bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving high-fidelity single-qubit gates in a strongly driven charge qubit with 1/f charge noise
Authors: Yang Yuan-Chi , Coppersmith S. N. , Friesen Mark
Published: January 2019

Charge qubits formed in double quantum dots represent quintessential two-level systems that enjoy both ease of control and efficient readout. Unfortunately, charge noise can cause rapid decoherence, with typical single-qubit gate fidelities falling below 90%. Here we develop analytical methods to study the evolution of strongly driven charge qubits, for general and 1/f charge-noise spectra. We show that special pulsing techniques can simultaneously suppress errors due to strong driving and charge noise, yielding single-qubit gates with fidelities above 99.9%. These results demonstrate that quantum dot charge qubits provide a potential route to high-fidelity quantum computation.
Chitosan-capped gold nanoparticles for indicating temperature abuse in frozen stored products
Authors: Mohan Chitradurga Obaiah , Gunasekaran S. , Ravishankar C. N.
Published: January 2019

The present study aimed to optimize the conditions for the synthesis of gold nanoparticles (AuNP) using chitosan and to assess its effectiveness as temperature threshold indication for frozen storage conditions. Chitosan concentration of 0.25% and temperature of 90 °C for 15 min was optimum for synthesizing AuNP. The maximum absorbance (λmax) was observed at 530 and 540 nm for 0.125% and 0.25% chitosan, respectively, indicating shifting of peak toward longer wavelengths (red shift) with increasing chitosan concentration indicating larger AuNPs. A prominent absorption peak at 1367 cm−1 by Fourier transform-infrared (FTIR) spectrum corresponding to C−C stretching of the glucosamine group of chitosan indicates the chitosan capping on the AuNP. Higher peak intensity and a peak shift toward shorter wavelength were observed for AuNPs exposed to frozen temperature abused conditions. Distinctly clear visible color variation from cherry red to gray indicates its application as temperature abuse indicator in frozen products.
Spatial heterogeneity of heavy metal contamination in soils and plants in Hefei, China
Authors: Zhang Qianjin , Yu Ruoyun , Fu Songling , Wu Zemin , Chen Han Y. H. , Liu Hua
Published: January 2019

The contamination of soil and plants with heavy metals, which has detrimental influences on plant growth, water purification, and food safety, has emerged as a serious global issue. To better understand the spatial variations of contamination of heavy metals associated city development and land use types, we collected soil samples and Magnolia grandiflora branches to quantify lead (Pb) and cadmium (Cd) contents of the roadside, industrial, residential, and park greenbelts in Hefei City, China. We found that Pb content in soil was the highest in roadside greenbelts and the lowest in parks with industrial and residential greenbelts being intermediate, while Cd in soil was the highest in greenbelts close to city center and decreased with the distance to city center. Pb in M. grandiflora, however, did not differ among greenbelt types but decreased with distance to the city center. Cd in M. grandiflora was the highest in roadside and lowest in parks and also decreased with the distance to the city center. Across all greenbelt types and the distances to the city center, Pb and Cd contents were positively correlated in soil and plants. Our findings suggest that vehicle traffic, population density, and age of urbanization collectively contribute to soil and plant contamination of Pb and Cd.
Fractional laser ablation for the targeted cutaneous delivery of an anti-CD29 monoclonal antibody – OS2966
Authors: Lapteva Maria , del Río-Sancho Sergio , Wu Eric , Carbonell W. Shawn , Böhler Christof , Kalia Yogeshvar N.
Published: January 2019

Monoclonal antibodies targeting cytokines are administered parenterally for the systemic treatment of severe psoriasis. However, systemic exposure to the biologic increases the risk of side-effects including immunosuppression, whereas only a small fraction of the active molecules actually reaches the target organ, the skin. This preclinical study examines the feasibility of delivering a humanized anti-CD29 monoclonal antibody (OS2966) topically to skin using minimally-invasive fractional laser ablation. This approach would enable the targeted use of a biologic for the treatment of recalcitrant psoriatic plaques in patients with less widespread disease while minimizing the risk of systemic exposure. First, the effect of a wide range of laser poration conditions on skin permeation and deposition of OS2966 was tested in vitro to determine optimal microporation parameters. Subsequently, confocal laser scanning microscopy was employed to visualize the distribution of fluorescently-labelled OS2966 in skin. The results demonstrated that delivery of OS2966 into and across skin was feasible. Above fluences of 35.1 J/cm2, skin deposition and permeation were statistically superior to passive delivery reaching values up to 3.7 ± 1.2 µg/cm2 at the most aggressive condition. Selective targeting of the skin was also possible since ≥70% of the OS2966 was delivered locally to the skin. Although nanogramme quantities were able to permeate across skin, these amounts were orders of magnitude lower than levels seen following subcutaneous or intravenous injection and would result in minimal systemic exposure in vivo. The diffusion of fluorescently-labelled OS2966 into the skin surrounding the pores was clearly higher than in intact skin and demonstrated the feasibility of delivering the antibody at least as deep as the dermo-epithelial junction, a critical border region where inflammatory cells cross to promote disease progression. These preliminary results confirm that fractional laser ablation can be used for the cutaneous delivery of OS2966 and now preclinical/clinical studies are required to demonstrate therapeutic efficacy.
Craniobot: A computer numerical controlled robot for cranial microsurgeries
Authors: Ghanbari Leila , Rynes Mathew L. , Hu Jia , Schulman Daniel S. , Johnson Gregory W. , Laroque Michael , Shull Gabriella M. , Kodandaramaiah Suhasa B.
Published: January 2019

