underpinning growth domain morphogenesis. Surprisingly, we find that neither the global cell shape regulators Cdc42-Scd1-Scd2 nor the major cell wall synthesis regulators Bgs1-Bgs4-Rgf1 are reliable predictors of growth domain geometry. Instead, their geometry can be defined by cell wall mechanics and the cortical localization pattern of the exocytic factors Sec6-Syb1-Exo70. Forceful re-directioning of exocytic vesicle fusion to broader cortical areas induces proportional shape changes to growth domains, demonstrating that both features are causally linked.
Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects
Authors: Shang Renfu , Zhang Fengjuan , Xu Beiying , Xi Hairui , Zhang Xue , Wang Weihua , Wu Ligang
Published: October 2015

Short-hairpin RNAs (shRNAs) are widely used to produce small-interfering RNAs (siRNAs) for gene silencing. Here we design an alternative siRNA precursor, named single-stranded, Argonaute 2 (Ago2)-processed interfering RNA (saiRNA), containing a 16–18 bp stem and a loop complementary to the target transcript. The introduction of a self-cleaving ribozyme derived from hepatitis delta virus to the 3′ end of the transcribed saiRNA dramatically improves its silencing activity by generating a short 3′ overhang that facilitates the efficient binding of saiRNA to Ago2. The same ribozyme also enhances the activity of Dicer-dependent shRNAs. Unlike a classical shRNA, the strand-specific cleavage of saiRNA by Ago2 during processing eliminates the passenger strand and prevents the association of siRNA with non-nucleolytic Ago proteins. As a result, off-target effects are reduced. In addition, saiRNA exhibits less competition with the biogenesis of endogenous miRNAs. Therefore, ribozyme-enhanced saiRNA provides a reliable tool for RNA interference applications.
Structural diversity of supercoiled DNA
Authors: Irobalieva Rossitza N. , Fogg Jonathan M. , Catanese Daniel J. , Sutthibutpong Thana , Chen Muyuan , Barker Anna K. , Ludtke Steven J. , Harris Sarah A. , Schmid Michael F. , Chiu Wah , Zechiedrich Lynn
Published: October 2015

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.
A biosynthetic model of cytochrome c oxidase as an electrocatalyst for oxygen reduction
Authors: Mukherjee Sohini , Mukherjee Arnab , Bhagi-Damodaran Ambika , Mukherjee Manjistha , Lu Yi , Dey Abhishek
Published: October 2015

Creating an artificial functional mimic of the mitochondrial enzyme cytochrome c oxidase (CcO) has been a long-term goal of the scientific community as such a mimic will not only add to our fundamental understanding of how CcO works but may also pave the way for efficient electrocatalysts for oxygen reduction in hydrogen/oxygen fuel cells. Here we develop an electrocatalyst for reducing oxygen to water under ambient conditions. We use site-directed mutants of myoglobin, where both the distal Cu and the redox-active tyrosine residue present in CcO are modelled. In situ Raman spectroscopy shows that this catalyst features very fast electron transfer rates, facile oxygen binding and O–O bond lysis. An electron transfer shunt from the electrode circumvents the slow dissociation of a ferric hydroxide species, which slows down native CcO (bovine 500 s−1), allowing electrocatalytic oxygen reduction rates of 5,000 s−1 for these biosynthetic models.
Quantum engineering of spin and anisotropy in magnetic molecular junctions
Authors: Jacobson Peter , Herden Tobias , Muenks Matthias , Laskin Gennadii , Brovko Oleg , Stepanyuk Valeri , Ternes Markus , Kern Klaus
Published: October 2015

Single molecule magnets and single spin centres can be individually addressed when coupled to contacts forming an electrical junction. To control and engineer the magnetism of quantum devices, it is necessary to quantify how the structural and chemical environment of the junction affects the spin centre. Metrics such as coordination number or symmetry provide a simple method to quantify the local environment, but neglect the many-body interactions of an impurity spin coupled to contacts. Here, we utilize a highly corrugated hexagonal boron nitride monolayer to mediate the coupling between a cobalt spin in CoHx (x=1,2) complexes and the metal contact. While hydrogen controls the total effective spin, the corrugation smoothly tunes the Kondo exchange interaction between the spin and the underlying metal. Using scanning tunnelling microscopy and spectroscopy together with numerical simulations, we quantitatively demonstrate how the Kondo exchange interaction mimics chemical tailoring and changes the magnetic anisotropy.
Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate
Authors: Kassmer Susannah H. , Rodriguez Delany , Langenbacher Adam D. , Bui Connor , De Tomaso Anthony W.
Published: October 2015

