bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat
Authors: Wu Hemmings , Ghekiere Hartwin , Beeckmans Dorien , Tambuyzer Tim , van Kuyck Kris , Aerts Jean-Marie , Nuttin Bart 
Published: April 2015

AbstractConventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability and affordability. Our open-source closed-loop DBS system is effective and warrants further research using open-source hardware for closed-loop neuromodulation.
Comparing the model-simulated global warming signal to observations using empirical estimates of unforced noise
Authors: Brown Patrick T. , Li Wenhong , Cordero Eugene C. , Mauget Steven A. 
Published: April 2015

AbstractThe comparison of observed global mean surface air temperature (GMT) change to the mean change simulated by climate models has received much public and scientific attention. For a given global warming signal produced by a climate model ensemble, there exists an envelope of GMT values representing the range of possible unforced states of the climate system (the Envelope of Unforced Noise; EUN). Typically, the EUN is derived from climate models themselves, but climate models might not accurately simulate the correct characteristics of unforced GMT variability. Here, we simulate a new, empirical, EUN that is based on instrumental and reconstructed surface temperature records. We compare the forced GMT signal produced by climate models to observations while noting the range of GMT values provided by the empirical EUN. We find that the empirical EUN is wide enough so that the interdecadal variability in the rate of global warming over the 20th century does not necessarily require corresponding variability in the rate-of-increase of the forced signal. The empirical EUN also indicates that the reduced GMT warming over the past decade or so is still consistent with a middle emission scenario’s forced signal, but is likely inconsistent with the steepest emission scenario’s forced signal.
Effects of substrate conductivity on cell morphogenesis and proliferation using tailored, atomic layer deposition-grown ZnO thin films
Authors: Choi Won Jin , Jung Jongjin , Lee Sujin , Chung Yoon Jang , Yang Cheol-Soo , Lee Young Kuk , Lee You-Seop , Park Joung Kyu , Ko Hyuk Wan , Lee Jeong-O 
Published: April 2015

AbstractWe demonstrate that ZnO films grown by atomic layer deposition (ALD) can be employed as a substrate to explore the effects of electrical conductivity on cell adhesion, proliferation and morphogenesis. ZnO substrates with precisely tunable electrical conductivity were fabricated on glass substrates using ALD deposition. The electrical conductivity of the film increased linearly with increasing duration of the ZnO deposition cycle (thickness), whereas other physical characteristics, such as surface energy and roughness, tended to saturate at a certain value. Differences in conductivity dramatically affected the behavior of SF295 glioblastoma cells grown on ZnO films, with high conductivity (thick) ZnO films causing growth arrest and producing SF295 cell morphologies distinct from those cultured on insulating substrates. Based on simple electrostatic calculations, we propose that cells grown on highly conductive substrates may strongly adhere to the substrate without focal-adhesion complex formation, owing to the enhanced electrostatic interaction between cells and the substrate. Thus, the inactivation of focal adhesions leads to cell proliferation arrest. Taken together, the work presented here confirms that substrates with high conductivity disturb the cell-substrate interaction, producing cascading effects on cellular morphogenesis and disrupting proliferation and suggests that ALD-grown ZnO offers a single-variable method for uniquely tailoring conductivity.
Intrinsic Functional Plasticity of the Sensory-Motor Network in Patients with Cervical Spondylotic Myelopathy
Authors: Zhou F. Q. , Tan Y. M. , Wu L. , Zhuang Y. , He L. C. , Gong H. H. 
Published: April 2015

AbstractSeveral neuroimaging studies have suggested brain reorganisation in patients with cervical spondylotic myelopathy (CSM); however, the changes in spontaneous neuronal activity that are associated with connectedness remain largely unknown. In this study, functional connectivity strength (FCS), a data-driven degree centrality method based on a theoretical approach, was applied for the first time to investigate changes in the sensory-motor network (SMN) at the voxel level. Comparatively, CSM not only showed significantly decreased FCS in the operculum-integrated regions, which exhibited reduced resting-state functional connectivity (rsFC) around the Rolandic sulcus, but it also showed increased FCS in the premotor, primary somatosensory and parietal-integrated areas, which primarily showed an enhanced rsFC pattern. Correlation analysis showed that altered FCS (in the left premotor-ventral/precentral-operculum, right operculum-parietale 4 and right S1) was associated with worsening Japanese Orthopaedic Association scores and that the rsFC pattern was influenced by cervical cord micro-structural damage at the C2 level. Together, these findings suggest that during myelopathy, the intrinsic functional plasticity of the SMN responds to the insufficient sensory and motor experience in CSM patients. This knowledge may improve our understanding of the comprehensive functional defects found in CSM patients and may inspire the development of new therapeutic strategies in the future.
Therapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin
Authors: Chan King Chi , Chan Lai Sheung , Ip Joseph Chok Yan , Lo Carman , Yip Timothy Tak Chun , Ngan Roger Kai Cheong , Wong Ricky Ngok Shun , Lo Kwok Wai , Ng Wai Tong , Lee Anne Wing Mui , Tsao George Sai Wah , Kahn Michael , Lung Maria Li , Mak Nai Ki 
Published: April 2015

