bluuebunny/crossref_metadata_2025 huggingface dataset:
The apoptosome molecular timer synergises with XIAP to suppress apoptosis execution and contributes to prognosticating survival in colorectal cancer
Authors: Fullstone Gavin , Bauer Tabea L. , Guttà Cristiano , Salvucci Manuela , Prehn Jochen H. M. , Rehm Markus
Published: April 2020

The execution phase of apoptosis is a critical process in programmed cell death in response to a multitude of cellular stresses. A crucial component of this pathway is the apoptosome, a platform for the activation of pro-caspase 9 (PC9). Recent findings have shown that autocleavage of PC9 to Caspase 9 (C9) p35/p12 not only permits XIAP-mediated C9 inhibition but also temporally shuts down apoptosome activity, forming a molecular timer. In order to delineate the combined contributions of XIAP and the apoptosome molecular timer to apoptosis execution we utilised a systems modelling approach. We demonstrate that cooperative recruitment of PC9 to the apoptosome, based on existing PC9-apoptosome interaction data, is important for efficient formation of PC9 homodimers, autocatalytic cleavage and dual regulation by XIAP and the molecular timer across biologically relevant PC9 and APAF1 concentrations. Screening physiologically relevant concentration ranges of apoptotic proteins, we discovered that the molecular timer can prevent apoptosis execution in specific scenarios after complete or partial mitochondrial outer membrane permeabilisation (MOMP). Furthermore, its ability to prevent apoptosis is intricately tied to a synergistic combination with XIAP. Finally, we demonstrate that simulations of these processes are prognostic of survival in stage III colorectal cancer and that the molecular timer may promote apoptosis resistance in a subset of patients. Based on our findings, we postulate that the physiological function of the molecular timer is to aid XIAP in the shutdown of caspase-mediated apoptosis execution. This shutdown potentially facilitates switching to pro-inflammatory caspase-independent responses subsequent to Bax/Bak pore formation.
Chidamide epigenetically represses autophagy and exerts cooperative antimyeloma activity with bortezomib
Authors: Xu Li , Feng Juan , Tang Hailong , Dong Ying , Shu Mimi , Chen Xiequn
Published: April 2020

Autophagy and ubiquitin proteasome system are two distinct and cooperative proteolytic pathways. The dual-pathway suppression represents a promising therapeutic strategy for multiple myeloma. Chidamide is a novel benzamide inhibitor of histone deacetylase, and shows potent antimyeloma activity. Here, we revealed the autophagy-suppressive role of chidamide in myeloma cells. We then demonstrated that chidamide treatment markedly downregulated histone deacetylase SIRT1, and simultaneously resulted in dose-dependent upregulation of acetyltransferase hMOF and histone methyltransferase EZH2, which contributed to an increase in global levels of histone H4 lysine 16 acetylation (H4k16ac) and histone H3 lysine 27 trimethylation (H3k27me3). We next confirmed concomitant upregulation of H4k16ac and H3k27me3 in the same promoter regions of the autophagy-related gene LC3B, reinforcing the specific roles for H4k16ac and H3k27me3 in mediating chidamide-induced transcriptional repression of LC3B. Finally, we provided experimental evidence that co-treatment with chidamide and proteasome inhibitor bortezomib induced clear synergistic cytotoxicity against MM cells, which was associated with increased accumulation of ubiquitinated proteins and excessive endoplasmic reticulum stress or dysregulated unfolded protein response. Our results altogether suggest that chidamide cooperatively potentiates antimyeloma activity of bortezomib, at least in part, by epigenetically repressing autophagic degradation of ubiquitinated proteins.
Autonomous discovery of optically active chiral inorganic perovskite nanocrystals through an intelligent cloud lab
Authors: Li Jiagen , Li Junzi , Liu Rulin , Tu Yuxiao , Li Yiwen , Cheng Jiaji , He Tingchao , Zhu Xi
Published: April 2020

We constructed an intelligent cloud lab that integrates lab automation with cloud servers and artificial intelligence (AI) to detect chirality in perovskites. Driven by the materials acceleration operating system in cloud (MAOSIC) platform, on-demand experimental design by remote users was enabled in this cloud lab. By employing artificial intelligence of things (AIoT) technology, synthesis, characterization, and parameter optimization can be autonomously achieved. Through the remote collaboration of researchers, optically active inorganic perovskite nanocrystals (IPNCs) were first synthesized with temperature-dependent circular dichroism (CD) and inversion control. The inter-structure (structural patterns) and intra-structure (screw dislocations) dual-pattern-induced mechanisms detected by MAOSIC were comprehensively investigated, and offline theoretical analysis revealed the thermodynamic mechanism inside the materials. This self-driving cloud lab enables efficient and reliable collaborations across the world, reduces the setup costs of in-house facilities, combines offline theoretic analysis, and is practical for accelerating the speed of material discovery.
Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction
Authors: Trembinski D. Julia , Bink Diewertje I. , Theodorou Kosta , Sommer Janina , Fischer Ariane , van Bergen Anke , Kuo Chao-Chung , Costa Ivan G. , Schürmann Christoph , Leisegang Matthias S. , Brandes Ralf P. , Alekseeva Tijna , Brill Boris , Wietelmann Astrid , Johnson Christopher N. , Spring-Connell Alexander , Kaulich Manuel , Werfel Stanislas , Engelhardt Stefan , Hirt Marc N. , Yorgan Kaja , Eschenhagen Thomas , Kirchhof Luisa , Hofmann Patrick , Jaé Nicolas , Wittig Ilka , Hamdani Nazha , Bischof Corinne , Krishnan Jaya , Houtkooper Riekelt H. , Dimmeler Stefanie , Boon Reinier A.
Published: April 2020