The colonial ascidian Botryllus schlosseri continuously regenerates entire bodies in an asexual budding process. The germ line of the newly developing bodies is derived from migrating germ cell precursors, but the signals governing this homing process are unknown. Here we show that germ cell precursors can be prospectively isolated based on expression of aldehyde dehydrogenase and integrin alpha-6, and that these cells express germ cell markers such as vasa, pumilio and piwi, as well as sphingosine-1-phosphate receptor. In vitro, sphingosine-1-phosphate (S1P) stimulates migration of germ cells, which depends on integrin alpha-6 activity. In vivo, S1P signalling is essential for homing of germ cells to newly developing bodies. S1P is generated by sphingosine kinase in the developing germ cell niche and degraded by lipid phosphate phosphatase in somatic tissues. These results demonstrate a previously unknown role of the S1P signalling pathway in germ cell migration in the ascidian Botryllus schlosseri.
MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas
Authors: Gruosso Tina , Garnier Camille , Abelanet Sophie , Kieffer Yann , Lemesre Vincent , Bellanger Dorine , Bieche Ivan , Marangoni Elisabetta , Sastre-Garau Xavier , Mieulet Virginie , Mechta-Grigoriou Fatima
Published: October 2015

Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease.
Magnetic dipolar interaction between correlated triplets created by singlet fission in tetracene crystals
Authors: Wang Rui , Zhang Chunfeng , Zhang Bo , Liu Yunlong , Wang Xiaoyong , Xiao Min
Published: October 2015

Singlet fission can potentially break the Shockley–Queisser efficiency limit in single-junction solar cells by splitting one photoexcited singlet exciton (S1) into two triplets (2T1) in organic semiconductors. A dark multiexciton state has been proposed as the intermediate connecting S1 to 2T1. However, the exact nature of this multiexciton state, especially how the doubly excited triplets interact, remains elusive. Here we report a quantitative study on the magnetic dipolar interaction between singlet-fission-induced correlated triplets in tetracene crystals by monitoring quantum beats relevant to the multiexciton sublevels at room temperature. The resonances of multiexciton sublevels approached by tuning an external magnetic field are observed to be avoided, which agrees well with the theoretical predictions considering a magnetic dipolar interaction of ∼0.008 GHz. Our work quantifies the magnetic dipolar interaction in certain organic materials and marks an important step towards understanding the underlying physics of the multiexciton state in singlet fission.
Single Abrikosov vortices as quantized information bits
Authors: Golod T. , Iovan A. , Krasnov V. M.
Published: October 2015

Superconducting digital devices can be advantageously used in future supercomputers because they can greatly reduce the dissipation power and increase the speed of operation. Non-volatile quantized states are ideal for the realization of classical Boolean logics. A quantized Abrikosov vortex represents the most compact magnetic object in superconductors, which can be utilized for creation of high-density digital cryoelectronics. In this work we provide a proof of concept for Abrikosov-vortex-based random access memory cell, in which a single vortex is used as an information bit. We demonstrate high-endurance write operation and two different ways of read-out using a spin valve or a Josephson junction. These memory cells are characterized by an infinite magnetoresistance between 0 and 1 states, a short access time, a scalability to nm sizes and an extremely low write energy. Non-volatility and perfect reproducibility are inherent for such a device due to the quantized nature of the vortex.
Open–closed switching of synthetic tubular pores
Authors: Kim Yongju , Kang Jiheong , Shen Bowen , Wang Yanqiu , He Ying , Lee Myongsoo
Published: October 2015

While encouraging progress has been made on switchable nanopores to mimic biological channels and pores, it remains a great challenge to realize long tubular pores with a dynamic open–closed motion. Here we report μm-long, dynamic tubular pores that undergo rapid switching between open and closed states in response to a thermal signal in water. The tubular walls consist of laterally associated primary fibrils stacked from disc-shaped molecules in which the discs readily tilt by means of thermally regulated dehydration of the oligoether chains placed on the wall surfaces. Notably, this pore switching mediates a controlled water-pumping catalytic action for the dehydrative cyclization of adenosine monophosphate to produce metabolically active cyclic adenosine monophosphate. We believe that our work may allow the creation of a variety of dynamic pore structures with complex functions arising from open–closed motion.
Obesity changes the human gut mycobiome
Authors: Mar Rodríguez M. , Pérez Daniel , Javier Chaves Felipe , Esteve Eduardo , Marin-Garcia Pablo , Xifra Gemma , Vendrell Joan , Jové Mariona , Pamplona Reinald , Ricart Wifredo , Portero-Otin Manuel , Chacón Matilde R. , Fernández Real José Manuel
Published: October 2015