AbstractNasopharyngeal carcinoma (NPC) is an EBV-associated epithelial malignancy prevalent in southern China. Presence of treatment-resistant cancer stem cells (CSC) may associate with tumor relapse and metastasis in NPC. ICG-001 is a specific CBP/β-catenin antagonist that can block CBP/β-catenin-mediated transcription of stem cell associated genes and enhance p300/β-catenin-mediated transcription, thereby reducing the CSC-like population via forced differentiation. In this study, we aimed to evaluate the effect of ICG-001 on the CSC-like population and the combination effect of ICG-001 with cisplatin in the C666-1 EBV-positive NPC cells. Results showed that ICG-001 inhibited C666-1 cell growth and reduced expression of CSC-associated proteins with altered expression of epithelial-mesenchymal transition (EMT) markers. ICG-001 also inhibited C666-1 tumor sphere formation, accompanied with reduced SOX2hi/CD44hi CSC-like population. ICG-001 was also found to restore the expression of a tumor suppressive microRNA-145 (miR-145). Ectopic expression of miR-145 effectively repressed SOX2 protein expression and inhibited tumor sphere formation. Combination of ICG-001 with cisplatin synergistically suppressed in vitro growth of C666-1 cells and significantly suppressed growth of NPC xenografts. These results suggested that therapeutically targeting of the CBP/β-catenin signaling pathway with ICG-001 can effectively reduce the CSC-like population and combination with cisplatin can effectively suppress the growth of NPC.
Compact tri‐band bandpass filter with stub‐loaded stepped‐impedance resonator
Authors: Yu Bin , Jia Baofu , Zhu Zhaojun 
Published: April 2015

A compact microstrip tri‐band bandpass filter (BPF) based on two open stub‐loaded multimode λ/4 stepped‐impedance resonators (SIRs) with two separate coupling paths is investigated. A source–load coupling configuration is arranged to produce several extra transmission zeros for realising high‐isolation performance. The centre frequencies of three passbands can be controlled by tuning the dimensions of two high impedance lines of the proposed open stub‐loaded SIRs. The bandwidth of the three passbands could be conventionally controlled by adjusting the coupling strength of two coupling paths. The prototype of the BPF achieved insertion losses of 0.46, 1.05 and 1.4 dB at 0.82, 1.67 and 2.17 GHz, respectively. The measured results are in good agreement with electromagnetic simulation. The circuit only occupies 0.126λg × 0.108λg, where λg is the guided wavelength at a lower passband centre frequency.
Radiation pattern reconfigurable microstrip antenna for WiMAX application
Authors: Shi S.‐J. , Ding W.‐P. 
Published: April 2015

A microstrip antenna with reconfigurable radiation pattern characteristics in the wireless interoperability for microwave access (WiMAX) band is presented. By controlling the states of these four pin diodes, different radiating elements can be activated, which leads to four different radiation patterns for WiMAX application in the 3.44–3.6 GHz range. By sequentially activating the pin diodes, the antenna main beam rotates by 90° in azimuth planes, with 30° deflection in the elevation plane. Moreover, the proposed antenna has a compact structure and good realised gain levels with a minimum value of 8 dBi. The measured results of the fabricated antenna prototype verify the simulation analysis.
Simple versus complex models of trait evolution and stasis as a response to environmental change
Authors: Hunt Gene , Hopkins Melanie J. , Lidgard Scott 
Published: April 2015

SignificancePaleontologists have long argued about what the fossil record call tell us about how species evolve over long periods. Simple models such as stasis and random walks have been used to explore evolutionary patterns, but these have not always adequately captured the ways in which traits change over time in fossil species. Here we find that models with complex evolutionary dynamics are often favored, especially for fossil series that sample many populations, suggesting that the underlying evolutionary reality is likely more complex than represented by simplified—though still useful—models of trait change.
Organogenesis in deep time: A problem in genomics, development, and paleontology
Authors: Pieretti Joyce , Gehrke Andrew R. , Schneider Igor , Adachi Noritaka , Nakamura Tetsuya , Shubin Neil H. 
Published: April 2015

