bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Algorithm for Lane Level Irregular Driving Identification
Authors: Sun Rui , Ochieng Washington , Fang Cheng , Feng Shaojun
Published: July 2015

Global Navigation Satellite Systems (GNSS) are used widely in the provision of Intelligent Transportation System (ITS) services. Today, there is an increasing demand on GNSS to support applications at lane level. These applications required at lane level include lane control, collision avoidance and intelligent speed assistance. In lane control, detecting irregular driving behaviour within the lane is a basic requirement for safety related lane level applications. There are two major issues involved in lane level irregular driving identification: access to high accuracy positioning and vehicle dynamic parameters, and extraction of erratic driving behaviour from this and other related information. This paper proposes an integrated algorithm for lane level irregular driving identification. Access to high accuracy positioning is enabled by GNSS and its integration with an Inertial Navigation System (INS) using filtering with precise vehicle motion models and lane information. The identification of irregular driving behaviour is achieved by algorithms developed for different types of events based on the application of a Fuzzy Inference System (FIS). The results show that decimetre level accuracy can be achieved and that different types of lane level irregular driving behaviour can be identified.
Developing a Phenomenological Approach to Music Notation
Authors: Casey Rob
Published: July 2015

Sound art theorists Seth Kim-Cohen and Salomé Voegelin regard the fixed conceptual structures of notation either as an obstacle to pure sensorial engagement with sound (Voegelin 2010), or as the site of arrogant musical exceptionalism (Kim-Cohen 2009). While sound, whether constituted in phenomenological or idealist terms, is evolving and dynamic, notation is characterised by its ossifying imperative (Kim-Cohen 2009; Voegelin 2010). For Voegelin, a music score is regarded as conceptual, not perceptual. It is read as text and, it seems, has no meaningful place within a phenomenological practice of sound art (Voegelin 2010). The criticism that Vogelin’s phenomenalism, in particular, levels at notation invites close examination of notational practice and the semiotic structures that underwrite it. In this article, I seek to challenge the conceptual imperative of fixed notation through the presentation of a case study in the form of an original composition for string quartet and tape. Drawing on research by Rudolf Arnheim and Mark Johnson, a form of notation will be proposed that enables the score to escape singularly semiotic structures so that it may address the dynamic, phenomenological mode of experience that recent theories of sound art imply is beyond the reach of musical notation.
A ‘Sound Grammar’ for the City: The spatial and temporal dimension of Barber’s concerts
Authors: García Sánchez María Teresa
Published: July 2015

This article focuses on one of the most suggestive proposals within the sound domain of the twentieth century: the concerts for bells and bell towers devised by the Spanish musician Llorenç Barber. His original idea of transforming the city into a monumental instrument provides the starting point for the analysis. In order to access the competing claims of sound art versus music, the text approaches Barber’s creative thinking as if it were a sound grammar devised specifically for the city: materials and performance techniques become a ‘phonetics’, structural elements as a ‘morphology’, the ‘syntax’ of sound-handling strategies, and the formal structure of the score as a ‘narrative’ of the concert. Within each dimension, the text shows how the ‘city instrument’ has extended Barber’s creative horizon by transforming musical problems into unclassifiable strategies of dealing with sound, which are capable of producing a sonic experience deeply rooted in the historical and cultural development of the city. Finally, this research shows how uncertainty, indeterminacy, ambiguity, accident or change (unacceptable concepts for the traditional musical domain) become an essential part of these works. Inevitably, such aspects require from the ‘composer’ a kind of pragmatism that seems to be inherent in the outdoor sound design.
Wavefront Aesthetics: Attuning to a dark ecology
Authors: Højlund Marie , Riis Morten
Published: July 2015