Over the last few decades, a plethora of tools has been developed for neuroscientists to interface with the brain. Implementing these tools requires precisely removing sections of the skull to access the brain. These delicate cranial microsurgical procedures need to be performed on the sub-millimeter thick bone without damaging the underlying tissue and therefore, require significant training. Automating some of these procedures would not only enable more precise microsurgical operations, but also facilitate widespread use of advanced neurotechnologies. Here, we introduce the “Craniobot”, a cranial microsurgery platform that combines automated skull surface profiling with a computer numerical controlled (CNC) milling machine to perform a variety of cranial microsurgical procedures on mice. The Craniobot utilizes a low-force contact sensor to profile the skull surface and uses this information to perform precise milling operations within minutes. We have used the Craniobot to perform intact skull thinning and open small to large craniotomies over the dorsal cortex.
Stabilities and novel electronic structures of three carbon nitride bilayers
Authors: Lin Wanxing , Liang Shi-Dong , He Chunshan , Xie Wucheng , He Haiying , Mai Quanxiang , Li Jiesen , Yao Dao-Xin
Published: January 2019

We predict three novel phases of the carbon nitride (CN) bilayer, denoted α-C2N2, β-C2N2 and γ-C4N4, respectively. All of them consist of two CN sheets connected by C-C covalent bonds. The phonon dispersions reveal that all these phases are dynamically stable, because no imaginary frequency is present. The transition pathway between α-C2N2 and β-C2N2 is investigated, which involves bond-breaking and bond-reforming between C and N. This conversion is difficult, since the activation energy barrier is 1.90 eV per unit cell, high enough to prevent the transformation at room temperature. Electronic structure calculations show that all three phases are semiconductors with indirect band gaps of 3.76/5.22 eV, 4.23/5.75 eV and 2.06/3.53 eV, respectively, by PBE/HSE calculation. The β-C2N2 has the widest band gap among the three phases. All three bilayers can become metallic under tensile strain, and the indirect gap of γ-C4N4 can turn into a direct one. γ-C4N4 can become an anisotropic Dirac semimetal under uniaxial tensile strain. Anisotropic Dirac cones with high Fermi velocity of the order of 105 m/s appear under 12% strain. Our results suggest that the three two-dimensional materials have potential applications in electronics, semiconductors, optics and spintronics.
Design and assembly of a chemically switchable and fluorescently traceable light-driven proton pump system for bionanotechnological applications
Authors: Hirschi S. , Fischer N. , Kalbermatter D. , Laskowski P. R. , Ucurum Z. , Müller D. J. , Fotiadis D.
Published: January 2019

Energy-supplying modules are essential building blocks for the assembly of functional multicomponent nanoreactors in synthetic biology. Proteorhodopsin, a light-driven proton pump, is an ideal candidate to provide the required energy in form of an electrochemical proton gradient. Here we present an advanced proteoliposome system equipped with a chemically on-off switchable proteorhodopsin variant. The proton pump was engineered to optimize the specificity and efficiency of chemical deactivation and reactivation. To optically track and characterize the proteoliposome system using fluorescence microscopy and nanoparticle tracking analysis, fluorescenlty labelled lipids were implemented. Fluorescence is a highly valuable feature that enables detection and tracking of nanoreactors in complex media. Cryo-transmission electron microscopy, and correlative atomic force and confocal microscopy revealed that our procedure yields polylamellar proteoliposomes, which exhibit enhanced mechanical stability. The combination of these features makes the presented energizing system a promising foundation for the engineering of complex nanoreactors.
Analysis of chemical exchange saturation transfer contributions from brain metabolites to the Z-spectra at various field strengths and pH
Authors: Khlebnikov Vitaliy , van der Kemp Wybe J. M. , Hoogduin Hans , Klomp Dennis W. J. , Prompers Jeanine J.
Published: January 2019

Chemical exchange saturation transfer (CEST) exploits the chemical exchange of labile protons of an endogenous or exogenous compound with water to image the former indirectly through the water signal. Z-spectra of the brain have traditionally been analyzed for two most common saturation phenomena: downfield amide proton transfer (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body of brain metabolites, many of interest in neurology and oncology, contributes to the downfield saturation in Z-spectra. The extraction of these “hidden” metabolites from Z-spectra requires careful design of CEST sequences and data processing models, which is only possible by first obtaining CEST signatures of the brain metabolites possessing labile protons. In this work, we measured exchange rates of all major-for-CEST brain metabolites in the physiological pH range at 37 °C. Analysis of their contributions to Z-spectra revealed that regardless of the main magnetic field strength and pH, five main contributors, i.e. myo-inositol, creatine, phosphocreatine, glutamate, and mobile (poly)peptides, account for ca. 90% of downfield CEST effect. The fundamental CEST parameters presented in this study can be exploited in the design of novel CEST sequences and Z-spectra processing models, which will enable simultaneous and quantitative CEST imaging of multiple metabolites: multicolor CEST.
Optofluidic platform using liquid crystals in lithium niobate microchannel
Authors: Bonfadini Silvio , Ciciulla Fabrizio , Criante Luigino , Zaltron Annamaria , Simoni Francesco , Reshetnyak Victor , Lucchetti Liana
Published: January 2019

