bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Studies on the Structure, Optoelectronic and Photosensitizer Applications of NKX Class of Coumarin Dye Molecules
Authors: Manzoor Taniya , Pandith Altaf Hussain
Published: February 2018

Coumarin based NKX class of molecules have been recently investigated for their promising sensitizing applications in dye Sensitized Solar Cells (DSSCs). However, the various factors limiting the sensitizing properties of these molecules such as charge transport efficiency and electron back recombination still remain to be understood properly. Herein, we report a detailed theoretical study on the structural, opto‐electronic and photo‐sensitizer applications of 2‐cyano‐3‐[5‐(1, 1, 6,6‐tetramethyl‐10‐oxo‐2,3,5,6‐tetrahydro‐1H,4H,10H‐11‐oxa‐3a‐aza‐benzo[de]anthracen‐9‐yl)‐thiophen‐2‐yl]‐acrylicacid (NKX 2587) based dye molecules. Structural variation of the dye molecule through derivatization has been attempted, with the main emphasis on the minimization of the back electron recombination rates through reduced dye – I2 interaction. The optical and photovoltaic properties of these dyes were studied in terms of the key parameters like, HOMO‐LUMO energy gap, maximum absorption wavelength, λmax, light harvesting efficiency, charge injection efficiency, open voltage, reorganization energy etc. using density functional theory methods. The results reflect that the dyes with more electron withdrawing substituents exhibit lower dye – I2 interaction, thus minimizing the back recombination. Moreover, the dyes with chloro (C3), bromo (C4), iodo (C5) and cyano (C7) substituents exhibit almost double electronic injection efficiency in comparison to the parent sensitizer molecule and are hence, expected to enhance the efficiency of the DSSCs based on such systems.
Discovery of Trypanocidal Bioactive Leads by Docking Study, Molecular Dynamic Simulation and In Vivo Screening
Authors: Ibezim Akachukwu , Obi Chukwunonso B. , Oforkansi Nneoma M. , Mbah Chika J. , Nwodo Ngozi J.
Published: February 2018

Nine selected potential antitrypanosomal hits from plants obtained by docking calculation according to the docking protocols implemented in Molecular Operating Environment were further screened by evaluating their binding affinities toward an ‘all important’ antitrypanosomal drug target – trypanothione reductase (TryR), which is absent in humans, using a more stringent scoring function obtainable in AutoDock vina. All the compounds showed binding affinity for TryR at the range of −4.90±1.78 to −8.70±0.22 Kcal/mol. Also, the compounds demonstrated affinity toward an analogous enzyme to TryR, glutathione reductase (GR) that is found in vertebrates which suggests that they could pose a selectivity challenge. However, on comparison, β‐sitosterol; the candidate that scored topmost against three out of six earlier studied antitrypanosomal drug targets (uridylyl transferase ‐ UTF, farnesyl diphosphate synthase ‐ FDS and adenosine kinase ‐ ADK), showed a significant (P<0.05) binding affinity for TryR (‐8.70±0.22 Kcal/mol) over GR (‐7.50±0.36 Kcal/mol). The complexes formed between β‐sitosterol and the proteins: UTF, FDS and ADK, remained stable over 100 ps molecular dynamic simulation. Moreover, 200 mg/kg b.w. of the candidate significantly (P<0.05) killed the pathogen in T. b. brucei infected mice from third day post treatment. This study presents β‐sitosterol as an interesting antitrypanosomal candidate.
Acetylenic Indole‐Encapsulated Schiff Bases: Synthesis, In Silico Studies as Potent Antimicrobial Agents, Cytotoxic Evaluation and Synergistic Effects
Authors: Singh Gurjaspreet , Kalra Pooja , Arora Aanchal , Singh Akshpreet , Sharma Geetika , Sanchita  , Maurya Indresh Kumar , Dutta Sanjay , Munshi Parthapratim , Verma Vikas
Published: February 2018

A family of pharmacophore acetylenic indole‐3‐carboxaldehyde (3) and acetylenic indole schiff bases (5 a‐5 i) bearing indole framework were synthesized to afford structurally diverse moieties. Acetylenic indole‐3‐carboxaldehyde was coupled with various amines to furnish the novel scaffolds 5 a‐5 i. These acetylenic indole Schiff bases (AISB) were synthesized in shorter times under microwave irradiation in comparison to classical reaction conditions. AISB were experimentally characterized by using IR, 1H NMR, 13C NMR, X ray crystallographic and mass spectrometric methods. The synthesized compounds showed promising anti‐bacterial and anti‐fungal properties when tested in vitro against six bacterial and seven fungal strains. Among these, hybrids 5 a, 5 c, 5 e and 5 g were found to be even more potent than the standard drugs and were more influential against the bacterial than the fungal strains. These more potent compounds were then evaluated for their cytotoxicity by MTT assay on Hek293 and HeLa cells. The synergistic effect of bis‐acetylenic compound 5 g with kanamycin and amphotericin B has also been scrutinized. Further, the structural and electronic properties of the molecules were investigated theoretically by performing density functional theory (DFT).
pH‐Controlled Nanoparticles Formation and Tracking of Lysosomal Zinc Ions in Cancer Cells by Fluorescent Carbazole–Bipyridine Conjugates
Authors: Sudheesh Karivachery V. , Joseph Manu M. , Philips Divya S. , Samanta Animesh , Kumar Maiti Kaustabh , Ajayaghosh Ayappanpillai
Published: February 2018