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found.Mucor racemosusandM. fuscuswere the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of theMucorgenus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity.
Band Structure Engineering and Thermoelectric Properties of Charge-Compensated Filled Skutterudites
Authors: Shi Xiaoya , Yang Jiong , Wu Lijun , Salvador James R. , Zhang Cheng , Villaire William L. , Haddad Daad , Yang Jihui , Zhu Yimei , Li Qiang
Published: October 2015

Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co4Sb12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature and judiciously doping the materials by increasing the Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively.
The development of pressure across membranes in Donnan systems
Authors: Ilani Asher
Published: October 2015

The pressure that develops between the two sides of a Donnan system is equal to the difference between the osmotic values of the two solutions, even though permeant ions may constitute a significant part of that difference. This is amply documented for the case of membranes that allow water movement through them by single molecules diffusing in isolation or in series through specific proteins (such as aquaporins). In this article, the development of pressure was analysed for a system in which membranes contain a few bulk aqueous pores that prevent charged polymers from entering them due to their size. It is shown analytically that the pressure that develops by the action of the electric field on the net charges in the pores is equal to the difference in the osmotic values of the solutions contributed by the permeant ions. Thus, the sum of the pressures that develop in the system due to the action of the electric field in the pores (a pushing force) and the concentration of the impermeant polymers at the interface (a sucking force), accounts for the total colloid osmotic pressure in these systems.
The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
Authors: Safronetz David , Rosenke Kyle , Westover Jonna B. , Martellaro Cynthia , Okumura Atsushi , Furuta Yousuke , Geisbert Joan , Saturday Greg , Komeno Takashi , Geisbert Thomas W. , Feldmann Heinz , Gowen Brian B.
Published: October 2015

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.
Reevaluation of the BRCA2 truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context
Authors: Thompson Ella R. , Gorringe Kylie L. , Rowley Simone M. , Li Na , McInerny Simone , Wong-Brown Michelle W. , Devereux Lisa , Li Jason ,   Lifepool Investigators, Campbell Ian G. , Devereux Lisa , Hopper John , Pridmore Vicki , Kavanagh Anne , Mitchell Gillian , Mann Bruce , Fox Stephen , Trainer Alison H. , Mitchell Gillian , Scott Rodney J. , James Paul A. , Campbell Ian G.
Published: October 2015

The breast cancer predisposition gene, BRCA2, has a large number of genetic variants of unknown effect. The variant rs11571833, an A > T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326*), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichment in the breast cancer cases (p = 0.047, OR 1.53, 95% CI 1.00–2.34). This data is consistent with recent iCOGs data suggesting that this variant is not neutral with respect to breast cancer risk. rs11571833 may need to be included in SNP panels for evaluating breast cancer risk.
Enhanced orbital magnetic moments in magnetic heterostructures with interface perpendicular magnetic anisotropy
Authors: Ueno Tetsuro , Sinha Jaivardhan , Inami Nobuhito , Takeichi Yasuo , Mitani Seiji , Ono Kanta , Hayashi Masamitsu
Published: October 2015

We have studied the magnetic layer thickness dependence of the orbital magnetic moment in magnetic heterostructures to identify contributions from interfaces. Three different heterostructures, Ta/CoFeB/MgO, Pt/Co/AlOx and Pt/Co/Pt, which possess significant interface contribution to the perpendicular magnetic anisotropy, are studied as model systems. X-ray magnetic circular dichroism spectroscopy is used to evaluate the relative orbital moment, i.e. the ratio of the orbital to spin moments, of the magnetic elements constituting the heterostructures. We find that the relative orbital moment of Co in Pt/Co/Pt remains constant against its thickness whereas the moment increases with decreasing Co layer thickness for Pt/Co/AlOx, suggesting that a non-zero interface orbital moment exists for the latter system. For Ta/CoFeB/MgO, a non-zero interface orbital moment is found only for Fe. X-ray absorption spectra shows that a particular oxidized Co state in Pt/Co/AlOx, absent in other heterosturctures, may give rise to the interface orbital moment in this system. These results show element specific contributions to the interface orbital magnetic moments in ultrathin magnetic heterostructures.
Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity
Authors: Panagopoulos Dimitris J. , Johansson Olle , Carlo George L.
Published: October 2015