SignificancePhylogenetic data inclusive of rich paleontological records can be used to inform hypotheses on evolutionary transformations. These data, when combined with developmental studies and functional genomic assays in model and nonmodel organisms, expand our understanding of the evolutionary processes that build and pattern the vertebrate body plan. Here, we highlight a direction of the fossil record, one of “experimental paleontology,” where morphological transformations inferred from the fossil record can be experimentally assayed in the lab. With the addition of genomic techniques to test hypotheses, researchers can now begin to explore genomic states that have influenced both past and present morphological diversity.
Syringyl lignin production in conifers: Proof of concept in a Pine tracheary element system
Authors: Wagner Armin , Tobimatsu Yuki , Phillips Lorelle , Flint Heather , Geddes Barbara , Lu Fachuang , Ralph John 
Published: April 2015

Significance
This study shows that metabolic engineering can be used to imbue pine tracheary elements with an ability to synthesize sinapyl alcohol, a lignin monomer not normally used for lignification in conifers such as pine. The dynamic nature of the lignification process enables pines to incorporate this monolignol, allowing them to produce hardwood-like lignins that are known to facilitate refining processes such as biofuel production and chemical pulping. The potential to improve the refining of conifer-derived biomass through lignin manipulations is important, as even small improvements in yield can lead to significant environmental and economic benefits in such processes.
Highly polarized C-terminal transition state of the leucine-rich repeat domain of PP32 is governed by local stability
Authors: Dao Thuy Phuong , Majumdar Ananya , Barrick Doug 
Published: April 2015

Significance
Proteins fold to their native structure in significantly shorter timescales than expected for a random search mechanism. Rapid folding, which is likely to be important to optimize yield and avoid misfolded, aggregated states, has been proposed to result from specific folding pathways. However, mapping such pathways and understanding the principles by which they are selected remain central problems in protein science. Repeat proteins, containing tandem repeated structural units, greatly simplify folding studies. Here, we exploit the linear architecture of a β-strand-containing leucine-rich repeat protein and discover that folding is highly polarized toward the C terminus. By measuring the energy distribution, we observe that polarization is guided by local stability.
Geologic carbon storage is unlikely to trigger large earthquakes and reactivate faults through which CO2could leak
Authors: Vilarrasa Victor , Carrera Jesus 
Published: April 2015

SignificanceGeologic carbon storage remains a safe option to mitigate anthropogenic climate change. Properly sited and managed storage sites are unlikely to induce felt seismicity because (i) sedimentary formations, which are softer than the crystalline basement, are rarely critically stressed; (ii) the least stable situation occurs at the beginning of injection, which makes it easy to control; (iii) CO2will dissolve into brine at a significant rate, reducing overpressure; and (iv) CO2will not flow across the caprock because of capillarity, but brine will, which will reduce overpressure further. Furthermore, CO2leakage through fault reactivation is unlikely because the high clay content of caprocks ensures a reduced permeability and increased entry pressure along localized deformation zones.
Declining vulnerability to river floods and the global benefits of adaptation
Authors: Jongman Brenden , Winsemius Hessel C. , Aerts Jeroen C. J. H. , Coughlan de Perez Erin , van Aalst Maarten K. , Kron Wolfgang , Ward Philip J. 
Published: April 2015

Significance
Understanding the vulnerability of societies around the world is crucial for understanding historical trends in flood risk and for producing accurate projections of fatalities and losses. We reproduced historical river flood occurrence using daily climate data for the period 1980–2010 and quantified the natural and socioeconomic contributions to flood risk trends. We show that the fatalities and losses as a share of the exposed population and gross domestic product are decreasing with rising income. We also show that there is a tendency of convergence in vulnerability levels between low- and high-income countries. Projections based on a wide range of climate change and socioeconomic development scenarios demonstrate that amplified adaptation efforts have the potential to largely contain losses from future floods.
Buried ionizable networks are an ancient hallmark of G protein-coupled receptor activation
Authors: Isom Daniel G. , Dohlman Henrik G. 
Published: April 2015

Significance
In the early 1980s, scientists began searching for cell-surface receptors that bind to hormones and neurotransmitters. Among the first was the β-adrenergic receptor, a G protein-coupled receptor (GPCR) that is activated by norepinephrine and epinephrine. Recent breakthroughs have provided more than 100 new GPCR structures, including several in activated conformations. This new structural information presents an opportunity to identify features that distinguish unactivated and activated receptors. Here we use a computational approach to identify structural signatures unique to activated GPCRs. Remarkably, we find that these signatures also are present in distantly related receptors from archaea and bacteria. We propose that these new structural indicators are central to GPCR function and are indicative of GPCR activation.
On the factors that promote the diversity of herbivorous insects and plants in tropical forests
Authors: Becerra Judith X. 
Published: April 2015