Abstract

Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
Orbital ordering and magnetism in layered Perovskite Ruthenate Sr2RuO4
Authors: Huang Hung-Lung , Jeng Horng-Tay
Published: April 2020

Local density approximation plus on-site Coulomb interaction U electronic structure calculations reveal that layered perovskite oxide Sr2RuO4 exhibits the ferromagnetic (FM) half-metallic ground state, which is nearly degenerate with the antiferromagnetic (AFM) phase with a slightly higher total energy. The nearly degenerate FM/AFM total energies provide a reasonable explanation for the experimentally observed spin-fluctuation. In addition, a dumbbell-shape 4d − t2g recombined dxz − dyz orbital ordering on the Ru sublattice is obtained owing to the on-site Coulomb interaction U associated with the elongated RuO6 octahedron local structure. The discovered orbital ordering is robust against the spin-orbit interaction as well as the surface terminations. Our findings unravel the on-site Coulomb correlation as the driving force of the Ru-4d orbital ordering as well as the inherent magnetic degeneracy.
Artificial sounds following biological rules: A novel approach for non-verbal communication in HRI
Authors: Korcsok Beáta , Faragó Tamás , Ferdinandy Bence , Miklósi Ádám , Korondi Péter , Gácsi Márta
Published: April 2020

Emotionally expressive non-verbal vocalizations can play a major role in human-robot interactions. Humans can assess the intensity and emotional valence of animal vocalizations based on simple acoustic features such as call length and fundamental frequency. These simple encoding rules are suggested to be general across terrestrial vertebrates. To test the degree of this generalizability, our aim was to synthesize a set of artificial sounds by systematically changing the call length and fundamental frequency, and examine how emotional valence and intensity is attributed to them by humans. Based on sine wave sounds, we generated sound samples in seven categories by increasing complexity via incorporating different characteristics of animal vocalizations. We used an online questionnaire to measure the perceived emotional valence and intensity of the sounds in a two-dimensional model of emotions. The results show that sounds with low fundamental frequency and shorter call lengths were considered to have a more positive valence, and samples with high fundamental frequency were rated as more intense across all categories, regardless of the sound complexity. We conclude that applying the basic rules of vocal emotion encoding can be a good starting point for the development of novel non-verbal vocalizations for artificial agents.
Glyoxylic acid overcomes 1-MCP-induced blockage of fruit ripening in Pyrus communis L. var. ‘D’Anjou’
Authors: Hewitt Seanna L. , Ghogare Rishikesh , Dhingra Amit
Published: April 2020

1-methylcyclopropene (1-MCP) in an ethylene receptor antagonist that blocks ethylene perception and downstream ripening responses in climacteric fruit imparting a longer shelf life. However, in European pear, the application of 1-MCP irreversibly obstructs the onset of system 2 ethylene production resulting in perpetually unripe fruit with undesirable quality. Application of exogenous ethylene, carbon dioxide and treatment to high temperatures is not able to reverse the blockage in ripening. We recently reported that during cold conditioning, activation of alternative oxidase (AOX) occurs pre-climacterically. In this study, we report that activation of AOX via exposure of 1-MCP treated ‘D’Anjou’ pear fruit to glyoxylic acid triggers an accelerated ripening response. Time course physiological analysis revealed that ripening is evident from decreased fruit firmness and increased internal ethylene. Transcriptomic and functional enrichment analyses revealed genes and ontologies implicated in glyoxylic acid-mediated ripening, including AOX, TCA cycle, fatty acid metabolism, amino acid metabolism, organic acid metabolism, and ethylene-responsive pathways. These observations implicate the glyoxylate cycle as a biochemical hub linking multiple metabolic pathways to stimulate ripening through an alternate mechanism. The results provide information regarding how blockage caused by 1-MCP may be circumvented at the metabolic level, thus opening avenues for consistent ripening in pear and possibly other fruit.
Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds
Authors: Vidal Luciano , Kampleitner Carina , Krissian Stéphanie , Brennan Meadhbh Á , Hoffmann Oskar , Raymond Yago , Maazouz Yassine , Ginebra Maria-Pau , Rosset Philippe , Layrolle Pierre
Published: April 2020