Fluorescent probes for simultaneous detection of multiple organelle specific analytes in cancer cells are essential for bioimaging applications. During abnormalities in cells, among other important parameters (metal ions, reactive oxygen species (ROS), enzymes, etc.) pH and Zn2+ are also altered in cells. Herein, we report the formation of nanoparticles of the fluorescent molecules based on carbazole‐bipyridine conjugates (CBL1‐3) and their use as nanoprobes to simultaneously detect Zn2+ and pH variations in lysosome. Upon increasing the pH from 4–6, these probes form nanoparticles with increased size and enhanced fluorescence at 510 nm. Among CBL1‐3, nanoparticles of CBL2 upon Zn2+ binding, exhibit pH responsive intensity change only at lysosomal pH window at 610 nm and become silent above pH 7. Fluorescent imaging experiments on cancer cells revealed that the CBL2 nanoprobe is capable of localizing at lysosomes and facilitates the detection of endogenous Zn2+ and pH variations. Furthermore, the lysosomal Zn2+ variation with external stimuli induced programmed cell death was visualized using the nanoprobe.
‘À La Carte’ Cyclic Hexapeptides: Fine Tuning Conformational Diversity while Preserving the Peptide Scaffold.
Authors: Ciudad Sonia , Bayó‐Puxán Núria , Varese Monica , Seco Jesús , Teixidó Meritxell , García Jesús , Giralt Ernest
Published: February 2018

Cyclic peptides have recently emerged as promising modulators of challenging protein‐protein interactions. Here we report on the design, synthesis and conformational behavior of a small library composed of C2 symmetric cyclic hexapeptides of type c(Xaa‐D‐Pro‐Yaa)2, where Xaa and Yaa are chosen from alanine, isoleucine, serine, glutamic acid, arginine and tryptophan due to the favorable properties of the side chains of these residues to recognize complex protein surfaces. We used a combination of nuclear magnetic resonance and molecular dynamic simulations to perform an extensive conformational analysis of a representative set of cyclic hexapeptides. Our results indicated that both the chemical nature and the chirality of the variable Xaa and Yaa positions play an important role in the cis/trans configuration of the Xaa‐D‐Pro bonds and in the conformational preferences of this family of peptides. This structural tuning can be exploited in design strategies seeking to optimize the binding efficiency and selectivity of cyclic hexapeptides towards protein surfaces.
A systematic literature review of the use of formal methods in medical software systems
Authors: Bonfanti Silvia , Gargantini Angelo , Mashkoor Atif
Published: February 2018

The use of formal methods is often recommended to guarantee the provision of necessary services and to assess the correctness of critical properties, such as functional safety, cybersecurity, and reliability, in medical and health care devices. In the past, several formal and rigorous methods have been proposed and consequently applied for trustworthy development of medical software and systems. In this paper, we perform a systematic literature review on the available state of the art in this domain. We collect the relevant literature on the use of formal methods for modeling, design, development, verification, and validation of software‐intensive medical systems. We apply standard systematic literature review techniques and run several queries in well‐known repositories to obtain information that can be useful for people who are either already working in this field or planning to start. Our study covers both quantitative and qualitative aspects of the subject.
Balanced Electric Field Dependent Mobilities: A Key to Access High Fill Factors in Organic Bulk Heterojunction Solar Cells
Authors: Yin Hang , Bi Pengqing , Cheung Sin Hang , Cheng Wai Leong , Chiu Ka Lok , Ho Carr Hoi Yi , Li Ho Wa , Tsang Sai Wing , Hao Xiaotao , So Shu Kong
Published: February 2018

The compositions of most lab‐based bulk‐heterojunction (BHJ) solar cells are optimized by their power conversion efficiencies (PCEs). In this report, we suggest that the compositions should be optimized by their fill‐factors (FFs) instead. With the optimized‐FF approach, BHJ cells tend to have higher acceptor contents and possess better thermal and operational stabilities. Three model systems, namely, PTB7:PC71BM, PTB7‐Th:ITIC, and PBDB‐T:ITIC BHJs, are chosen as case studies. Charge carrier transport measurements are used to reveal the origin of the enhanced FFs of these BHJ solar cells. We demonstrate that these acceptor‐rich BHJs possess better balanced field‐dependent electron‐to‐hole mobility ratios due to improved electron mobilities near open‐circuit conditions. We introduce a new parameter, known as charge imbalance factor (Δ), to quantify the impact of field dependent mobilities on the FF of the OPV cells. The improved mobility ratio (reduced Δ) suppresses carrier recombinations (especially at the open‐circuit conditions). Despite having slightly reduced PCEs, the FF‐optimized cells enjoy a much better stability. Our results suggest that FF‐optimized BHJ cells with higher acceptor contents should be considered for practical applications, due to better thermal and operational stability.
Combating Human Trafficking at the Local Level: Better Informing (Inter)national Action Plans
Authors: Winterdyk John
Published: February 2018

