bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxyl‐Terminated Dendrimer Acting as a High Exhaustion Agent for Chrome Tanning
Authors: Yao Qi , Chen Hualin , Jiao Qi , Huang Henghui , Liu Bailing , Ding Keyi
Published: January 2018

Severe restrictions for chromium discharge and scarcity of chromium resources have forced the tanners to seek for low‐waste and high exhaust chrome tanning technology. Based on the structural traits of dendrimers, in this paper, a series of hydroxyl terminated dendrimers (HTD) with different molecules weight (Mw) was synthesized and applied in the chrome tanning of pigskin. The effect of HTD was investigated on chromium discharge in effluent, and on the shrinkage temperature (Ts), denaturation temperature (Td), mechanical properties, and microstructure of the leather. The experimental results indicated that the chromium discharge in effluent by applying HTD (A1) was reduced to 236.0 mg/L, almost one‐sixth of the conventional chrome tanning. HTD that, possesses high hydroxyl density, has endowed the obtained leather with higher chrome uptake, Ts, and mechanical properties. Specially, HTD could slow down the basification process by the forming of hydrogen bonds with collagen residues. In addition, HTD could combine more chromium and form net crosslink, notably improve the chrome uptake and hydrothermal stability. Therefore, it is conceivable that the HTD could act as a high exhaustion agent in chrome tanning process.
A Highly Selective “On‐Off‐On” Optical Switch for Sequential Detection of Cu2+and S2−Ions Based on 2, 6‐Diformyl‐4‐methyl Phenol and Catecholase Activity by Its Copper Complex
Authors: Parua Sankar P. , Sinha Debopam , Rajak Kajal K.
Published: January 2018

A new highly selective chemosensor for Cu2+and S2−ions, Ethyl 2‐cyano‐3‐(2‐hydroxy‐5‐methyl‐3‐(p‐tolylimino)methyl)phenyl)acrylate) (HL) based on 2, 6‐diformyl‐4‐methylphenol was designed and synthesized. The ligand exhibited excellent sensitivity towards copper ion by the emission quenching even in the presence of other biologically important metal ions. Once HL combine with Cu2+it can display a rapid response and high selectivity toward sulfide anion resulting in off‐on sensingviaCu2+displacement assay. The signal transduction happen via reversible formation–separation of complex L–Cu and CuS and the complex L−Cu was synthesized by the reaction of HL and Cu2+and characterized by single‐crystal X‐ray diffraction and DFT optimization studies. The catecholase like activity for L−Cu complex have been studied by using 3,5‐di‐tertbutylcatechol (3,5‐DTBC) as the substrate.
Unprecedented Synthesis of 2‐Aminochromones and 2‐Aminoquinolones through an Electrophilic C–Cyanation and 6‐exo‐dig Cyclization Cascade with the Intermediary of β‐Ketonitriles
Authors: Sudhakar Kadari , Goud Erukala Yadaiah , Thirupathi Gogula , Hemasri Yerrabelly , Mahesh Kasthuri , Raghavendar Avula , Babu H. Sharath , Kumar K. Shiva
Published: January 2018

For the first time, a domino electrophilic cyanation, using environmentally benign electrophilic cyanating reagent N‐cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) to form β‐ketonitriles, and 6‐exo‐dig cyclization were employed for the synthesis of 2‐aminochromones and 2‐aminoquinolones in very good yields. This protocol can also be regulated to get β‐ketonitriles as the products.
Metal‐Free Reduction of NO over a Fullerene‐like Boron Nitride Nanocluster: A Mechanistic Study by DFT Calculations
Authors: Esrafili Mehdi D. , Abdollahpour Hadi , Saeidi Nasibeh
Published: January 2018

Density functional theory calculations are performed to investigate how the incorporation of a C atom into B12N12 fullerene‐like nanocluster modifies its catalytic activity towards the reduction of nitric oxide (NO) in the presence of CO molecule. The most stable adsorption configurations, adsorption energies, binding distances and net charge transfers are obtained to understand the impact of NO and CO molecules on the electronic properties of B12N12 and B11N12C nanoclusters. Our results suggest a dimer mechanism for the reduction of NO over both surfaces. First, two NO molecules are attached together to form (NO)2 dimer. Then, (NO)2 is dissociated into N2O molecule and an activated O atom (O*). The O* is then removed by a CO or NO molecule, due to a small activation energy. The results indicate that the C‐doping can significantly decrease the activation energies needed for the reduction of NO over B12N12.
Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis-Supportive Function of Fanconi Anemia Mesenchymal Stromal Cells
Authors: Xu Jian , Li Xue , Cole Allison , Sherman Zachary , Du Wei
Published: January 2018