In this article, we offer an object-oriented ontological perspective to complement the diversity of sounding ontologies, challenging the human perspective as the only valid perspective and call for the necessity of including perspectives of objects such as a speakers, voices and light sensors. Subscribing to this view also confronts music and sound art as consistent autonomous categories and focuses on how the pieces attune to the environment, emphasising meetings, transformations and translations through and with other objects. These meetings generate an ecological awareness of causal aesthetics where objectstimeandspaceeach other. This contrasts with traditional analysis of music and sound art, which is based on the assumption that time and space are containers in which sound and music unfold. We analyse two contemporary pieces by the authors in an attempt to unfold a dark ecological1approach to test the implications, limits and potentials for future use and development.
Dead Logics and Worlds: Sound art and sonorous objects
Authors: Hudson Martyn , Shaw Tim
Published: July 2015

From the early experimentation with specific sounds in musique concrète (Palombini 1999) to the ‘anecdotal’ music of Luc Ferrari (1996) and the ecological sound activism of Hildegard Westerkamp (2002), the collecting, composition and recomposition of sonorous objects has been central to sound practice. Some sound art has privileged a relationship with visual arts and the structuring of objects in curated spaces (Licht 2007), others with the sound worlds beyond the exhibition (Schafer 1994). By examining a specific sound art installation,Sound and Seclusionby Tim Shaw, this article reworks the idea of sonorous objects as artefacts displaying different kinds of representations, knowledges or data. This question of sonorous ‘knowledge-objects’ is particularly important as ‘collected sounds’ become incorporated into compositions away from their, often remote, spatio-temporal origin out there in the landscape. This article raises three areas for discussion. First, what can sonorous objects tell us about the pre-compositional world (Impett 2007)? Second, in what ways can we understand sonorous objects as they are reworked in compositions which re-narrate them? Third, how can we understand sonorous objects as traces and pieces of data as well as aesthetic productions? The article concludes with a case for reworking the very idea of a sonorous object in sound practices as a product of dead logics and dead worlds as it emerges in new ensembles of composition away from its origin.
The Neurobiological Platform for Moral Values
Authors: Churchland Patricia S.
Published: July 2015

What we humans callethicsormoralitydepends on four interlocking brain processes: (1)caring(supported by the neuroendocrine system, and emerging in the young as a function of parental care). (2)Learning local social practices and the ways of others– by positive and negative reinforcement, by imitation, by trial and error, by various kinds of conditioning, and by analogy. (3)Recognition of others' psychological states (goals, feelings etc.).(4)Problem-solving in a social context. These four broad capacities are not unique to humans, but are probably uniquely developed in human brains by virtue of the expansion of the prefrontal cortex.1
LONGEVITY, GROWTH, AND INTERGENERATIONAL EQUITY: THE DETERMINISTIC CASE
Authors: Andersen Torben M. , Gestsson Marias H.
Published: July 2015

Challenges raised by aging (increasing longevity) have prompted policy debates featuring policy proposals justified by reference to some notion of intergenerational equity. However, very different policies ranging from presavings to indexation of retirement ages have been justified in this way. We develop an overlapping-generations model in continuous time that encompasses different generations with different mortality rates and thus longevity. Allowing for trend increases in both longevity and productivity, we address the normative issue of intergenerational equity under a utilitarian criterion when future generations are better off in terms of both material and nonmaterial well-being. Increases in productivity and longevity are shown to have very different implications for intergenerational distribution. Further, the socially optimal retirement age, dependency ratio, and intergenerational burden sharing in the case of a trend increase in longevity are shown to depend on how individuals' utility for time/leisure is affected by age and longevity.
The effect of language proficiency on executive functions in balanced and unbalanced Spanish–English bilinguals
Authors: ROSSELLI MÓNICA , ARDILA ALFREDO , LALWANI LAXMI N. , VÉLEZ-URIBE IDALY
Published: July 2015