We demonstrate the all optical control of the molecular orientation of nematic liquid crystals confined in microfluidic channels engraved in lithium niobate. Microchannels are obtained by a novel approach based on femtosecond pulse laser micromachining carried on in controlled atmosphere. The combined effect of photovoltaic and pyroelectric fields generated by light in lithium niobate crystals on the liquid crystal orientation, is reported for the first time. The total space charge field and its dependence on the incident light intensity can be controlled by changing the direction of pump light propagation through the microfluidic chip. The results reported in this manuscript demonstrate that liquid crystals and lithium niobate can efficiently be combined in microfluidic configuration, in order to push forward a novel class of optofluidic devices.
Limbic control over the homeostatic need for sodium
Authors: Verharen Jeroen P. H. , Roelofs Theresia J. M. , Menting-Henry Shanice , Luijendijk Mieneke C. M. , Vanderschuren Louk J. M. J. , Adan Roger A. H.
Published: January 2019

The homeostatic need for sodium is one of the strongest motivational drives known in animals. Although the brain regions involved in the sensory detection of sodium levels have been mapped relatively well, data about the neural basis of the motivational properties of salt appetite, including a role for midbrain dopamine cells, have been inconclusive. Here, we employed a combination of fiber photometry, behavioral pharmacology and c-Fos immunohistochemistry to study the involvement of the mesocorticolimbic dopamine system in salt appetite in rats. We observed that sodium deficiency affected the responses of dopaminergic midbrain neurons to salt tasting, suggesting that these neurons encode appetitive properties of sodium. We further observed a significant reduction in the consumption of salt after pharmacological inactivation of the nucleus accumbens (but not the medial prefrontal cortex), and microstructure analysis of licking behavior suggested that this was due to decreased motivation for, but not appreciation of salt. However, this was not dependent on dopaminergic neurotransmission in that area, as infusion of a dopamine receptor antagonist into the nucleus accumbens did not alter salt appetite. We conclude that the nucleus accumbens, but not medial prefrontal cortex, is important for the behavioral expression of salt appetite by mediating its motivational component, but that the switch in salt appreciation after sodium depletion, although detected by midbrain dopamine neurons, must arise from other areas.
Microplastics in marine mammals stranded around the British coast: ubiquitous but transitory?
Authors: Nelms S. E. , Barnett J. , Brownlow A. , Davison N. J. , Deaville R. , Galloway T. S. , Lindeque P. K. , Santillo D. , Godley B. J.
Published: January 2019

Plastic pollution represents a pervasive and increasing threat to marine ecosystems worldwide and there is a need to better understand the extent to which microplastics (<5 mm) are ingested by high trophic-level taxa, such as marine mammals. Here, we perform a comprehensive assessment by examining whole digestive tracts of 50 individuals from 10 species whilst operating strict contamination controls. Microplastics were ubiquitous with particles detected in every animal examined. The relatively low number per animal (mean = 5.5) suggests these particles are transitory. Stomachs, however, were found to contain a greater number than intestines, indicating a potential site of temporary retention. The majority of particles were fibres (84%) while the remaining 16% was fragments. Particles were mainly blue and black (42.5% and 26.4%) in colour and Nylon was the most prevalent (60%) polymer type. A possible relationship was found between the cause of death category and microplastic abundance, indicating that animals that died due to infectious diseases had a slightly higher number of particles than those that died of trauma and other drivers of mortality. It is not possible, however, to draw any firm conclusions on the potential biological significance of this observation and further research is required to better understand the potential chronic effects of microplastic exposure on animal health, particularly as marine mammals are widely considered important sentinels for the implications of pollution for the marine environment.
Integrative metabolomics reveals unique metabolic traits in Guillain-Barré Syndrome and its variants
Authors: Park Soo Jin , Kim Jong Kuk , Kim Hyun-Hwi , Yoon Byeol-A. , Ji Dong Yoon , Lee Chang-Wan , Kim Ho Jin , Kim Kyoung Heon , Shin Ha Young , Park Sung Jean , Lee Do Yup
Published: January 2019

