bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual‐polarity slice‐GRAPPA for concurrent ghost correction and slice separation in simultaneous multi‐slice EPI
Authors: Hoge W. Scott , Setsompop Kawin , Polimeni Jonathan R.
Published: February 2018

Purpose

A ghost correction strategy for Simultaneous Multi‐Slice (SMS) EPI methods that provides improved ghosting artifact reduction compared to conventional methods is presented. Conventional Nyquist ghost correction methods for SMS‐EPI rely on navigator data that contain phase errors from all slices in the simultaneously acquired slice‐group. These navigator data may contain spatially nonlinear phase differences near regions of B0 inhomogeneity, which violates the linear model employed by most EPI ghost correction algorithms, resulting in poor reconstructions.

Methods

Dual‐Polarity GRAPPA (DPG) was previously shown to accurately model and correct both spatially nonlinear and 2D phase errors in conventional single‐slice EPI data. Here, an extension we call Dual‐Polarity slice‐GRAPPA (DPsG) is adapted to the slice‐GRAPPA method and applied to SMS‐EPI data for slice separation and ghost correction concurrently—eliminating the need for a separate ghost correction step while also providing improved slice‐specific EPI phase error correction.

Results

Images from in vivo SMS‐EPI data reconstructed using DPsG in place of conventional Nyquist ghost correction and slice‐GRAPPA are presented. DPsG is shown to reduce ghosting artifacts and provide improved temporal SNR compared to the conventional reconstruction.

Conclusion

The proposed use of DPsG for SMS‐EPI reconstruction can provide images with lower artifact levels, higher image fidelity, and improved time‐series stability compared to conventional reconstruction methods.
Mobile Microscopy and Automated Image Analysis
Authors: Pfeil Juliane , Frohme Marcus , Schulze Katja
Published: February 2018

Mobile microscopy and automated image analysis are powerful techniques for many applications. A mobile system that consists of a smartphone, an optical attachment and automated image recognition software in a cloud laboratory and its current and possible future applications are described in this article. The idea is to create a very fast, cheap, location‐ and knowledge‐independent system for many use cases.
Multiphoton Tomography for In Vivo Skin‐Age Determination
Authors: Schindele A. , Breunig H. G. , König K.
Published: February 2018

Nothing represents our age better than our most outer layer: the skin. But the age of the skin may differ from the person's chronological age due to a complex interplay of external and internal factors. A non‐invasive method to determine the skin age on a microscopic level in vivo is clinical multiphoton tomography which allows for direct non‐invasive imaging of biological tissue with subcellular resolution.
Preferences for physician weight status among women with overweight
Authors: Goldring M. R. , Persky S.
Published: February 2018

Background

Women with overweight experience stigma in clinical interactions. Emerging evidence suggests that one near‐term approach to offset the negative consequences of weight stigma could be to capitalize on benefits of patient–physician weight concordance. However, it is likely that patient attitudes towards physicians with overweight are complicated and multifaceted and may include stigmatization of providers with overweight.

Methods

Two‐hundred ninety‐eight women with overweight completed an online questionnaire and indicated preference for a physician who is ‘overweight’, ‘not overweight’, or indicated no preference. Participants provided reasons for their choice and answered questions about their weight‐related beliefs and experiences.

Results

The majority of women indicated no weight preference (63%), and a portion (36%) of the sample explicitly preferred physicians who are not overweight. Reasons provided for these preferences were primarily based on stereotyped notions of physician aptitude based on weight. Compared with having no preference, those who preferred physicians who are not overweight had fewer previous negative weight‐related physician interactions and had increased beliefs about the controllability of weight.

Conclusions

These findings elucidate patient attitudes towards physicians with overweight in a sample at increased risk for weight stigmatization. Findings underscore the need for stigma‐reducing interventions so that clinical experiences for both women and physicians with overweight can be improved.
Discovery and Validation of Novel Protein Biomarkers in Ovarian Cancer Patient Urine
Authors: Sandow Jarrod J. , Rainczuk Adam , Infusini Giuseppe , Makanji Ming , Bilandzic Maree , Wilson Amy L. , Fairweather Nicole , Stanton Peter G. , Garama Daniel , Gough Daniel , Jobling Thomas W. , Webb Andrew I. , Stephens Andrew N.
Published: February 2018

Purpose

For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker‐based test, to preoperatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit‐for‐purpose biomarkers have yet been identified.

Experimental design

We conducted a pilot study consisting of 40 patient urine samples (20 from each group), using label‐free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in urine from individual ovarian cancer patients. To validate these changes, we used parallel reaction monitoring (PRM) to investigate their abundance in an independent validation cohort (n = 20) of patient urine samples.

Results

LFQ analyses identified 4394 proteins (17 027 peptides) in a discovery set of 20 urine samples. Twenty‐three proteins were significantly elevated in the malignant patient group compared to patients with benign disease. Several proteins, including LYPD1, LYVE1, PTMA, and SCGB1A1 were confirmed to be enriched in the urine of ovarian cancer patients using PRM. We also identified the established ovarian cancer biomarkers WFDC2 (HE4) and mesothelin (MSLN), validating our approach.