This study analyzed the association between levels of language proficiency and levels of bilingualism and performance on verbal and nonverbal executive functions (working memory, updating, shifting, and inhibition tasks) in young bilinguals. Forty balanced (high and low proficiency), 34 unbalanced bilinguals, and 40 English monolinguals, were selected. The Bilingual Verbal Ability Test was used as a measure of language proficiency; WAIS Block design test was used as a measure of non-verbal intelligence. High proficiency balanced bilinguals performed better than low proficiency balanced bilinguals; unbalanced bilinguals scored in between both balanced groups. High proficiency monolinguals scored higher than low proficiency monolinguals and similar to high proficiency bilinguals. Regression analyses demonstrated that nonverbal intelligence significantly predicted performances on verbal working memory and verbal and nonverbal inhibition tasks. It was concluded that nonverbal intelligence scores are better predictors of executive function performance than bilingualism or language proficiency.
A Shear Strain Route Dependency of Martensite Formation in 316L Stainless Steel
Authors: Kang Suk Hoon , Kim Tae Kyu , Jang Jinsung , Oh Kyu Hwan
Published: July 2015

In this study, the effect of simple shearing on microstructure evolution and mechanical properties of 316L austenitic stainless steel were investigated. Two different shear strain routes were obtained by twisting cylindrical specimens in the forward and backward directions. The strain-induced martensite phase was effectively obtained by alteration of the routes. Formation of the martensite phase clearly resulted in significant hardening of the steel. Grain-size reduction and strain-induced martensitic transformation within the deformed structures of the strained specimens were characterized by scanning electron microscopy – electron back-scattered diffraction, X-ray diffraction, and the TEM-ASTAR (transmission electron microscopy – analytical scanning transmission atomic resolution, automatic crystal orientation/phase mapping for TEM) system. Significant numbers of twin networks were formed by alteration of the shear strain routes, and the martensite phases were nucleated at the twin interfaces.
Immunogenicity and functional evaluation of iPSC-derived organs for transplantation
Authors: Wang Libin , Cao Jiani , Wang Yukai , Lan Tianshu , Liu Lei , Wang Weixu , Jin Ning , Gong Jiaqi , Zhang Chao , Teng Fei , Yan Guoliang , Li Chun , Li Jiali , Wan Haifeng , Hu Baoyang , Li Wei , Zhao Xiaoyang , Qi Zhongquan , Zhao Tongbiao , Zhou Qi
Published: July 2015

Whether physiologically induced pluripotent stem cell (iPSC)-derived organs are immunogenic and can be used for transplantation is unclear. Here, we generated iPSC-derived skin, islet, and heart representing three germ layers of the body through 4n complementation and evaluated their immunogenicity and therapeutic efficacy. Upon transplantation into recipient mice, iPSC-derived skin successfully survived and repaired local tissue wounds. In diabetic mouse models, explanted iPSC-derived islets effectively produced insulin and lowered blood glucose to basal levels. iPSC-derived heart grafts maintained normal beating for more than 3 months in syngeneic recipients. Importantly, no obvious immune rejection responses against iPSC-derived organs were detected long after transplantation. Our study not only demonstrates the fundamental immunogenicity and function of iPSC derivatives, but also provides preclinical evidence to support the feasibility of using iPSC-derived skin, islet, and heart for therapeutic use.
Genomic potential for arsenic efflux and methylation varies among global Prochlorococcus populations
Authors: Saunders Jaclyn K , Rocap Gabrielle
Published: July 2015