Hematopoietic stem cells preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By using two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs). We found that MSCs deficient for Fanca or Fancc gene are defective in proliferation and prone to undergo senescence in vitro. Mechanistically, we show that the activity of cell division control protein 42 (Cdc42), a Rho GTPase known to be a critical regulator for cytoskeleton organization, is significantly reduced in FA MSCs. Furthermore, we demonstrate that this reduction in Cdc42 activity plays a causal role in defective hematopoiesis-supportive function of the FA MSCs. The progenies of wild-type hematopoietic stem and progenitor cells cocultured on FA MSCs exhibit compromised self-renewal capacity both in vitro and in vivo. Genetic correction of FA deficiency restores Cdc42 activity and improves the hematopoiesis-supportive capacity of FA MSC. Finally, ectopic expression of a constitutively active Cdc42 mutant, Cdc42F28L, or pretreatment with Wnt5a, increases the active Cdc42 level and rescues the hematopoietic supportive defects of FA MSCs. Taken together, our results identify a novel link between Cdc42 activity and the hematopoiesis-supportive function of MSCs and suggest that a niche-specific increase of Cdc42 activity may be beneficial for FA therapy.
Inhibition of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells with Vascular Regenerative Function
Authors: Cooper Tyler T. , Sherman Stephen E. , Kuljanin Miljan , Bell Gillian I. , Lajoie Gilles A. , Hess David A.
Published: January 2018

Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDHhi) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDHhi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDHhi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during ex vivo expansion of UCB ALDHhi cells would prevent differentiation and expand progeny that retained pro-angiogenic functions after transplantation into non-obese diabetic/severe combined immunodeficient mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human UCB ALDHhi cells were cultured under serum-free conditions for 9 days, with or without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although total cell numbers were increased >70-fold, the frequency of cells that retained ALDHhi/CD34+ phenotype was significantly diminished under basal conditions. In contrast, DEAB-inhibition increased total ALDHhi/CD34+ cell number by ≥ 10-fold, reduced differentiation marker (CD38) expression, and enhanced the retention of multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB-treated cells upregulated anti-apoptotic protein expression and diminished production of proteins implicated with megakaryocyte differentiation. The i.m. transplantation of DEAB-treated cells into mice with hind-limb ischemia stimulated endothelial cell proliferation and augmented recovery of hind-limb perfusion. DEAB-inhibition of ALDH-activity delayed hematopoietic differentiation and expanded multipotent myeloid cells that accelerated vascular regeneration following i.m. transplantation in vivo.
Sensitivity analysis methods for mitigating uncertainty in engineering system design
Authors: Curran Qinxian Chelsea , Allaire Douglas , Willcox Karen E.
Published: January 2018

For many engineering systems, current design methodologies do not adequately quantify and manage uncertainty as it arises during the design process, which can lead to unacceptable risks, increases in programmatic cost, and schedule overruns. This paper develops new sensitivity analysis methods that can be used to better understand and mitigate the effects of uncertainty in system design. In particular, a new entropy‐based sensitivity analysis methodology is introduced, which apportions output uncertainty into contributions due to not only the variance of input factors and their interactions, but also to features of the underlying probability distributions that are related to distribution shape and extent. Local sensitivity analysis techniques are also presented, which provide computationally inexpensive estimates of the change in output uncertainty resulting from design modifications. The proposed methods are demonstrated on an engineering example to show how they can be used in the design context to systematically manage uncertainty budgets—which specify the allowable level of uncertainty for a system—by helping to identify design alternatives, evaluate trade‐offs between available options, and guide decisions regarding the allocation of resources.
Modelling and optimization of a flexible poly(vinyl chloride) compound formulation for mine cables
Authors: Fechter Reinhard H. , Sandrock Carl , Kühnert Ines , Labuschagné F.J.W.J.
Published: January 2018

Developments by Labuschagné et al. (Patent, WO 2006/123284 A2, 2006) in the manufacture of Layered Double Hydroxides (LDHs) have led to a patent describing a new effluent free synthesis method. A promising application for the LDH is as an additive for a flexible poly(vinyl chloride) (PVC) compound used for the insulation for cables used in South African underground mines. Consequently, a new formulation is required. Unfortunately formulating a PVC compound is a complex problem. The purpose of the investigation is to develop a method that can be used to find an optimum PVC formulation where the material requirements are met while also allowing for the quantitative analysis of the effect of the ingredients on the material properties. This is achieved by modeling the thermal stability, fire retardancy, and basic mechanical properties of the compound as a function of the relative proportions of the ingredients using 2nd order Scheffé polynomials. The empirical models are determined using statistical experimental design. Each model is interpreted using statistical analysis of the model terms which allows for the quantification of the effects and interactions of all the ingredients on the various response variables. The models are also used as constraints in the optimization of the PVC formulation for minimum cost. Parametric analyses are done to demonstrate how the optimization can be used to analyze the entire system taking into account the cost performance of the ingredients. Finally, it is demonstrated how the above approach requires significantly less time and labor to find an optimum formulation than the traditional approach. J. VINYL ADDIT. TECHNOL., 25:E44–E58, 2019. © 2017 Society of Plastics Engineers
Membrane engineering via trans-unsaturated fatty acids production improves succinic acid production in Mannheimia succiniciproducens
Authors: Ahn Jung Ho , Lee Jong An , Bang Junho , Lee Sang Yup
Published: January 2018

Engineering of microorganisms to produce desired bio-products with high titer, yield, and productivity is often limited by product toxicity. This is also true for succinic acid (SA), a four carbon dicarboxylic acid of industrial importance. Acid products often cause product toxicity to cells through several different factors, membrane damage being one of the primary factors. In this study, cis–trans isomerase from Pseudomonas aeruginosa was expressed in Mannheimia succiniciproducens to produce trans-unsaturated fatty acid (TUFA) and to reinforce the cell membrane of M. succiniciproducens. The engineered strain showed significant decrease in membrane fluidity as production of TUFA enabled tight packing of fatty acids, which made cells to possess more rigid cell membrane. As a result, the membrane-engineered M. succiniciproducens strain showed higher tolerance toward SA and increased production of SA compared with the control strain without membrane engineering. The membrane engineering approach employed in this study will be useful for increasing tolerance to, and consequently enhancing production of acid products.
Blurring the boundaries between networking and IT security
Authors: Nicholson Dave
Published: January 2018

Networking and security used to be largely separate IT methodologies. They were even built separately. Traditionally, networks were constructed on standard building blocks (switches, routers etc) and security solutions such as perimeter firewalls, intrusion prevention systems and the like were applied afterwards.

