bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of
zmm28
increases maize grain yield in the field
Authors: Wu Jingrui , Lawit Shai J. , Weers Ben , Sun Jindong , Mongar Nick , Van Hemert John , Melo Rosana , Meng Xin , Rupe Mary , Clapp Joshua , Haug Collet Kristin , Trecker Libby , Roesler Keith , Peddicord Layton , Thomas Jill , Hunt Joanne , Zhou Wengang , Hou Zhenglin , Wimmer Matthew , Jantes Justin , Mo Hua , Liu Lu , Wang Yiwei , Walker Carl , Danilevskaya Olga , Lafitte Renee H. , Schussler Jeffrey R. , Shen Bo , Habben Jeffrey E.
Published: November 2019

Increasing maize grain yield has been a major focus of both plant breeding and genetic engineering to meet the global demand for food, feed, and industrial uses. We report that increasing and extending expression of a maize MADS-box transcription factor gene,
zmm28
, under the control of a moderate-constitutive maize promoter, results in maize plants with increased plant growth, photosynthesis capacity, and nitrogen utilization. Molecular and biochemical characterization of
zmm28
transgenic plants demonstrated that their enhanced agronomic traits are associated with elevated plant carbon assimilation, nitrogen utilization, and plant growth. Overall, these positive attributes are associated with a significant increase in grain yield relative to wild-type controls that is consistent across years, environments, and elite germplasm backgrounds.
Pat1 activates late steps in mRNA decay by multiple mechanisms
Authors: Lobel Joseph H. , Tibble Ryan W. , Gross John D.
Published: November 2019

Pat1 is a hub for mRNA metabolism, acting in pre-mRNA splicing, translation repression, and mRNA decay. A critical step in all 5′-3′ mRNA decay pathways is removal of the 5′ cap structure, which precedes and permits digestion of the RNA body by conserved exonucleases. During bulk 5′-3′ decay, the Pat1/Lsm1-7 complex engages mRNA at the 3′ end and promotes hydrolysis of the cap structure by Dcp1/Dcp2 at the 5′ end through an unknown mechanism. We reconstitute Pat1 with 5′ and 3′ decay factors and show how it activates multiple steps in late mRNA decay. First, we find that Pat1 stabilizes binding of the Lsm1-7 complex to RNA using two conserved short-linear interaction motifs. Second, Pat1 directly activates decapping by binding elements in the disordered C-terminal extension of Dcp2, alleviating autoinhibition and promoting substrate binding. Our results uncover the molecular mechanism of how separate domains of Pat1 coordinate the assembly and activation of a decapping messenger ribonucleoprotein (mRNP) that promotes 5′-3′ mRNA degradation.
Immunological ignorance is an enabling feature of the oligo-clonal T cell response to melanoma neoantigens
Authors: Linette Gerald P. , Becker-Hapak Michelle , Skidmore Zachary L. , Baroja Miren Lorea , Xu Chong , Hundal Jasreet , Spencer David H. , Fu Weixuan , Cummins Casey , Robnett Maya , Kaabinejadian Saghar , Hildebrand William H. , Magrini Vincent , Demeter Ryan , Krupnick Alexander S. , Griffith Obi L. , Griffith Malachi , Mardis Elaine R. , Carreno Beatriz M.
Published: November 2019

The impact of intratumoral heterogeneity (ITH) and the resultant neoantigen landscape on T cell immunity are poorly understood. ITH is a widely recognized feature of solid tumors and poses distinct challenges related to the development of effective therapeutic strategies, including cancer neoantigen vaccines. Here, we performed deep targeted DNA sequencing of multiple metastases from melanoma patients and observed ubiquitous sharing of clonal and subclonal single nucleotide variants (SNVs) encoding putative HLA class I-restricted neoantigen epitopes. However, spontaneous antitumor CD8+ T cell immunity in peripheral blood and tumors was restricted to a few clonal neoantigens featuring an oligo-/monoclonal T cell-receptor (TCR) repertoire. Moreover, in various tumors of the 4 patients examined, no neoantigen-specific TCR clonotypes were identified despite clonal neoantigen expression. Mature dendritic cell (mDC) vaccination with tumor-encoded amino acid-substituted (AAS) peptides revealed diverse neoantigen-specific CD8+ T responses, each composed of multiple TCR clonotypes. Isolation of T cell clones by limiting dilution from tumor-infiltrating lymphocytes (TILs) permitted functional validation regarding neoantigen specificity. Gene transfer of TCRαβ heterodimers specific for clonal neoantigens confirmed correct TCR clonotype assignments based on high-throughput TCRBV CDR3 sequencing. Our findings implicate immunological ignorance of clonal neoantigens as the basis for ineffective T cell immunity to melanoma and support the concept that therapeutic vaccination, as an adjunct to checkpoint inhibitor treatment, is required to increase the breadth and diversity of neoantigen-specific CD8+ T cells.
Mercury source changes and food web shifts alter contamination signatures of predatory fish from Lake Michigan
Authors: Lepak Ryan F. , Hoffman Joel C. , Janssen Sarah E. , Krabbenhoft David P. , Ogorek Jacob M. , DeWild John F. , Tate Michael T. , Babiarz Christopher L. , Yin Runsheng , Murphy Elizabeth W. , Engstrom Daniel R. , Hurley James P.
Published: November 2019