The globally significant picocyanobacterium Prochlorococcus is the main primary producer in oligotrophic subtropical gyres. When phosphate concentrations are very low in the marine environment, the mol:mol availability of phosphate relative to the chemically similar arsenate molecule is reduced, potentially resulting in increased cellular arsenic exposure. To mediate accidental arsenate uptake, some Prochlorococcus isolates contain genes encoding a full or partial efflux detoxification pathway, consisting of an arsenate reductase (arsC), an arsenite-specific efflux pump (acr3) and an arsenic-related repressive regulator (arsR). This efflux pathway was the only previously known arsenic detox pathway in Prochlorococcus. We have identified an additional putative arsenic mediation strategy in Prochlorococcus driven by the enzyme arsenite S-adenosylmethionine methyltransferase (ArsM) which can convert inorganic arsenic into more innocuous organic forms and appears to be a more widespread mode of detoxification. We used a phylogenetically informed approach to identify Prochlorococcus linked arsenic genes from both pathways in the Global Ocean Sampling survey. The putative arsenic methylation pathway is nearly ubiquitously present in global Prochlorococcus populations. In contrast, the complete efflux pathway is only maintained in populations which experience extremely low PO4:AsO4, such as regions in the tropical and subtropical Atlantic. Thus, environmental exposure to arsenic appears to select for maintenance of the efflux detoxification pathway in Prochlorococcus. The differential distribution of these two pathways has implications for global arsenic cycling, as their associated end products, arsenite or organoarsenicals, have differing biochemical activities and residence times.
Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients
Authors: de Steenhuijsen Piters Wouter A A , Huijskens Elisabeth G W , Wyllie Anne L , Biesbroek Giske , van den Bergh Menno R , Veenhoven Reinier H , Wang Xinhui , Trzciński Krzysztof , Bonten Marc J , Rossen John W A , Sanders Elisabeth A M , Bogaert Debby
Published: July 2015

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.
Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion
Authors: Alam Mahmood M. , Solyakov Lev , Bottrill Andrew R. , Flueck Christian , Siddiqui Faiza A. , Singh Shailja , Mistry Sharad , Viskaduraki Maria , Lee Kate , Hopp Christine S. , Chitnis Chetan E. , Doerig Christian , Moon Robert W. , Green Judith L. , Holder Anthony A. , Baker David A. , Tobin Andrew B.
Published: July 2015

Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum, remains rudimentary. Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for PfPKG. These PfPKG targets include proteins involved in cell signalling, proteolysis, gene regulation, protein export and ion and protein transport, indicating that cGMP/PfPKG acts as a signalling hub that plays a central role in a number of core parasite processes. We also show that PfPKG activity is required for parasite invasion. This correlates with the finding that the calcium-dependent protein kinase, PfCDPK1, is phosphorylated by PfPKG, as are components of the actomyosin complex, providing mechanistic insight into the essential role of PfPKG in parasite egress and invasion.
Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography
Authors: Irkle Agnese , Vesey Alex T. , Lewis David Y. , Skepper Jeremy N. , Bird Joseph L. E. , Dweck Marc R. , Joshi Francis R. , Gallagher Ferdia A. , Warburton Elizabeth A. , Bennett Martin R. , Brindle Kevin M. , Newby David E. , Rudd James H. , Davenport Anthony P.
Published: July 2015

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification.
SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair
Authors: van Cuijk Loes , van Belle Gijsbert J. , Turkyilmaz Yasemin , Poulsen Sara L. , Janssens Roel C. , Theil Arjan F. , Sabatella Mariangela , Lans Hannes , Mailand Niels , Houtsmuller Adriaan B. , Vermeulen Wim , Marteijn Jurgen A.
Published: July 2015

XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have shown that the SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. However, the exact regulatory function of these modifications in vivo remains elusive. Here we show that RNF111 is required for efficient repair of ultraviolet-induced DNA lesions. RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation, and is needed for stable incorporation of the NER endonucleases XPG and ERCC1/XPF. Our data suggest that RNF111, together with the CRL4DDB2 ubiquitin ligase complex, is responsible for sequential XPC ubiquitylation, which regulates the recruitment and release of XPC and is crucial for efficient progression of the NER reaction, thereby providing an extra layer of quality control of NER.
Kindlin-2 controls TGF-β signalling and Sox9 expression to regulate chondrogenesis
Authors: Wu Chuanyue , Jiao Hongli , Lai Yumei , Zheng Wei , Chen Ka , Qu Hong , Deng Weimin , Song Pingping , Zhu Ke , Cao Huiling , Galson Deborah L. , Fan Jie , Im Hee-Jeong , Liu Yujie , Chen Ju , Chen Di , Xiao Guozhi
Published: July 2015