In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell’s electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects.
Specific binding of eukaryotic ORC to DNA replication origins depends on highly conserved basic residues
Authors: Kawakami Hironori , Ohashi Eiji , Kanamoto Shota , Tsurimoto Toshiki , Katayama Tsutomu
Published: October 2015

In eukaryotes, the origin recognition complex (ORC) heterohexamer preferentially binds replication origins to trigger initiation of DNA replication. Crystallographic studies using eubacterial and archaeal ORC orthologs suggested that eukaryotic ORC may bind to origin DNA via putative winged-helix DNA-binding domains and AAA+ ATPase domains. However, the mechanisms how eukaryotic ORC recognizes origin DNA remain elusive. Here, we show in budding yeast that Lys-362 and Arg-367 residues of the largest subunit (Orc1), both outside the aforementioned domains, are crucial for specific binding of ORC to origin DNA. These basic residues, which reside in a putative disordered domain, were dispensable for interaction with ATP and non-specific DNA sequences, suggesting a specific role in recognition. Consistent with this, both residues were required for origin binding of Orc1 in vivo. A truncated Orc1 polypeptide containing these residues solely recognizes ARS sequence with low affinity and Arg-367 residue stimulates sequence specific binding mode of the polypeptide. Lys-362 and Arg-367 residues of Orc1 are highly conserved among eukaryotic ORCs, but not in eubacterial and archaeal orthologs, suggesting a eukaryote-specific mechanism underlying recognition of replication origins by ORC.
Diagnostic Value of Vestibular Evoked Myogenic Potentials in Endolymphatic Hydrops: A Meta-Analysis
Authors: Zhang Sulin , Leng Yangming , Liu Bo , Shi Hao , Lu Meixia , Kong Weijia
Published: October 2015

In this study, we evaluated the clinical diagnostic value of vestibular evoked myogenic potentials (VEMPs) for endolymphatic hydrops (EH) by systematic review and Meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under summary receiver operating characteristic curves (AUC) were calculated. Subgroup analysis and publication bias assessment were also conducted. The pooled sensitivity and the specificity were 49% (95% CI: 46% to 51%) and 95% (95% CI: 94% to 96%), respectively. The pooled positive likelihood ratio was 18.01 (95% CI: 9.45 to 34.29) and the pooled negative likelihood ratio was 0.54 (95% CI: 0.47 to 0.61). AUC was 0.78 and the pooled diagnostic odds ratio of VEMPs was 39.89 (95% CI: 20.13 to 79.03). In conclusion, our present meta-analysis has demonstrated that VEMPs test alone is not sufficient for Meniere’s disease or delayed endolymphatic hydrops diagnosis, but that it might be an important component of a test battery for diagnosing Meniere’s disease or delayed endolymphatic hydrops. Moreover, VEMPs, due to its high specificity and non-invasive nature, might be used as a screening tool for EH.
Mice lacking GPR3 receptors display late-onset obese phenotype due to impaired thermogenic function in brown adipose tissue
Authors: Godlewski Grzegorz , Jourdan Tony , Szanda Gergő , Tam Joseph , Resat Cinar  , Harvey-White Judith , Liu Jie , Mukhopadhyay Bani , Pacher Pál , Ming Mo Fong , Osei-Hyiaman Douglas , George Kunos
Published: October 2015

We report an unexpected link between aging, thermogenesis and weight gain via the orphan G protein-coupled receptor GPR3. Mice lacking GPR3 and maintained on normal chow had similar body weights during their first 5 months of life, but gained considerably more weight thereafter and displayed reduced total energy expenditure and lower core body temperature. By the age of 5 months GPR3 KO mice already had lower thermogenic gene expression and uncoupling protein 1 protein level and showed impaired glucose uptake into interscapular brown adipose tissue (iBAT) relative to WT littermates. These molecular deviations in iBAT of GPR3 KO mice preceded measurable differences in body weight and core body temperature at ambient conditions, but were coupled to a failure to maintain thermal homeostasis during acute cold challenge. At the same time, the same cold challenge caused a 17-fold increase in Gpr3 expression in iBAT of WT mice. Thus, GPR3 appears to have a key role in the thermogenic response of iBAT and may represent a new therapeutic target in age-related obesity.
Controllable Preparation of Ultrathin Sandwich-Like Membrane with Porous Organic Framework and Graphene Oxide for Molecular Filtration
Authors: Zhu Yuanzhi , Xu Danyun , Zhao Qingshan , Li Yang , Peng Wenchao , Zhang Guoliang , Zhang Fengbao , Fan Xiaobin
Published: October 2015