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds.
Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha
Authors: Rodgers Kyla R. , Lin Yufan , Langan Thomas J. , Iwakura Yoichiro , Chou Richard C.
Published: April 2020

Acute inflammation is a key feature of innate immunity that initiates clearance and repair in infected or damaged tissues. Alternatively, chronic inflammation is implicated in numerous disease processes. The contribution of neuroinflammation to the pathogenesis of neurological conditions, including infection, traumatic brain injury, and neurodegenerative diseases, has become increasingly evident. Potential drivers of such neuroinflammation include toll-like receptors (TLRs). TLRs confer a wide array of functions on different cell types in the central nervous system (CNS). Importantly, how TLR activation affects astrocyte functioning is unclear. In the present study, we examined the role of TLR2/4 signaling on various astrocyte functions (i.e., proliferation, pro-inflammatory mediator production, regulatory mechanisms, etc) by stimulating astrocytes with potent exogenous TLR2/4 agonist, bacterial lipopolysaccharide (LPS). Newborn astrocytes were derived from WT, Tnfα−/−, Il1α−/−/Il1β−/−, and Tlr2−/−/Tlr4−/− mice as well as Sprague Dawley rats for all in vitro studies. LPS activated mRNA expression of different pro-inflammatory cytokines and chemokines in time- and concentration-dependent manners, and upregulated the proliferation of astrocytes based on increased 3H-thymidine update. Following LPS-mediated TLR2/4 activation, TNF-α and IL-1β self-regulated and modulated the expression of pro-inflammatory cytokines and chemokines. Polyclonal antibodies against TNF-α suppressed TLR2/4-mediated upregulation of astrocyte proliferation, supporting an autocrine/paracrine role of TNF-α on astrocyte proliferation. Astrocytes perform classical innate immune functions, which contradict the current paradigm that microglia are the main immune effector cells of the CNS. TNF-α plays a pivotal role in the LPS-upregulated astrocyte activation and proliferation, supporting their critical roles in in CNS pathogenesis.
Non-cell autonomous promotion of astrogenesis at late embryonic stages by constitutive YAP activation
Authors: Han Dasol , Kwon Mookwang , Lee Sun Min , Pleasure Samuel J. , Yoon Keejung
Published: April 2020

Although astrocytes have gained increased recognition as an important regulator in normal brain function and pathology, the mechanisms underlying their genesis are not well understood. In this study, we show that constitutive YAP activation by in utero introduction of a non-degradable form of the YAP gene (YAP 5SA) causes productive GFAP+ cell generation at late embryonic periods, and this activity is nuclear localization- and TEAD transcription factor-dependent. Moreover, we found that the GFAP+ cells were not YAP 5SA-expressing cells themselves but cells in the vicinity in vivo. Conditioned medium prepared from YAP 5SA-expressing cells induced GFAP+ cell production in vitro, suggesting that a soluble factor(s) was mediating the astrogenic activity of YAP 5SA. Indeed, YAP 5SA expression greatly increased CNTF and BMP4 transcription in neural progenitor cells, and a neutralizing antibody against CNTF reduced the astrogenic effects of YAP 5SA-conditioned medium. Furthermore, the YAP 5SA-expressing cells were identified as FN1+ mesenchymal cells which are responsible for the precocious astrogenesis. These results suggest a novel molecular mechanism by which YAP activation can induce astrogenesis in a non-cell autonomous manner.
Mapping of QTL for Grain Yield Components Based on a DH Population in Maize
Authors: Yang Jiwei , Liu Zonghua , Chen Qiong , Qu Yanzhi , Tang Jihua , Lübberstedt Thomas , Li Haochuan
Published: April 2020

The elite maize hybrid Zhengdan 958 (ZD958), which has high and stable yield and extensive adaptability, is widely grown in China. To elucidate the genetic basis of yield and its related traits in this elite hybrid, a set of doubled haploid (DH) lines derived from ZD958 were evaluated in four different environments at two locations over two years, and a total of 49 quantitative trait loci (QTL) and 24 pairs of epistatic interactions related to yield and yield components were detected. Furthermore, 21 QTL for six investigated phenotypic traits were detected across two different sites. Combining the results of these QTL in each environment and across both sites, three main QTL hotspots were found in chromosomal bins 2.02, 2.05–2.06, and 6.05 between the simple sequence repeat (SSR) markers umc1165-bnlg1017, umc1065-umc1637, and nc012-bnlg345, respectively. The existence of three QTL hotspots associated with various traits across multiple environments could be explained by pleiotropic QTL or multiple tightly linked QTL. These genetic regions could provide targets for genetic improvement, fine mapping, and marker-assisted selection in future studies.
A cyclic dipeptide from the Chilean hazelnut cotyledons (Gevuina avellana Mol., Proteaceae)
Authors: Schmeda-Hirschmann Guillermo , de Andrade Jean Paulo , Jiménez-Aspee Felipe , Mieres-Castro Daniel
Published: April 2020