The signals that control skeletogenesis are incompletely understood. Here we show that deleting Kindlin-2 in Prx1-expressing mesenchymal progenitors in mice causes neonatal lethality, chondrodysplasia and loss of the skull vault. Kindlin-2 ablation reduces chondrocyte density by decreasing cell proliferation and increasing apoptosis, and disrupts column formation, thus impairing the formation of the primary ossification center and causing severe limb shortening. Remarkably, Kindlin-2 localizes to not only focal adhesions, but also to the nuclei of chondrocytes. Loss of Kindlin-2 reduces, while the overexpression of Kindlin-2 increases, Sox9 expression. Furthermore, the overexpression of Sox9 restores the defects in chondrogenic differentiation induced by Kindlin-2 deletion in vitro. In addition, Kindlin-2 ablation inhibits TGF-β1-induced Smad2 phosphorylation and chondrocyte differentiation. Finally, deleting Kindlin-2 in chondrocytes directly impairs chondrocyte functions, resulting in progressive dwarfism and kyphosis in mice. These studies uncover a previously unrecognized function for Kindlin-2 and a mechanism for regulation of the chondrocyte differentiation programme and chondrogenesis.
Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation
Authors: Tan Tien-Chye , Kracher Daniel , Gandini Rosaria , Sygmund Christoph , Kittl Roman , Haltrich Dietmar , Hällberg B. Martin , Ludwig Roland , Divne Christina
Published: July 2015

A new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem-binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled via CYT to LPMO. Here we present structural analyses that provide a comprehensive picture of CDH conformers, which govern the electron transfer between redox centres. Using structure-based site-directed mutagenesis, rapid kinetics analysis and molecular docking, we demonstrate that flavin-to-haem interdomain electron transfer (IET) is enabled by a haem propionate group and that rapid IET requires a closed CDH state in which the propionate is tightly enfolded by DH. Following haem reduction, CYT reduces LPMO to initiate oxygen activation at the copper centre and subsequent cellulose depolymerization.
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
Authors: Thiffault Isabelle , Wolf Nicole I. , Forget Diane , Guerrero Kether , Tran Luan T. , Choquet Karine , Lavallée-Adam Mathieu , Poitras Christian , Brais Bernard , Yoon Grace , Sztriha Laszlo , Webster Richard I. , Timmann Dagmar , van de Warrenburg Bart P. , Seeger Jürgen , Zimmermann Alíz , Máté Adrienn , Goizet Cyril , Fung Eva , van der Knaap Marjo S. , Fribourg Sébastien , Vanderver Adeline , Simons Cas , Taft Ryan J. , Yates III John R. , Coulombe Benoit , Bernard Geneviève
Published: July 2015

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genesPOLR3AandPOLR3B. Here we report eight of these cases carrying recessive mutations inPOLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, inPOLR1Cimpair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes’ availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.
Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study
Authors: Chen Pei-Lung , Shih Shyang-Rong , Wang Pei-Wen , Lin Ying-Chao , Chu Chen-Chung , Lin Jung-Hsin , Chen Szu-Chi , Chang Ching-Chung , Huang Tien-Shang , Tsai Keh Sung , Tseng Fen-Yu , Wang Chih-Yuan , Lu Jin-Ying , Chiu Wei-Yih , Chang Chien-Ching , Chen Yu-Hsuan , Chen Yuan-Tsong , Fann Cathy Shen-Jang , Yang Wei-Shiung , Chang Tien-Chun
Published: July 2015

Graves’ disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves’ disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10−32) and HLA-DRB1*08:03 (Pcombined=1.83 × 10−9) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10−21, 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.
The minimal work cost of information processing
Authors: Faist Philippe , Dupuis Frédéric , Oppenheim Jonathan , Renner Renato
Published: July 2015