Porous organic frameworks (POFs) based membranes have potential applications in molecular filtration, despite the lack of a corresponding study. This study reports an interesting strategy to get processable POFs dispersion and a novel ultrathin sandwich-like membrane design. It was accidentally found that the hydrophobic N-rich Schiff based POFs agglomerates could react with lithium-ethylamine and formed stable dispersion in water. By successively filtrating the obtained POFs dispersion and graphene oxide (GO), we successfully prepared ultrathin sandwich-like hybrid membranes with layered structure, which showed significantly improved separation efficiency in molecular filtration of organic dyes. This study may provide a universal way to the preparation of processable POFs and their hybrid membranes with GO.
Ageing and Caloric Restriction in a Marine Planktonic Copepod
Authors: Saiz Enric , Calbet Albert , Griffell Kaiene , Bersano José Guilherme F. , Isari Stamatina , Solé Montserrat , Peters Janna , Alcaraz Miquel
Published: October 2015

Planktonic copepods are a key group in the marine pelagic ecosystem, linking primary production with upper trophic levels. Their abundance and population dynamics are constrained by the life history tradeoffs associated with resource availability, reproduction and predation pressure. The tradeoffs associated with the ageing process and its underlying biological mechanisms are, however, poorly known. Our study shows that ageing in copepods involves a deterioration of their vital rates and a rise in mortality associated with an increase in oxidative damage (lipid peroxidation); the activity of the cell-repair enzymatic machinery also increases with age. This increase in oxidative damage is associated with an increase in the relative content of the fatty acid 22:6(n-3), an essential component of cell membranes that increases their susceptibility to peroxidation. Moreover, we show that caloric (food) restriction in marine copepods reduces their age-specific mortality rates and extends the lifespan of females and their reproductive period. Given the overall low production of the oceans, this can be a strategy, at least in certain copepod species, to enhance their chances to reproduce in a nutritionally dilute, temporally and spatially patchy environment.
Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity
Authors: Sun Yun , Wang Keyi , Li Min-Xia , He Wei , Chang Jin-Rui , Liao Cheng-Cheng , Lin Fan , Qi Yong-Fen , Wang Rui , Chen Ya-Hong
Published: October 2015

Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.
Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation
Authors: Schelhorn Constanze , Martín-Malpartida Pau , Suñol David , Macias Maria J.
Published: October 2015

The Cytoplasmic Polyadenylation Element Binding proteins are RNA binding proteins involved in the translational regulation of mRNA. During cell cycle progression, CPEB1 is labeled for degradation by phosphorylation-dependent ubiquitination by the SCFβ−TrCP ligase. The peptidyl-prolyl isomerase Pin1 plays a key role in CPEB1 degradation. Conditioned by the cell cycle stage, CPEB1 and Pin1 interactions occur in a phosphorylation-independent or -dependent manner. CPEB1 contains six potential phosphorylatable Pin1 binding sites. Using a set of biophysical techniques, we discovered that the pS210 site is unique, since it displays binding activity not only to the WW domain but also to the prolyl-isomerase domain of Pin1. The NMR structure of the Pin1 WW-CPEB1 pS210 (PDB ID: 2n1o) reveals that the pSerPro motif is bound in trans configuration through contacts with amino acids located in the first turn of the WW domain and the conserved tryptophan in the β3-strand. NMR relaxation analyses of Pin1 suggest that inter-domain flexibility is conferred by the modulation of the interaction with peptides containing the pS210 site, which is essential for degradation.
Synthesis of ultrasmall Li–Mn spinel oxides exhibiting unusual ion exchange, electrochemical and catalytic properties
Authors: Miyamoto Yumi , Kuroda Yoshiyuki , Uematsu Tsubasa , Oshikawa Hiroyuki , Shibata Naoya , Ikuhara Yuichi , Suzuki Kosuke , Hibino Mitsuhiro , Yamaguchi Kazuya , Mizuno Noritaka
Published: October 2015