The Chilean hazelnut (Gevuina avellana Mol., Proteaceae) is a southern South American nut consumed as a snack and included in different preparations of traditional Chilean cuisine. Recently we described the fatty acid profile, oxylipins, phenolic compounds, as well as the antioxidant capacity. The main compounds of the phenolic-enriched extract were only tentatively identified by spectrometric means. In the present work, we describe the isolation and full characterization of a cyclic dipeptide cyclo(Arg-Trp) and other compounds from the phenolic enriched extracts of the G. avellana cotyledons. Compounds were isolated by means of counter-current chromatography and structures were established by spectroscopic and spectrometric methods. This is the first report on small peptides in G. avellana and adds evidence on the possible beneficial effects of this nut in human health.
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Authors: Karadagi Ahmad , Cavedon Alex G. , Zemack Helen , Nowak Greg , Eybye Marianne E. , Zhu Xuling , Guadagnin Eleonora , White Rebecca A. , Rice Lisa M. , Frassetto Andrea L. , Strom Stephen , Jorns Carl , Martini Paolo G. V. , Ellis Ewa
Published: April 2020

Alpha 1-antitrypsin (AAT) deficiency arises from an inherited mutation in the SERPINA1 gene. The disease causes damage in the liver where the majority of the AAT protein is produced. Lack of functioning circulating AAT protein also causes uninhibited elastolytic activity in the lungs leading to AAT deficiency-related emphysema. The only therapy apart from liver transplantation is augmentation with human AAT protein pooled from sera, which is only reserved for patients with advanced lung disease caused by severe AAT deficiency. We tested modified mRNA encoding human AAT in primary human hepatocytes in culture, including hepatocytes from AAT deficient patients. Both expression and functional activity were investigated. Secreted AAT protein increased from 1,14 to 3,43 µg/ml in media from primary human hepatocytes following mRNA treatment as investigated by ELISA and western blot. The translated protein showed activity and protease inhibitory function as measured by elastase activity assay. Also, mRNA formulation in lipid nanoparticles was assessed for systemic delivery in both wild type mice and the NSG-PiZ transgenic mouse model of AAT deficiency. Systemic intravenous delivery of modified mRNA led to hepatic uptake and translation into a functioning protein in mice. These data support the use of systemic mRNA therapy as a potential treatment for AAT deficiency.
Robust high-Q filter with complete transmission by conjugated topological photonic crystals
Authors: Lin Yu-Chuan , Chou Shih-Han , Hsueh Wen-Jeng
Published: April 2020

High quality factor (High-Q) and transmission optical devices are required for various applications in the fields of physics and engineering. Critical for these applications is the realization of a structure with high-Q, complete transmission and small volume. A robust high-Q filter with complete transmission by conjugated topological photonic crystals (CTPC) is presented. The study shows that an ultra-high-Q of more than 108 with complete transmission is obtained by the CTPC with 2 μm long due to the excitation of conjugated topological edge-states (CTES). It is also found that even though the quality factor of resonances increases as the periodic number of multilayers increases, these resonances are still complete transmission. A novel concept of CTES is first proposed in this study and investigated the effect of its topological phenomenon on high quality factor via CTPC. We theoretically realize the robust high-Q and complete transmission in the CTPC, which is different from those in periodic, quasi-periodic, Fabry-Perot photonic crystals and traditional topological photonic crystals (TPC).
Dynamic network interactions among distinct brain rhythms as a hallmark of physiologic state and function
Authors: Lin Aijing , Liu Kang K. L. , Bartsch Ronny P. , Ivanov Plamen Ch.
Published: April 2020

Brain rhythms are associated with a range of physiologic states, and thus, studies have traditionally focused on neuronal origin, temporal dynamics and fundamental role of individual brain rhythms, and more recently on specific pair-wise interactions. Here, we aim to understand integrated physiologic function as an emergent phenomenon of dynamic network interactions among brain rhythms. We hypothesize that brain rhythms continuously coordinate their activations to facilitate physiologic states and functions. We analyze healthy subjects during sleep, and we demonstrate the presence of stable interaction patterns among brain rhythms. Probing transient modulations in brain wave activation, we discover three classes of interaction patterns that form an ensemble representative for each sleep stage, indicating an association of each state with a specific network of brain-rhythm communications. The observations are universal across subjects and identify networks of brain-rhythm interactions as a hallmark of physiologic state and function, providing new insights on neurophysiological regulation with broad clinical implications.
The role of an unintentional carbon dopant in resolving the controversial conductivity aspects in BiFeO3
Authors: Ameer Shaan , Jindal Kajal , Tomar Monika , Jha Pradip K. , Gupta Vinay
Published: April 2020

The electronic structure and properties of carbon incorporated BiFeO3, and resolution to the conductivity aspects of BiFeO3.
Near-infrared laser driven white light continuum generation: materials, photophysical behaviours and applications
Authors: Wu Jianhong , Zheng Guojun , Liu Xiaofeng , Qiu Jianrong
Published: April 2020

