bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian Vertex Nomination Using Content and Context
Authors: Suwan Shakira , Lee Dominic S. , Priebe Carey E.
Published: September 2015

Using attributed graphs to model network data has become an attractive approach for various graph inference tasks. Consider a network containing a small subset of interesting entities whose identities are not fully known and that discovering them will be of some significance. Vertex nomination, a subclass of recommender systems relying on the exploitation of attributed graphs, is a task which seeks to identify the unknown entities that are similarly interesting or exhibit analogous latent attributes. This task is a specific type of community detection and is increasingly becoming a subject of current research in many disciplines. Recent studies have shown that information relevant to this task is contained in both the structure of the network and its attributes, and that jointly exploiting them can provide superior vertex nomination performance than either one used alone. We adopt this new approach to formulate a Bayesian model for the vertex nomination problem. Specifically, the goal here is to construct a ‘nomination list’ where entities that are truly interesting are concentrated at the top of the list. Inference with the model is conducted using a Metropolis‐within‐Gibbs algorithm. Performance of the model is illustrated by a Monte Carlo simulation study and on the well‐known Enron email dataset. WIREs Comput Stat 2015, 7:400–416. doi: 10.1002/wics.1365

This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Bayesian Methods and Theory

Statistical and Graphical Methods of Data Analysis > Markov Chain Monte Carlo (MCMC)
Streptomyces metabolites in divergent microbial interactions
Authors: Takano Hideaki , Nishiyama Tatsuya , Amano Sho-ichi , Beppu Teruhiko , Kobayashi Michihiko , Ueda Kenji
Published: September 2015

Streptomyces and related bacteria produce a wide variety of secondary metabolites. Of these, many compounds have industrial applications, but the question of why this group of microorganism produces such various kinds of biologically active substances has not yet been clearly answered. Here, we overview the results from our studies on the novel function and role of Streptomyces metabolites. The diverged action of negative and positive influences onto the physiology of various microorganisms infers the occurrence of complex microbial interactions due to the effect of small molecules produced by Streptomyces. The interactions may serve as a basis for the constitution of biological community.
A Research Framework for Understanding the Practical Impact of Family Involvement in the Juvenile Justice System: The Juvenile Justice Family Involvement Model
Authors: Walker Sarah Cusworth , S. Bishop Asia , D. Pullmann Michael , Bauer Grace
Published: September 2015

Family involvement is recognized as a critical element of service planning for children’s mental health, welfare and education. For the juvenile justice system, however, parents’ roles in this system are complex due to youths’ legal rights, public safety, a process which can legally position parents as plaintiffs, and a historical legacy of blaming parents for youth indiscretions. Three recent national surveys of juvenile justice‐involved parents reveal that the current paradigm elicits feelings of stress, shame and distrust among parents and is likely leading to worse outcomes for youth, families and communities. While research on the impact of family involvement in the justice system is starting to emerge, the field currently has no organizing framework to guide a research agenda, interpret outcomes or translate findings for practitioners. We propose a research framework for family involvement that is informed by a comprehensive review and content analysis of current, published arguments for family involvement in juvenile justice along with a synthesis of family involvement efforts in other child‐serving systems. In this model, family involvement is presented as an ascending, ordinal concept beginning with (1) exclusion, and moving toward climates characterized by (2) information‐giving, (3) information‐eliciting and (4) full, decision‐making partnerships. Specific examples of how courts and facilities might align with these levels are described. Further, the model makes predictions for how involvement will impact outcomes at multiple levels with applications for other child‐serving systems.
Exploitation of the invasive Acacia pycnantha pollen and nectar resources by the native bee Apis mellifera
Authors: Giovanetti Manuela , Mariotti Lippi Marta , Foggi Bruno , Giuliani Claudia
Published: September 2015

The importance of broad ecological perspectives has been well recognised with regard to the spread of alien species. However, less attention has been paid to single plant‐animal relationships such as the mechanism through which interactions with pollinators take place, which is responsible for the evolution of new mutualistic relationships and the outcome of sexual reproduction and distribution of plants. Because the majority of plant‐pollinator relationships are based on food collection by pollinators, we investigated the extent of exploitation of Acacia pycnantha by Apis mellifera. A. pycnantha is native to Australia, but is invasive in many Mediterranean countries, including Italy. We investigated whether visits by the native pollinator A. mellifera to a non‐native food source (A. pycnantha) were occasional, or dictated by a precise pattern matching resource availability. Showing that a native pollinator's foraging strategy has readily adapted to a potential resource offered by an invasive plant allows us to understand better the mechanisms promoting invasiveness of alien angiosperms. We collected data on pollen and nectar characteristics and variation in their availability, and conducted behavioural observations of foraging honey bees. Acacia pycnantha flower heads and extrafloral nectaries are sources of food actively selected by honey bees, which display behaviours strongly associated with resource availability. Our results showed clear evidence of a strong invasive plant‐native pollinator relationship, enhancing the success of sexual reproduction of the alien species. Future studies may highlight to which extent this relationship has influenced the spread of this invasive plant.
Fractures of the knee in children—what can go wrong? A case file study of closed claims in the Patient Compensation Association covering 16 years
Authors: Leeberg V. , Sonne-Holm S. , Krogh Christoffersen J. , Wong C.
Published: September 2015

Introduction

Intra-articular knee fractures in children are rare. The Patient Compensation Association (PCA) receives claims for financial compensation from patients who believe they have sustained damage from their treatment in the health care system. We used relevant cases of closed claims to identify causality and co-factors contributing to these apparent malpractices.