Networking and security used to be largely separate IT methodologies. As such, they could be treated as separate domains of the business.

That's not the case today. There is now a huge overlap between the two areas. It is becoming common to think about the network itself as a security enforcement platform and these two elements of modern technology systems are becoming inextricably entwined. This development will be overwhelmingly positive both for solutions providers and their end customers, says Dave Nicholson of Axial Systems.
The trajectory of φ-features on Old French D and n
Authors: Déchaine Rose-Marie , Dufresne Monique , Tremblay Mireille
Published: January 2018

Old French (OF) determiners (D), which are optional, show a three-way split between definite (def), indefinite(indf), and expletive(expl)D. We develop a nano-syntactic analysis of these three paradigms, according to which the nominal spine is associated with a series of functional heads that include Number, Gender, D, and Kase. We test the predictions of the formal analysis with a quantitative analysis of corpus data from two 12thcentury Anglo-Norman texts –Le voyage de saint Brendan(B) andLais de Marie de France(MdF) – which indicates that over a 60-year span, there are changes in the distribution of D. This presents itself in three ways. First, a decline in expletive D inMdFcorrelates with an increase in the use of D with masculine (m) non-count nouns (nNON-CT) Second, whileBlacks an overt indefinite plural (pl) D,MdFhas one in the form ofdes. Third, with count nouns(nCT), while feminine (f) nouns favour the absence of determiners inB, there is no gender effect inMdF. While the first two changes are predicted by the formal analysis, the third is not. More broadly, the results of our quantitative study provide a more nuanced picture of the factors that govern the distribution of D in OF: they confirm that – relative to conditioning the absence of D (D-drop) – definiteness, grammatical function, and number are stable factors, gender is not a stable factor, and word order does not play a significant role.
Vortex dynamics and sound emission in excited high-speed jets
Authors: Crawley Michael , Gefen Lior , Kuo Ching-Wen , Samimy Mo , Camussi Roberto
Published: January 2018

This work aims to study the dynamics of and noise generated by large-scale structures in a Mach 0.9 turbulent jet of Reynolds number $6.2\times 10^{5}$ using plasma-based excitation of shear layer instabilities. The excitation frequency is varied to produce individual or periodic coherent ring vortices in the shear layer. First, two-point cross-correlations are used between the acoustic near field and far field in order to identify the dominant noise source region. The large-scale structure interactions are then investigated by stochastically estimating time-resolved velocity fields using time-resolved near-field pressure traces and non-time-resolved planar velocity snapshots (obtained by particle image velocimetry) by means of an artificial neural network. The estimated time-resolved velocity fields show multiple mergings of large-scale structures in the shear layer, and indicate that disintegration of coherent ring vortices is the dominant aeroacoustic source mechanism for the jet studied here. However, the merging of vortices in the initial shear layer is also identified as a non-trivial noise source mechanism.
Classification Accuracy as a Substantive Quantity of Interest: Measuring Polarization in Westminster Systems
Authors: Peterson Andrew , Spirling Arthur
Published: January 2018

Measuring the polarization of legislators and parties is a key step in understanding how politics develops over time. But in parliamentary systems—where ideological positions estimated from roll calls may not be informative—producing valid estimates is extremely challenging. We suggest a new measurement strategy that makes innovative use of the “accuracy” of machine classifiers, i.e., the number of correct predictions made as a proportion of all predictions. In our case, the “labels” are the party identifications of the members of parliament, predicted from their speeches along with some information on debate subjects. Intuitively, when the learner is able to discriminate members in the two main Westminster parties well, we claim we are in a period of “high” polarization. By contrast, when the classifier has low accuracy—and makes a relatively large number of mistakes in terms of allocating members to parties based on the data—we argue parliament is in an era of “low” polarization. This approach is fast and substantively valid, and we demonstrate its merits with simulations, and by comparing the estimates from 78 years of House of Commons speeches with qualitative and quantitative historical accounts of the same. As a headline finding, we note that contemporary British politics is approximately as polarized as it was in the mid-1960s—that is, in the middle of the “postwar consensus”. More broadly, we show that the technical performance of supervised learning algorithms can be directly informative about substantive matters in social science.
The Sequence of Events that led to the 1963 Publications in Nature of 3C 273, the First Quasar and the First Extragalactic Radio Jet
Authors: Hazard Cyril , Jauncey David , Goss W. M. , Herald David
Published: January 2018