Irreversible information processing cannot be carried out without some inevitable thermodynamical work cost. This fundamental restriction, known as Landauer’s principle, is increasingly relevant today, as the energy dissipation of computing devices impedes the development of their performance. Here we determine the minimal work required to carry out any logical process, for instance a computation. It is given by the entropy of the discarded information conditional to the output of the computation. Our formula takes precisely into account the statistically fluctuating work requirement of the logical process. It enables the explicit calculation of practical scenarios, such as computational circuits or quantum measurements. On the conceptual level, our result gives a precise and operational connection between thermodynamic and information entropy, and explains the emergence of the entropy state function in macroscopic thermodynamics.
Microsecond protein dynamics observed at the single-molecule level
Authors: Otosu Takuhiro , Ishii Kunihiko , Tahara Tahei
Published: July 2015

How polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochromec. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.
Green to red photoconversion of GFP for protein tracking in vivo
Authors: Sattarzadeh Amirali , Saberianfar Reza , Zipfel Warren R. , Menassa Rima , Hanson Maureen R.
Published: July 2015

A variety of fluorescent proteins have been identified that undergo shifts in spectral emission properties over time or once they are irradiated by ultraviolet or blue light. Such proteins are finding application in following the dynamics of particular proteins or labelled organelles within the cell. However, before genes encoding these fluorescent proteins were available, many proteins have already been labelled with GFP in transgenic cells; a number of model organisms feature collections of GFP-tagged lines and organisms. Here we describe a fast, localized and non-invasive method for GFP photoconversion from green to red. We demonstrate its use in transgenic plant, Drosophila and mammalian cells in vivo. While genes encoding fluorescent proteins specifically designed for photoconversion will usually be advantageous when creating new transgenic lines, our method for photoconversion of GFP allows the use of existing GFP-tagged transgenic lines for studies of dynamic processes in living cells.
Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities
Authors: Yu Chen , Qi Dong , Sun Ju-Feng , Li Peng , Fan Hua-Ying
Published: July 2015

This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.
Synthesis of magnetic metal-organic framework (MOF) for efficient removal of organic dyes from water
Authors: Zhao Xiaoli , Liu Shuangliu , Tang Zhi , Niu Hongyun , Cai Yaqi , Meng Wei , Wu Fengchang , Giesy John P.
Published: July 2015

A novel, simple and efficient strategy for fabricating a magnetic metal-organic framework (MOF) as sorbent to remove organic compounds from simulated water samples is presented and tested for removal of methylene blue (MB) as an example. The novel adsorbents combine advantages of MOFs and magnetic nanoparticles and possess large capacity, low cost, rapid removal and easy separation of the solid phase, which makes it an excellent sorbent for treatment of wastewaters. The resulting magnetic MOFs composites (also known as MFCs) have large surface areas (79.52 m2 g−1), excellent magnetic response (14.89 emu g−1) and large mesopore volume (0.09 cm3 g−1), as well as good chemical inertness and mechanical stability. Adsorption was not drastically affected by pH, suggesting π–π stacking interaction and/or hydrophobic interactions between MB and MFCs. Kinetic parameters followed pseudo-second-order kinetics and adsorption was described by the Freundlich isotherm. Adsorption capacity was 84 mg MB g−1 at an initial MB concentration of 30 mg L−1, which increased to 245 mg g−1 when the initial MB concentration was 300 mg L−1. This capacity was much greater than most other adsorbents reported in the literature. In addition, MFC adsorbents possess excellent reusability, being effective after at least five consecutive cycles.
Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18
Authors: Guo Peng-Chao , Dong Zhaoming , Zhao Ping , Zhang Yan , He Huawei , Tan Xiang , Zhang Weiwei , Xia Qingyou
Published: July 2015

Serpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development.
Predictability Bounds of Electronic Health Records
Authors: Dahlem Dominik , Maniloff Diego , Ratti Carlo
Published: July 2015