Significance

Elevated mercury in fish poses risks to fish-consuming wildlife and humans. Tracing sources of mercury by analyzing stable isotope ratios leads to improved source-receptor understanding and natural resource management. This work utilizes fish and sediment archives to trace the response to recent domestic mercury mitigation actions. Fish and sediments rapidly responded to a source perturbation contemporaneous with the reduction of mercury in the late 1980s. Subsequently, energetic pathways were altered due to dreissenid invasions, which dampened the expected decrease in fish mercury concentration. These findings reveal the importance of domestic mercury sources relative to global mercury to the Great Lakes. Results also show methylmercury concentrations in fish are sensitive to changes in trophic structure and diet driven by invasive species.
A single combination gene therapy treats multiple age-related diseases
Authors: Davidsohn Noah , Pezone Matthew , Vernet Andyna , Graveline Amanda , Oliver Daniel , Slomovic Shimyn , Punthambaker Sukanya , Sun Xiaoming , Liao Ronglih , Bonventre Joseph V. , Church George M.
Published: November 2019

Significance

Human and animal longevity is directly bound to their health span. While previous studies have provided evidence supporting this connection, therapeutic implementation of this knowledge has been limited. Traditionally, diseases are researched and treated individually, which ignores the interconnectedness of age-related conditions, necessitates multiple treatments with unrelated substances, and increases the accumulative risk of side effects. In this study, we address and overcome this deadlock by creating adeno-associated virus (AAV)-based antiaging gene therapies for simultaneous treatment of several age-related diseases. We demonstrate the modular and extensible nature of combination gene therapy by testing therapeutic AAV cocktails that confront multiple diseases in a single treatment. We observed that 1 treatment comprising 2 AAV gene therapies was efficacious against all 4 diseases.
Cognitive and noncognitive predictors of success
Authors: Duckworth Angela L. , Quirk Abigail , Gallop Robert , Hoyle Rick H. , Kelly Dennis R. , Matthews Michael D.
Published: November 2019

When predicting success, how important are personal attributes other than cognitive ability? To address this question, we capitalized on a full decade of prospective, longitudinal data from
n
= 11,258 cadets entering training at the US Military Academy at West Point. Prior to training, cognitive ability was negatively correlated with both physical ability and grit. Cognitive ability emerged as the strongest predictor of academic and military grades, but noncognitive attributes were more prognostic of other achievement outcomes, including successful completion of initiation training and 4-y graduation. We conclude that noncognitive aspects of human capital deserve greater attention from both scientists and practitioners interested in predicting real-world success.
Improving breast cancer sensitivity to paclitaxel by increasing aneuploidy
Authors: Rodrigues-Ferreira Sylvie , Nehlig Anne , Moindjie Hadia , Monchecourt Clarisse , Seiler Cynthia , Marangoni Elisabetta , Chateau-Joubert Sophie , Dujaric Marie-Eglantine , Servant Nicolas , Asselain Bernard , de Cremoux Patricia , Lacroix-Triki Magali , Arnedos Monica , Pierga Jean-Yves , André Fabrice , Nahmias Clara
Published: November 2019

Significance

Low levels of ATIP3 in breast tumors are associated with increased response to neoadjuvant chemotherapy, and ATIP3 silencing in breast cancer cells potentiates the effects of paclitaxel, highlighting the importance of this predictive biomarker to select breast cancer patients who are sensitive to taxane-based chemotherapy. ATIP3 depletion promotes mitotic abnormalities, including centrosome amplification and multipolar spindle formation, which is a source of chromosome segregation errors and aneuploidy. Excessive aneuploidy in ATIP3-deficient cells treated with low doses of paclitaxel results in massive cell death.
Flow directionality of pristine meandering rivers is embedded in the skewing of high-amplitude bends and neck cutoffs
Authors: Guo Xingyan , Chen Dong , Parker Gary
Published: November 2019

Significance

The bends of alluvial meandering rivers often double back on themselves, showing skewing. This skewing may be directed upstream or downstream. How skewing evolves as bends develop remains incompletely understood. Our analysis shows that, on 20 reaches of nearly pristine alluvial meandering rivers, downstream skewing dominates when the bends are relatively straight, but upstream skewing increasingly dominates as bend sinuosity increases. This provides a guide for interpreting bend evolution and offers a useful comparison with numerical models. The results suggest that rivers often carry an imprint of the direction of the flow that created them, through the shape of their high-amplitude bends and neck cutoffs. This provides a reference tool for estimating paleoflow direction on Earth and other planets.
Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions
Authors: Miyamoto Junki , Ohue-Kitano Ryuji , Mukouyama Hiromi , Nishida Akari , Watanabe Keita , Igarashi Miki , Irie Junichiro , Tsujimoto Gozoh , Satoh-Asahara Noriko , Itoh Hiroshi , Kimura Ikuo
Published: November 2019