We have undertaken a detailed investigation, based on the available evidence, of the sequence of events that led to the historical discovery of the first quasar, 3C 273.
Understanding the Asian American Vote in the 2016 Election
Authors: Masuoka Natalie , Han Hahrie , Leung Vivien , Zheng Bang Quan
Published: January 2018

As the number of Asian American voters has increased with each election, more research is needed to understand the participation and voting patterns of this diverse electorate. This paper offers an analysis of Asian American political participation and vote choice preferences during the 2016 presidential election. The paper begins by addressing the concerns related to Asian American political incorporation. We disaggregate Asian Americans into three voting types—voters, those who are eligible to vote but are not registered, and those who are ineligible to vote—and compare the demographic differences found across these three groups. The second half of the paper turns to Asian American candidate preferences in the 2016 election. We find that voters who report high levels of media consumption and those with a strong sense of political efficacy were more likely to support Clinton. Our analysis of non-voters suggests that the potential incorporation of these Asian Americans would result in a continued base of support for the Democratic party.
Panalesis: towards global synthetic palaeogeographies using integration and coupling of manifold models
Authors: VÉRARD CHRISTIAN
Published: January 2018

Palaeogeographic reconstructions have been proposed for years. The technique employed, however, is more or less always the same: it consists of determining the palaeoenvironment at the local scale and extending it to the regional scale. Such work is carried out in a maximum number of locations all over the planet and the global palaeogeography is the result of interpolation of those reconstructions. Advances in palaeogeography can be made via an alternative way, which consists of integrating and then coupling various global models. It results in the proposal of synthetic palaeogeographies that can be compared a posteriori to local or regional data. The advantage is twofold: (1) the view is really global and it avoids gaps (in particular in the oceanic realm) in the reconstructions, and it is very much less focused on the coastline; (2) it takes advantages from almost all the fields of geosciences, so that reconstructions can be constrained from a large variety of data. The two techniques – the ‘classic’ and the ‘alternative’ – are not contradictory but complementary, and it is desirable that one feeds the other and the study of palaeogeography be revived.
Dimensional synthesis and concept design of a novel minimally invasive surgical robot
Authors: Niu Guojun , Pan Bo , Zhang Fuhai , Feng Haibo , Gao Wenpeng , Fu Yili
Published: January 2018

A new minimally invasive surgical (MIS) robot consisting of a spherical remote center motion (RCM) mechanism with modular design is proposed. A multi-objective dimensional synthesis model is presented to obtain the excellent performance indices. There are four objectives: a global kinematic index, a compactness index, a global comprehensive stiffness index, and a global dynamic index. Other indices characterizing the design requirement, such as workspace, mechanical parameter, and mass, are chosen as constraints. A new decoupled mechanism is raised to solve the coupled motion between the linear platform and the four degrees of freedom (DoF) of surgical instrument as a result of post-driving motors. Another new mechanical decoupled method is proposed to eliminate the coupled motion between the wrist and the forceps, enhance the dexterity of surgical instrument, and improve the independence of each motor. Then, a 7-DoF MIS robotic prototype based on optimization results has been built up. Experiment results validate the effectiveness of the two mechanical decoupled methods. The position change of the RCM point, accuracy, and repeatability of the MIS robot meet the requirements of MIS. Successful animal experiments validate the effectiveness of the novel MIS robot.
Weeds, nitrogen and yield: measuring the effectiveness of an organic cover cropped vegetable no-till system
Authors: Robb David , Zehnder Geoff , Kloot Robin , Bridges William , Park Dara
Published: January 2018

Organic vegetable growers rely heavily on mechanical methods such as tillage and other forms of labor-intensive soil cultivation for weed management despite the negative effects to soil health associated with intensive soil disturbance. The use of cover crops and no-till (NT) vegetable production represents an alternative approach to weed control that can enhance rather than degrade soil health; however, there are challenges inherent with this practice and previous results in vegetable production have been mixed. Field experiments were conducted over 2 yr at the Clemson Student Organic Farm to examine the effects of tillage [NT versus conventional tillage (CT)] on weed development and management in organic tomato and summer squash production under different nitrogen (N) fertility regimes, and to assess soil N dynamics in both systems. Squash yields were similar between tillage treatments in both years. NT tomato yields were 43% greater than CT yields in 2014, whereas CT tomato yields were 46% greater than NT yields in 2015. Squash and tomato yields per unit of management labor (time) were significantly greater in NT compared with CT treatments for both years. There were no statistical differences in squash and tomato yields between N fertilization treatments in either year. Pre- and post-season soil N results were mixed. Pre-season soil N levels were significantly higher in NT tomato plots in 2014 but similar between tillage treatments in tomato plots in 2015 and in squash plots both years. Post-season soil N levels in tomato plots were similar between tillage treatments both years. Post-season soil N levels were significantly higher in NT squash plots in 2014 and in CT squash plots in 2015. Roller-crimped NT mulches provided adequate early-season weed suppression in both years and saved considerable weed management and seedbed preparation labor. Overall, the results demonstrated that organic NT is a viable method for reduced tillage summer vegetable production in the southeastern Piedmont region.
Polymer nanofibre composite nonwovens with metal-like electrical conductivity
Authors: Reich Steffen , Burgard Matthias , Langner Markus , Jiang Shaohua , Wang Xueqin , Agarwal Seema , Ding Bin , Yu Jianyong , Greiner Andreas
Published: January 2018