The ability to intervene in disease progression given a person’s disease history has the potential to solve one of society’s most pressing issues: advancing health care delivery and reducing its cost. Controlling disease progression is inherently associated with the ability to predict possible future diseases given a patient’s medical history. We invoke an information-theoretic methodology to quantify the level of predictability inherent in disease histories of a large electronic health records dataset with over half a million patients. In our analysis, we progress from zeroth order through temporal informed statistics, both from an individual patient’s standpoint and also considering the collective effects. Our findings confirm our intuition that knowledge of common disease progressions results in higher predictability bounds than treating disease histories independently. We complement this result by showing the point at which the temporal dependence structure vanishes with increasing orders of the time-correlated statistic. Surprisingly, we also show that shuffling individual disease histories only marginally degrades the predictability bounds. This apparent contradiction with respect to the importance of time-ordered information is indicative of the complexities involved in capturing the health-care process and the difficulties associated with utilising this information in universal prediction algorithms.
Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies
Authors: O’Brien Eóin C. , Abdulahad Wayel H. , Rutgers Abraham , Huitema Minke G. , O’Reilly Vincent P. , Coughlan Alice M. , Harrington Mark , Heeringa Peter , Little Mark A. , Hickey Fionnuala B.
Published: July 2015

ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
In situ microscopic observation of chitin and fungal cells with chitinous cell walls in hydrothermal conditions
Authors: Deguchi Shigeru , Tsujii Kaoru , Horikoshi Koki
Published: July 2015

Recent findings of intact chitin in fossil records suggest surprisingly high recalcitrance of this biopolymer during hydrothermal treatments. We also know in the experience of everyday life that mushroom, cells of which have chitinous cell walls, do not fall apart however long they are simmered. We used in situ optical microscopy to examine chitin and fungal cells with chitinous cell walls during hydrothermal treatments and obtained direct evidence that they remained undegraded at temperatures well over 200 °C. The results show very hot and compressed water is needed to make mushrooms mushy.
Single Nanoparticle Detection Using Far-field Emission of Photonic Molecule around the Exceptional Point
Authors: Zhang Nan , Liu Shuai , Wang Kaiyang , Gu Zhiyuan , Li Meng , Yi Ningbo , Xiao Shumin , Song Qinghai
Published: July 2015

Highly sensitive, label-free detection methods have important applications in fundamental research and healthcare diagnostics. To date, the detection of single nanoparticles has remained largely dependent on extremely precise spectral measurement, which relies on high-cost equipment. Here, we demonstrate a simple but very nontrivial mechanism for the label-free sizing of nanoparticles using the far-field emission of a photonic molecule (PM) around an exceptional point (EP). By attaching a nanoparticle to a PM around an EP, the main resonant behaviors are strongly disturbed. In addition to typical mode splitting, we find that the far-field pattern of the PM is significantly changed. Taking a heteronuclear diatomic PM as an example, we demonstrate that a single nanoparticle, whose radius is as small as 1 nm to 7 nm, can be simply monitored through the variation of the far-field pattern. Compared with conventional methods, our approach is much easier and does not rely on high-cost equipment. In addition, this research will illuminate new advances in single nanoparticle detection.
Trace element fingerprinting of cockle (Cerastoderma edule) shells can reveal harvesting location in adjacent areas
Authors: Ricardo Fernando , Génio Luciana , Costa Leal Miguel , Albuquerque Rui , Queiroga Henrique , Rosa Rui , Calado Ricardo
Published: July 2015