Materials and methods

A partial root core analysis was performed on closed claims from the PCA database concerning proximal tibial fractures in children aged ≤15 years.

Results

We identified 13 cases. The main complaint was missed diagnosis (6 cases)—fractures of the tibial eminence were the main culprit, with damage to the popliteal artery caused by a medial condyle fracture being the most serious. All cases were missed by junior doctors. Secondary complaints were problems with casting, dissatisfaction with correct treatment, and insufficient surgery or complications relating to surgery. Eight of the complaints were acknowledged, with six receiving financial compensation ranging from EUR 9,600 to EUR 70,000. Five out of the six cases of missed diagnosis were acknowledged.

Conclusions

This study indicates that recognizing the degree of injury to the knee in children, which should include an X-ray examination, is key to preventing missed diagnosis and delayed and potentially more difficult surgery with long-lasting sequelae for the child. The PCA database seems to be a useful way to highlight systematic problems in the Danish health care system and could potentially be an important means to improving patient safety and preventing treatment-related injuries.
The response of tropical rainforests to drought—lessons from recent research and future prospects
Authors: Bonal Damien , Burban Benoit , Stahl Clément , Wagner Fabien , Hérault Bruno
Published: September 2015

Key message

We review the recent findings on the influence of drought on tree mortality, growth or ecosystem functioning in tropical rainforests. Drought plays a major role in shaping tropical rainforests and the response mechanisms are highly diverse and complex. The numerous gaps identified here require the international scientific community to combine efforts in order to conduct comprehensive studies in tropical rainforests on the three continents. These results are essential to simulate the future of these ecosystems under diverse climate scenarios and to predict the future of the global earth carbon balance.

Context

Tropical rainforest ecosystems are characterized by high annual rainfall. Nevertheless, rainfall regularly fluctuates during the year and seasonal soil droughts do occur. Over the past decades, a number of extreme droughts have hit tropical rainforests, not only in Amazonia but also in Asia and Africa. The influence of drought events on tree mortality and growth or on ecosystem functioning (carbon and water fluxes) in tropical rainforest ecosystems has been studied intensively, but the response mechanisms are complex.

Aims

Herein, we review the recent findings related to the response of tropical forest ecosystems to seasonal and extreme droughts and the current knowledge about the future of these ecosystems.

Results

This review emphasizes the progress made over recent years and the importance of the studies conducted under extreme drought conditions or in through-fall exclusion experiments in understanding the response of these ecosystems. It also points to the great diversity and complexity of the response of tropical rainforest ecosystems to drought.

Conclusion

The numerous gaps identified here require the international scientific community to combine efforts in order to conduct comprehensive studies in tropical forest regions. These results are essential to simulate the future of these ecosystems under diverse climate scenarios and to predict the future of the global earth carbon balance.
The Rubber Hand Illusion Paradigm as a Sensory Learning Process in Patients with Schizophrenia
Authors: Lev-Ari L. , Hirschmann S. , Dyskin O. , Goldman O. , Hirschmann I.
Published: September 2015

Objective:

The Rubber Hand Illusion (RHI) has previously been used to depict the hierarchy between visual, tactile and perceptual stimuli. Studies on schizophrenia inpatients (SZs) have found mixed results in the ability to first learn the illusion, and have yet to explain the learning process involved. This study's aim was two-fold: to examine the learning process of the RHI in SZs and healthy controls over time, and to better understand the relationship between psychotic symptoms and the RHI.

Method:

Thirty schizophrenia inpatients and 30 healthy controls underwent five different trials of the RHI over a two-week period.

Results:

As has been found in previous studies, SZs felt the initial illusion faster than healthy controls did, but their learning process throughout the trials was inconsistent. Furthermore, for SZs, no correlations between psychotic symptoms and the learning of the illusion emerged.