Bendable and breathable polymer nanofibre nonwovens with metal-like electrical conductivity are required for lightweight electrodes and electric shielding design with applications in batteries, functional textiles, sensors, cars, aerospace, constructions, mobile phones, and medical devices. Metal-like conductivity in polymer nonwovens has not been achieved till now due to the limitation of the existing processing techniques. We show here, the metal-like electrical conductivity of 750,000 S/m in polyacrylonitrile (PAN), poly(ε-caprolactone) (PCL) nonwoven using very low content of silver nanowires (AgNW; 3.35 vol%). The key to the high conductivity was the homogenous distribution of AgNW in nonwoven made by wet-laid process using short electrospun fibre and AgNW dispersion. Above a threshold of 0.36 vol% AgNW, the conductivity of the nonwoven increased by seven orders of magnitude, which we attribute to the onset of percolation of the AgNW. Our nonwoven-AgNW composites show fast heating and cooling within a few seconds at a voltage of 1.1 V, which is in the range of portable devices. These composites are also breathable and bendable. The electrical conductivity was independent of the bending angle of the composite, which is important for applications mentioned above and would help other scientists to design new conductive materials in the future.
Increased risk of coronary heart disease among patients with primary Sjögren’s syndrome: a nationwide population-based cohort study
Authors: Wu Xue-Fen , Huang Jing-Yang , Chiou Jeng-Yuan , Chen Huang-Hsi , Wei James Cheng-Chung , Dong Ling-Li
Published: January 2018

To investigate the association between primary Sjögren’s syndrome (pSS) and coronary heart disease (CHD), and the influence of medications for pSS patients on risk of CHD. The authors identified 4175 patients with a new diagnosis of pSS between 2002 and 2013 from the National Health Insurance Research database. The control-to-case ratio was 4:1. The risk and cumulative incidences of CHD were calculated. The adjusted hazard ratio (HR) of CHD for pSS patients was 1.17 (1.03–1.34) after adjusting for age, sex, comorbidities, and medications. The cumulative incidence for CHD in the pSS group was significantly higher than that in the control group (log-rank p < 0.0001). The risk of CHD in pSS patients was increased with age by 4% per year, and 45- to 59-year-olds were at the highest risk (HR = 1.464, 1.195–1.794). The application of corticosteroids (HR = 1.45, 1.07–1.97) as well as NSAIDs (HR = 1.31, 1.05–1.65) both increased the risk of CHD among pSS patients. pSS is associated with an increased risk of subsequent CHD in Taiwan. Primary Sjögren’s syndrome might be an independent risk factor for CHD. Use of corticosteroids and NSAIDs in the treatment of pSS patients increased the risk of developing CHD.
Mutant torsinA in the heterozygous DYT1 state compromises HSV propagation in infected neurons and fibroblasts
Authors: György Bence , Cruz Lilian , Yellen David , Aufiero Massimo , Alland Isabel , Zhang Xuan , Ericsson Maria , Fraefel Cornel , Li Yu-Ching , Takeda Shuko , Hyman Bradley T. , Breakefield Xandra O.
Published: January 2018

Most cases of early onset torsion dystonia (DYT1) are caused by a 3-base pair deletion in one allele of the TOR1A gene causing loss of a glutamate in torsinA, a luminal protein in the nuclear envelope. This dominantly inherited neurologic disease has reduced penetrance and no other medical manifestations. It has been challenging to understand the neuronal abnormalities as cells and mouse models which are heterozygous (Het) for the mutant allele are quite similar to wild-type (WT) controls. Here we found that patient fibroblasts and mouse neurons Het for this mutation showed significant differences from WT cells in several parameters revealed by infection with herpes simplex virus type 1 (HSV) which replicates in the nucleus and egresses out through the nuclear envelope. Using a red fluorescent protein capsid to monitor HSV infection, patient fibroblasts showed decreased viral plaque formation as compared to controls. Mouse Het neurons had a decrease in cytoplasmic, but not nuclear HSV fluorescence, and reduced numbers of capsids entering axons as compared to infected WT neurons. These findings point to altered dynamics of the nuclear envelope in cells with the patient genotype, which can provide assays to screen for therapeutic agents that can normalize these cells.
hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage
Authors: Cloutier Alexandre , Shkreta Lulzim , Toutant Johanne , Durand Mathieu , Thibault Philippe , Chabot Benoit
Published: January 2018

Little is known about how RNA binding proteins cooperate to control splicing, and how stress pathways reconfigure these assemblies to alter splice site selection. We have shown previously that SRSF10 plays an important role in the Bcl-x splicing response to DNA damage elicited by oxaliplatin in 293 cells. Here, RNA affinity assays using a portion of the Bcl-x transcript required for this response led to the recovery of the SRSF10-interacting protein 14-3-3ε and the Sam68-interacting protein hnRNP A1. Although SRSF10, 14-3-3ε, hnRNP A1/A2 and Sam68 do not make major contributions to the regulation of Bcl-x splicing under normal growth conditions, upon DNA damage they become important to activate the 5′ splice site of pro-apoptotic Bcl-xS. Our results indicate that DNA damage reconfigures the binding and activity of several regulatory RNA binding proteins on the Bcl-x pre-mRNA. Moreover, SRSF10, hnRNP A1/A2 and Sam68 collaborate to drive the DNA damage-induced splicing response of several transcripts that produce components implicated in apoptosis, cell-cycle control and DNA repair. Our study reveals how the circuitry of splicing factors is rewired to produce partnerships that coordinate alternative splicing across processes crucial for cell fate.
Electrophilic fatty acid nitroalkenes regulate Nrf2 and NF-κB signaling:A medicinal chemistry investigation of structure-function relationships
Authors: Khoo Nicholas K. H. , Li Lihua , Salvatore Sonia R. , Schopfer Francisco J. , Freeman Bruce A.
Published: January 2018