Determining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. Here, we use trace element fingerprinting (TEF) of bivalve shells to discriminate the geographic origin of specimens. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells (Cerastoderma edule) captured with two fishing methods (by hand and by hand-raking) and from five adjacent fishing locations within an estuarine system (Ria de Aveiro, Portugal). Results suggest no differences in TEF of cockle shells captured by hand or by hand-raking, thus confirming that metal rakes do not act as a potential source of metal contamination that could somehow bias TEF results. In contrast, significant differences were recorded among locations for all trace elements analysed. A Canonical Analysis of Principal Coordinates (CAP) revealed that 92% of the samples could be successfully classified according to their fishing location using TEF. We show that TEF can be an accurate, fast and reliable method to determine the geographic origin of bivalves, even among locations separated less than 1 km apart within the same estuarine system. Nonetheless, follow up studies are needed to determine if TEF can reliably discriminate between bivalves originating from different ecosystems.
Rice_Phospho 1.0: a new rice-specific SVM predictor for protein phosphorylation sites
Authors: Lin Shoukai , Song Qi , Tao Huan , Wang Wei , Wan Weifeng , Huang Jian , Xu Chaoqun , Chebii Vivien , Kitony Justine , Que Shufu , Harrison Andrew , He Huaqin
Published: July 2015

Experimentally-determined or computationally-predicted protein phosphorylation sites for distinctive species are becoming increasingly common. In this paper, we compare the predictive performance of a novel classification algorithm with different encoding schemes to develop a rice-specific protein phosphorylation site predictor. Our results imply that the combination of Amino acid occurrence Frequency with Composition of K-Spaced Amino Acid Pairs (AF-CKSAAP) provides the best description of relevant sequence features that surround a phosphorylation site. A support vector machine (SVM) using AF-CKSAAP achieves the best performance in classifying rice protein phophorylation sites when compared to the other algorithms. We have used SVM with AF-CKSAAP to construct a rice-specific protein phosphorylation sites predictor, Rice_Phospho 1.0 (http://bioinformatics.fafu.edu.cn/rice_phospho1.0). We measure the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) of Rice_Phospho 1.0 to be 82.0% and 0.64, significantly higher than those measures for other predictors such as Scansite, Musite, PlantPhos and PhosphoRice. Rice_Phospho 1.0 also successfully predicted the experimentally identified phosphorylation sites in LOC_Os03g51600.1, a protein sequence which did not appear in the training dataset. In summary, Rice_phospho 1.0 outputs reliable predictions of protein phosphorylation sites in rice and will serve as a useful tool to the community.
Anthropogenically enhanced chemical weathering and carbon evasion in the Yangtze Basin
Authors: Guo Jingheng , Wang Fushun , Vogt Rolf David , Zhang Yuhang , Liu Cong-Qiang
Published: July 2015

Chemical weathering is a fundamental geochemical process regulating the atmosphere-land-ocean fluxes and earth’s climate. It is under natural conditions driven primarily by weak carbonic acid that originates from atmosphere CO2 or soil respiration. Chemical weathering is therefore assumed as positively coupled with its CO2 consumption in contemporary geochemistry. Strong acids (i.e. sulfuric- and nitric acid) from anthropogenic sources have been found to influence the weathering rate and CO2 consumption, but their integrated effects remain absent in the world largest river basins. By interpreting the water chemistry and overall proton budget in the Yangtze Basin, we found that anthropogenic acidification had enhanced the chemical weathering by 40% during the past three decades, leading to an increase of 30% in solute discharged to the ocean. Moreover, substitution of carbonic acid by strong acids increased inorganic carbon evasion, offsetting 30% of the CO2 consumption by carbonic weathering. Our assessments show that anthropogenic loadings of sulfuric and nitrogen compounds accelerate chemical weathering but lower its CO2 sequestration. These findings have significant relevance to improving our contemporary global biogeochemical budgets.
Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients
Authors: Liu De-Qing , Li Fang-Fang , Zhang Jiang-Bo , Zhou Tie-Jun , Xue Wen-Qiong , Zheng Xiao-Hui , Chen Yuan-Bin , Liao Xiao-Yu , Zhang Lan , Zhang Shao-Dan , Hu Ye-Zhu , Jia Wei-Hua
Published: July 2015

Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC) and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16INK4a. Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.