Conclusion:

Healthy individuals show a delayed reaction to first feeling the illusion (due to latent inhibition), but easily learn the illusion over time. For SZs, both strength of the illusion and the ability to learn the illusion over time are inconsistent. The cognitive impairment in SZ impedes the learning process of the RHI, and SZs are unable to utilize the repetition of the process as healthy individuals can.
Effect of DISC1 Polymorphisms on the Long-term Course of Neurocognitive Deficits in Non-affective Psychosis
Authors: Vázquez-Bourgon J. , Ayesa-Arriola R. , Fatjó-Vilas M. , Roiz-Santiañez R. , Fañanás L. , Crespo-Facorro B.
Published: September 2015

Neurocognitive deficits are core symptoms of schizophrenia that determine a poorer outcome. High variability in the progression of neuropsychological deficits in schizophrenia has been described. It is still unknown whether genetic variations can affect the course of cognitive deficits. Variations in the Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with neurocognitive deficits. This study investigated the association between 3 DISC1 polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped. Cognitive function was assessed at baseline and after 3 years of initiating treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects. Patients carrying the A allele of rs1000731 exhibited a significant improvement in Working Memory and Attention domains, and the homozygosity of the A allele of rs821616 showed a significant improvement in Motor Dexterity performance over 3 years of follow-up. In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.
Factor Structure of the Bern Psychopathology Scale in a Sample of Patients with Schizophrenia Spectrum Disorders
Authors: Lang Fabian U. , Stierlin Annabel S. , Stegmayer Katharina , Walther Sebastian , Becker Thomas , Jäger Markus
Published: September 2015

Background:

The Bern Psychopathology Scale (BPS) is based on a system-specific approach to classifying the psychopathological symptom pattern of schizophrenia. It consists of subscales for three domains (language, affect and motor behaviour) that are hypothesized to be related to specific brain circuits. The aim of the study was to examine the factor structure of the BPS in patients with schizophrenia spectrum disorders.

Methods:

One hundred and forty-nine inpatients with schizophrenia spectrum disorders were recruited at the Department of Psychiatry II, Ulm University, Germany (n = 100) and at the University Hospital of Psychiatry, Bern, Switzerland (n = 49). Psychopathology was assessed with the BPS. The VARCLUS procedure of SAS® (a type of oblique component analysis) was used for statistical analysis.

Results:

Six clusters were identified (inhibited language, inhibited motor behaviour, inhibited affect, disinhibited affect, disinhibited language/motor behaviour, inhibited language/motor behaviour) which explained 40.13% of the total variance of the data. A binary division of attributes into an inhibited and disinhibited cluster was appropriate, although an overlap was found between the language and motor behaviour domains. There was a clear distinction between qualitative and quantitative symptoms.

Conclusions:

The results argue for the validity of the BPS in identifying subsyndromes of schizophrenia spectrum disorders according to a dimensional approach. Future research should address the longitudinal assessment of dimensional psychopathological symptoms and elucidate the underlying neurobiological processes.
Preparing an Academic Medical Center to Manage Patients Infected With Ebola: Experiences of a University Hospital
Authors: Schultz Carl H. , Koenig Kristi L. , Alassaf Wajdan
Published: September 2015

As Ebola has spread beyond West Africa, the challenges confronting health care systems with no experience in managing such patients are enormous. Not only is Ebola a significant threat to a population’s health, it can infect the medical personnel trying to treat it. As such, it represents a major challenge to those in public health, emergency medical services (EMS), and acute care hospitals. Our academic medical center volunteered to become an Ebola Treatment Center as part of the US effort to manage the threat. We developed detailed policies and procedures for Ebola patient management at our university hospital. Both the EMS system and county public health made significant contributions during the development process. This article shares information about this process and the outcomes to inform other institutions facing similar challenges of preparing for an emerging threat with limited resources. The discussion includes information about management of (1) patients who arrive by ambulance with prior notification, (2) spontaneous walk-in patients, and (3) patients with confirmed Ebola who are interfacility transfers. Hospital management includes information about Ebola screening procedures, personal protective equipment selection and personnel training, erection of a tent outside the main facility, establishing an Ebola treatment unit inside the facility, and infectious waste and equipment management. Finally, several health policy considerations are presented. (Disaster Med Public Health Preparedness. 2015;9:558–567)
The reception of Hermann of Reichenau at St Michelsberg: some observations on fragments of interval notation
Authors: WENDLING MIRIAM
Published: September 2015

The bindings of a large number of manuscripts formerly held in the library of the Benedictine monastery of St Michelsberg in Bamberg preserve fragments of medieval chantbooks documenting a culture in which practical singing and music theory were closely intertwined. These remnants, the work of generations of scribes, reveal a sustained concern for correctness ranging from the use of pitch-clarifying neume notations, to the use of letters, to the recording of melodies along lines prescribed in theoretical works. The influence the music theorist Hermann of Reichenau on St Michelsberg's own theorist, Frutolf, raises two questions. First, what is the nature of the relationship between practical chant and music theory books at St Michelsberg? Second, how was Hermann's notation used at the monastery?
McEwen Receives 2015 Whipple Award
Authors:   AGU
Published: September 2015