Despite increasing awareness of human trafficking in Canada (and internationally), there is limited knowledge about how local communities are responding to the experiences of trafficked persons. By focusing on the case of counter-trafficking responses in a major city in western Canada, this project represents the first Canadian attempt to document how a major urban centre is addressing human trafficking. The exploratory project surveyed 53 respondents representing agencies involved in the counter-trafficking response, which in various capacities serve individuals victimized by trafficking. Building on the survey findings, five focus group discussions were also conducted. The article suggests that, while a criminal justice framework is important for addressing human trafficking, local strategies will benefit from an emphasis on cross-sector collaboration that emphasizes the rights of the trafficked persons above the needs of law enforcement. Implications for (inter)national responses are also presented.
HILBERT STRATIFOLDS AND A QUILLEN TYPE GEOMETRIC DESCRIPTION OF COHOMOLOGY FOR HILBERT MANIFOLDS
Authors: KRECK MATTHIAS , TENE HAGGAI
Published: February 2018

In this paper we use tools from differential topology to give a geometric description of cohomology for Hilbert manifolds. Our model is Quillen’s geometric description of cobordism groups for finite-dimensional smooth manifolds [Quillen, ‘Elementary proofs of some results of cobordism theory using steenrod operations’, Adv. Math., 7 (1971)]. Quillen stresses the fact that this construction allows the definition of Gysin maps for ‘oriented’ proper maps. For finite-dimensional manifolds one has a Gysin map in singular cohomology which is based on Poincaré duality, hence it is not clear how to extend it to infinite-dimensional manifolds. But perhaps one can overcome this difficulty by giving a Quillen type description of singular cohomology for Hilbert manifolds. This is what we do in this paper. Besides constructing a general Gysin map, one of our motivations was a geometric construction of equivariant cohomology, which even for a point is the cohomology of the infinite-dimensional space $BG$, which has a Hilbert manifold model. Besides that, we demonstrate the use of such a geometric description of cohomology by several other applications. We give a quick description of characteristic classes of a finite-dimensional vector bundle and apply it to a generalized Steenrod representation problem for Hilbert manifolds and define a notion of a degree of proper oriented Fredholm maps of index $0$.
BUDDHIST LAW IN EARLY TIBET: THE EMERGENCE OF AN IDEOLOGY
Authors: Pirie Fernanda
Published: February 2018

Tibet is distinct within the Buddhist regions of Asia for its claims to have developed religious laws. The rulers of its early empire civilized their people by creating laws on the basis of Buddhist principles—or so it is claimed by the writers of Tibetan historical narratives. In fact, the earliest Tibetan laws were not linked in any significant way with Buddhist principles, even after the religion had been firmly established in the region. In this article I explore why and how the idea of Buddhist law first emerged, examining its development through a number of texts from the empire (sixth to ninth centuries) and the immediate postimperial period (tenth to twelfth centuries). It turns out that more ideological accounts of Buddhist law were developed only as the structures of the empire were collapsing. Nevertheless, they do seem to have resonated with at least one, tenth-century ruler. These narratives set the scene for a long series of historical accounts in which the idea that Tibetan law was based on Buddhist principles took hold—an idea that was maintained well into the twentieth century.
The prosodic representation of composite structures in Brazilian Portuguese
Authors: GUZZO NATÁLIA BRAMBATTI
Published: February 2018

In previous research, word–word compounds and stressed affix + word structures have been assigned to the same prosodic domain in Brazilian Portuguese (BP), on account of certain similarities in phonological behaviour (Silva 2010, Toneli 2014): both types of composite structures undergo vowel raising at the right edge of each element in the construction, and vowel sandhi processes between their elements. In this paper, I show that word–word compounds and stressed affix + word structures exhibit significant differences in stress patterns in BP, which supports their prosodization in two separate domains. While stressed affix + word structures are assigned secondary stress following the phonological word (PWd) stress algorithm, each element in word–word compounds behaves as an independent PWd with regard to the stress pattern that it exhibits. I thus propose that while stressed affix + word structures are recursively prosodized in the PWd domain, word–word compounds are prosodized in the composite group, the domain proposed by Vogel (2008, 2009) that immediately dominates the PWd and accounts for the prosodization of structures with compositional characteristics. The analysis reconciles two views on prosodic structure that are traditionally assumed to be mutually exclusive: the view that prosodic domains can be recursive (e.g. Inkelas 1990, Selkirk 1996) and the view that the prosodic hierarchy includes an additional domain specific to composite structures above the PWd (e.g. Vogel 2009, Vigário 2010).
Suboptimality in perceptual decision making
Authors: Rahnev Dobromir , Denison Rachel N.
Published: February 2018