Ketone bodies, including β-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. β-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system. Under ketogenic conditions, such as starvation and low-carbohydrate diets, plasma acetoacetate levels increased markedly, whereas plasma and cecal SCFA levels decreased dramatically, along with an altered gut microbiota composition. In addition,
Gpr43
-deficient mice showed reduced weight loss and suppressed plasma lipoprotein lipase activity during fasting and eucaloric ketogenic diet feeding. Moreover,
Gpr43
-deficient mice exhibited minimal weight decrease after intermittent fasting. These observations provide insight into the role of ketone bodies in energy metabolism under shifts in nutrition and may contribute to the development of preventive medicine via diet and foods.
Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2
Authors: Wang Xiumin , Lu Jianping , Xie Weiguo , Lu Xiaoyun , Liang Yujie , Li Min , Wang Zichen , Huang Xiaodong , Tang Mingxi , Pfaff Donald W. , Tang Ya-Ping , Yao Paul
Published: November 2019

Significance

Hyperglycemia induces persistent oxidative stress and superoxide dismutase 2 (SOD2) suppression in neurons. SOD2 suppression is caused by oxidative stress-mediated histone methylation and subsequent dissociation of Egr1 on the SOD2 promoter. Maternal diabetes induces autism-like behavior in offspring with SOD2 suppression in the amygdala in rats, while SOD2 overexpression in the amygdala ameliorates autism-like behavior. Postnatal treatment of the blood–brain barrier-permeable antioxidant resveratrol partly restores this effect. This study describes a potential mechanism for maternal diabetes-induced autism-like behavior in offspring.
Unintegrated HIV-1 DNAs are loaded with core and linker histones and transcriptionally silenced
Authors: Geis Franziska K. , Goff Stephen P.
Published: November 2019

Significance

Retroviruses are characterized by the reverse transcription of the viral RNA genome into DNA and the integration of that DNA to form the provirus. However, little is known about the nature of unintegrated HIV-1 DNAs early upon delivery into the nucleus. Using chromatin immunoprecipitation assays, we found that both core and H1 linker histones are deposited onto unintegrated HIV-1 DNAs. We also confirmed transcriptional silencing of unintegrated HIV-1 DNAs and determined the presence of posttranslational histone modifications characteristic of inactive chromatin. Our results will help to increase the efficiency of expression from nonintegrating HIV-1–based vectors and after transient transfections with DNA.
The generation and propagation of the human alpha rhythm
Authors: Halgren Mila , Ulbert István , Bastuji Hélène , Fabó Dániel , Erőss Lorand , Rey Marc , Devinsky Orrin , Doyle Werner K. , Mak-McCully Rachel , Halgren Eric , Wittner Lucia , Chauvel Patrick , Heit Gary , Eskandar Emad , Mandell Arnold , Cash Sydney S.
Published: November 2019

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.
Sec17 (α-SNAP) and Sec18 (NSF) restrict membrane fusion to R-SNAREs, Q-SNAREs, and SM proteins from identical compartments
Authors: Jun Youngsoo , Wickner William
Published: November 2019

Significance

Although each intracellular fusion event is catalyzed by similar proteins, organelle-specific fusion is essential for accurate protein compartmentation. Prior studies have suggested that specificity resides in the SNARE proteins or in SNAREs and their Sec1/Munc18 (SM) chaperones. The current work, with combinations of SM proteins, R-SNAREs, and Q-SNAREs from yeast vacuole homotypic fusion and from endoplasmic reticulum/
cis
-Golgi fusion, finds that some noncognate combinations support fusion. However, in the presence of the SNARE disassembly chaperones Sec17/α-SNAP and Sec18/NSF, fusion only occurs when the R-SNARE, Q-SNAREs, and SM protein are derived from the same organelle.
The frequency-domain infrared spectrum of ammonia encodes changes in molecular dynamics caused by a DC electric field
Authors: Park Youngwook , Kang Hani , Field Robert W. , Kang Heon
Published: November 2019

Significance

Our experiment captures the detailed sequence of molecular processes that occur when a uniquely strong (∼10
8
V/m) direct current (DC) electric field is imposed on ammonia molecules isolated in a solid Ar matrix. Electric fields are of singular importance in chemistry, materials science, and molecular biology. Intermolecular interactions, resulting in rearrangements of electrons and nuclei, are driven by strong electric fields. The detailed responses of molecules to external electric fields of interatomic strength are incompletely understood, because techniques for applying such strong DC electric fields and observing the molecular responses to these fields do not yet exist. Ammonia, with its extreme amplitude intramolecular dynamics and extreme sensitivity to electric fields, is an ideal subject for study by DC-infrared 2-dimensional spectroscopy.
Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain–containingLegionellaeffectors
Authors: Wan Min , Sulpizio Alan G. , Akturk Anil , Beck Wendy H. J. , Lanz Michael , Faça Vitor M. , Smolka Marcus B. , Vogel Joseph P. , Mao Yuxin
Published: November 2019