Alfred McEwen will receive the 2015 Whipple Award at the 2015 American Geophysical Union Fall Meeting, to be held 14–18 December in San Francisco, Calif. The award recognizes an individual who has made an outstanding contribution in the field of planetary science.
Global distribution and vertical patterns of a prymnesiophyte–cyanobacteria obligate symbiosis
Authors: Cabello Ana M , Cornejo-Castillo Francisco M , Raho Nicolas , Blasco Dolors , Vidal Montserrat , Audic Stéphane , de Vargas Colomban , Latasa Mikel , Acinas Silvia G , Massana Ramon
Published: September 2015

A marine symbiosis has been recently discovered between prymnesiophyte species and the unicellular diazotrophic cyanobacterium UCYN-A. At least two different UCYN-A phylotypes exist, the clade UCYN-A1 in symbiosis with an uncultured small prymnesiophyte and the clade UCYN-A2 in symbiosis with the larger Braarudosphaera bigelowii. We targeted the prymnesiophyte–UCYN-A1 symbiosis by double CARD-FISH (catalyzed reporter deposition-fluorescence in situ hybridization) and analyzed its abundance in surface samples from the MALASPINA circumnavigation expedition. Our use of a specific probe for the prymnesiophyte partner allowed us to verify that this algal species virtually always carried the UCYN-A symbiont, indicating that the association was also obligate for the host. The prymnesiophyte–UCYN-A1 symbiosis was detected in all ocean basins, displaying a patchy distribution with abundances (up to 500 cells ml−1) that could vary orders of magnitude. Additional vertical profiles taken at the NE Atlantic showed that this symbiosis occupied the upper water column and disappeared towards the Deep Chlorophyll Maximum, where the biomass of the prymnesiophyte assemblage peaked. Moreover, sequences of both prymnesiophyte partners were searched within a large 18S rDNA metabarcoding data set from the Tara-Oceans expedition around the world. This sequence-based analysis supported the patchy distribution of the UCYN-A1 host observed by CARD-FISH and highlighted an unexpected homogeneous distribution (at low relative abundance) of B. bigelowii in the open ocean. Our results demonstrate that partners are always in symbiosis in nature and show contrasted ecological patterns of the two related lineages.
Genomic and metagenomic surveys of hydrogenase distribution indicate H2 is a widely utilised energy source for microbial growth and survival
Authors: Greening Chris , Biswas Ambarish , Carere Carlo R , Jackson Colin J , Taylor Matthew C , Stott Matthew B , Cook Gregory M , Morales Sergio E
Published: September 2015

Recent physiological and ecological studies have challenged the long-held belief that microbial metabolism of molecular hydrogen (H2) is a niche process. To gain a broader insight into the importance of microbial H2 metabolism, we comprehensively surveyed the genomic and metagenomic distribution of hydrogenases, the reversible enzymes that catalyse the oxidation and evolution of H2. The protein sequences of 3286 non-redundant putative hydrogenases were curated from publicly available databases. These metalloenzymes were classified into multiple groups based on (1) amino acid sequence phylogeny, (2) metal-binding motifs, (3) predicted genetic organisation and (4) reported biochemical characteristics. Four groups (22 subgroups) of [NiFe]-hydrogenase, three groups (6 subtypes) of [FeFe]-hydrogenases and a small group of [Fe]-hydrogenases were identified. We predict that this hydrogenase diversity supports H2-based respiration, fermentation and carbon fixation processes in both oxic and anoxic environments, in addition to various H2-sensing, electron-bifurcation and energy-conversion mechanisms. Hydrogenase-encoding genes were identified in 51 bacterial and archaeal phyla, suggesting strong pressure for both vertical and lateral acquisition. Furthermore, hydrogenase genes could be recovered from diverse terrestrial, aquatic and host-associated metagenomes in varying proportions, indicating a broad ecological distribution and utilisation. Oxygen content (pO2) appears to be a central factor driving the phylum- and ecosystem-level distribution of these genes. In addition to compounding evidence that H2 was the first electron donor for life, our analysis suggests that the great diversification of hydrogenases has enabled H2 metabolism to sustain the growth or survival of microorganisms in a wide range of ecosystems to the present day. This work also provides a comprehensive expanded system for classifying hydrogenases and identifies new prospects for investigating H2 metabolism.
Structure and function of natural sulphide-oxidizing microbial mats under dynamic input of light and chemical energy
Authors: Klatt Judith M , Meyer Steffi , Häusler Stefan , Macalady Jennifer L , de Beer Dirk , Polerecky Lubos
Published: September 2015