Human perceptual decisions are often described as optimal. Critics of this view have argued that claims of optimality are overly flexible and lack explanatory power. Meanwhile, advocates for optimality have countered that such criticisms single out a few selected papers. To elucidate the issue of optimality in perceptual decision making, we review the extensive literature on suboptimal performance in perceptual tasks. We discuss eight different classes of suboptimal perceptual decisions, including improper placement, maintenance, and adjustment of perceptual criteria; inadequate tradeoff between speed and accuracy; inappropriate confidence ratings; misweightings in cue combination; and findings related to various perceptual illusions and biases. In addition, we discuss conceptual shortcomings of a focus on optimality, such as definitional difficulties and the limited value of optimality claims in and of themselves. We therefore advocate that the field drop its emphasis on whether observed behavior is optimal and instead concentrate on building and testing detailed observer models that explain behavior across a wide range of tasks. To facilitate this transition, we compile the proposed hypotheses regarding the origins of suboptimal perceptual decisions reviewed here. We argue that verifying, rejecting, and expanding these explanations for suboptimal behavior – rather than assessing optimality per se – should be among the major goals of the science of perceptual decision making.
2. German Retrospect
Authors: Meyer Ludwig
Published: February 2018

The granule-cells which Dr. Westphal found in the posterior and lateral columns of the cord in progressive general paralysis led that observer to the conclusion at once that in it consisted a universal lesion of the cord in the paralytic insane, as he had before proved of the grey degeneration of the posterior columns. Prof. Meyer, however, has not succeeded in detecting any connection between the discovery of granule-cells and a lesion of the cord to which these inflammation products (Entzündungskugeln) owed their origin; and so these formations prove a chronic myelitis merely, and do not lead to the conclusion that “hereby the universal product of spinal diseases among the paralytic insane is indubitably settled.”
Dr. Davey the read the following Paper on the Relations between Crime and Insanity.
Authors: J. C. B.
Published: February 2018

If a faithful history of medical science during this nineteenth century or rather up to this present time be ever attempted, the author of the work will be required to devote a very considerable share of his energies and attention to Psychological matters. He will have to record the greatly increased interest of the public in the care taken of insane persons, and to register the origin and development of various legislative enactments, having for then object the well doing of the same. His duty will be to chronicle the labours of Pinel, Hill, Conolly, and others—in so far as these led to the disuse of mechanical restraints—and to the avoidance of heedless and cruel physical coercion. The same author will be required also to chronicle an improved medical treatment of mental disorders, one based on a better knowledge of their nature and proximate cause &c. Towards the completion of the above very pleasing and satisfactory task, the medical historian will have to tell his readers that among those things which were and are not, must be enumerated:—1st, the practise at the old Bethlehem Hospital of exhibiting to an ignorant and curious public its much afflicted inmates, for a mere money consideration; 2nd, the common and unjustifiable incarceration of those merely eccentric, within the walls of a licensed asylum, and this the act of unsympathizing, and, not unlikely, selfish relatives; 3rd, the general bad management of all establishments set apart for the detention of those alienated in mind and feeling; 4th, the neglect and wretchedness manifest among the patients, inmates thereof, and their supervision, if such it could be called, not by the accomplished medical man, but by the rude and coarse keeper, male or female, as such servitors were called. The same medical historian will have to tell his readers, as among the things which were and are not; 5thly, the infrequent recoveries from this dire malady (insanity); and to demonstrate also the premature and painful deaths which so commonly fell to the lot of those whose misfortune it was to be stricken with cerebro-mental disease. But after all this, the question very naturally suggested to one interested in the subject is, does the contrast as between the past and the present, i. e. the were and the are leave nothing to be desired, has the climax of what is good, of what is rational and humane been achieved, can no omissions be proved, is there not yet room for advancement, yet a further field for lunatic-amelioration. Does no speck remain on the crystal, no flaw in the diamond? There is, sir, much reason to fear, that however beautiful a picture of progress the facts of the case may warrant; however eminently successful the writer may prove himself, both in the conception and execution of his self-imposed task; there is, I say, much reason to fear that the great work will lack completeness and entirety, i. e. if this comparatively early period of the nineteenth century is to witness the beginning and ending of this literary, or, if you will, pictorial labour.
On the existing relation between the Lunacy Commission and Medical Superintendents of Public Asylums.
Authors: Huxley J. E. , Robertson C. L.
Published: February 2018