Conclusions and clinical relevance

This is the first application of a LFQ‐PRM workflow to identify and validate ovarian cancer–specific biomarkers in patient urine samples.
Introduction of an algorithm for planning of autologous fibular transfer in mandibular reconstruction based on individual bone curvatures
Authors: Raith Stefan , Rauen Alexandra , Möhlhenrich Stephan Christian , Ayoub Nassim , Peters Florian , Steiner Timm , Hölzle Frank , Modabber Ali
Published: February 2018

Background

Reconstruction of the mandible with autologous transplants is a challenging task and current computer‐aided surgical planning remains cumbersome. Thus, the aim of the present study was to create an automated computational approach for this procedure.

Methods

The developed algorithm is based on curves following characteristic anatomical features. Geometrical data from a physiological mandible and a fibula were used to generate six different defects, and geometrical accordance was investigated to demonstrate the applicability of the method with different reconstruction parameters (n = 309).

Results

The method proved to be applicable, it recognized given clinical constraints and the values of accordance could be used to quantify the success of reconstructions.

Conclusions

With the present approach, the complex three‐dimensional task of mandibular reconstruction was simplified, and thus it allows implementation in clinical routine. The computational planning that is proposed may be used to design cutting guides or as geometrical input data for real‐time navigated surgery.
Unavoidable trees in tournaments
Authors: Mycroft Richard , Naia Tássio
Published: February 2018

An oriented tree T on n vertices is unavoidable if every tournament on n vertices contains a copy of T. In this paper, we give a sufficient condition for T to be unavoidable, and use this to prove that almost all labeled oriented trees are unavoidable, verifying a conjecture of Bender and Wormald. We additionally prove that every tournament on vertices contains a copy of every oriented tree T on n vertices with polylogarithmic maximum degree, improving a result of Kühn, Mycroft, and Osthus.
High Density Energetic Zwitterionic Diazonium 1,2,4‐Triazolate Resulting from an Interesting Bond Cleavage of E‐1,2‐Bis(3,4‐diamino‐1,2,4‐triazol‐5‐yl)‐ethane
Authors: Ma Qing , Zhang Guojie , Li Jie , Liao Longyu , Huang Jinglun , Fan Guijuan , Nie Fude
Published: February 2018

An energetic zwitterion 5‐diazonium‐3‐trinitromethyl‐1,2,4‐triazolate (DTNMTz) was synthesized by an interesting bond cleavage of E‐1,2‐Bis(3,4‐diamino‐1,2,4‐triazol‐5‐yl)‐ethane. Its structure was confirmed by single‐crystal X‐ray diffraction. The physicochemical properties such as electrostatic potential, thermal properties and sensitivity towards impact, friction and electrostatic discharge were evaluated. Its heat of formation, detonation pressure and velocity were calculated. It is worth noting that this zwitterion behaves zero CO2 oxygen balance, and it has high density at ambient temperature (1.89 g cm−3), considerable detonation performance (D: 9317 m s−1, P: 37.6 GPa).
2‐Mercaptoquinoline Analogues: A Potent Antileishmanial Agent
Authors: Koley Suvajit , Tiwari Neeraj , Neelabh  , Singh Rakesh Kumar , Singh Maya Shankar
Published: February 2018

Leishmaniases are endemic in various countries and parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemist. In order to meet this challenge, a series of 2‐mercaptoquinoline derivatives have been synthesized and docked into the active site of Trypanothione reductase (TryR) enzyme required for redox balance of parasite. These were screened on promastigote and intracellular amastigote stages of L. donovani and found to show high levels of antileishmanial activity together with no cytotoxicity. Some of the synthesized compounds tested here, exhibited very steady and promising leishmanicidal activity against both promastigotes & intracellular amastigotes form, and the observations have been superbly supported by the docking results.
Chiral Shell Core–Satellite Nanostructures for Ultrasensitive Detection of Mycotoxin
Authors: Cai Jiarong , Hao Changlong , Sun Maozhong , Ma Wei , Xu Chuanlai , Kuang Hua
Published: February 2018

Herein, the design of a DNA‐based chiral biosensor is described utilizing the self‐assembly of shell core–gold (Au) satellite nanostructures for the detection of mycotoxin, ochratoxin A (OTA). The assembly of core–satellite nanostructures based on OTA‐aptamer binding exhibits a strong chiral signal with an intense circular dichroism (CD) peak. The integrity of the assembly of core–satellite nanostructures is limited to some extent in the presence of different levels of OTA. Correspondingly, the chiral intensity of assembly is weakened with increasing OTA concentrations, allowing quantitative determination of the target. The developed chiral sensor shows an excellent linear relationship between the CD signal and concentrations of OTA in the range of 0.1–5 pg mL−1 with a limit of detection as low as 0.037 pg mL−1. The effectiveness of the biosensor in a sample of red wine is verified and a good recovery rate is obtained. These results suggest that the strategy has great potential for practical application.
Oat Fiber as Reinforcement for Starch/Polyvinyl Alcohol Materials Produced by Injection Molding
Authors: Zanela Juliano , Bilck Ana P. , Casagrande Maira , Grossmann Maria V. E. , Yamashita Fabio
Published: February 2018