We studied the interaction between phototrophic and chemolithoautotrophic sulphide-oxidizing microorganisms in natural microbial mats forming in sulphidic streams. The structure of these mats varied between two end-members: one characterized by a layer dominated by large sulphur-oxidizing bacteria (SOB; mostly Beggiatoa-like) on top of a cyanobacterial layer (B/C mats) and the other with an inverted structure (C/B mats). C/B mats formed where the availability of oxygen from the water column was limited (<5 μm). Aerobic chemolithotrophic activity of the SOB depended entirely on oxygen produced locally by cyanobacteria during high light conditions. In contrast, B/C mats formed at locations where oxygen in the water column was comparatively abundant (>45 μm) and continuously present. Here SOB were independent of the photosynthetic activity of cyanobacteria and outcompeted the cyanobacteria in the uppermost layer of the mat where energy sources for both functional groups were concentrated. Outcompetition of photosynthetic microbes in the presence of light was facilitated by the decoupling of aerobic chemolithotrophy and oxygenic phototrophy. Remarkably, the B/C mats conserved much less energy than the C/B mats, although similar amounts of light and chemical energy were available. Thus ecosystems do not necessarily develop towards optimal energy usage. Our data suggest that, when two independent sources of energy are available, the structure and activity of microbial communities is primarily determined by the continuous rather than the intermittent energy source, even if the time-integrated energy flux of the intermittent energy source is greater.
Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike
Authors: Lee Jeong Hyun , Leaman Daniel P. , Kim Arthur S. , Torrents de la Peña Alba , Sliepen Kwinten , Yasmeen Anila , Derking Ronald , Ramos Alejandra , de Taeye Steven W. , Ozorowski Gabriel , Klein Florian , Burton Dennis R. , Nussenzweig Michel C. , Poignard Pascal , Moore John P. , Klasse Per Johan , Sanders Rogier W. , Zwick Michael B. , Wilson Ian A. , Ward Andrew B.
Published: September 2015

The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120–gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120–gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.
Sub-10-fs population inversion in N2+ in air lasing through multiple state coupling
Authors: Xu Huailiang , Lötstedt Erik , Iwasaki Atsushi , Yamanouchi Kaoru
Published: September 2015

Laser filamentation generated when intense laser pulses propagate in air has been an attractive phenomenon having a variety of potential applications such as detection and spectroscopy of gases at far distant places. It was discovered recently that the filamentation in air induces ‘lasing’, showing that electronically excited N2+ is population-inverted, exhibiting marked contrast to the common understanding that molecular ions generated by intense laser fields are prepared mostly in their electronic ground states. Here, to clarify the mechanism of the population inversion, we adopt few-cycle laser pulses, and experimentally demonstrate that the lasing at 391 nm occurs instantaneously after N2+ is produced. Numerical simulations clarify that the population inversion is realized by the post-ionization couplings among the lowest three electronic states of N2+. Our results shed light on the controversy over the mechanism of the air lasing, and show that this post-ionization coupling can be a general mechanism of the atmospheric lasing.
Femtosecond structural transformation of phase-change materials far from equilibrium monitored by coherent phonons
Authors: Hase Muneaki , Fons Paul , Mitrofanov Kirill , Kolobov Alexander V. , Tominaga Junji
Published: September 2015

Multicomponent chalcogenides, such as quasi-binary GeTe–Sb2Te3 alloys, are widely used in optical data storage media in the form of rewritable optical discs. Ge2Sb2Te5 (GST) in particular has proven to be one of the best-performing materials, whose reliability allows more than 106 write–erase cycles. Despite these industrial applications, the fundamental kinetics of rapid phase change in GST remain controversial, and active debate continues over the ultimate speed limit. Here we explore ultrafast structural transformation in a photoexcited GST superlattice, where GeTe and Sb2Te3 are spatially separated, using coherent phonon spectroscopy with pump–pump–probe sequences. By analysing the coherent phonon spectra in different time regions, complex structural dynamics upon excitation are observed in the GST superlattice (but not in GST alloys), which can be described as the mixing of Ge sites from two different coordination environments. Our results suggest the possible applicability of GST superlattices for ultrafast switching devices.
Swarming bacteria migrate by Lévy Walk
Authors: Ariel Gil , Rabani Amit , Benisty Sivan , Partridge Jonathan D. , Harshey Rasika M. , Be'er Avraham
Published: September 2015

Individual swimming bacteria are known to bias their random trajectories in search of food and to optimize survival. The motion of bacteria within a swarm, wherein they migrate as a collective group over a solid surface, is fundamentally different as typical bacterial swarms show large-scale swirling and streaming motions involving millions to billions of cells. Here by tracking trajectories of fluorescently labelled individuals within such dense swarms, we find that the bacteria are performing super-diffusion, consistent with Lévy walks. Lévy walks are characterized by trajectories that have straight stretches for extended lengths whose variance is infinite. The evidence of super-diffusion consistent with Lévy walks in bacteria suggests that this strategy may have evolved considerably earlier than previously thought.
Metal oxide-resistive memory using graphene-edge electrodes
Authors: Lee Seunghyun , Sohn Joon , Jiang Zizhen , Chen Hong-Yu , Philip Wong H.-S.
Published: September 2015