The existence of a right relation between the two bodies named, is of vast importance to the due administration of a great public trust, and of no mean consequence as affecting the honour, safety, and utility of a class of gentlemen (Superintendents) contributing largely and worthily to the public benefit. of late years, circumstances, both acts and expressions of opinion, proceeding from the lunacy board, have occurred to arouse attention and call for deliberate inquiry into this relation. The profession of Superintendents collectively, have regarded the Commission with respect, and have, on several occasions, sought to confer honour on individual Commissioners (at the same time reflecting it on their own body) by opening the ranks of their association to the admission of Commissioners as honorary members thereof. This mark of respect, the only public token the association have had it in their power to offer, they have offered generously and confidingly, whenever, judging by the antecedents of a new Commissioner, his appointment has seemed a matter for congratulation; such as the allocation of an eligible man to a handsome place, prospectively to the general good.
A hunter-gatherer–farmer population model: Lie symmetries, exact solutions and their interpretation
Authors: CHERNIHA R. M. , DAVYDOVYCH V. V.
Published: February 2018

The Lie symmetry classification of the known three-component reaction–diffusion system modelling the spread of an initially localized population of farmers into a region occupied by hunter-gatherers is derived. The Lie symmetries obtained for reducing the system in question to systems of ordinary differential equations (ODEs) and constructing exact solutions are applied. Several exact solutions of travelling front type are also found, their properties are identified and biological interpretation is discussed.
An Early-Killed Rye (Secale cereale) Cover Crop Has Potential for Weed Management in Edamame (Glycine max)
Authors: Crawford Laura E. , Williams Martin M. , Wortman Sam E.
Published: February 2018

The potential role of fall-seeded cover crops for weed management in edamame [soybean, Glycine max (L.) Merr.] is unknown. Field experiments were conducted over three edamame growing seasons to (1) determine the extent to which cover crop–residue management systems influence edamame emergence while selectively suppressing weed density and biomass, and (2) determine whether cultivars differed in emergence in cover crop–residue management systems. Cover crop treatments included a winter-killed oilseed radish (Raphanus sativus L.), two canola (Brassica napus L.) treatments (early-killed and late-killed), two cereal rye (Secale cereale L.) treatments (early-killed and late-killed), and a bare-soil control. Two spring timings of a cover crop burndown application created the early-killed and late-killed treatments for canola and cereal rye. Twelve soybean cultivars were tested, including 11 edamame cultivars differing in seed size and a grain-type soybean control. Spring residue biomass in cover crop treatments ranged from 438 kg ha−1 for winter-killed radish to 9,003 kg ha−1 for late-killed cereal rye. Cultivars responded similarly to cover crop treatments, and with the exception of late-killed cereal rye, cover crop treatments resulted in similar crop emergence as the bare-soil control. While all cover crop treatments reduced weed biomass 6 wk after planting compared with the bare soil, winter-killed radish and both canola treatments increased weed density. Early-killed cereal rye has potential for weed management in edamame, as evidenced by the fact that the treatment did not interfere with planting or crop establishment, yet reduced weed density 20% and suppressed early-season weed growth 85%.
Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer
Authors: Beadnell Thomas C. , Nassar Kelsey W. , Rose Madison M. , Clark Erin G. , Danysh Brian P. , Hofmann Marie-Claude , Pozdeyev Nikita , Schweppe Rebecca E.
Published: February 2018

Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway. Therefore, we examined the efficacy of the combination therapy across a panel of thyroid cancer cell lines representing common oncogenic drivers (BRAF, RAS, and PIK3CA). Interestingly, combined inhibition of Src and the MAPK pathway overcomes intrinsic dasatinib resistance in cell lines where both the MAPK and PI3K pathways are inhibited, which we show is likely due to the regulation of the PI3K pathway by Src in these responsive cells. Interestingly, we have mapped downstream phosphorylation of rpS6 as a key biomarker of response, and cells that maintain rpS6 phosphorylation likely represent drug tolerant persisters. Altogether, the combined inhibition of Src and the MAPK pathway holds great promise for improving the overall survival of advanced thyroid cancer patients with BRAF and RAS mutations, and activation of the PI3K pathway and rpS6 phosphorylation represent important biomarkers of response for patients treated with this therapy.
Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue
Authors: Sinha Mithun , Sen Chandan K. , Singh Kanhaiya , Das Amitava , Ghatak Subhadip , Rhea Brian , Blackstone Britani , Powell Heather M. , Khanna Savita , Roy Sashwati
Published: February 2018

Inflammation, following injury, induces cellular plasticity as an inherent component of physiological tissue repair. The dominant fate of wound macrophages is unclear and debated. Here we show that two-thirds of all granulation tissue fibroblasts, otherwise known to be of mesenchymal origin, are derived from myeloid cells which are likely to be wound macrophages. Conversion of myeloid to fibroblast-like cells is impaired in diabetic wounds. In cross-talk between keratinocytes and myeloid cells, miR-21 packaged in extracellular vesicles (EV) is required for cell conversion. EV from wound fluid of healing chronic wound patients is rich in miR-21 and causes cell conversion more effectively compared to that by fluid from non-healing patients. Impaired conversion in diabetic wound tissue is rescued by targeted nanoparticle-based delivery of miR-21 to macrophages. This work introduces a paradigm wherein myeloid cells are recognized as a major source of fibroblast-like cells in the granulation tissue.
In situ atomic-scale observation of oxidation and decomposition processes in nanocrystalline alloys
Authors: Guo Jinming , Haberfehlner Georg , Rosalie Julian , Li Lei , Duarte María Jazmin , Kothleitner Gerald , Dehm Gerhard , He Yunbin , Pippan Reinhard , Zhang Zaoli
Published: February 2018