The use of low‐cost natural fibers is an interesting alternative to both improve the mechanical properties and reduce the cost of biodegradable materials. Oat fibers are studied as reinforcer or filler in starch/PVA biodegradable materials produced by an injection molding process, using native and cationic cassava starches. The formulations contain 45 wt% of starch + fiber, 25 wt% of PVA, and 30 wt% of glycerol, and the oat fiber proportions are 0, 2.5, 5.0, 7.5, and 10.0 wt%. All materials have good processability, and the tensile strength, Young's modulus, and elongation at break range from 4.7 to 5.5 MPa, 7.1–12.4 MPa, and 180–260%, respectively. The type of starch (native or cationic) does not influence the biodegradable material properties. The oat fiber presents a good dispersion and compatibility with the polymeric matrix, acting mainly as a filler, reducing the material costs.
Laparoscopic Versus Open Right Posterior Sectionectomy for Hepatocellular Carcinoma in a High‐Volume Center: A Propensity Score Matched Analysis
Authors: Rhu Jinsoo , Kim Sung Joo , Choi Gyu Seong , Kim Jong Man , Joh Jae‐Won , Kwon Choon Hyuck David
Published: February 2018

Background

While minimal invasive surgery is becoming popular in liver resection, right posterior sectionectomy (RPS) is still considered as a difficult procedure. We summarize the clinical data and investigate the feasibility of laparoscopic right posterior sectionectomy (LRPS) in hepatocellular carcinoma (HCC) by comparing its outcomes with those of open right posterior sectionectomy (ORPS).

Methods

We retrospectively reviewed 191 patients who underwent RPS for HCC during January 2009 to August 2016 at Samsung Medical Center. After 1:2 propensity score matching, 53 patients in LRPS group were matched to 97 patients in ORPS group.

Results

There was no statistical difference in preoperative data. While operation time was significantly longer in LRPS group (381.1 ± 118.7 vs. 234.4 ± 63.7 min, P < 0.001), transfusion rate (13.2 vs. 2.1%, P = 0.061) and complication rate (9.4 vs. 8.3%, P = 0.709) were not statistically different between groups. Clustered Cox proportional hazards regression analysis for matched paired data showed no difference in both disease‐free survival (P = 0.607) and overall survival (P = 0.858).

Conclusions

In HCC, LRPS can be performed safely compared to ORPS, regarding the operative outcome, patient recovery, and oncological outcomes.
Reduction of Health Care Costs and Improved Appropriateness of Incoming Test Orders: the Impact of Genetic Counselor Review in an Academic Genetic Testing Laboratory
Authors: Wakefield Emily , Keller Haley , Mianzo Hannah , Nagaraj Chinmayee B. , Tawde Sanjukta , Ulm Elizabeth
Published: February 2018

The goal of this study was to evaluate the impact of genetic counselor (GC) review of incoming test orders received in an academic diagnostic molecular genetics laboratory. The GC team measured the proportion of orders that could be modified to improve efficiency or sensitivity, tracked provider uptake of GC proposed testing changes, and calculated the health care dollar savings resulting from GC intervention. During this 6‐month study, the GC team reviewed 2367 incoming test orders. Of these, 109 orders (4.6%) were flagged for review for potentially inefficient or inappropriate test ordering. These flagged orders corresponded to a total of 51 cases (1–5 orders for each patient), representing 54 individuals and including 3 sibling pairs. The GC team proposed a modification for each flagged case and the ordering providers approved the proposed change for 49 of 51 cases (96.08%). For the 49 modifications, the cost savings totaled $98,750.64, for an average of $2015.32 saved per modification. This study provides evidence of the significant contribution of genetic counselors in a laboratory setting and demonstrates the benefit of laboratories working with ordering providers to identify the best test for their patients. The review of test orders by a genetic counselor both improves genetic test ordering strategies and decreases the amount of health care dollars spent on genetic testing.
On the Majorana condition for nonlinear Dirac systems
Authors: Candy Timothy , Herr Sebastian
Published: February 2018

For arbitrarily large initial data in an open set defined by an approximate Majorana condition, global existence and scattering results for solutions to the Dirac equation with Soler-type nonlinearity and the Dirac–Klein–Gordon system in critical spaces in spatial dimension three are established.
Evaluación del desempeño docente en Yucatán: un análisis a partir de las características de los docentes
Authors: Kú Hernández Omar Eduardo , Pool Cibrián Wilson Jesús
Published: February 2018