The emerging paradigm of ‘abundant-data’ computing requires real-time analytics on enormous quantities of data collected by a mushrooming network of sensors. Todays computing technology, however, cannot scale to satisfy such big data applications with the required throughput and energy efficiency. The next technology frontier will be monolithically integrated chips with three-dimensionally interleaved memory and logic for unprecedented data bandwidth with reduced energy consumption. In this work, we exploit the atomically thin nature of the graphene edge to assemble a resistive memory (∼3 Å thick) stacked in a vertical three-dimensional structure. We report some of the lowest power and energy consumption among the emerging non-volatile memories due to an extremely thin electrode with unique properties, low programming voltages, and low current. Circuit analysis of the three-dimensional architecture using experimentally measured device properties show higher storage potential for graphene devices compared that of metal based devices.
CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis
Authors: Murayama Masanori A. , Kakuta Shigeru , Inoue Asuka , Umeda Naoto , Yonezawa Tomo , Maruhashi Takumi , Tateishi Koichiro , Ishigame Harumichi , Yabe Rikio , Ikeda Satoshi , Seno Akimasa , Chi Hsi-Hua , Hashiguchi Yuriko , Kurata Riho , Tada Takuya , Kubo Sachiko , Sato Nozomi , Liu Yang , Hattori Masahira , Saijo Shinobu , Matsushita Misao , Fujita Teizo , Sumida Takayuki , Iwakura Yoichiro
Published: September 2015

The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6−/− mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6−/− mice and C1qtnf6−/− embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases.
EZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma
Authors: Liu Haiou , Liu Yidong , Liu Weisi , Zhang Weijuan , Xu Jiejie
Published: September 2015

The CXC chemokine receptor 4 (CXCR4) exerts a variety of functions at different steps of hepatocellular carcinoma (HCC) progression. The molecular mechanisms and therapeutic value of CXCR4 in the development of HCC remain undefined. Here we show that aberrant CXCR4 overexpression is associated with poor prognosis and aggressive characteristics of HCC. Suppression of CXCR4 activity via CXCR4 knockdown, AMD3100 or neutralizing antibody administration inhibits hepatoma cell tumorigenesis in vitro and in vivo. CXCR4 overexpression displays the opposite effects. Using Mir library screening we identify miR-622 as a regulator of CXCR4. Further studies show that miR-622 directly target the 3′ untranslated region of CXCR4 and is transcriptionally repressed by EZH2-induced H3K27 trimethylation and promoter methylation. EZH2/miR-622 promotes tumorigenesis through CXCR4. EZH2-mediated loss of miR-622 is found to correlate with CXCR4 overexpression and unfavourable prognosis in HCC patients. This study establishes EZH2/miR-622/CXCR4 as a potential adverse prognostic factor and therapeutic target for HCC patients.
‘Purpose in Life’ as a psychosocial resource in healthy aging: an examination of cortisol baseline levels and response to the Trier Social Stress Test
Authors: Fogelman Nia , Canli Turhan
Published: September 2015

‘Purpose in Life’ (Purpose) is associated with healthy aging, but it is unknown whether this association is causal. Conceptualizing Purpose as a form of psychosocial resource, one mechanism promoting health could be the regulation of stress hormones. To test this hypothesis, we recruited 44 older community-dwelling adults to examine the association between Purpose and cortisol at baseline, in response to, and recovery from, an acute social laboratory stressor. Purpose did not predict cortisol baseline or reactivity, but did predict a faster recovery to pre-stress baseline levels. The health benefits of Purpose in aging may therefore reflect the combination of a normal stress response, which serves an adaptive benefit of allostasis, with an accelerated stress recovery, which reduces the burden of allostatic load. This model should be tested in future studies using larger samples, multiple related constructs, and longitudinal designs that include participants’ health records.
High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations
Authors: Mott Bryan T. , Eastman Richard T. , Guha Rajarshi , Sherlach Katy S. , Siriwardana Amila , Shinn Paul , McKnight Crystal , Michael Sam , Lacerda-Queiroz Norinne , Patel Paresma R. , Khine Pwint , Sun Hongmao , Kasbekar Monica , Aghdam Nima , Fontaine Shaun D. , Liu Dongbo , Mierzwa Tim , Mathews-Griner Lesley A. , Ferrer Marc , Renslo Adam R. , Inglese James , Yuan Jing , Roepe Paul D. , Su Xin-zhuan , Thomas Craig J.
Published: September 2015

Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy.
The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis
Authors: Gabarrini Giorgio , de Smit Menke , Westra Johanna , Brouwer Elisabeth , Vissink Arjan , Zhou Kai , A. Rossen John W. , Stobernack Tim , van Dijl Jan Maarten , Jan van Winkelhoff Arie
Published: September 2015