Fatty acid nitroalkene derivatives (NO2-FA) activate Nrf2-regulated antioxidant gene expression and inhibit NF-κB-dependent cytokine expression. To better define NO2-FA structure-function relationships, a series of 22 new chemical entities (NCEs) containing an electrophilic nitroalkene functional group were synthesized and screened for both Nrf2- and NF-κB activities using luciferase-based assays. The structural variables were acyl chain length (11 to 24 carbons) and position of the electrophilic nitroalkene group. In luciferase-based reporter assays, Nrf2 was maximally activated by omega-12 nitroalkene fatty acids while TNFα stimulated NF-κB-inhibition was maximal for omega-5 nitroalkenes. The top pathway-modulating NO2-FAs were a) evaluated for an ability to activate Nrf2-dependent signaling and inhibit NF-κB-dependent inflammatory responses of RAW264.7 cells and b) compared to electrophilic compounds in clinical development. These findings revealed that 8/9-nitro-eicos-8-enoic acid (NCE−10) was collectively the most effective NCE and that both the α and ω acyl chain lengths influence nitroalkene activation of Nrf2 and inhibition of NF-κB signaling. This insight will guide development of more effective non-natural homologs of endogenously-detectable fatty acid nitroalkenes as anti-inflammatory and anti-fibrotic drug candidates.
Application of Assisted Design of Antibody and Protein Therapeutics (ADAPT) improves efficacy of a Clostridium difficile toxin A single-domain antibody
Authors: Sulea Traian , Hussack Greg , Ryan Shannon , Tanha Jamshid , Purisima Enrico O.
Published: January 2018

Assisted Design of Antibody and Protein Therapeutics (ADAPT) is an affinity maturation platform interleaving predictions and testing that was previously validated on monoclonal antibodies (mAbs). This study expands the applicability of ADAPT to single-domain antibodies (sdAbs), a promising class of recombinant antibody-based biologics. As a test case, we used the camelid sdAb A26.8, a VHH that bindsClostridium difficiletoxin A (TcdA) relatively weakly but displays a reasonable level of TcdA neutralization. ADAPT-guided A26.8 affinity maturation resulted in an improvement of one order of magnitude by point mutations only, reaching an equilibrium dissociation constant (KD) of 2 nM, with the best binding mutants having similar or improved stabilities relative to the parent sdAb. This affinity improvement generated a 6-fold enhancement of efficacy at the cellular level; the A26.8 double-mutant T56R,T103R neutralizes TcdA cytotoxicity with an IC50of 12 nM. The designed mutants with increased affinities are predicted to establish novel electrostatic interactions with the antigen. Almost full additivity of mutation effects is observed, except for positively charged residues introduced at adjacent positions. Furthermore, analysis of false-positive predictions points to general directions for improving the ADAPT platform. ADAPT guided the efficacy enhancement of an anti-toxin sdAb, an alternative therapeutic modality forC. difficile.
Floquet Topological Superfluid and Majorana Zero Modes in Two-Dimensional Periodically Driven Fermi Systems
Authors: Yang Xiaosen , Huang Beibing , Wang Zhengling
Published: January 2018

We propose a simple approach to realize two-dimensional Floquet topological superfluid by periodically tuning the depth of square optical lattice potentials. We show that the periodic driving can induce topological phase transitions between trivial superfluid and Floquet topological superfluid. For this systems we verify the anomalous bulk-boundary correspondence, namely that the robust chiral Floquet edge states can appear even when the winding number of all the bulk Floquet bands is zero. We establish the existence of two Floquet Majorana zero modes separated in the quasienergy space, with ε0,π = 0,π/T at the topological defects.
Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation
Authors: Furube Eriko , Kawai Shintaro , Inagaki Haruna , Takagi Shohei , Miyata Seiji
Published: January 2018

Numerous studies have reported the importance of microglial activation in various pathological conditions, whereas little attention has been given to the point for dynamics of microglial population under infection-induced inflammation. In the present study, the single systemic stimulation of 100 μg/kg lipopolysaccharide (LPS) induced robust microglial proliferation only in the circumventricular organs (CVOs) and their neighboring brain regions. More than half of microglia similarly showed proliferative activity in the CVOs and their neighboring brain regions after 1 mg/kg LPS stimulation, while this stimulation expanded microglia-proliferating brain regions including the hypothalamus, medulla oblongata, and limbic system. Microglia proliferation resulted in a transient increase of microglial density, since their density almost returned to basal levels within 3 weeks. Divided microglia survived at the same rate as non-divided ones. Proliferating microglia frequently expressed a resident microglia marker Tmem119, indicating that increase of microglia density is due to the proliferation of resident microglia. Thus, the present study demonstrates that transient increase in microglia density depends on the brain region and dose of LPS during infection-induced inflammation and could provide a new insight on microglia functions in inflammation and pathogenesis of brain diseases.
Nitrogen supply influences photosynthesis establishment along the sugarcane leaf
Authors: Bassi Denis , Menossi Marcelo , Mattiello Lucia
Published: January 2018