Oxygen contamination is a problem which inevitably occurs during severe plastic deformation of metallic powders by exposure to air. Although this contamination can change the morphology and properties of the consolidated materials, there is a lack of detailed information about the behavior of oxygen in nanocrystalline alloys. In this study, aberration-corrected high-resolution transmission electron microscopy and associated techniques are used to investigate the behavior of oxygen during in situ heating of highly strained Cu–Fe alloys. Contrary to expectations, oxide formation occurs prior to the decomposition of the metastable Cu–Fe solid solution. This oxide formation commences at relatively low temperatures, generating nanosized clusters of firstly CuO and later Fe2O3. The orientation relationship between these clusters and the matrix differs from that observed in conventional steels. These findings provide a direct observation of oxide formation in single-phase Cu–Fe composites and offer a pathway for the design of nanocrystalline materials strengthened by oxide dispersions.
Life times of metastable states guide regulatory signaling in transcriptional riboswitches
Authors: Helmling Christina , Klötzner Dean-Paulos , Sochor Florian , Mooney Rachel Anne , Wacker Anna , Landick Robert , Fürtig Boris , Heckel Alexander , Schwalbe Harald
Published: February 2018

Transcriptional riboswitches modulate downstream gene expression by a tight coupling of ligand-dependent RNA folding kinetics with the rate of transcription. RNA folding pathways leading to functional ON and OFF regulation involve the formation of metastable states within well-defined sequence intervals during transcription. The kinetic requirements for the formation and preservation of these metastable states in the context of transcription remain unresolved. Here, we reversibly trap the previously defined regulatory relevant metastable intermediate of the Mesoplasma florum 2′-deoxyguanosine (2′dG)-sensing riboswitch using a photocaging-ligation approach, and monitor folding to its native state by real-time NMR in both presence and absence of ligand. We further determine transcription rates for two different bacterial RNA polymerases. Our results reveal that the riboswitch functions only at transcription rates typical for bacterial polymerases (10–50 nt s−1) and that gene expression is modulated by 40–50% only, while subtle differences in folding rates guide population ratios within the structural ensemble to a specific regulatory outcome.
Experimental observation of photonic nodal line degeneracies in metacrystals
Authors: Gao Wenlong , Yang Biao , Tremain Ben , Liu Hongchao , Guo Qinghua , Xia Lingbo , Hibbins Alastair P. , Zhang Shuang
Published: February 2018

Nodal line semimetals (NLS) are three-dimensional (3D) crystals that support band crossings in the form of one-dimensional rings in the Brillouin zone. In the presence of spin–orbit coupling or lowered crystal symmetry, NLS may transform into Dirac semimetals, Weyl semimetals, or 3D topological insulators. In the photonics context, despite the realization of topological phases, such as Chern insulators, topological insulators, Weyl, and Dirac degeneracies, no experimental demonstration of photonic nodal lines (NLs) has been reported so far. Here, we experimentally demonstrate NL degeneracies in microwave cut-wire metacrystals with engineered negative bulk plasma dispersion. Both the bulk and surface states of the NL metamaterial are observed through spatial Fourier transformations of the scanned near-field distributions. Furthermore, we theoretically show that the NL degeneracy can transform into two Weyl points when gyroelectric materials are incorporated into the metacrystal design. Our findings may inspire further advances in topological photonics.
Inhibitory effects of superoxide dismutase 3 on Propionibacterium acnes-induced skin inflammation
Authors: Nguyen Cuong Thach , Sah Shyam Kishor , Zouboulis Christos C. , Kim Tae-Yoon
Published: February 2018

Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on P. acnes- or peptidoglycan (PGN)-induced inflammation in vitro and in vivo. Our data demonstrated that SOD3 suppressed toll-like receptor-2 (TLR-2) expression in P. acnes- or PGN-treated keratinocytes and sebocytes. Moreover, we found that SOD3 suppressed the expressions of phosphorylated nuclear factor-κB (NF-κB) and p38 in P. acnes- or PGN-treated cells. SOD3 also exhibited an anti-inflammatory role by reducing the expression of inflammasome-related proteins (NLRP3, ASC, caspase-1) and inhibiting the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8. In addition, SOD3 reduced lipid accumulation and expression of lipogenic regulators in P. acnes-treated sebocytes. Recombinant SOD3-treated wild-type mice and SOD3 transgenic mice, which were subcutaneously infected with P. acnes, showed tolerance to inflammation through reducing inflammatory cell infiltration in skin, ear thickness, and expression of inflammatory mediators. Our result showed that SOD3 could suppress the inflammation through inhibition of TLR2/p38/NF-κB axis and NLRP3 inflammasome activation. Therefore, SOD3 could be a promising candidate for treatment of P. acnes-mediated skin inflammation.
Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice
Authors: Wang Yongzhi , Luo Lingtao , Braun Oscar Ö , Westman Johannes , Madhi Raed , Herwald Heiko , Mörgelin Matthias , Thorlacius Henrik
Published: February 2018

Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TGin vivowas reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis. Isolated NETs increased TG and co-incubation with DNAse abolished NET-induced formation of thrombin. TG triggered by NETs was inhibited by blocking factor XII and abolished in factor XII-deficient plasma but intact in factor VII-deficient plasma. Activation of neutrophils simultaneously generated large amount of neutrophil-derived MPs, which were found to bind to NETs via histone-phosphatidylserine interactions. These findings show for the first time that NETs and MPs physically interact, and that NETs might constitute a functional assembly platform for MPs. We conclude that NET-MP complexes induce TG via the intrinsic pathway of coagulation and that neutrophil-derived MPs play a key role in NET-dependent coagulation.
Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice
Authors: Kamezaki Michitsugu , Kusaba Tetsuro , Komaki Kazumi , Fushimura Yohei , Watanabe Noriko , Ikeda Kisho , Kitani Takashi , Yamashita Noriyuki , Uehara Masahiro , Kirita Yuhei , Shiotsu Yayoi , Sakai Ryosuke , Fukuda Takuya , Yamazaki Masahiro , Fukui Michiaki , Matoba Satoaki , Tamagaki Keiichi
Published: February 2018

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.
Thermal Expansion in Layered Na
x
MO2
Authors: Kobayashi Wataru , Yanagita Ayumu , Akaba Takahiro , Shimono Takahiro , Tanabe Daiki , Moritomo Yutaka
Published: February 2018

Layered oxide Na
x
MO2 (M: transition metal) is a promising cathode material for sodium-ion secondary battery. Crystal structure of O3- and P2-type Na
x
MO2 with various M against temperature (T) was systematically investigated by synchrotron x-ray diffraction mainly focusing on the T-dependences of a- and c-axis lattice constants (a and c) and z coordinate (z) of oxygen. Using a hard-sphere model with minimum Madelung energy, we confirmed that c/a and z values in O3-type Na
x
MO2 were reproduced. We further evaluated the thermal expansion coefficients (α
a
and α
c
) along a- and c-axis at 300 K. The anisotropy of the thermal expansion was quantitatively reproduced without adjustable parameters for O3-type Na
x
MO2. Deviations of z from the model for P2-type Na
x
MO2 are ascribed to Na vacancies characteristic to the structure.
The earliest evidence for a supraorbital salt gland in dinosaurs in new Early Cretaceous ornithurines
Authors: Wang Xia , Huang Jiandong , Hu Yuanchao , Liu Xiaoyu , Peteya Jennifer , Clarke Julia A.
Published: February 2018

Supraorbital fossae occur when salt glands are well developed, a condition most pronounced in marine and desert-dwelling taxa in which salt regulation is key. Here, we report the first specimens from lacustrine environments of the Jehol Biota that preserve a distinct fossa above the orbit, where the salt gland fossa is positioned in living birds. The Early Cretaceous ornithurine bird specimens reported here are about 40 million years older than previously reported Late Cretaceous marine birds and represent the earliest described occurrence of the fossa. We find no evidence of avian salt gland fossae in phylogenetically earlier stem birds or non-avialan dinosaurs, even in those argued to be predominantly marine or desert dwelling. The apparent absence of this feature in more basal dinosaurs may indicate that it is only after miniaturization close to the origin of flight that excretory mechanisms were favored over exclusively renal mechanisms of salt regulation resulting in an increase in gland size leaving a bony trace. The ecology of ornithurine birds is more diverse than in other stem birds and may have included seasonal shifts in foraging range, or, the environments of some of the Jehol lakes may have included more pronounced periods of high salinity.
Single-plane retroperitoneoscopic adrenalectomy: a new operative procedure for benign adrenal disease
Authors: Li Songchao , Wang Jun , Zhang Erwei , Gao Wansheng , Yang Jinjian , Jia Zhankui
Published: February 2018

To evaluate the therapeutic effect of single-plane retroperitoneoscopic adrenalectomy. From February 2014 to March 2017, 251 patients underwent single-plane retroperitoneoscopic adrenalectomy, and their operative outcomes were compared with those of 98 patients who underwent anatomical three-plane retroperitoneoscopic adrenalectomy. Among 35 patients with a body mass index (BMI) of ≥30 kg/m2, their operative outcomes were compared between two operative procedures. The demographic data and perioperative outcomes of the patients were statistically analysed. The single-plane and three-plane groups were comparable in terms of estimated blood loss, time to oral intake, hospital stay, and incidence of complications among patients with similar baseline demographics. The single-plane group had a significantly shorter operation time (46.9 ± 5.8 vs 54.8 ± 7.0 mins, P < 0.0001) and lower analgesia requirement (56/251 vs 33/98, p = 0.03). For obese patients with a BMI of ≥30 kg/m2, single-plane adrenalectomy was also associated with a significantly shorter operation time(48.1 ± 6.2 vs 64.1 ± 5.1 mins, p < 0.0001). Single-plane retroperitoneoscopic adrenalectomy is feasible, safe, and effective in the treatment of adrenal masses <5 cm in size and provides a shorter operation time and better pain control than anatomical retroperitoneal adrenalectomy, especially in obese patients.
The Apicomplexa-specific glucosamine-6-phosphate N-acetyltransferase gene family encodes a key enzyme for glycoconjugate synthesis with potential as therapeutic target
Authors: Cova Marta , López-Gutiérrez Borja , Artigas-Jerónimo Sara , González-Díaz Aida , Bandini Giulia , Maere Steven , Carretero-Paulet Lorenzo , Izquierdo Luis
Published: February 2018