Guillain–Barré syndrome (GBS) is an acute fatal progressive disease caused by autoimmune mechanism mainly affecting peripheral nervous system. Although the syndrome is clinically sub-classified into several variants, specific biomarker and exact pathomechanism of each subtypes are not well elucidated yet. In current study, integrative metabolomic and lipidomic profiles were acquisitioned from cerebrospinal fluid samples of 86 GBS from three variants and 20 disease controls. And the data were systematically compared to our previous result on inflammatory demyelination disorders of central nervous system (IDDs) and healthy controls. Primary metabolite profiles revealed unique metabolic traits in which 9 and 7 compounds were specifically changed in GBS and IDD, respectively. Next, the biomarker panel with 10 primary metabolites showed a fairly good discrimination power among 3 GBS subtypes, healthy controls, and disease controls (AUCs ranged 0.849–0.999). The robustness of the biomarker panel was vigorously validated by multi-step statistical evaluation. Subsequent lipidomics revealed GBS variant-specific alteration where the significant elevations of lyso-phosphatidylcholines and sphingomyelins were unique to AIDP (acute inflammatory demyelinating polyneuropathy) and AMAN (acute motor axonal neuropathy), respectively. And metabolome-wide multivariate correlation analysis identified potential clinical association between GBS disability scale (Hughes score) and CSF lipids (monoacylglycerols, and sphingomyelins). Finally, Bayesian network analysis of covarianced structures of primary metabolites and lipids proposed metabolic hub and potential biochemical linkage associated with the pathology.
Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke
Authors: Mulder I. A. , Ogrinc Potočnik N. , Broos L. A. M. , Prop A. , Wermer M. J. H. , Heeren R. M. A. , van den Maagdenberg A. M. J. M.
Published: January 2019

Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression.
Small changes in synaptic gain lead to seizure-like activity in neuronal network at criticality
Authors: Du Jiaxin , Vegh Viktor , Reutens David C.
Published: January 2019

Epilepsy is a neurological disorder characterised by spontaneous recurrent seizures. The mechanisms by which multiple molecular and cellular changes lead to seizures is not well understood. Here, we study cortical seizure generation by simulating the activity of neuron groups in a network using the laminar cortex model. We identified a clear boundary between low-amplitude, asynchronous activity and high-amplitude, rhythmic activity, around which small changes in excitatory synaptic gain led to strong oscillatory activity. Neuron groups only responded significantly to stimulation around the boundary. The consequences of biophysical changes induced by epilepsy-related SCN1A mutations were also examined. Marked reduction in neuronal inhibition, as caused by mutations underlying Dravet syndrome, invariably led to strong neuronal firing, whereas small reductions in inhibition could cause significant changes when the network was poised close to the boundary. The study highlights the critical role of network dynamics in seizure genesis.
Dependence of fullerene aggregation on lipid saturation due to a balance between entropy and enthalpy
Authors: Nalakarn Pornkamon , Boonnoy Phansiri , Nisoh Nililla , Karttunen Mikko , Wong-ekkabut Jirasak
Published: January 2019

It is well-known that fullerenes aggregate inside lipid membranes and that increasing the concentration may lead to (lethal) membrane rupture. It is not known, however, how aggregation and rupture depend on the lipid type, what physical mechanisms control this behavior and what experimental signatures detect such changes in membranes. In this paper, we attempt to answer these questions with molecular simulations, and we show that aggregation and membrane damage depend critically on the degree of saturation of the lipid acyl chains: unsaturated bonds, or “kinks”, impose a subtle but crucial compartmentalization of the bilayer into core and surface regions leading to three distinct fullerene density maxima. In contrast, when the membrane has only fully saturated lipids, fullerenes prefer to be located close to the surface under the head groups until the concentration becomes too large and the fullerenes begin clustering. No clustering is observed in membranes with unsaturated lipids. The presence of “kinks” reverses the free energy balance; although the overall free energy profiles are similar, entropy is the dominant component in unsaturated bilayers whereas enthalpy controls the fully saturated ones. Fully saturated systems show two unique signatures: 1) membrane thickness behaves non-monotonously while the area per lipid increases monotonously. We propose this as a potential reason for the observations of low fullerene concentrations being effective against bacteria. 2) The fullerene-fullerene radial distribution function (RDF) shows splitting of the second peak indicating the emergence short-range order and the importance of the second-nearest neighbor interactions. Similar second peak splitting has been reported in metal glasses.
Sputum Proteomics Reveals a Shift in Vitamin D-binding Protein and Antimicrobial Protein Axis in Tuberculosis Patients
Authors: Bishwal Subasa C. , Das Mrinal K. , Badireddy Vinod K. , Dabral Deepti , Das Aleena , Mahapatra Alok R. , Sahu Sukanya , Malakar Dipankar , Singh I. Ibungo , Mazumdar Himanghsu , Patgiri Saurav J. , Deka Trinayan , Kapfo Wetetsho , Liegise Kevideme , Kupa Rukuwe-u , Debnath Sanjita , Bhowmik Rajesh , Debnath Rahul , Behera Rajendra K. , Pillai Manoj G. , Deuri Pranjal , Nath Reema , Khalo K. Pewezo , Sing W. Asoka , Pandit Bhaswati , Das Anjan , Bhattacharya Sibabrata , Behera Digambar , Saikia Lahari , Khamo Vinotsole , Nanda Ranjan K.
Published: January 2019