Nitrogen (N) is a major component of the photosynthetic apparatus and is widely used as a fertilizer in crops. However, to the best of our knowledge, the dynamic of photosynthesis establishment due to differential N supply in the bioenergy crop sugarcane has not been reported to date. To address this question, we evaluated physiological and metabolic alterations along the sugarcane leaf in two contrasting genotypes, responsive (R) and nonresponsive (NR), grown under high- and low-N conditions. We found that the N supply and the responsiveness of the genotype determined the degree of senescence, the carboxylation process mediated by phosphoenolpyruvate carboxylase (PEPcase) and differential accumulation of soluble sugars. The metabolite profiles indicated that the NR genotype had a higher respiration rate in the youngest tissues after exposure to high N. We observed elevated levels of metabolites related to photosynthesis in almost all leaf segments from the R genotype under high-N conditions, suggesting that N supply and the ability to respond to N influenced photosynthesis. Therefore, we observed that N influence on photosynthesis and other pathways is dependent on the genotype and the leaf region.
Non quasi-Hemispherical Seismological Pattern of the Earth’s Uppermost Inner Core
Authors: Ivan Marian , Wang Rongjiang , Hofstetter Rami
Published: January 2018

We assembled a database consisting of 5,404 PKIKP/PKiKP observations from 555 events, where PKIKP is the phase sampling the inner core (IC) and PKiKP is the phase reflected at the inner core boundary (ICB). Around 138° distances, their differential arrival times and amplitude ratio are mostly sensitive to the seismic velocity and attenuation structure in the uppermost IC (UIC), respectively. Our observations do not support a large-scale anisotropy in the UIC, but do not exclude its presence in some restricted areas. A robust inversion for the isotropic P-wave velocity perturbations shows a higher velocity cap with a radius of ~60°, approximately centered beneath the Northern Sumatra, with a local low velocity zone beneath the central Indian Ocean. The rest of the UIC, including the Northern part of Eurasia and of the Atlantic Ocean, exhibits mostly lower velocity. Amplitude ratio values of PKIKIP/PKiKP (observed vs. computed) from 548 high signal-to-noise (>5) recordings show a large variance, suggesting only a faint correlation between higher velocity and lower attenuation in the UIC. Our results provide better constraints to the models invoking a heat transfer in the UIC, with a complex temperature pattern near ICB.
Metals Enhance the Killing of Bacteria by Bacteriophage in Human Blood
Authors: Ma Li , Green Sabrina I. , Trautner Barbara W. , Ramig Robert F. , Maresso Anthony W.
Published: January 2018

Multidrug-resistant bacterial pathogens are a major medical concern.E.coli, particularly the pathotype extraintestinal pathogenicE.coli(ExPEC), is a leading cause of bloodstream infections. As natural parasites of bacteria, bacteriophages are considered a possible solution to treat patients infected with antibiotic resistant strains of bacteria. However, the development of phage as an anti-infective therapeutic is hampered by limited knowledge of the physiologic factors that influence their properties in complex mammalian environments such as blood. To address this barrier, we tested the ability of phage to kill ExPEC in human blood. Phages are effective at killing ExPEC in conventional media but are substantially restricted in this ability in blood. This phage killing effect is dependent on the levels of free metals and is inhibited by the anticoagulant EDTA. The EDTA-dependent inhibition of ExPEC killing is overcome by exogenous iron, magnesium, and calcium. Metal-enhanced killing of ExPEC by phage was observed for several strains of ExPEC, suggesting a common mechanism. The addition of metals to a murine host infected with ExPEC stimulated a phage-dependent reduction in ExPEC levels. This work defines a role for circulating metals as a major factor that is essential for the phage-based killing of bacteria in blood.
Comparing the Intramedullary Nail and Extramedullary Fixation in Treatment of Unstable Intertrochanteric Fractures
Authors: Zhang Wen-Qiang , Sun Jian , Liu Chun-Yu , Zhao Hong-Yao , Sun Yi-Feng
Published: January 2018

Treatment options for unstable intertrochanteric fractures include intramedullary nail and extramedullary fixation, although evidence regarding the most appropriate treatment for such fractures remains controversial. Our hypothesis was that there would be no obvious differences in mortality rates, functional outcomes and complications between the two groups. We therefore conducted a meta-analysis to compare the relative advantages of intramedullary nail and extramedullary fixation. A total of 10 randomized controlled trials including only patients with unstable intertrochanteric fractures were included in the final analysis. We found that no statistically significant difference in one-year mortality was observed between the two groups (RR: 0.78, 95% CI: 0.55–1.10, p = 0.160). Analysis of exact p values from five included studies indicated that functional outcomes were markedly better for patients of the intramedullary nail group when compared with those of the extramedullary fixation group (p = 0.0028), although evidence remains controversial. Higher incidences of all complications were noted for extramedullary fixation (RR:1.48, 95% CI: 1.12–1.96, p = 0.006). However, no significant differences in implant-related complications were observed between the two groups (RR:1.20, 95% CI: 0.73–1.97, p = 0.475). Therefore, comparing with extramedullary fixation, the intramedullary nail method would be more reliable and should be encouraging for unstable intertrochanteric fractures.
An Accord of Nuclear Receptor Expression in M. tuberculosis Infected Macrophages and Dendritic Cells
Authors: Saini Ankita , Mahajan Sahil , Ahuja Nancy , Bhagyaraj Ella , Kalra Rashi , Janmeja Ashok Kumar , Gupta Pawan
Published: January 2018