The efficient surface reaction and rapid ion diffusion of nanocrystalline metal oxides have prompted considerable research interest for the development of high functional materials. Herein, we present a novel low-temperature method to synthesize ultrasmall nanocrystalline spinel oxides by controlling the hydration of coexisting metal cations in an organic solvent. This method selectively led to Li–Mn spinel oxides by tuning the hydration of Li+ ions under mild reaction conditions (i.e., low temperature and short reaction time). These particles exhibited an ultrasmall crystallite size of 2.3 nm and a large specific surface area of 371 ± 15 m2 g−1. They exhibited unique properties such as unusual topotactic Li+/H+ ion exchange, high-rate discharge ability and high catalytic performance for several aerobic oxidation reactions, by creating surface phenomena throughout the particles. These properties differed significantly from those of Li–Mn spinel oxides obtained by conventional solid-state methods.
Designing ultrathin film composite membranes: the impact of a gutter layer
Authors: Kattula Moon , Ponnuru Koushik , Zhu Lingxiang , Jia Weiguang , Lin Haiqing , Furlani Edward P.
Published: October 2015

Industrial membranes comprised of a thin selective layer (<100 nm) requires a gutter layer (<100 nm) between the selective layer and the porous support to achieve high permeance for gas separation. The gutter layer materials must be carefully chosen to enhance overall membrane performance, i.e., high permeance and high selectivity. However, the experimental determination of the optimum gutter layer properties is very challenging. Herein we address this need using a three dimensional (3D) computational model to systematically determine the effects of the gutter layer thickness and permeability on membrane performance. A key finding is that the introduction of a gutter layer between the selective layer and porous support can enhance the overall permeance of the penetrant by up to an order of magnitude, but this gain is accompanied by an undesired decrease in selectivity. The analysis also shows for the first time that a maximum increase in permeance with negligible decrease in selectivity is realized when the thickness of the gutter layer is 1-2 times the pore radius. The modeling approach provides clear and practical guidelines for designing ultrathin multilayer composite membranes to achieve high permeance and selectivity for low-cost and energy-efficient molecular separations.
Mutual medication in capuchin monkeys – Social anointing improves coverage of topically applied anti-parasite medicines
Authors: Bowler Mark , Messer Emily J. E. , Claidière Nicolas , Whiten Andrew
Published: October 2015

Wild and captive capuchin monkeys will anoint themselves with a range of strong smelling substances including millipedes, ants, limes and onions. Hypotheses for the function of the behaviour range from medicinal to social. However, capuchin monkeys may anoint in contact with other individuals, as well as individually. The function of social anointing has also been explained as either medicinal or to enhance social bonding. By manipulating the abundance of an anointing resource given to two groups of tufted capuchins, we tested predictions derived from the main hypotheses for the functions of anointing and in particular, social anointing. Monkeys engaged in individual and social anointing in similar proportions when resources were rare or common and monkeys holding resources continued to join anointing groups, indicating that social anointing has functions beyond that of gaining access to resources. The distribution of individual and social anointing actions on the monkeys’ bodies supports a medicinal function for both individual and social anointing, that requires no additional social bonding hypotheses. Individual anointing targets hard-to-see body parts that are harder to groom, whilst social anointing targets hard-to-reach body parts. Social anointing in capuchins is a form of mutual medication that improves coverage of topically applied anti-parasite medicines.
DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs
Authors: Ramathal Cyril , Angulo Benjamin , Sukhwani Meena , Cui Jun , Durruthy-Durruthy Jens , Fang Fang , Schanes Paula , Turek Paul J. , Orwig Kyle E. , Reijo Pera Renee
Published: October 2015

Deletions of the AZFa region (AZoospermia Factor-a) region of the human Y chromosome cause irreversible spermatogenic failure that presents clinically in men as Sertoli-cell only (SCO) pathology of the testis. Deletions of the AZFa region typically encompass two genes: DDX3Y and USP9Y. However, human genetic evidence indicates that SCO is most tightly linked to deletion of DDX3Y and that deletions/mutations of USP9Y can be transmitted from one generation to the next. Here, we generated stable iPSC lines with AZFa deletions, tested complementation via introduction of DDX3Y, and assessed ability to form germ cells in vivo in a xenotransplantation model. We observed a quantifiable improvement in formation of germ cell like cells (GCLCs) from complemented donor iPSCs. Moreover, expression of UTF1, a prospermatogonial protein, was restored in cells complemented by introduction of DDX3Y on the AZFa background. Whole-genome RNA sequencing of purified GCLCs revealed an enrichment of genes involved in translational suppression and transcriptional control in DDX3Y-rescued GCLCs over mutant GCLCs, which maintained a molecular phenotype more similar to undifferentiated iPSCs. This study demonstrates the ability to probe fundamental genetics of human germ cell formation by complementation and indicates that DDX3Y functions in the earliest stages of human germ cell development.