Existing understanding of molecular composition of sputum and its role in tuberculosis patients is variously limited to its diagnostic potential. We sought to identify infection induced sputum proteome alteration in active/non tuberculosis patients (A/NTB) and their role in altered lung patho-physiology. Out of the study population (n = 118), sputum proteins isolated from discovery set samples (n = 20) was used for an 8-plex isobaric tag for relative and absolute concentration analysis. A minimum set of protein with at least log2(ATB/NTB) >±1.0 in ATB was selected as biosignature and validated in 32 samples. Predictive accuracy was calculated from area under the receiver operating characteristic curve (AUC of ROC) using a confirmatory set (n = 50) by Western blot analysis. Mass spectrometry analysis identified a set of 192 sputum proteins, out of which a signature of β-integrin, vitamin D binding protein:DBP, uteroglobin, profilin and cathelicidin antimicrobial peptide was sufficient to differentiate ATB from NTB. AUC of ROC of the biosignature was calculated to 0.75. A shift in DBP-antimicrobial peptide (AMP) axis in the lungs of tuberculosis patients is observed. The identified sputum protein signature is a promising panel to differentiate ATB from NTB groups and suggest a deregulated DBP-AMP axis in lungs of tuberculosis patients.
Biological activities of Ficus carica latex for potential therapeutics in Human Papillomavirus (HPV) related cervical cancers
Authors: Ghanbari Arshia , Le Gresley Adam , Naughton Declan , Kuhnert Nikolai , Sirbu Diana , Ashrafi G. Hossein
Published: January 2019

Infection caused by high-risk human papillomaviruses (HPVs) are implicated in the aetiology of cervical cancer. Although current methods of treatment for cervical cancer can ablate lesions, preventing metastatic disseminations and excessive tissue injuries still remains a major concern. Hence, development of a safer and more efficient treatment modality is of vital importance. Natural products from plants are one of the principal sources of precursors to lead compounds with direct pharmaceutical application across all disease classes. One of these plants is Ficus carica, whose fruit latex, when applied on HPV-induced skin warts, has shown potential as a possible cure for this virus related lesions. This study explores the in vitro biological activities of fig latex and elucidates its possible mechanisms of action on cervical cancer cell lines CaSki and HeLa positive for HPV type 16 and 18, respectively. Our data shows that fig latex inhibits properties that are associated with HPV-positive cervical cancer transformed cells such as rapid growth and invasion and substantially downregulated the expression of p16 and HPV onco-proteins E6, E7. These findings suggest Ficus carica latex has the potential to be used in the development of therapeutic modalities for the possible treatment, cure and prevention of HPV related cervical cancer.
Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration
Authors: Sivapathasuntharam Chrishne , Hayes Matthew John , Shinhmar Harpreet , Kam Jaimie Hoh , Sivaprasad Sobha , Jeffery Glen
Published: January 2019

Age related macular degeneration (AMD) is the most common blinding disease in those over 60 years. In 50% of cases it is associated with polymorphisms of complement factor H (FH), implicating immune vulnerability. But such individuals may exhibit abnormal outer retinal blood flow decades before disease initiation, suggesting an early disease footprint. FH is expressed in the retinal pigmented epithelium (RPE). During development the RPE is adjacent to the site of retinal mitosis and complex regulatory interactions occur between the relatively mature RPE and retinal neuronal precursors that control the cell cycle. Here we ask if the absence of FH from the RPE influences retinal development using a mouse CFH knockout (Cfh−/−) with an aged retinal degenerative phenotype. We reveal that from birth, these mice have significantly disrupted and delayed retinal development. However, once development is complete, their retinae appear relatively normal, although many photoreceptor and RPE mitochondria are abnormally large, suggesting dysfunction consistent with premature ATP decline in Cfh−/−. Total retinal mtDNA is also reduced and these deficits are associated shortly after with reduced retinal function. Cfh−/+ mice also show significant abnormal patterns of cell production but not as great as in Cfh−/−. These results reveal that not only is FH an important player in sculpting retinal development but also that the developmental abnormality in Cfh−/− likely establishes critical vulnerability for later aged retinal degeneration.
Europium (III) as a Circularly Polarized Luminescence Probe of DNA Structure
Authors: Wu Tao , Bouř Petr , Andrushchenko Valery
Published: January 2019

We report as a proof-of-concept the first application of circularly polarized luminescence (CPL) measured with a Raman optical activity (ROA) spectrometer to differentiate several DNA structures without need of sensitizing complexes. The ROA/CPL approach provides sufficiently high CPL intensity to use hydrated Eu3+ ions, thus avoiding DNA structural changes associated with binding of sensitizers and overcoming the sensitizer quenching issue. We showed that deoxyguanosine monophosphate (dGMP), single- and double-stranded DNA provide different CPL spectra, which could be used for their discrimination. Our results demonstrate that ROA/CPL method is a promising approach to measure CPL spectra of complex biomolecules when the use of sensitizers is not possible. The method can be extended to other biomolecules, such as proteins, lipids, sugars, etc.
A 64-pin Nanowire Surface Fastener Like a Ball Grid Array Applied for Room-temperature Electrical Bonding
Authors: Toku Yuhki , Ichioka Kazuma , Morita Yasuyuki , Ju Yang
Published: January 2019