Apicomplexa form a phylum of obligate parasitic protozoa of great clinical and veterinary importance. These parasites synthesize glycoconjugates for their survival and infectivity, but the enzymatic steps required to generate the glycosylation precursors are not completely characterized. In particular, glucosamine-phosphate N-acetyltransferase (GNA1) activity, needed to produce the essential UDP-N-acetylglucosamine (UDP-GlcNAc) donor, has not been identified in any Apicomplexa. We scanned the genomes of Plasmodium falciparum and representatives from six additional main lineages of the phylum for proteins containing the Gcn5-related N-acetyltransferase (GNAT) domain. One family of GNAT-domain containing proteins, composed by a P. falciparum sequence and its six apicomplexan orthologs, rescued the growth of a yeast temperature-sensitive GNA1 mutant. Heterologous expression and in vitro assays confirmed the GNA1 enzymatic activity in all lineages. Sequence, phylogenetic and synteny analyses suggest an independent origin of the Apicomplexa-specific GNA1 family, parallel to the evolution of a different GNA1 family in other eukaryotes. The inability to disrupt an otherwise modifiable gene target suggests that the enzyme is essential for P. falciparum growth. The relevance of UDP-GlcNAc for parasite viability, together with the independent evolution and unique sequence features of Apicomplexa GNA1, highlights the potential of this enzyme as a selective therapeutic target against apicomplexans.
Exponential energy harvesting through repetitive reconfigurations of a system of capacitors
Authors: Yu Jian , Ma Enze , Ma Tianwei
Published: February 2018

In conventional energy harvesting systems, energy can be extracted from a fixed-level source at a constant rate at best. The resulting growth of harvested energy is bound by a linear function. Here we show that exponential energy harvesting can be achieved in a system of reconfigurable energy storage elements. The exponential extraction results from the positive feedback of the system potential energy due to repetitive system reconfigurations. The concept is studied theoretically and validated with results from systems of droplet capacitors. A device with three 300 μL mercury drops can generate an exponentially growing voltage that reaches 168 V within a few cycles of a low-level and low-frequency mechanical excitation. The same device with water drops can generate a similarly growing voltage that reaches 56 V. This concept holds potential in DC power generation and may be applied in other energy domains.
ImmPort, toward repurposing of open access immunological assay data for translational and clinical research
Authors: Bhattacharya Sanchita , Dunn Patrick , Thomas Cristel G. , Smith Barry , Schaefer Henry , Chen Jieming , Hu Zicheng , Zalocusky Kelly A. , Shankar Ravi D. , Shen-Orr Shai S. , Thomson Elizabeth , Wiser Jeffrey , Butte Atul J.
Published: February 2018

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components–Private Data, Shared Data, Data Analysis, and Resources—for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the Shared Data portal (www.immport.org/immport-open), which allows research data to be repurposed to accelerate the translation of new insights into discoveries.
A new, short-recorded photoplethysmogram dataset for blood pressure monitoring in China
Authors: Liang Yongbo , Chen Zhencheng , Liu Guiyong , Elgendi Mohamed
Published: February 2018

Open clinical trial data provide a valuable opportunity for researchers worldwide to assess new hypotheses, validate published results, and collaborate for scientific advances in medical research. Here, we present a health dataset for the non-invasive detection of cardiovascular disease (CVD), containing 657 data segments from 219 subjects. The dataset covers an age range of 20–89 years and records of diseases including hypertension and diabetes. Data acquisition was carried out under the control of standard experimental conditions and specifications. This dataset can be used to carry out the study of photoplethysmograph (PPG) signal quality evaluation and to explore the intrinsic relationship between the PPG waveform and cardiovascular disease to discover and evaluate latent characteristic information contained in PPG signals. These data can also be used to study early and noninvasive screening of common CVD such as hypertension and other related CVD diseases such as diabetes.
High-quality science requires high-quality open data infrastructure
Authors: Sansone Susanna-Assunta , Cruse Patricia , Thorley Mark
Published: February 2018

Resources for data management, discovery and (re)use are numerous and diverse, and more specifically we need data resources that enable the FAIR principles1 of Findability, Accessibility, Interoperability and Reusability of data.