A partir de la Reforma Integral de la Educación Básica en México, se contemplan procesos de evaluación de los docentes regulados por la LeyGeneral del Servicio Profesional Docente, la cual establece mecanismos para el ingreso, la permanencia, la promoción y el reconocimiento dentrodel Servicio Profesional Docente. Dado que se trata de una evaluación de alto impacto por las consecuencias que tiene para los docentes, se haceindispensable analizar las variables que podrían ayudar a mejorar su desempe˜no. Por tanto, el propósito de este trabajo es describir el resultado delos docentes que sustentaron el examen de desempe˜no para Educación Básica en el ciclo escolar 2015-2016 en el estado de Yucatán, en función delas características personales, profesionales y del contexto escolar donde labora el docente. Los resultados obtenidos demuestran que la prácticaeducativa es un fenómeno complejo en el que se encuentran en interacción diversas variables que confluyen para el logro de la calidad educativa.Dichos resultados se discuten bajo las similitudes y diferencias con la investigación nacional e internacional en la materia.© 2018 Universidad Nacional Autónoma de México, Asociación Mexicana de Comportamiento y Salud. Este es un artículo Open Access bajo lalicencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Escribir rápido, escribir mejor: interacción entre parámetros temporales y criterios funcionales en universitarios
Authors: Morales Germán , Hernández Alfredo , Peña Benjamín , Chávez Edgar , Carpio Claudio
Published: February 2018

En el presente trabajo se identifican los problemas y las limitantes que ofrecen 2 tipos de acercamiento a la escritura: los cuestionarios de opinióny los programas que miden la velocidad al escribir. Se propone una forma de evaluación en la que se integran factores temporales y funcionales.Se evaluó la velocidad al escribir, como caso de los parámetros temporales, sobre el número de palabras escritas y el cumplimiento de criterios de diferente complejidad en estudiantes universitarios. Se aplicó una prueba de restricción temporal y diferentes criterios funcionales en estudiantes de los diferentes semestres de la carrera de Psicología. Se encontró una relación directa entre el semestre cursado y la cantidad de palabras escritas, pero no con la satisfacción de diferentes tipos de criterios funcionales. Se discute la modulación entre la morfología con diferentes interacciones escritoras.© 2018 Universidad Nacional Autónoma de México, Asociación Mexicana de Comportamiento y Salud. Este es un artículo Open Access bajo lalicencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Local microstructure-based material performance and damage in design and finite element simulations of cast components
Authors: Olofsson Jakob
Published: February 2018

A novel approach to incorporate local microstructure-based material performance into finite element method (FEM) simulations of cast components is presented. By adopting perspectives from natural designs as dinosaur skulls and trees, the discipline-wide approach enables accurate prediction of damage in structures based on a heterogeneous distribution of sub-scale features. It is shown that heterogeneous damage tolerance dictates the performance and failure of cast aluminum, and simulations are compared with experimental results of heterogeneous tensile samples using digital image correlation (DIC). The numerical application of the approach in the industrial product realization process of an industrial casting is demonstrated, and the applicability of the approach to understand the behavior and failure of natural as well as synthetic structures is discussed.

Highlights A new discipline-wide approach to predict failure of heterogeneous structures. Based on natural designs, the approach enables tailored performance of castings. Heterogeneous damage tolerance reveal fracture and enables damage tolerant designs. The approach is implemented into numerical casting and load simulations. Future pathways to design high performing castings are explored.
Heat treatment of PM parts by Hot Isostatic Pressing
Authors: Eklund Anders , Ahlfors Magnus
Published: February 2018

Hot Isostatic Pressing (HIP) is a technology that has been around for 60+ years. By using high temperature and high gas pressure, dry metal and ceramic powders can be consolidated and a volume decrease can be achieved. Later developments include rapid cooling and rapid quenching to enable higher productivity and high-pressure heat treatment. This paper shows the advantages of having HIPing and Heat Treatment combined for Powder metallurgy parts.
Non-contact mechanical and chemical analysis of single living cells by microspectroscopic techniques
Authors: Mattana Sara , Mattarelli Maurizio , Urbanelli Lorena , Sagini Krizia , Emiliani Carla , Serra Mauro Dalla , Fioretto Daniele , Caponi Silvia
Published: February 2018

Innovative label-free microspectroscopy, which can simultaneously collect Brillouin and Raman signals, is used to characterize the viscoelastic properties and chemical composition of living cells with sub-micrometric resolution. The unprecedented statistical accuracy of the data combined with the high-frequency resolution and the high contrast of the recently built experimental setup permits the study of single living cells immersed in their buffer solution by contactless measurements. The Brillouin signal is deconvoluted in the buffer and the cell components, thereby revealing the mechanical heterogeneity inside the cell. In particular, a 20% increase is observed in the elastic modulus passing from the plasmatic membrane to the nucleus as distinguished by comparison with the Raman spectroscopic marker. Brillouin line shape analysis is even more relevant for the comparison of cells under physiological and pathological conditions. Following oncogene expression, cells show an overall reduction in the elastic modulus (15%) and apparent viscosity (50%). In a proof-of-principle experiment, the ability of this spectroscopic technique to characterize subcellular compartments and distinguish cell status was successfully tested. The results strongly support the future application of this technique for fundamental issues in the biomedical field.
The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion
Authors: Barbui Tiziano , Thiele Jürgen , Gisslinger Heinz , Kvasnicka Hans Michael , Vannucchi Alessandro M. , Guglielmelli Paola , Orazi Attilio , Tefferi Ayalew
Published: February 2018