Significance

Ubiquitination is a vital posttranslational modification in eukaryotes. A variety of microbial pathogens exploit this pathway during their infection.Legionella pneumophila, the causative bacterial pathogen of Legionnaires’ disease, has been shown to hijack host ubiquitination pathway via a large number of effectors. Recent studies revealed a family of effectors catalyzing a type of ubiquitin (Ub)-dependent posttranslational modification, namely PR-ubiquitination. Here we report 2 players, DupA and DupB, involved in this unconventional pathway. We found that DupA and DupB function as PR-Ub–specific deubiquitinases and play a role in regulating the PR-ubiquitination levels of host targets. Our results not only provide an expanding view of the PR-ubiquitination pathway, but also may facilitate the future identification of PR-ubiquitination pathways in eukaryotes.
Metaphors in German newspaper articles on multidrug-resistant bacteria in clinical contexts, 1995–2015
Authors: Peters Joachim , Dykes Natalie , Habermann Mechthild , Ostgathe Christoph , Heckel Maria
Published: November 2019

The study investigates the usage of metaphorical structures in the German press discourse on multi-resistant pathogens in the clinical context by applying methods of qualitative discourse analysis to a corpus of 900 newspaper and magazine articles published between 1995–2015. The study shows that metaphors are of key importance for the processes of knowledge transfer, emotion production and persuasion. Metaphors are assigned to one of three general principles (mechanising explanation patterns, gain and loss of control, agentivity and personification) and to seven dominant source domains which structure the discourse through frequent argumentation structures: war, economy, space, machines, water, police and crime, sports and games. The occurrence of metaphor is – as previous research in other areas has shown – universal to all examined press texts; variation is limited to the thematic focus of individual argumentation structures between the different texts.
Las creencias de los profesores de español como lengua extranjera sobre los estilos de aprendizaje
Authors: Domínguez Pelegrín Javier , López Quero Salvador , Andión Herrero María Antonieta
Published: November 2019

Este estudio se adscribe al ámbito de la cognición del profesor de idiomas. En él analizamos las creencias sobre
los estilos de aprendizaje de una muestra de 301 profesores de español como lengua extranjera. Centramos el análisis en dos
cuestiones: la delimitación conceptual sobre los estilos de aprendizaje y sus implicaciones en la enseñanza de la lengua. En ambos
casos, el análisis parte de una revisión bibliográfica que permitirá contrastar las creencias de los profesores con las
aportaciones de los expertos en la materia. De este modo, podemos determinar las relaciones existentes entre sus creencias, sus
conocimientos y su práctica docente. De la interpretación de los datos se desprenden tanto coincidencias como incongruencias entre
las creencias de los profesores y las propuestas de los investigadores. Asimismo, se constata una relación discordante entre lo
que los profesores creen y lo que hacen en el aula.
Valoración de profesores y alumnos coreanos sobre el componente cultural en aulas de ELE
Authors: Song Yerim
Published: November 2019

En este estudio se analiza la valoración de profesores y alumnos acerca del tratamiento del componente cultural en
cursos universitarios de español como lengua extranjera en la República de Corea. Una vez analizados los cuestionarios
administrados a la planta de profesores y a 312 alumnos de una universidad coreana, se examinan los resultados resaltando las
similitudes y diferencias entre docentes y educandos. Las respuestas se agrupan en tres temas: tratamiento del componente
cultural, actividades culturales en clase y contenidos culturales. Finalmente, se considera tanto la reflexión sobre la práctica
docente en los cuestionarios del profesorado como la experiencia de aprendizaje en los del alumnado. El objetivo de este artículo
es mostrar la importancia de la selección del componente cultural y su incorporación a la clase de lengua, así como una mayor
integración de la lengua española y la cultura hispánica dentro del plan de estudios universitarios en Corea del Sur.
Confinement hinders motility by inducing RhoA-mediated nuclear influx, volume expansion, and blebbing
Authors: Mistriotis Panagiotis , Wisniewski Emily O. , Bera Kaustav , Keys Jeremy , Li Yizeng , Tuntithavornwat Soontorn , Law Robert A. , Perez-Gonzalez Nicolas A. , Erdogmus Eda , Zhang Yuqi , Zhao Runchen , Sun Sean X. , Kalab Petr , Lammerding Jan , Konstantopoulos Konstantinos
Published: November 2019

Cells migrate in vivo through complex confining microenvironments, which induce significant nuclear deformation that may lead to nuclear blebbing and nuclear envelope rupture. While actomyosin contractility has been implicated in regulating nuclear envelope integrity, the exact mechanism remains unknown. Here, we argue that confinement-induced activation of RhoA/myosin-II contractility, coupled with LINC complex-dependent nuclear anchoring at the cell posterior, locally increases cytoplasmic pressure and promotes passive influx of cytoplasmic constituents into the nucleus without altering nuclear efflux. Elevated nuclear influx is accompanied by nuclear volume expansion, blebbing, and rupture, ultimately resulting in reduced cell motility. Moreover, inhibition of nuclear efflux is sufficient to increase nuclear volume and blebbing on two-dimensional surfaces, and acts synergistically with RhoA/myosin-II contractility to further augment blebbing in confinement. Cumulatively, confinement regulates nuclear size, nuclear integrity, and cell motility by perturbing nuclear flux homeostasis via a RhoA-dependent pathway.
The complexity of the serine glycine one-carbon pathway in cancer
Authors: Reina-Campos Miguel , Diaz-Meco Maria T. , Moscat Jorge
Published: November 2019