Surface-mount techniques primarily depend on soldering. However, soldering techniques have encountered some challenges in recent years. These challenges include rare metal recycling, thermal problems, and Pb toxicity. We recently developed a metallic nanowire surface fastener (NSF) to resolve the abovementioned problems. This fastener can be used to connect electronic components on a substrate at room temperature using the van der Waals force between each nanowire. This study demonstrates a 64-pin NSF that behaves like a ball grid array (BGA) for application to actual electronic devices. The adhesion strength and electrical properties of the NSF were investigated by adjusting the nanowire parameters, such as diameter, length, density (number per area), preload, and shape. The shape control of the nanowires greatly contributed to the improvement of the properties. A maximum adhesion strength of 16.4 N/cm2 was achieved using a bent, hook-like NSF. This strength was 4–5 times the value of the straight NSF. The contact resistivity was 2.98 × 10−2 Ω∙cm2. The NSF fabricated through the simple template method showed the room temperature bonding ability and adaptability to a highly ordered electrode like the BGA.
A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold
Authors: Ramalingam Sandeep , Graham Catriona , Dove Jenny , Morrice Lynn , Sheikh Aziz
Published: January 2019

There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log10/day (p = 0.04). We hence need a larger trial to confirm our findings.
Integrated Cognitive Assessment: Speed and Accuracy of Visual Processing as a Reliable Proxy to Cognitive Performance
Authors: Khaligh-Razavi Seyed-Mahdi , Habibi Sina , Sadeghi Maryam , Marefat Haniye , Khanbagi Mahdiyeh , Nabavi Seyed Massood , Sadeghi Elham , Kalafatis Chris
Published: January 2019

Various mental disorders are accompanied by some degree of cognitive impairment. Particularly in neurodegenerative disorders, cognitive impairment is the phenotypical hallmark of the disease. Effective, accurate and timely cognitive assessment is key to early diagnosis of this family of mental disorders. Current standard-of-care techniques for cognitive assessment are primarily paper-based, and need to be administered by a healthcare professional; they are additionally language and education-dependent and typically suffer from a learning bias. These tests are thus not ideal for large-scale pro-active cognitive screening and disease progression monitoring. We developed the Integrated Cognitive Assessment (referred to as CGN_ICA), a 5-minute computerized cognitive assessment tool based on a rapid visual categorization task, in which a series of carefully selected natural images of varied difficulty are presented to participants. Overall 448 participants, across a wide age-range with different levels of education took the CGN_ICA test. We compared participants’ CGN_ICA test results with a variety of standard pen-and-paper tests, such as Symbol Digit Modalities Test (SDMT) and Montreal Cognitive Assessment (MoCA), that are routinely used to assess cognitive performance. CGN_ICA had excellent test-retest reliability, showed convergent validity with the standard-of-care cognitive tests used here, and demonstrated to be suitable for micro-monitoring of cognitive performance.
Bioinformatics Analysis of Metabolism Pathways of Archaeal Energy Reserves
Authors: Wang Liang , Liu Qinghua , Wu Xiang , Huang Yue , Wise Michael J. , Liu Zhanzhong , Wang Wei , Hu Junfeng , Wang Chunying
Published: January 2019

Energy storage compounds play crucial roles in prokaryotic physiology. Five chemical compounds have been identified in prokaryotes as energy reserves: polyphosphate (polyP), polyhydroxyalkanoates (PHAs), glycogen, wax ester (WE) and triacylglycerol (TAG). Currently, no systematic study of archaeal energy storage metabolism exists. In this study, we collected 427 archaeal reference sequences from UniProt database. A thorough pathway screening of energy reserves led to an overview of distribution patterns of energy metabolism in archaea. We also explored how energy metabolism might have impact on archaeal extremophilic phenotypes. Based on the systematic analyses of archaeal proteomes, we confirmed that metabolism pathways of polyP, PHAs and glycogen are present in archaea, but TAG and WE are completely absent. It was also confirmed that PHAs are tightly related to halophilic archaea with larger proteome size and higher GC contents, while polyP is mainly present in methanogens. In sum, this study systematically investigates energy storage metabolism in archaea and provides a clear correlation between energy metabolism and the ability to survive in extreme environments. With more genomic editing tools developed for archaea and molecular mechanisms unravelled for energy storage metabolisms (ESMs), there will be a better understanding of the unique lifestyle of archaea in extreme environments.
Bacterial communities associated to Chilean altiplanic native plants from the Andean grasslands soils
Authors: Fernández-Gómez Beatriz , Maldonado Jonathan , Mandakovic Dinka , Gaete Alexis , Gutiérrez Rodrigo A. , Maass Alejandro , Cambiazo Veronica , González Mauricio
Published: January 2019