The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. In this regard, the 2016 changes were aimed at facilitating the distinction between masked PV and JAK2-mutated ET and between prefibrotic/early and overtly fibrotic PMF. In the current communication, we (i) provide practically useful resource tables and graphs on the new diagnostic criteria including outcome, (ii) elaborate on the rationale for the 2016 changes, (iii) discuss the complementary role of mutation screening, (iv) address ongoing controversies and propose solutions, (v) attend to the challenges of applying WHO criteria in routine clinical practice, and (vi) outline future directions from the perspectives of the clinical pathologist.
Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes
Authors: Darlington Alexander P. S. , Kim Juhyun , Jiménez José I. , Bates Declan G.
Published: February 2018

Introduction of synthetic circuits into microbes creates competition between circuit and host genes for shared cellular resources, such as ribosomes. This can lead to the emergence of unwanted coupling between the expression of different circuit genes, complicating the design process and potentially leading to circuit failure. By expressing a synthetic 16S rRNA with altered specificity, we can partition the ribosome pool into host-specific and circuit-specific activities. We show mathematically and experimentally that the effects of resource competition can be alleviated by targeting genes to different ribosomal pools. This division of labour can be used to increase flux through a metabolic pathway. We develop a model of cell physiology which is able to capture these observations and use it to design a dynamic resource allocation controller. When implemented, this controller acts to decouple genes by increasing orthogonal ribosome production as the demand for translational resources by a synthetic circuit increases.
A community approach to mortality prediction in sepsis via gene expression analysis
Authors: Sweeney Timothy E. , Perumal Thanneer M. , Henao Ricardo , Nichols Marshall , Howrylak Judith A. , Choi Augustine M. , Bermejo-Martin Jesús F. , Almansa Raquel , Tamayo Eduardo , Davenport Emma E. , Burnham Katie L. , Hinds Charles J. , Knight Julian C. , Woods Christopher W. , Kingsmore Stephen F. , Ginsburg Geoffrey S. , Wong Hector R. , Parnell Grant P. , Tang Benjamin , Moldawer Lyle L. , Moore Frederick E. , Omberg Larsson , Khatri Purvesh , Tsalik Ephraim L. , Mangravite Lara M. , Langley Raymond J.
Published: February 2018

Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups by using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance is validated in five cohorts of community-onset sepsis patients in which the models show summary AUROCs ranging from 0.765–0.89. Similar performance is observed in four cohorts of hospital-acquired sepsis. Combining the new gene-expression-based prognostic models with prior clinical severity scores leads to significant improvement in prediction of 30-day mortality as measured via AUROC and net reclassification improvement index These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis.
Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens
Authors: Hover Bradley M. , Kim Seong-Hwan , Katz Micah , Charlop-Powers Zachary , Owen Jeremy G. , Ternei Melinda A. , Maniko Jeffrey , Estrela Andreia B. , Molina Henrik , Park Steven , Perlin David S. , Brady Sean F.
Published: February 2018

Despite the wide availability of antibiotics, infectious diseases remain a leading cause of death worldwide
1
. In the absence of new therapies, mortality rates due to untreatable infections are predicted to rise more than tenfold by 2050. Natural products (NPs) made by cultured bacteria have been a major source of clinically useful antibiotics. In spite of decades of productivity, the use of bacteria in the search for new antibiotics was largely abandoned due to high rediscovery rates2,3. As only a fraction of bacterial diversity is regularly cultivated in the laboratory and just a fraction of the chemistries encoded by cultured bacteria are detected in fermentation experiments, most bacterial NPs remain hidden in the global microbiome. In an effort to access these hidden NPs, we have developed a culture-independent NP discovery platform that involves sequencing, bioinformatic analysis and heterologous expression of biosynthetic gene clusters captured on DNA extracted from environmental samples. Here, we describe the application of this platform to the discovery of the malacidins, a distinctive class of antibiotics that are commonly encoded in soil microbiomes but have never been reported in culture-based NP discovery efforts. The malacidins are active against multidrug-resistant pathogens, sterilize methicillin-resistant Staphylococcus aureus skin infections in an animal wound model and did not select for resistance under our laboratory conditions.
Author Correction: Remora cranial vein morphology and its functional implications for attachment
Authors: Flammang Brooke E. , Kenaley Christopher P.
Published: February 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells
Authors: Elgueta Claudio , Leroy Felix , Vielma Alex H. , Schmachtenberg Oliver , Palacios Adrian G.
Published: February 2018

A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.
Lateral Force Microscopy of Interfacial Nanobubbles: Friction Reduction and Novel Frictional Behavior
Authors: Yang Chih-Wen , Leung Kwan-tai , Ding Ren-Feng , Ko Hsien-Chen , Lu Yi-Hsien , Fang Chung-Kai , Hwang Ing-Shouh
Published: February 2018