The serine glycine and one-carbon pathway (SGOCP) is a crucially important metabolic network for tumorigenesis, of unanticipated complexity, and with implications in the clinic. Solving how this network is regulated is key to understanding the underlying mechanisms of tumor heterogeneity and therapy resistance. Here, we review its role in cancer by focusing on key enzymes with tumor-promoting functions and important products of the SGOCP that are of physiological relevance for tumorigenesis. We discuss the regulatory mechanisms that coordinate the metabolic flux through the SGOCP and their deregulation, as well as how the actions of this metabolic network affect other cells in the tumor microenvironment, including endothelial and immune cells.
Unconventional transport of metal ions and protons by Nramps
Authors: Rudnick Gary
Published: November 2019

Rudnick highlights a kinetic analysis of a bacterial Nramp transporter that focuses on how H+ gradients are coupled to metal transport.
In silico evaluation of the thermal stress induced by MRI switched gradient fields in patients with metallic hip implant
Authors: Arduino Alessandro , Bottauscio Oriano , Brühl Rüdiger , Chiampi Mario , Zilberti Luca
Published: November 2019

This work focuses on the in silico evaluation of the energy deposed by MRI switched gradient fields in bulk metallic implants and the consequent temperature increase in the surrounding tissues. An original computational strategy, based on the subdivision of the gradient coil switching sequences into sub-signals and on the time-harmonic electromagnetic field solution, allows to realistically simulate the evolution of the phenomena produced by the gradient coils fed according to any MRI sequence. Then, Pennes’ bioheat equation is solved through a Douglas–Gunn time split scheme to compute the time-dependent temperature increase. The procedure is validated by comparison with laboratory results, using a component of a realistic hip implant embedded within a phantom, obtaining an agreement on the temperature increase better than 5%, lower than the overall measurement uncertainty. The heating generated inside the body of a patient with a unilateral hip implant when undergoing an Echo-Planar Imaging (EPI) MRI sequence is evaluated and the role of the parameters affecting the thermal results (body position, coil performing the frequency encoding, effects of thermoregulation) is discussed. The results show that the gradient coils can generate local increases of temperature up to some kelvin when acting without radiofrequency excitation. Hence, their contribution in general should not be disregarded when evaluating patients’ safety.
Structural and transport mechanism studies of copper selenide nanoparticles
Authors: Liew Josephine Ying Chyi , Talib Zainal Abidin , Zainal Zulkarnain , Kamarudin Mazliana Ahmad , Osman Nurul Huda , Lee Han Kee
Published: November 2019

Copper selenide (CuSe) nanoparticles were successfully prepared via chemical precipitation method at room temperature. The field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and atomic force microsccopy (AFM) micrograph showed the synthesized CuSe powder is nanoparticles. The energy dispersive x-ray (EDX) analysis and inductively coupling plasma (ICP) analysis showed the formation of the stoichiometric CuSe compound. In-situ x-ray diffraction (XRD) at temperatures ranging from 100 to 473 K was performed to study the structure stability of the CuSe compound. The electrical conductivity, Hall mobility, carrier sheet density and thermal diffusivity of the CuSe compound have been investigated at various temperatures to study the electron-phonon transport mechanism in the compound.
Determination of intrinsic effective fields and microwave polarizations by high-resolution spectroscopy of single nitrogen-vacancy center spins
Authors: Kölbl J , Kasperczyk M , Bürgler B , Barfuss A , Maletinsky P
Published: November 2019

We present high-resolution optically detected magnetic resonance spectroscopy on single nitrogen-vacancy (NV) center spins in diamond at and around zero magnetic field. The experimentally observed transitions depend sensitively on the interplay between the microwave (MW) probing field and the local intrinsic effective field comprising strain and electric fields, which act on the NV spin. Based on a theoretical model of the magnetic dipole transitions and the MW driving field, we extract both the strength and the direction of the transverse component of the effective field. Our results reveal that for the diamond crystal under study, strain is the dominant contribution to the effective field. Our experiments further yield a method for MW polarization analysis in a tunable, linear basis, which we demonstrate on a single NV spin. Our results are of importance to low-field quantum sensing applications using NV spins and form a relevant addition to the ever-growing toolset of spin-based quantum sensing.
Occurrence and health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in water resources of the typical plain river network area
Authors: Du Haonan
Published: November 2019

Drinking water sources play a significant role in providing water for urban residents and public services. The pollution and health risk of polycyclic aromatic hydrocarbons in drinking water sources have attracted extensive attention. In this study, river water samples were collected from two drinking water resources of the typical plain river network area in eastern China, and tap water samples were collected from public places. The concentration of the 16 priority PAHs in river water and drinking water were determined by SPE-GC-MS. The results indicated that the concentrations of Σ16PAHs ranged 128-183 ng/L in the autumn and 61.3-87.3 ng/L in the winter, respectively. The cancer risks and non-cancer risks of adults associated with drinking water intake were low, but it still deserved more attention.
Physical and mechanical properties of urea formaldehyde and phenol formaldehyde-bonded particleboards made from corn stalk
Authors: Prasetiyo K W , Astari L , Syamani F A , Subyakto
Published: November 2019