Mycobacterium tuberculosisinstigates interactions with host factors to promote its survival within the host inimical conditions. Among such factors, nuclear receptors (NRs) seem to be promising candidates owing to their role in bacterial pathogenesis. However, only few members of NR superfamily have been implicated inM. tuberculosisinfection and there is a dearth of comprehensive knowledge about expression or function of the entire superfamily. In this study, we performed detailed expression analysis and identified key NRs getting differentially regulated in murine macrophages and dendritic cells (DC) upon infection withH37Rv. The murine macrophages and DCs infected withH37Rventailed overlapping changes in the expression of certain NRs which reflect upon the possibility that both cells might utilize similar transcriptional programs uponM. tuberculosisinfection. We identified Nr4a3 and Rora, which have not been implicated inM. tuberculosispathogenesis, undergo similar changes in expression in macrophages and DCs uponH37Rvinfection. Interestingly, a similar pattern in their expression was also observed in infected human monocyte derived macrophages and the findings corroborated well with PBMCs obtained from TB patients. This all-inclusive analysis provides the basis for a precise approach in identifying NRs that can be targeted therapeutically in intracellular bacterial infections.
The odd one out: Arabidopsis reticulon 20 does not bend ER membranes but has a role in lipid regulation
Authors: Kriechbaumer Verena , Maneta-Peyret Lilly , Fouillen Laetitia , Botchway Stanley W. , Upson Jessica , Hughes Louise , Richardson Jake , Kittelmann Maike , Moreau Patrick , Hawes Chris
Published: January 2018

Reticulons are integral ER membrane proteins characterised by a reticulon homology domain comprising four transmembrane domains which results in the proteins sitting in the membrane in a W-topology. Here we report on a novel subgroup of reticulons with an extended N-terminal domain and in particular on arabidopsis reticulon 20. Using high resolution confocal microscopy we show that reticulon 20 is located in a unique punctate pattern on the ER membrane. Its closest homologue reticulon 19 labels the whole ER. Other than demonstrated for the other members of the reticulon protein family RTN20 and 19 do not display ER constriction phenotypes on over expression. We show that mutants in RTN20 or RTN19, respectively, display a significant change in sterol composition in roots indicating a role in lipid regulation. A third homologue in this family -3BETAHSD/D1- is unexpectedly localised to ER exit sites resulting in an intriguing location difference for the three proteins.
Correction: Corrigendum: Dislocation Strengthening without Ductility Trade-off in Metastable Austenitic Steels
Authors: Liu Jiabin , Jin Yongbin , Fang Xiaoyang , Chen Chenxu , Feng Qiong , Liu Xiaowei , Chen Yuzeng , Suo Tao , Zhao Feng , Huang Tianlin , Wang Hongtao , Wang Xi , Fang Youtong , Wei Yujie , Meng Liang , Lu Jian , Yang Wei
Published: January 2018

Scientific Reports 6: Article number: 35345; published online: 14 October 2016; updated: 29 January 2018. The original version of this Article contained errors in the affiliation list. Affiliations 1, 2 and 3 were incorrectly listed as affiliations 2, 3 and 1 respectively. In addition, Jiabin Liu was incorrectly affiliated with ‘State Key Laboratory for Strength and Vibration of Mechanical Structures, Xi’an Jiaotong University, Xi’an 710049’.
Technical aspects of nicking enzyme assisted amplification
Authors: Wang Liu , Qian Cheng , Wu Hui , Qian Wenjuan , Wang Rui , Wu Jian
Published: January 2018

Guidance to enhance the sensitivity and specificity of nicking enzyme assisted amplification has been provided.
New hole transporting materials for planar perovskite solar cells
Authors: Li Dongmei , Shao Jiang-Yang , Li Yiming , Li Yusheng , Deng Li-Ye , Zhong Yu-Wu , Meng Qingbo
Published: January 2018

Two HTMs with triphenylamine and carbazole moieties for planar perovskite solar cells are designed, exhibiting 18.2% power conversion efficiency and better stability.
Retracted Article: Visible-light-induced oxidative difunctionalization of styrenes: synthesis of α-trifluoromethylthio-substituted ketones
Authors: Yadav Arvind Kumar , Singh Krishna Nand
Published: January 2018

Synthesis of α-trifluoromethylthio-substituted ketones has been accomplished through photoredox catalysis from easily accessible styrenes. The present approach involves the use of inexpensive eosin Y as an organophotoredox catalyst and a CF3SO2Na/CS2 blend as a new source of SCF3 radicals at room temperature.