Atomic force microscopy is used to conduct single-asperity friction measurements at a water-graphite interface. Local mapping of the frictional force, which is based on the degree of the cantilever twisting, shows nearly friction-free when a tip scans over a nanobubble. Surprisingly, apart from being gapless, the associated friction loop exhibits a tilt in the cantilever twisting versus the tip’s lateral displacement with the slope depending on the loading force. The sign of the slope reverses at around zero loading force. In addition, the measured normal and lateral tip-sample interactions exhibit unison versus tip-sample separation. Theoretical analysis, based on the balance of forces on the tip originated from the capillary force of the nanobubble and the torsion of the cantilever, offers quantitative explanations for both the tilted friction loop and the unison of force curves. The analysis may well apply in a wider context to the lateral force characterization on cap-shaped fluid structures such as liquid droplets on a solid substrate. This study further points to a new direction for friction reduction between solids in a liquid medium.
In-situ visualization of sound-induced otolith motion using hard X-ray phase contrast imaging
Authors: Schulz-Mirbach Tanja , Olbinado Margie , Rack Alexander , Mittone Alberto , Bravin Alberto , Melzer Roland R. , Ladich Friedrich , Heß Martin
Published: February 2018

Regarding the basics of ear structure-function relationships in fish, the actual motion of the solid otolith relative to the underlying sensory epithelium has rarely been investigated. Otolith motion has been characterized based on a few experimental studies and on approaches using mathematical modeling, which have yielded partially conflicting results. Those studies either predicted a simple back-and-forth motion of the otolith or a shape-dependent, more complex motion. Our study was designed to develop and test a new set-up to generate experimental data on fish otolith motion in-situ. Investigating the basic parameters of otolith motion requires an approach with high spatial and temporal resolution. We therefore used hard X-ray phase contrast imaging (XPCI). We compared two anatomically well-studied cichlid species, Steatocranus tinanti and Etroplus maculatus, which, among other features, differ in the 3D shape of their otoliths. In a water-filled tank, we presented a pure tone of 200 Hz to 1) isolated otoliths embedded in agarose serving as a simple model or 2) to a fish (otoliths in-situ). Our new set-up successfully visualized the motion of otoliths in-situ and therefore paves the way for future studies evaluating the principles of otolith motion.
Red blood cells are dynamic reservoirs of cytokines
Authors: Karsten Elisabeth , Breen Edmond , Herbert Benjamin R.
Published: February 2018

Red blood cells (RBCs) have been shown to affect immune function and can induce inflammatory responses after transfusion. The transfusion of washed RBCs can significantly reduce adverse effects, however, the soluble factors that may mediate these effects have not been identified. Previous studies have identified, but not quantified, a small number of chemokines associated with RBCs. We isolated RBCs from healthy volunteers and quantified of a panel of 48 cytokines, chemokines, and growth factors in the lysate, cytosol, and conditioned media of these cells using Luminex®technology. This analysis revealed that, after correcting for white blood cell and platelet contamination, 46 cytokines were detected in RBC lysates, and the median concentration in RBCs was 12-fold higher than in the plasma. In addition, extensive washing of RBCs, such as that performed in proteomics analyses or prior to some RBC transfusions, significantly attenuated the release of six cytokines following incubation at 37 °C. This supports the hypothesis that, alongside its gas exchange function, RBCs play a role in cytokine signalling. This discovery may help supplement disease biomarker research and may shed light on adverse inflammatory processes that can follow RBC transfusion.
Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney disease patients: a meta-analysis of randomized controlled trials and trial sequential analysis
Authors: Wang Guoqi , Liu Hongyan , Wang Chengzhi , Ji Xiaojian , Gu Weijun , Mu Yiming
Published: February 2018

To assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched until March 2016. Trial sequential analysis (TSA) was conducted to control the risks of type I and II errors and calculate required information size (RIS). A total of 25 articles with 8481 participants were included. Compared with controls, cinacalcet administration did not reduce all-cause mortality (RR = 0.97, 95% CI = 0.89–1.05, P = 0.41, TSA-adjusted 95% CI = 0.86–1.08, RIS = 5260, n = 8386) or cardiovascular mortality (RR = 0.95, 95% CI = 0.83–1.07, P = 0.39, TSA-adjusted 95% CI = 0.70–1.26, RIS = 3780 n = 5418), but it reduced the incidence of parathyroidectomy (RR = 0.48, 95% CI = 0.40–0.50, P < 0.001, TSA-adjusted 95% CI = 0.39–0.60, RIS = 5787 n = 5488). Cinacalcet increased the risk of hypocalcemia (RR = 8.48, 95% CI = 6.37–11.29, P < 0.001, TSA-adjusted 95% CI = 5.25–13.70, RIS = 6522, n = 7785), nausea (RR = 2.12, 95% CI = 1.62–2.77, P < 0.001, TSA-adjusted 95% CI = 1.45–3.04, RIS = 4684, n = 7512), vomiting (RR = 2.00, 95% CI = 1.79–2.24, P < 0.001, TSA-adjusted 95% CI = 1.77–2.26, RIS = 1374, n = 7331) and diarrhea (RR = 1.17, 95% CI = 1.05–1.32, P = 0.006, TSA-adjusted 95% CI = 1.02–1.36, RIS = 8388, n = 6116). Cinacalcet did not significantly reduce the incidence of fractures (RR = 0.58, 95% CI = 0.21–1.59, P = 0.29, TSA-adjusted 95% CI = 0.01–35.11, RIS = 76376, n = 4053). Cinacalcet reduced the incidence of parathyroidectomy, however, it did not reduce all-cause and cardiovascular mortality, and increased the risk of adverse events including hypocalcemia and gastrointestinal disorders.
Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin
Authors: Vizoso-Vázquez Ángel , Lamas-Maceiras Mónica , González-Siso M. Isabel , Cerdán M. Esperanza
Published: February 2018

Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic regulon and also controls the expression of other genes involved in the oxidative stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and modulates DNA repair. The influence of Ixr1 on transcription in the absence or presence of cisplatin has been analyzed in this work. Ixr1 regulates other transcriptional factors that respond to nutrient availability or extracellular and intracellular stress stimuli, some controlled by the TOR pathway and PKA signaling. Ixr1 controls transcription of ribosomal RNAs and genes encoding ribosomal proteins or involved in ribosome assembly. qPCR, ChIP, and 18S and 25S rRNAs measurement have confirmed this function. Ixr1 binds directly to several promoters of genes related to rRNA transcription and ribosome biogenesis. Cisplatin treatment mimics the effect of IXR1 deletion on rRNA and ribosomal gene transcription, and prevents Ixr1 binding to specific promoters related to these processes.
Stereochemical identification of glucans by oligothiophenes enables cellulose anatomical mapping in plant tissues
Authors: Choong Ferdinand X. , Bäck Marcus , Schulz Anette , Nilsson K. Peter. R. , Edlund Ulrica , Richter-Dahlfors Agneta
Published: February 2018

Efficient use of plant-derived materials requires enabling technologies for non-disruptive composition analysis. The ability to identify and spatially locate polysaccharides in native plant tissues is difficult but essential. Here, we develop an optical method for cellulose identification using the structure-responsive, heptameric oligothiophene h-FTAA as molecular fluorophore. Spectrophotometric analysis of h-FTAA interacting with closely related glucans revealed an exceptional specificity for β-linked glucans. This optical, non-disruptive method for stereochemical differentiation of glycosidic linkages was next used for in situ composition analysis in plants. Multi-laser/multi-detector analysis developed herein revealed spatial localization of cellulose and structural cell wall features such as plasmodesmata and perforated sieve plates of the phloem. Simultaneous imaging of intrinsically fluorescent components revealed the spatial relationship between cell walls and other organelles, such as chloroplasts and lignified annular thickenings of the trachea, with precision at the sub-cellular scale. Our non-destructive method for cellulose identification lays the foundation for the emergence of anatomical maps of the chemical constituents in plant tissues. This rapid and versatile method will likely benefit the plant science research fields and may serve the biorefinery industry as reporter for feedstock optimization as well as in-line monitoring of cellulose reactions during standard operations.
Heparan sulfates facilitate harmless amyloidogenic fibril formation interacting with elastin-like peptides
Authors: Boraldi Federica , Moscarelli Pasquale , Bochicchio Brigida , Pepe Antonietta , Salvi Anna M. , Quaglino Daniela
Published: February 2018

Heparan sulfates (HSs) modulate tissue elasticity in physiopathological conditions by interacting with various matrix constituents as tropoelastin and elastin-derived peptides. HSs bind also to protein moieties accelerating amyloid formation and influencing cytotoxic properties of insoluble fibrils. Interestingly, amyloidogenic polypeptides, despite their supposed pathogenic role, have been recently explored as promising bio-nanomaterials due to their unique and interesting properties. Therefore, we investigated the interactions of HSs, obtained from different sources and exhibiting various degree of sulfation, with synthetic amyloidogenic elastin-like peptides (ELPs), also looking at the effects of these interactions on cell viability and cell behavior using in vitro cultured fibroblasts, as a prototype of mesenchymal cells known to modulate the soft connective tissue environment. Results demonstrate, for the first time, that HSs, with differences depending on their sulfation pattern and chain length, interact with ELPs accelerating aggregation kinetics and amyloid-like fibril formation as well as self-association. Furthermore, these fibrils do not negatively affect fibroblasts’ cell growth and parameters of redox balance, and influence cellular adhesion properties. Data provide information for a better understanding of the interactions altering the elastic component in aging and in pathologic conditions and may pave the way for the development of composite matrix-based biomaterials.
6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2
Authors: Chuang Shang-Ju , Cheng Shu-Chun , Tang Hui-Chi , Sun Chiao-Yin , Chou Chi-Yuan
Published: February 2018

Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells’ survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.
Image Transport Through Meter-Long Randomly Disordered Silica-Air Optical Fiber
Authors: Zhao Jian , Lopez Jose Enrique Antonio , Zhu Zheyuan , Zheng Donghui , Pang Shuo , Correa Rodrigo Amezcua , Schülzgen Axel
Published: February 2018

We present a randomly disordered silica-air optical fiber featuring a 28.5% air filling fraction in the structured region, and low attenuation below 1 dB per meter at visible wavelengths. The quality of images transported through this fiber is shown to be comparable to, or even better than, that of images sent through commercial multicore imaging fiber. We demonstrate robust high-quality optical image transfer through 90 cm-long fibers with disordered silica-air structure, more than an order of magnitude improvement compared to previous disordered fiber imaging distances. The effects of variations of wavelength and feature size on transported image quality are investigated experimentally.
Prediction of vaginal birth after cesarean delivery in Chinese parturients
Authors: Wen Juan , Song Xuejing , Ding Hongjuan , Shen Xiaofeng , Shen Rong , Hu Ling-qun , Long Wei
Published: February 2018

There is an urgent need in China to better predict vaginal birth after cesarean (VBAC) to face the challenge of the second child policy. We aimed to validate a widely used VBAC prediction model (Grobman’s model) and a modified version of this model in a Chinese population. In this retrospective cohort study, 444 women with one cesarean delivery and at least one subsequent attempt for a trial of labor in Nanjing, China were included. The considered potential VBAC predictors included Grobman’s background variables and five new variables. Overall, a total of 370 women had VBAC, with a success rate of 83.3%. The new background variables “maternal height” and “estimated fetal weight” were considered as two additional predictors for VBAC. The AUC of Grobman’s model was 0.831 (95%CI = 0.775–0.886) while the AUC of our modified model with two new variables added was 0.857 (sensitivity = 72.2%, specificity = 83.8%). However, the difference between the AUC of the two models was not significant (Z = −1.69, P = 0.091). We confirmed that Grobman’s model was accepted in the Chinese population. A modified model that is supplemented with maternal height and estimated fetal weight needs to be further studied in the Chinese population.
Mapping the band structure of GeSbTe phase change alloys around the Fermi level
Authors: Kellner J. , Bihlmayer G. , Liebmann M. , Otto S. , Pauly C. , Boschker J. E. , Bragaglia V. , Cecchi S. , Wang R. N. , Deringer V. L. , Küppers P. , Bhaskar P. , Golias E. , Sánchez-Barriga J. , Dronskowski R. , Fauster T. , Rader O. , Calarco R. , Morgenstern M.
Published: February 2018

Phase change alloys are used for non-volatile random-access memories exploiting the conductivity contrast between amorphous and metastable, crystalline phase. However, this contrast has never been directly related to the electronic band structure. Here we employ photoelectron spectroscopy to map the relevant bands for metastable, epitaxial GeSbTe films. The constant energy surfaces of the valence band close to the Fermi level are hexagonal tubes with little dispersion perpendicular to the (111) surface. The electron density responsible for transport belongs to the tails of this bulk valence band, which is broadened by disorder, i.e., the Fermi level is 100 meV above the valence band maximum. This result is consistent with transport data of such films in terms of charge carrier density and scattering time. In addition, we find a state in the bulk band gap with linear dispersion, which might be of topological origin.
The effects of surface bioactivity and sustained-release of genistein from a mesoporous magnesium-calcium-silicate/PK composite stimulating cell responses in vitro, and promoting osteogenesis and enhancing osseointegration in vivo
Authors: Cai Liang , Zhang Jue , Qian Jun , Li Quan , Li Hong , Yan Yonggang , Wei Shicheng , Wei Jie , Su Jiacan
Published: February 2018

Genistein loaded MPCm-Ge with osteogenesis and osseointegration.
Self-aggregation of water-dispersible nanocollagen helices
Authors: Van Duong Hau , Chau Trang The Lieu , Dang Nhan Thi Thanh , Nguyen Duc Van , Le Son Lam , Ho Thang Sy , Vu Tuyen Phi , Tran Thi Thi Van , Nguyen Thanh-Dinh
Published: February 2018

The self-aggregation of water-dispersible native collagen nanofibrils has been investigated to generate hierarchical networks with structural variation from helicity to layering.
A self-supported amorphous Ni–P alloy on a CuO nanowire array: an efficient 3D electrode catalyst for water splitting in alkaline media
Authors: Chang Bing , Hao Shuai , Ye Zhixiang , Yang Yingchun
Published: February 2018

An amorphous Ni–P alloy shell electrodeposited on a CuO nanowire array to synergistically boost the catalytic activity toward alkaline water splitting is reported, and this core@shell CuO@Ni–P nanowire array is durable with a cell voltage of only 1.71 V reaching a current density of 30 mA cm−2 using a two-electrode configuration in an alkaline water electrolyzer.