The rhizosphere is considered the primary place for soil microbiome differentiation and plays a key role in plant survival, especially for those subjected to environmental stress. Using high-throughput sequencing of the 16S rRNA gene, we analyzed and compared soil bacterial communities associated to four of the most abundant high altitude native plant species of the Chilean Andean grasslands. We examined three soil compartments: the rhizosphere (bacteria firmly attached to the roots), the rhizosphere-surrounding soil (bacteria loosely attached to the roots) and the bulk soil (plant-free soil). The rhizosphere microbiome was in all cases the least diverse, exposing that the bulk soil was a more complex environment. Taxonomic analysis revealed an abrupt change between the rhizosphere and the rest of the non-rhizospheric soils. Thus, while rhizobacterial communities were enriched in Proteobacteria (mainly Alphaproteobacteria), Actinobacteria (mostly Blastocatellia) dominated in bulk soils. Finally, we detected certain taxonomic rhizosphere signatures, which could be attributed to a particular genotype. Overall, our results indicate that the thin layer of soil surrounding the roots constitute a distinctive soil environment. This study contributes to expand the knowledge about soil bacterial communities in the Chilean highlands and takes the first step to understand the processes that might lead to the rhizosphere differentiation in that area.
Allabogdanite, the high-pressure polymorph of (Fe,Ni)2P, a stishovite-grade indicator of impact processes in the Fe–Ni–P system
Authors: Britvin Sergey N. , Shilovskikh Vladimir V. , Pagano Renato , Vlasenko Natalia S. , Zaitsev Anatoly N. , Krzhizhanovskaya Maria G. , Lozhkin Maksim S. , Zolotarev Andrey A. , Gurzhiy Vladislav V.
Published: January 2019

Allabogdanite, (Fe,Ni)2P, is the only known natural high-pressure phase reported in the Fe–Ni–P system. The mineral, which was previously described from a single meteorite, the Onello iron, is now discovered in the Santa Catharina and Barbianello nickel-rich ataxites. The occurrence of allabogdanite in Santa Catharina, one of the largest and well-studied meteorites, suggests that this mineral is more common than was believed. The formation of allabogdanite-bearing phosphide assemblages in a given meteorite provides evidence that it experienced peak pressure of at least 8 GPa at a temperature above 800 °C. Since the pressure-temperature stability parameters of allabogdanite fall within the margins of the stishovite (rutile-type SiO2) stability area, the former can be employed as a convenient stishovite-grade indicator of significant impact events experienced by iron and stony-iron meteorites and their parent bodies.
Quality evaluation of Panax quinquefolium from different cultivation regions based on their ginsenoside content and radioprotective effects on irradiated mice
Authors: Liao Dengqun , Jia Chan , Sun Peng , Qi Jianjun , Li Xian’en
Published: January 2019

Ginsenosides are one of major types of bioactive compounds in American ginseng (AG) and utilized to assess the quality of various AG samples. The contents of ginsenosides showed cultivation region-related variation, which is possibly associated with AG’s pharmacological effect difference. Therefore, to reveal the quality difference of AGs in different cultivation regions, AG samples from seven cultivation regions were evaluated via analyzing their contents of nine ginsenosides and the biochemical parameters in AG-treated irradiated mice. Pre-administration of AG decoctions could reversely modulate the irradiation-induced changes of antioxidant enzymatic activity, cytokine level and hormone level in irradiated mice, which demonstrated that AG had the radioprotective effects due to its antioxidative, immunomodulatory and anti-inflammatory properties. However, this radioprotection effect varied among different cultivation regions of AGs. Collectively, Beijing and Canada-cultivated AGs had the best radioprotection. Heilongjiang and Jilin-originated AGs had the similar pharmacological effects while USA, Shandong and Shaanxi-grown AGs had closer pharmacological effects. This biochemical measurements-based PCA and heatmap clustering of AGs from seven cultivation regions was nearly consistent with ginsencoside content- and the previous serum metabolome-based analyses. However, the pearson correlation analysis revealed that only Rb3 and Rd were significantly correlated with some of assayed biochemical parameters in irradiated mice pretreated with different cultivation regions of AG extracts.
Apparent Treatment-Resistant Hypertension and Cardiovascular Risk in Hemodialysis Patients: Ten-Year Outcomes of the Q-Cohort Study
Authors: Tanaka Shigeru , Ninomiya Toshiharu , Hiyamuta Hiroto , Taniguchi Masatomo , Tokumoto Masanori , Masutani Kosuke , Ooboshi Hiroaki , Nakano Toshiaki , Tsuruya Kazuhiko , Kitazono Takanari
Published: January 2019

There has been limited data discussing the relationship between apparent treatment-resistant hypertension (ATRH) and cardiovascular disease risk in patients receiving maintenance hemodialysis. We analyzed data for 2999 hypertensive patients on maintenance hemodialysis. ATRH was defined as uncontrolled blood pressure despite the use of three or more classes of antihypertensive medications, or four or more classes of antihypertensive medications regardless of blood pressure level. We examined the relationships between ATRH and cardiovascular events using a Cox proportional hazards model. The proportion of participants with ATRH was 18.0% (539/2999). During follow-up (median: 106.6 months, interquartile range: 51.3–121.8 months), 931 patients experienced cardiovascular events including coronary heart disease (n = 424), hemorrhagic stroke (n = 158), ischemic stroke (n = 344), and peripheral arterial disease (n = 242). Compared with the non-ATRH group, the ATRH group showed a significant increased risk of developing cardiovascular disease (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.08–1.49), coronary heart disease (HR: 1.28; 95% CI: 1.01–1.62), ischemic stroke (HR: 1.31; 95% CI: 1.01–1.69), and peripheral arterial disease (HR: 1.42; 95% CI: 1.06–1.91) even after adjusting for potential confounders. This study demonstrated that ATRH was significantly associated with increased cardiovascular risk in hemodialysis patients.
Arctic climate change and pollution impact little auk foraging and fitness across a decade
Authors: Amélineau Françoise , Grémillet David , Harding Ann M. A. , Walkusz Wojciech , Choquet Rémi , Fort Jérôme
Published: January 2019