Periodontitis is an infective process that ultimately leads to destruction of the soft and hard tissues that support the teeth (the periodontium). Periodontitis has been proposed as a candidate risk factor for development of the autoimmune disease rheumatoid arthritis (RA). Porphyromonas gingivalis, a major periodontal pathogen, is the only known prokaryote expressing a peptidyl arginine deiminase (PAD) enzyme necessary for protein citrullination. Antibodies to citrullinated proteins (anti-citrullinated protein antibodies, ACPA) are highly specific for RA and precede disease onset. Objective of this study was to assess P. gingivalis PAD (PPAD) gene expression and citrullination patterns in representative samples of P. gingivalis clinical isolates derived from periodontitis patients with and without RA and in related microbes of the Porphyromonas genus. Our findings indicate that PPAD is omnipresent in P. gingivalis, but absent in related species. No significant differences were found in the composition and expression of the PPAD gene of P. gingivalis regardless of the presence of RA or periodontal disease phenotypes. From this study it can be concluded that if P. gingivalis plays a role in RA, it is unlikely to originate from a variation in PPAD gene expression.
In situ biomarker discovery and label-free molecular histopathological diagnosis of lung cancer by ambient mass spectrometry imaging
Authors: Li Tiegang , He Jiuming , Mao Xinxin , Bi Ying , Luo Zhigang , Guo Chengan , Tang Fei , Xu Xin , Wang Xiaohao , Wang Mingrong , Chen Jie , Abliz Zeper
Published: September 2015

Sensitive and spatial exploration of the metabolism of tumors at the metabolome level is highly challenging. In this study, we developed an in situ metabolomics method based on ambient mass spectrometry imaging using air flow-assisted desorption electrospray ionization (AFADESI), which can spatially explore the alteration of global metabolites in tissues with high sensitivity. Using this method, we discovered potential histopathological diagnosis biomarkers (including lipids, amino acids, choline, peptides and carnitine) from 52 postoperative lung cancer tissue samples and then subsequently used these biomarkers to generate images for rapid and label-free histopathological diagnosis. These biomarkers were validated with a sensitivity and a specificity of 93.5% and 100%, respectively. Moreover, a single imaging analysis of a cryosection that visualized all these biomarkers, taking tens of minutes, revealed the type and subtype of the cancer. This method could potentially be used as a molecular pathological tool for rapid clinical lung cancer diagnosis and immediate image-guided surgery.
Genetic responses to seasonal variation in altitudinal stress: whole-genome resequencing of great tit in eastern Himalayas
Authors: Qu Yanhua , Tian Shilin , Han Naijian , Zhao Hongwei , Gao Bin , Fu Jun , Cheng Yalin , Song Gang , Ericson Per G. P. , Zhang Yong E. , Wang Dawei , Quan Qing , Jiang Zhi , Li Ruiqiang , Lei Fumin
Published: September 2015

Species that undertake altitudinal migrations are exposed to a considerable seasonal variation in oxygen levels and temperature. How they cope with this was studied in a population of great tit (Parus major) that breeds at high elevations and winters at lower elevations in the eastern Himalayas. Comparison of population genomics of high altitudinal great tits and those living in lowlands revealed an accelerated genetic selection for carbohydrate energy metabolism (amino sugar, nucleotide sugar metabolism and insulin signaling pathways) and hypoxia response (PI3K-akt, mTOR and MAPK signaling pathways) in the high altitudinal population. The PI3K-akt, mTOR and MAPK pathways modulate the hypoxia-inducible factors,HIF-1αandVEGFprotein expression thus indirectly regulate hypoxia induced angiogenesis, erythropoiesis and vasodilatation. The strategies observed in high altitudinal great tits differ from those described in a closely related species on the Tibetan Plateau, the sedentary ground tit (Parus humilis). This species has enhanced selection in lipid-specific metabolic pathways and hypoxia-inducible factor pathway (HIF-1). Comparative population genomics also revealed selection for larger body size in high altitudinal great tits.
Enhanced Reduction of Graphene Oxide on Recyclable Cu Foils to Fabricate Graphene Films with Superior Thermal Conductivity
Authors: Huang Sheng-Yun , Zhao Bo , Zhang Kai , Yuen Matthew M. F. , Xu Jian-Bin , Fu Xian-Zhu , Sun Rong , Wong Ching-Ping
Published: September 2015

Large-area freestanding graphene films are facilely fabricated by reducing graphene oxide films on recyclable Cu foils in H2-containing atmosphere at high temperature. Cu might act as efficient catalysts for considerably improved reduction of graphene oxide according to the SEM, EDS, XRD, XPS, Raman and TGA results. Comparing to the graphene films with ~30 μm thickness reduced without Cu substrate at 900 °C, the thermal conductivity and electrical conductivity of graphene films reduced on Cu foils are enhanced about 140% to 902 Wm−1K−1 and 3.6 × 104 S/m, respectively. Moreover, the graphene films demonstrate superior thermal conductivity of ~1219 Wm−1K−1 as decreasing the thickness of films to ~10 μm. The graphene films also exhibit excellent mechanical properties and flexibility.
Microfluidic cytometric analysis of cancer cell transportability and invasiveness
Authors: Liu Zongbin , Lee Yeonju , Jang Joon hee , Li Ying , Han Xin , Yokoi Kenji , Ferrari Mauro , Zhou Ledu , Qin Lidong
Published: September 2015