Biomass from annual fibers and agricultural wastes as a raw material to produce particleboard or other composite panels has gained increased popularity. The purpose of this study was to investigate the suitability of corn stalk as a material for particleboard manufacturing. The effect of adhesive type and concentration on the physical and mechanical properties of particleboard manufactured from corn stalk was evaluated. Particleboards were produced using hot-pressing machine at temperature of 130 °C for urea formaldehyde (UF) and 150 °C for phenol formaldehyde (PF) adhesives until 10 min. The size of particleboards and target density were 25 mm x 25 mm x 0.9 mm and 0.8 g/cm3, respectively. The adhesive content was varied from 8, 10 and 12 wt%. The results showed that the physical and mechanical properties of particleboards had better values with increasing the adhesive concentration. The board bonded with PF adhesive showed better physical and mechanical properties than the board bonded with UF adhesive. The modulus of rupture, modulus of elasticity and internal bond of the board bonded with 12 wt% of PF fulfilled the requirement of the JIS A 5908 (2003) for type 13 particleboard.
Application of Grassmann phase space theory to Cooper pair model
Authors: Kidwani N M , Dalton B J
Published: November 2019

This paper concerns the application of Grassmann phase space theory (GSPT) to treat the dynamical evolution of systems of identical fermions, such as ultracold gases of fermionic atoms. Phase space theory (which originated from quantum optics) is increasing in importance since it overcomes certain issues associated with other theoretical methods, such as Greens functions, variational methods, quantum-Monte-Carlo equations, etc. In phase-space theory quantum states are represented by quasi-probability distribution functions of phase space variables associated with canonical system operators—such as annihilation, creation operators. Evolution is described via a Fokker-Planck equation for the distribution function, which is equivalent to Ito stochastic equations for (time dependent) stochastic phase space variables. Quantum correlation functions given as averages of products of phase space variables over the quasi-probability distributions then become stochastic averages of products of stochastic phase space variables. In GSPT, the phase space variables are Grassmann numbers, but as computer representation of g-numbers is difficult, Grassmann phase space methods were regarded as being computationally inaccessible. However, previous work using the un-normalised B distribution shows that computer representation of Grassmann variables is unnecessary. Stochastic averages of products for quantum correlation functions at later times are related linearly to stochastic averages at earlier times via stochastic matrices only involving c-numbers. Thus, GSPT calculations of quantum correlation functions now only involve c-number computations. This paper presents the first correct numerical calculation of a quantum correlation function for a fermionic system using stochastic methods based on Grassmann phase space theory, namely the time dependence of the coherence between two Cooper pair states in a four-mode fermion system, where the short and finite time solutions can be compared to known exact results. Good agreement between the stochastic and exact results is found, showing that GPST is a valid approach for treating fermionic systems. The treatment of time evolution involves a novel use of the eigenvalues and biorthogonal column eigenvectors of a stochastically determined c-number matrix M and its transpose. Other topics of interest in ultra-cold fermi gases for which the GSPT could be applied are highlighted, such as the strong interaction regime for the BEC/BCS crossover achieved using magnetically tuned Feshbach resonance techniques.
Identification of normal modes responsible for ferroelectric properties in organic ferroelectric CBDC
Authors: Mukhopadhyay Sanghamitra
Published: November 2019

Structure and dynamics of hydrogen bonded organic ferroelectric CBDC (1-cyclobutene-1,2-dicarboxylic acid, C6H8O4) have been investigated using inelastic neutron scattering (INS) spectroscopy and first principles lattice dynamics. Vibrational modes of O–H–O bending, related with two different types of hydrogen bonds, inter and intra-molecular, are manifested as two sets of doublets in the range of 900–1400 cm−1 in the INS spectrum. First principles density functional theory (DFT) is used to assign these doublets to out-of-the-plane and in-plane vibrations of these two types of O–H—O bending modes. Correlating structure and dynamics we find that although the local structures of the hydrogen bonded protons are similar, their medium range order may influence their vibrational frequencies. Vibrational modes of non-hydrogen bonded protons also are assigned separately in the spectrum. Comparing the calculated and the experimental INS spectra it is predicted that hydrogen bonded O–H bonds are more anharmonic than non-hydrogen bonded C–H bonds. From the calculated Born effective charge tensor it is predicted that inter-molecular hydrogen bonds contribute more to the ferroelectric polarisation of CBDC than intra-molecular ones. A large LO-TO splitting of the O–H stretching mode at 2471 cm−1 is identified with the mode that has significant contribution to the ferroelectric polarisation. As this mode is sensitive to long range Coulomb interactions and is responsible for ferroelectric properties of the material, vibrational spectroscopy combined with DFT calculations is proposed as a characterisation tool to investigate ferroelectric properties in the CBDC molecular crystal.
Highlights of 2019 Protein Engineering Summit (PEGS) in Boston, USA: advancing antibody-based cancer therapies to the clinic
Authors: Li Hong , Li You , Wang Cheng , Wang Shouye , Ho Mitchell
Published: November 2019