Ongoing global changes apply drastic environmental forcing onto Arctic marine ecosystems, particularly through ocean warming, sea-ice shrinkage and enhanced pollution. To test impacts on arctic marine ecological functioning, we used a 12-year integrative study of little auks (Alle alle), the most abundant seabird in the Atlantic Arctic. We monitored the foraging ecology, reproduction, survival and body condition of breeding birds, and we tested linkages between these biological variables and a set of environmental parameters including sea-ice concentration (SIC) and mercury contamination. Little auks showed substantial plasticity in response to SIC, with deeper and longer dives but less time spent underwater and more time flying when SIC decreased. Their diet also contained less lipid-rich ice-associated prey when SIC decreased. Further, in contrast to former studies conducted at the annual scale, little auk fitness proxies were impacted by environmental changes: Adult body condition and chick growth rate were negatively linked to SIC and mercury contamination. However, no trend was found for adult survival despite high inter-annual variability. Our results suggest that potential benefits of milder climatic conditions in East Greenland may be offset by increasing pollution in the Arctic. Overall, our study stresses the importance of long-term studies integrating ecology and ecotoxicology.
Using DNA Barcoding to Investigate Patterns of Species Utilisation in UK Shark Products Reveals Threatened Species on Sale
Authors: Hobbs Catherine A. D. , Potts Robert W. A. , Bjerregaard Walsh Matthew , Usher Jane , Griffiths Andrew M.
Published: January 2019

Many shark populations are in decline, primarily due to overexploitation. In response, conservation measures have been applied at differing scales, often severely restricting sales of declining species. Therefore, DNA barcoding was used to investigate sales of shark products in fishmongers and fish and chip takeaways in England. The majority of samples were identified as Spiny Dogfish (Squalus acanthias), which is critically endangered in the Northeast Atlantic and landings have been prohibited (although there is evidence of importation of this species). Significant differences in the species sold between retailer types were also identified, suggesting differing supply chains. The results underline issues surrounding the use of ‘umbrella’ sales terms where many species are labelled with the same designation. This denies consumer choice as purchasers cannot easily avoid declining species or those associated with high levels of toxicants. For the first time in Europe, minibarcodes are also used to identify species from dried shark fins. Despite a small sample size, analysis of UK wholesaler fins identified threatened sharks, including the endangered and CITES listed Scalloped Hammerhead (Sphyrna lewini). This highlights the global nature of the damaging trade in endangered shark species, in which Europe and the UK have a continuing role.
Remote photoacoustic sensing using speckle-analysis
Authors: Lengenfelder Benjamin , Mehari Fanuel , Hohmann Martin , Heinlein Markus , Chelales Erika , Waldner Maximilian J. , Klämpfl Florian , Zalevsky Zeev , Schmidt Michael
Published: January 2019

Laser surgery is a rising surgical technique, which offers several advantages compared to the traditional scalpel. However, laser surgery lacks a contact-free feedback system which offers high imaging contrast to identify the tissue type ablated and also a high penetration depth. Photoacoustic imaging has the potential to fill this gap. Since photoacoustic detection is commonly contact based, a new non-interferometric detection technique based on speckle-analysis for remote detection is presented in this work. Phantom and ex-vivo experiments are carried out in transmission and reflection-mode for proof of concept. In summary, the potential of the remote speckle sensing technique for photoacoustic detection is demonstrated. In future, this technique might be applied for usage as a remote feedback system for laser surgery, which could help to broaden the applications of lasers as smart surgical tools.
Discovering highly selective and diverse PPAR-delta agonists by ligand based machine learning and structural modeling
Authors: Da’adoosh Benny , Marcus David , Rayan Anwar , King Fred , Che Jianwei , Goldblum Amiram
Published: January 2019

PPAR-δ agonists are known to enhance fatty acid metabolism, preserving glucose and physical endurance and are suggested as candidates for treating metabolic diseases. None have reached the clinic yet. Our Machine Learning algorithm called “Iterative Stochastic Elimination” (ISE) was applied to construct a ligand-based multi-filter ranking model to distinguish between confirmed PPAR-δ agonists and random molecules. Virtual screening of 1.56 million molecules by this model picked ~2500 top ranking molecules. Subsequent docking to PPAR-δ structures was mainly evaluated by geometric analysis of the docking poses rather than by energy criteria, leading to a set of 306 molecules that were sent for testing in vitro. Out of those, 13 molecules were found as potential PPAR-δ agonist leads with EC50 between 4–19 nM and 14 others with EC50 below 10 µM. Most of the nanomolar agonists were found to be highly selective for PPAR-δ and are structurally different than agonists used for model building.