The current understanding, applications and future perspectives on near-infrared laser driven white light continuum generation in different materials are reviewed.
Portable and field-deployed surface plasmon resonance and plasmonic sensors
Authors: Masson Jean-Francois
Published: April 2020

Plasmonic sensors are portable devices that can be employed in situ for the detection of analytes in environmental sciences, clinical diagnostics, infectious diseases, food, and industrial applications.
3D spongy nanofiber structure Fe–NC catalysts built by a graphene regulated electrospinning method
Authors: Ding Weiyuan , Yu Hongquan , Tang Yu , Li Zhuxin , Liu Bijiao , Liu Dechong , Wang Yuyu , Liu Shu hong , Zhao Hong , Mandler Daniel
Published: April 2020

A Fe–NC catalyst containing carbon nanotubes, mesopores and macropores with a measurable 3D framework structure was prepared by electrospinning.
Unravelling the role of active-site isolation in reactivity and reaction pathway control for acetylene hydrogenation
Authors: Liu Siyang , Niu Yiming , Wang Yongzhao , Chen Junnan , Quan Xueping , Zhang Xia , Zhang Bingsen
Published: April 2020

Supported PdxCuy bimetallic catalysts were prepared and characterized to illustrate the active-site isolation effect on controlling the reactivity and reaction pathway of acetylene hydrogenation.
Mesoporogen-free synthesis of hierarchical HZSM-5 for LDPE catalytic cracking
Authors: Zang Yunhao , Wang Jinying , Gu Jianfeng , Qu Jiangying , Gao Feng
Published: April 2020

We show how Stöber silica spheres can be transformed into hierarchical HZSM-5 by a mesoporogen-free and modified SAC route.
Role of surface phenomena in the reaction of molecular solids: the Diels–Alder reaction on pentacene
Authors: Piranej Selma , Shelhart Sayers Michael A. W. , Deye Gregory J. , Maximoff Sergey N. , Hopwood Jonathan P. , Park Haejun , Slavsky Jean G. , Ciszek Jacob W.
Published: April 2020

Reactivity trends for molecular solids cannot be explained exclusively through topochemical phenomenon (i.e. diffusivity, reaction cavities) or electronic structure of the molecules.
Mining the Cambridge Database for theoretical chemistry. Mi-LJC: a new set of Lennard-Jones–Coulomb atom–atom potentials for the computer simulation of organic condensed matter
Authors: Gavezzotti Angelo , Lo Presti Leonardo , Rizzato Silvia
Published: April 2020

A novel, universal Lennard-Jones–Coulomb (LJC) atom–atom force field parametrization reproduces the experimental sublimation enthalpies of 377 molecular crystals drawn from the CSD.
Substrate water exchange in the S2 state of photosystem II is dependent on the conformation of the Mn4Ca cluster
Authors: de Lichtenberg Casper , Messinger Johannes
Published: April 2020

The structural flexibility of the Mn4Ca cluster in photosystem II supports the exchange of the central O5 bridge.
Gas phase reactions of iodide and bromide anions with ozone: evidence for stepwise and reversible reactions
Authors: Bhujel Mahendra , Marshall David L. , Maccarone Alan T. , McKinnon Benjamin I. , Trevitt Adam J. , da Silva Gabriel , Blanksby Stephen J. , Poad Berwyck L. J.
Published: April 2020

Ion-trap mass spectrometry maps the discrete steps in the reaction of I− and Br− with gaseous ozone.
Binary aromatic self-assembled monolayers: electrostatic properties and charge tunneling rates across the molecular framework
Authors: Asyuda Andika , Wan Xianglong , Zharnikov Michael
Published: April 2020

Mixing of non- and fluorine-substituted mercaptobiphenyls in binary monolayers not only leads to work function variation but also electrostatic effects in photoemission and tunable charge tunneling rates across the films.
Dietary supplementation of l-arginine and N-carbamylglutamate enhances duodenal barrier and mitochondrial functions and suppresses duodenal inflammation and mitophagy in suckling lambs suffering from intrauterine-growth-restriction
Authors: Zhang Hao , Ma Yi , Wang Mengzhi , Elsabagh Mabrouk , Loor Juan J. , Wang Hongrong
Published: April 2020

The work aimed at investigating the effects of N-carbamylglutamate (NCG) or l-arginine (Arg) supplementation on the duodenal mitophagy, inflammation, and barrier function in suckling lambs suffering from intrauterine-growth-retardation (IUGR).
Usage of supercritical fluid techniques to obtain bioactive alkaloid-rich extracts from cherimoya peel and leaves: extract profiles and their correlation with antioxidant properties and acetylcholinesterase and α-glucosidase inhibitory activities
Authors: Galarce-Bustos Oscar , Fernández-Ponce Mª Teresa , Montes Antonio , Pereyra Clara , Casas Lourdes , Mantell Casimiro , Aranda Mario
Published: April 2020