The 15th Annual Protein Engineering Summit (PEGS) organized by Cambridge Healthtech Institute was held in Boston, USA, from 8 to 12 April 2019. This report highlights the presentations in the Oncology Stream of this meeting with a focus on bispecific antibodies (BsAbs). A variety of BsAb formats with different target antigens (CD3, CTLA4, PD-1, PD-L1, EGFR, HER2, BCMA, CD19, CD20, CD38, CD123, TGFβ, PSMA, etc.) have been discussed, in which the T-cell engaging (anti-CD3) BsAb is the most studied construct to exhibit promising immunotherapeutic activities. The BsAb formats include IgG-like structures or antibody fragments composed of antigen-binding sites only. Preclinical and clinical data from different BsAbs demonstrated the potential therapeutic applications in various solid tumors and hematological malignancies. The ongoing development of BsAb formats will help overcome current clinical issues, such as tumor selectivity and antigen coverage. This report also covers several presentations about emerging targets (e.g. mesothelin, CD47) and new technologies in the field of antibody engineering and therapeutics.
Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease
Authors: Crapser Joshua D , Ochaba Joseph , Soni Neelakshi , Reidling Jack C , Thompson Leslie M , Green Kim N
Published: November 2019

Huntington’s disease is associated with a reactive microglial response and consequent inflammation. To address the role of these cells in disease pathogenesis, we depleted microglia from R6/2 mice, a rapidly progressing model of Huntington’s disease marked by behavioural impairment, mutant huntingtin (mHTT) accumulation, and early death, through colony-stimulating factor 1 receptor inhibition (CSF1Ri) with pexidartinib (PLX3397) for the duration of disease. Although we observed an interferon gene signature in addition to downregulated neuritogenic and synaptic gene pathways with disease, overt inflammation was not evident by microglial morphology or cytokine transcript levels in R6/2 mice. Nonetheless, CSF1Ri-induced microglial elimination reduced or prevented disease-related grip strength and object recognition deficits, mHTT accumulation, astrogliosis, and striatal volume loss, the latter of which was not associated with reductions in cell number but with the extracellular accumulation of chondroitin sulphate proteoglycans (CSPGs)—a primary component of glial scars. A concurrent loss of proteoglycan-containing perineuronal nets was also evident in R6/2 mice, and microglial elimination not only prevented this but also strikingly increased perineuronal nets in the brains of naïve littermates, suggesting a new role for microglia as homeostatic regulators of perineuronal net formation and integrity.
Longitudinal neuroimaging following combat concussion: sub-acute, 1 year and 5 years post-injury
Authors: Mac Donald Christine L , Barber Jason , Andre Jalal , Panks Chris , Zalewski Kody , Temkin Nancy
Published: November 2019

Questions remain regarding the long-term impact of combat concussive blast exposure. While efforts have begun to highlight the clinical impact, less is known about neuroimaging trajectories that may inform underlying pathophysiological changes post-injury. Through collaborative efforts in combat, following medical evacuation, and at universities in the USA, this study followed service members both with and without blast concussion from the sub-acute to 1-year and 5-year outcomes with quantitative neuroimaging. The following two primary and two exploratory groups were examined: combat-deployed controls without blast exposure history ‘non-blast control’ and concussive blast patients (primary) and combat concussion arising not from blast ‘non-blast concussion’ and combat-deployed controls with blast exposure history ‘blast control’ (exploratory). A total of 575 subjects were prospectively enrolled and imaged; 347 subjects completed further neuroimaging examination at 1 year and 342 subjects completed further neuroimaging examination at 5 years post-injury. At each time point, MRI scans were completed that included high-resolution structural as well as diffusion tensor imaging acquisitions processed for quantitative volumetric and diffusion tensor imaging changes. Longitudinal evaluation of the number of abnormal diffusion tensor imaging and volumetric regions in patients with blast concussion revealed distinct trends by imaging modality. While the presence of abnormal volumetric regions remained quite stable comparing our two primary groups of non-blast control to blast concussion, the diffusion tensor imaging abnormalities were observed to have varying trajectories. Most striking was the fractional anisotropy ‘U-shaped’ curve observed for a proportion of those that, if we had only followed them to 1 year, would look like trajectories of recovery. However, by continuing the follow-up to 5 years in these very same patients, a secondary increase in the number of reduced fractional anisotropy regions was identified. Comparing non-blast controls to blast concussion at each time point revealed significant differences in the number of regions with reduced fractional anisotropy at both the sub-acute and 5-year time points, which held after adjustment for age, education, gender, scanner and subsequent head injury exposure followed by correction for multiple comparisons. The secondary increase identified in patients with blast concussion may be the earliest indications of microstructural changes underlying the ‘accelerated brain aging’ theory recently reported from chronic, cross-sectional studies of veterans following brain injury. These varying trajectories also inform potential prognostic neuroimaging biomarkers of progression and recovery.
Health Care as Vocation? Practicing Faithfully in an Age of Disenchantment
Authors: Kinghorn Warren A
Published: November 2019