SignificanceA central mission in ecology has been to explain differences in biodiversity across the world and across groups of organisms. This knowledge is not only fundamental as a scientific objective but also for practical issues of major concern to humankind. Plants and phytophagous insects comprise the highest macroscopic diversity on Earth, making it particularly important to know the mechanisms that allow their species to coexist. This study suggests that without insect specialization the maintenance of tropical plant diversity might not be possible. Also, without high divergence of defenses among plants, insect tropical diversity may not persist either.
Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display
Authors: Nair Pradeep M. , Flores Heather , Gogineni Alvin , Marsters Scot , Lawrence David A. , Kelley Robert F. , Ngu Hai , Sagolla Meredith , Komuves Laszlo , Bourgon Richard , Settleman Jeffrey , Ashkenazi Avi 
Published: April 2015

Significance
A recombinant soluble version of the transmembrane death ligand Apo2L/TRAIL has shown compelling preclinical results as a potential cancer therapeutic, but studies in cancer patients have demonstrated little efficacy. Supported membrane display of Apo2L/TRAIL, to mimic the endogenous ligand more faithfully, markedly augments receptor clustering and apoptosis stimulation in cancer cells. Covalent attachment of Apo2L/TRAIL to the surface of liposomes offers a therapeutically tractable approach to membrane display that substantially increases tumor exposure, caspase activation, and antitumor potency. These findings open new avenues for clinical investigation of Apo2L/TRAIL as a cancer therapeutic and may apply to other members of the TNF superfamily, such as FasL and CD70, which are expressed on immune-cell surfaces and are important candidates for cancer immunotherapy.
Large-area formation of self-aligned crystalline domains of organic semiconductors on transistor channels using CONNECT
Authors: Park Steve , Giri Gaurav , Shaw Leo , Pitner Gregory , Ha Jewook , Koo Ja Hoon , Gu Xiaodan , Park Joonsuk , Lee Tae Hoon , Nam Ji Hyun , Hong Yongtaek , Bao Zhenan 
Published: April 2015

Significance
Solution-processed organic electronics are expected to pave the way for low-cost large-area electronics with new and exciting applications. However, realizing solution-processed organic electronics requires densely packed transistors with patterned and precisely registered organic semiconductors (OSCs) within the transistor channel with uniform electrical properties over a large area, a task that remains a significant challenge. To address such a challenge, we have developed an innovative technique that generates self-patterned and self-registered OSC film with low variability in electrical properties over a large area. We have fabricated highest density of transistors with a yield of 99%, along with various logic circuits. This work significantly advances organic electronics field to enable large-scale circuit fabrication in a facile and economical manner.
Continental-scale distributions of dust-associated bacteria and fungi
Authors: Barberán Albert , Ladau Joshua , Leff Jonathan W. , Pollard Katherine S. , Menninger Holly L. , Dunn Robert R. , Fierer Noah 
Published: April 2015

Significance
We inhale thousands of microbial cells when we breathe in outdoor air, and some of these airborne microbes can serve as pathogens or triggers of allergic disorders. Using settled dust samples from ∼1,200 locations, we generated the first atlas, to our knowledge, of airborne bacterial and fungal distributions across the continental United States. We found that airborne microbial communities, such as terrestrial plants and animals, exhibit nonrandom geographic patterns, and we identified the factors that shape the continental-scale distributions of microbial taxa. Furthermore, we found that the airborne microbes found in urban and more rural areas are not distinct in composition, but the dust-associated communities found in more urbanized areas are more homogeneous across the United States.
Uranium isotopes fingerprint biotic reduction
Authors: Stylo Malgorzata , Neubert Nadja , Wang Yuheng , Monga Nikhil , Romaniello Stephen J. , Weyer Stefan , Bernier-Latmani Rizlan 
Published: April 2015

Significance
Throughout Earth’s history, redox transformations in sedimentary environments have occurred through chemical processes (abiotic pathways) or via the activity of living microorganisms (biotic pathway). Tools able to discriminate between these two mechanisms are of major interest, as they would contribute significantly to the understanding of biogeochemical events that shaped the evolution of life on our planet. Here, we show that there is a clear difference between the isotopic signature associated with abiotic and biotic transformations of uranium (U). Thus, U isotopic composition can serve as a marker for biological processes in many sedimentary rocks. Based on this result, we conclude that microbial activity has contributed to reductive sedimentary processes in many low-temperature redox-active terrestrial and marine environments.
The amplification of risk in experimental diffusion chains
Authors: Moussaïd Mehdi , Brighton Henry , Gaissmaier Wolfgang 
Published: April 2015

SignificancePublic risk perception of hazardous events such as contagious outbreaks, terrorist attacks, and climate change are difficult-to-anticipate social phenomena. It is unclear how risk information will spread through social networks, how laypeople influence each other, and what social dynamics generate public opinion. We examine how messages detailing risks are transmitted from one person to another in experimental diffusion chains and how people influence each other as they propagate this information. Although the content of a message is gradually lost over repeated social transmissions, subjective perceptions of risk propagate and amplify due to social influence. These results provide quantitative insights into the public response to risk and the formation of often unnecessary fears and anxieties.