The wastes generated by cherimoya cultivation and processing industries should be contemplated as a valuable source of bioactive alkaloids, with potential in pharmaceutical applications for the treatment or prevention of chronic diseases.
Superior hypoglycemic activity of mulberry lacking monosaccharides is accompanied by better activation of the PI3K/Akt and AMPK signaling pathways
Authors: Long Xiao-Shan , Liao Sen-Tai , Wen Peng , Zou Yu-Xiao , Liu Fan , Shen Wei-Zhi , Hu Teng-Gen
Published: April 2020

Mulberry removed monosaccharides (FM) displayed better hypoglycemic activity than untreated mulberry (MP), which may be attributed the stronger effects of FM on activating PI3K/Akt and AMPK signaling pathways.
Computer-aided nanotoxicology: risk assessment of metal oxide nanoparticlesvianano-QSAR
Authors: Cao Jiakai , Pan Yong , Jiang Yanting , Qi Ronghua , Yuan Beilei , Jia Zhenhua , Jiang Juncheng , Wang Qingsheng
Published: April 2020

A combined experimental and computational study is performed to estimate the acute cytotoxicity and develop predictive models for MeOx NPs.
Visible light-induced aerobic oxidation of diarylalkynes to α-diketones catalyzed by copper-superoxo at room temperature
Authors: Charpe Vaibhav Pramod , Sagadevan Arunachalam , Hwang Kuo Chu
Published: April 2020

We demonstrate an environmentally benign and economically feasible method for the oxidation of stable diarylalkynes to diketones at room temperature using the inexpensive copper(ii) chloride salt and molecular oxygen under low energy visible light irradiation.
Protein–fragment complex structures derived by NMR molecular replacement
Authors: Torres Felix , Ghosh Dhiman , Strotz Dean , Chi Celestine N. , Davis Ben , Orts Julien
Published: April 2020

The NMR2 method can derive protein–fragment structures with a cooperative assignment strategy, opening an avenue for NMR-based fragment lead discovery.
Synthesis of a new Ni complex supported on CoFe2O4and its application as an efficient and green catalyst for the synthesis of bis(pyrazolyl)methane and polyhydroquinoline derivatives
Authors: Tamoradi Taiebeh , Mousavi Seyedeh Masoumeh , Mohammadi Masoud
Published: April 2020

A novel and magnetic nanocatalyst was synthesized for the synthesis of multicomponent compounds.
Metallic nickel–cobalt phosphide/multilayer graphene composite for high-performance supercapacitors
Authors: Shuai Minmin , Lin Jianhui , Wu Wenzhi , Kuang Huifang , Zhang Wengong , Ling Qidan , Chen Hong , Komarneni Sridhar
Published: April 2020

A facile and low-cost method for preparing a nickel–cobalt phosphide/multilayer graphene (MLG) (NiCoP/MLG) composite was developed in this study using a new strategy.
Magnetic headspace adsorptive microextraction using Fe3O4@Cr(OH)3nanoparticles for effective determination of volatile phenols
Authors: Timofeeva Irina , Alikina Mariya , Osmolowsky Mikhail , Osmolovskaya Olga , Bulatov Andrey
Published: April 2020

Simple and available procedure for the determination of volatile phenols in food samples based on magnetic headspace adsorptive microextraction using Fe3O4@Cr(OH)3nanoparticles followed by HPLC with fluorescence detection was developed in this work.
An ionic covalent organic polymer toward highly selective removal of anionic organic dyes in aqueous solution
Authors: Song Pengfei , Zhang Zonglian , Yu Li , Wang Pei , Wang Qian , Chen Yalun
Published: April 2020

A novel ionic COP was prepared for the highly selective removal of anionic organic dyes in aqueous solution.
NMR probe effects on trans-philicity and trans-influence ladders in square planar Pt(ii) complexes
Authors: Tsipis Athanassios C.
Published: April 2020

trans-Philicity ladders for trans-Pt(PMe3)2(X)L (X = H, CH3, CO, NH2, OH2, Cl) complexes are built by σiso X NMR descriptors. Correlations of the σiso X vs popular electronic/structural parameters of L and X demonstrate the origin of trans philicity.
Iodide-doped precious metal nanoparticles: measuring oxidative stressin vivo viaphotoacoustic imaging
Authors: Mantri Yash , Davidi Barak , Lemaster Jeanne E. , Hariri Ali , Jokerst Jesse V.
Published: April 2020

Iodide-doping of silver coated gold nanorods increases sensitivity to RONS.
Blood microRNA 202-3p associates with the risk of essential hypertension by targeting soluble ST2
Authors: Li Lu , Zhong Danrong , Xie Yudan , Yang Xinlei , Yu Zuozhong , Zhang Dangui , Jiang Xinghua , Wu Yanqing , Wu Fangqin
Published: April 2020

MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P<0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36–1.82; P<0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II.
Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome
Authors: Cheng Yiping , Sun Yan , Ji Yiming , Jiang Dongqing , Teng Guoxin , Zhou Xiaoming , Zhou Xinli , Li Guimei , Xu Chao
Published: April 2020

Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C>A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C>T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS.
The proton radius puzzle – 9 years later
Authors: Bernauer Jan C.
Published: April 2020

High-precision measurements of the proton radius via scattering, electric hydrogen spectroscopy and muonic hydrogen spectroscopy do not agree on the level of more than 5 σ. This proton radius puzzle persists now for almost a decade. This paper gives a short summary over the progress in the solution of the puzzle as well as an overview over the planned experiments to finally solve this puzzle at the interface of atomic and nuclear physics.
The 4-loop slope of the Dirac form factor
Authors: Laporta Stefano
Published: April 2020

The 4-loop contribution to the slope of the Dirac form factor in QED has been evaluated with 1100 digits of precision. The value is $ {m^2}F_1^{(4)'}(0) = {\rm{0}}{\rm{.886545673946443145836821730610315359390424032660064745}} \cdots {\left( {{\alpha \over \pi }} \right)^4} $. We have also obtained a semi-analytical fit to the numerical value. The expression contains harmonic polylogiπ2iπ iπ arithms of argument $ {e^{{{i\pi } \over 3}}},{e^{{{2i\pi } \over 3}}},{e^{{{i\pi } \over 2}}} $, one-dimensional integrals of products of complete elliptic integrals and six finite parts of master integrals, evaluated up to 4800 digits. We show the correction to the energy levels of the hydrogen atom due to the slope.
Dark Matter Indirect Detection
Authors: Profumo Stefano
Published: April 2020

This is an overview of recent developments and future prospects in the search for dark matter and new physics with astronomical and astro-particle techniques.
B-anomalies in U(2) flavor symmetry
Authors: Yamamoto Kei
Published: April 2020

We analyzed how to test flavor and helicity structures of the corresponding amplitudes in view of future data, motivated by the recent hints of lepton flavor universality violation observed in semileptonic B decays. The general assumption that non-standard effects are controlled by a U(2)5 flavor symmetry, minimally broken as in the Standard Model Yukawa sector, leads to stringent predictions on leptonic and semileptonic B decays. Future measurements will allow to prove or falsify this general hypothesis independently of its dynamical origin.
Effects of pre-corrosion, water and detergent contamination on rolling contact fatigue
Authors: Wang Wen , Hao Xiaopeng , Chen Xiaomeng , Han Bo , Zhou Xiaobo
Published: April 2020

The effects of pre-corrosion, water and detergent contamination in Shell Turbo 32 (T32) mineral oil on rolling contact fatigue (RCF) life of rollers were experimentally investigated using a home-made ball-on-roller tester. The tested roller samples were analyzed by a scanning electron microscope (SEM) and an energy dispersive spectrum (EDS). The results show that the fatigue life of the rollers is reduced by all test conditions where the negative effect is enhanced with increasing the pre-corrosion time, from surfactant detergent to water contamination and to alkaline detergent. Microscopic analysis indicates that spalls on the rolling contact track are mainly surface initiated.
A framework of BSDEs with stochastic Lipschitz coefficients
Authors: O Hun , Kim Mun-Chol , Pak Chol-Kyu
Published: April 2020

In this paper, we suggest an effective technique based on random time-change for dealing with a large class of backward stochastic differential equations (BSDEs for short) with stochastic Lipschitz coefficients. By means of random time-change, we show the relation between the BSDEs with stochastic Lipschitz coefficients and the ones with bounded Lipschitz coefficients and stopping terminal time, so they are possible to be exchanged with each other from one type to another. In other words, the stochastic Lipschitz condition is not essential in the context of BSDEs with random terminal time. Using this technique, we obtain a couple of new results of BSDEs with stochastic Lipschitz (or monotone) coefficients.
Treg und Th17-Zellen: Verwandtschaft mit Folgen
Authors: Prelog Martina
Published: April 2020

Verschiedene Helfer-T-Zellen (Th) unterscheiden sich in Merkmalen und Funktionen. Th1 werden durch IL-12/IFN-gamma induziert, exprimieren T-bet und produzieren IFN-gamma. IL-17-produzierende Th17 exprimieren RORC, tragen den Chemokinrezeptor CCR6 und werden durch IL-1beta/IL-6/IL-23 stimuliert. Regulatorische T-Zellen (Treg) werden durch IL-2/TGF-beta stimuliert, exprimieren FoxP3 und produzieren IL-10. Th1 sind physiologischerweise an der intrazellulären Erregerabwehr beteiligt, Th2 von Parasiten, Th17 von extrazellulären Bakterien und Pilzen und Treg an der peripheren T-Zell-Homöostase. Eine Dysbalance zwischen Treg/Th1 und Th17 wird mit Autoimmunprozessen in Zusammenhang gebracht. Insbesondere synoviale Th1/Th17-Zellen, die CD161 exprimieren, zeigen enge Korrelationen mit schweren Verläufen der JIA, während IL-17-produzierende Treg/Th17-Zellen pro- und antiinflammatorische Fähigkeiten vereinen können. Alle Th weisen eine hohe Plastizität in unterschiedlichen inflammatorischen Milieus auf. Es gibt Hinweise, dass eine effiziente Hemmung von bestimmten Zytokinen zu einer Rekonstitution der Treg-Funktion beiträgt, was in neuen Therapieansätzen genutzt werden könnte.
Blood Flow Volume Measurement in Cervical and Intracranial Arteries using Quantitative Magnetic Resonance Angiography and Duplex Sonography (Bocaccia) – A Prospective Observational Study
Authors: Fiedler Jiří , Reiser Martin , Košťál Petr , Kubále Jiří , Ostrý Svatopluk , Hrbáč Tomáš , Kešnerová Petra , Fadrná Táňa , Langová Kateřina , Herzig Roman , Školoudík David
Published: April 2020