In his 1917 lecture “Science as a Vocation,” Max Weber challenged current and aspiring scholars to abandon any pretense that science (Wissenschaft) bears within itself any meaning. In a disenchanted age, he argued, science could at best offer “knowledge of the techniques whereby we can control life . . . through calculation,” and any meaning or moral direction to scientific research—including religious meaning—must be imposed on it from without. Weber presciently anticipated that many present-day health care practitioners would struggle to find meaning for their work within complex “state-capitalist” health care systems, along with predictable quasi-religious responses. But how are Christian practitioners to practice faithfully in a disenchanted age? The authors of this special issue lean deeply into the loci of Christian theology and Christian practice, some challenging the views of the body and of nature that informed Weber’s theory of disenchantment, and all offering resources and paths by which practitioners might “look the fate of the age full in the face” with courage and wisdom.
Calling, Virtue, and the Practice of Medicine
Authors: Whitt Jason D
Published: November 2019

This essay argues that an account of vocation that ties one’s work with divine calling stands counter to the biblical witness of calling in the New Testament. Rather than calling to a particular profession, the biblical account of calling is to a unique way of living that is to exemplify the followers of Christ. Therefore, the re-enchantment of medicine is not accomplished when one makes the practice itself sacred simply by imagining it as one’s divine calling. Rather, the sacredness of medicine is rooted in the character of the physician whose daily decisions and patient interactions are the outcomes of virtues inculcated in worship, prayer, Bible study, and all other practices that mark the life of faith. Thus, the practitioner avoiding burnout asks not “Am I called to be a physician?” but “How as a physician in the daily practice of medicine might I exemplify my calling to Christ-likeness?”
Comparing the performance of artificial intelligence and conventional diagnosis criteria for detecting left ventricular hypertrophy using electrocardiography
Authors: Kwon Joon-Myoung , Jeon Ki-Hyun , Kim Hyue Mee , Kim Min Jeong , Lim Sung Min , Kim Kyung-Hee , Song Pil Sang , Park Jinsik , Choi Rak Kyeong , Oh Byung-Hee
Published: November 2019

Aims 

Although left ventricular hypertrophy (LVH) has a high incidence and clinical importance, the conventional diagnosis criteria for detecting LVH using electrocardiography (ECG) has not been satisfied. We aimed to develop an artificial intelligence (AI) algorithm for detecting LVH.

Methods and results

This retrospective cohort study involved the review of 21 286 patients who were admitted to two hospitals between October 2016 and July 2018 and underwent 12-lead ECG and echocardiography within 4 weeks. The patients in one hospital were divided into a derivation and internal validation dataset, while the patients in the other hospital were included in only an external validation dataset. An AI algorithm based on an ensemble neural network (ENN) combining convolutional and deep neural network was developed using the derivation dataset. And we visualized the ECG area that the AI algorithm used to make the decision. The area under the receiver operating characteristic curve of the AI algorithm based on ENN was 0.880 (95% confidence interval 0.877–0.883) and 0.868 (0.865–0.871) during the internal and external validations. These results significantly outperformed the cardiologist’s clinical assessment with Romhilt-Estes point system and Cornell voltage criteria, Sokolov-Lyon criteria, and interpretation of ECG machine. At the same specificity, the AI algorithm based on ENN achieved 159.9%, 177.7%, and 143.8% higher sensitivities than those of the cardiologist’s assessment, Sokolov-Lyon criteria, and interpretation of ECG machine.

Conclusion 

An AI algorithm based on ENN was highly able to detect LVH and outperformed cardiologists, conventional methods, and other machine learning techniques.
Left ventricular apical pacing in children: feasibility and long-term effect on ventricular function
Authors: Kovanda Jan , Ložek Miroslav , Ono Shin , Kubuš Peter , Tomek Viktor , Janoušek Jan
Published: November 2019

Aims 

Left ventricular apical pacing (LVAP) has been reported to preserve left ventricular (LV) function in chronically paced children with complete atrioventricular block (CAVB). We sought to evaluate long-term feasibility of LVAP and the effect on LV mechanics and exercise capacity as compared to normal controls.

Methods and results 

Thirty-six consecutive paediatric patients with CAVB and LVAP in the absence (N = 22) or presence of repaired structural heart disease (N = 14, systemic LV in all) and 25 age-matched normal controls were cross-sectionally studied after a median of 3.9 (interquartile range 2.1–6.8) years of pacing using echocardiography and exercise stress testing. Pacemaker implantation was uneventful and there was no death. Probability of the absence of pacemaker-related surgical revision (elective generator replacement excluded) was 89.0% at 5 years after implantation. Left ventricular apical pacing patients had lower maximum oxygen uptake (P = 0.009), no septal to lateral but significant apical to basal LV mechanical delay (P < 0.001) which correlated with decreased LV contraction efficiency (P = 0.001). Left ventricular ejection fraction and global longitudinal LV strain were, however, not different from controls. Results were similar in both the presence and absence of structural heart disease.

Conclusion 

Left ventricular apical pacing is technically feasible with a low reintervention rate. Mechanical synchrony between LV septum and free wall is maintained at the price of an apical to basal mechanical delay associated with LV contraction inefficiency as compared to healthy controls. Global LV systolic function is, however, not negatively affected by LVAP.