The extensive phenotypic and functional heterogeneity of cancer cells plays an important role in tumor progression and therapeutic resistance. Characterizing this heterogeneity and identifying invasive phenotype may provide possibility to improve chemotherapy treatment. By mimicking cancer cell perfusion through circulatory system in metastasis, we develop a unique microfluidic cytometry (MC) platform to separate cancer cells at high throughput and further derive a physical parameter ‘transportability’ to characterize the ability to pass through micro-constrictions. The transportability is determined by cell stiffness and cell-surface frictional property and can be used to probe tumor heterogeneity, discriminate more invasive phenotypes and correlate with biomarker expressions in breast cancer cells. Decreased cell stiffness and cell-surface frictional force leads to an increase in transportability and may be a feature of invasive cancer cells by promoting cell perfusion through narrow spaces in circulatory system. The MC-Chip provides a promising microfluidic platform for studying cell mechanics and transportability could be used as a novel marker for probing tumor heterogeneity and determining invasive phenotypes.
Dynamic expression of chromatin modifiers during developmental transitions in mouse preimplantation embryos
Authors: Nestorov Peter , Hotz Hans-Rudolf , Liu Zichuan , Peters Antoine H.F.M.
Published: September 2015

During mouse preimplantation development, major changes in cell fate are accompanied by extensive alterations of gene expression programs. Embryos first transition from a maternal to zygotic program and subsequently specify the pluripotent and the trophectodermal cell lineages. These processes are regulated by key transcription factors, likely in cooperation with chromatin modifiers that control histone and DNA methylation. To characterize the spatiotemporal expression of chromatin modifiers in relation to developmental transitions, we performed gene expression profiling of 156 genes in individual oocytes and single blastomeres of developing mouse embryos until the blastocyst stage. More than half of the chromatin modifiers displayed either maternal or zygotic expression. We also detected lineage-specific expression of several modifiers, including Ezh1, Prdm14, Scmh1 and Tet1 underscoring possible roles in cell fate decisions. Members of the SET-domain containing SMYD family showed differential gene expression during preimplantation development. We further observed co-expression of genes with opposing biochemical activities, such as histone methyltransferases and demethylases, suggesting the existence of a dynamic chromatin steady-state during preimplantation development.
Crystal structure of Streptococcus pneumoniae pneumolysin provides key insights into early steps of pore formation
Authors: Lawrence Sara L. , Feil Susanne C. , Morton Craig J. , Farrand Allison J. , Mulhern Terrence D. , Gorman Michael A. , Wade Kristin R. , Tweten Rodney K. , Parker Michael W.
Published: September 2015

Pore-forming proteins are weapons often used by bacterial pathogens to breach the membrane barrier of target cells. Despite their critical role in infection important structural aspects of the mechanism of how these proteins assemble into pores remain unknown. Streptococcus pneumoniae is the world’s leading cause of pneumonia, meningitis, bacteremia and otitis media. Pneumolysin (PLY) is a major virulence factor of S. pneumoniae and a target for both small molecule drug development and vaccines. PLY is a member of the cholesterol-dependent cytolysins (CDCs), a family of pore-forming toxins that form gigantic pores in cell membranes. Here we present the structure of PLY determined by X-ray crystallography and, in solution, by small-angle X-ray scattering. The crystal structure reveals PLY assembles as a linear oligomer that provides key structural insights into the poorly understood early monomer-monomer interactions of CDCs at the membrane surface.
Promoting the Adsorption of Metal Ions on Kaolinite by Defect Sites: A Molecular Dynamics Study
Authors: Li Xiong , Li Hang , Yang Gang
Published: September 2015

Defect sites exist abundantly in minerals and play a crucial role for a variety of important processes. Here molecular dynamics simulations are used to comprehensively investigate the adsorption behaviors, stabilities and mechanisms of metal ions on defective minerals, considering different ionic concentrations, defect sizes and contents. Outer-sphere adsorbed Pb2+ ions predominate for all models (regular and defective), while inner-sphere Na+ ions, which exist sporadically only at concentrated solutions for regular models, govern the adsorption for all defective models. Adsorption quantities and stabilities of metal ions on kaolinite are fundamentally promoted by defect sites, thus explaining the experimental observations. Defect sites improve the stabilities of both inner- and outer-sphere adsorption and (quasi) inner-sphere Pb2+ ions emerge only at defect sites that reinforce the interactions. Adsorption configurations are greatly altered by defect sites but respond weakly by changing defect sizes or contents. Both adsorption quantities and stabilities are enhanced by increasing defect sizes or contents, while ionic concentrations mainly affect adsorption quantities. We also find that adsorption of metal ions and anions can be promoted by each other and proceeds in a collaborative mechanism. Results thus obtained are beneficial to comprehend related processes for all types of minerals.