Purpose Cerebral blood flow volume is an important factor for the accurate diagnosis of neurovascular diseases and treatment indication. This study aims to assess correlations of blood flow volume measurements in cervical and intracranial arteries between duplex sonography and quantitative magnetic resonance angiography (qMRA).

Materials and Methods Consecutive patients with suspicion of cerebral vascular pathology underwent qMRA and duplex sonography of cervical and intracranial arteries with measurement of blood flow volume in bilateral common (CCA), internal (ICA) and external carotid arteries, vertebral and basilar arteries, middle, anterior, posterior cerebral and posterior communicating arteries using 2 different ultrasound machines. Ten patients underwent all examinations twice. Correlations between blood flow volume measurements were evaluated using Spearman’s correlation coefficient and inter-class correlation coefficient (ICC).

Results In total, 21 subjects (15 males, mean age: 56.3 ± 6.2 years) were included in the study. Duplex sonography inter-investigator correlation was excellent (ICC = 0.972, p < 0.0001) as well as intra-investigator correlations of both qMRA and duplex sonography (ICC ˃ 0.990, p < 0.0001). Mostly high correlations were recorded between qMRA and duplex sonography in particular cervical arteries but only low to moderate correlations were obtained for intracranial arteries. The mean differences between blood flow volume measurements were 10.9 ± 8.1 % in the CCA and its branches when using qMRA and 15.0 ± 11.9 % when using duplex sonography, 13.5 ± 11.8 %/35.4 ± 34.2 % in the ICA siphon and its branches when using qMRA/duplex sonography, and 24.1 ± 19.7 %/44.9 ± 44.0 % in both vertebral arteries and the basilar artery when using qMRA/duplex sonography.

Conclusion Duplex sonography as well as qMRA allow for highly reproducible measurement of blood flow volume in cervical and intracranial arteries in routine clinical practice.
Analgetische Strahlentherapie gutartiger Erkrankungen des Skelettsystems
Authors: Niewald Marcus
Published: April 2020

Der entzündungshemmende Effekt kleiner Strahlendosen ist seit Langem bekannt und strahlenbiologisch gut untermauert. Zahlreiche retrospektive Arbeiten und einige randomisierte Studien weisen darauf hin, dass ein gutes Ansprechen bei Enthesiopathien wie der Fasciitis plantaris, der Achillodynie, der Epicondylitis und z. B. der Tendinitis calcarea der Schulter zu erzielen ist (Ansprechraten von 60–80 %). Auch bei Arthrosen weisen retrospektive Daten auf eine gute Wirksamkeit der Strahlentherapie hin, der randomisierte Nachweis wird derzeit diskutiert und ist Studienfrage. Indiziert ist die Strahlentherapie bei Patienten im Alter von > 40 Jahren und einer minimalen Anamnesedauer von 3–6 Monaten. In dieser Zeit sollten die konservativen Therapiemethoden durchgeführt worden sein. Eine Gesamtdosis von 3–6 Gy wird in zweimal wöchentlichen Sitzungen über 3 Wochen appliziert. Während und nach der Strahlentherapie kann es zu einer kurzzeitigen Schmerzzunahme kommen. Das Ansprechen ist frühestens 3 Monate nach Therapie zu beurteilen. Nebenwirkungen wie z. B. Hautreaktionen werden überaus selten gesehen. Ein vielfach diskutiertes Tumorrisiko liegt nach bisherigen Daten im Sub-Promillebereich.
Orthopädisch-unfallchirurgische Begutachtung unter besonderer Berücksichtigung von Schmerz
Authors: Middeldorf Stefan
Published: April 2020

Die Begutachtung unter besonderer Berücksichtigung von Schmerz kann nicht schematisch erfolgen. Sie muss stets auf den Einzelfall ausgerichtet sein und die gesamte biografische Anamnese mit einbeziehen, zum Beispiel auch die tatsächlich durchgeführten Therapiemaßnahmen und deren Ergebnis, Auswirkungen auf Alltagsaktivitäten sind so genau wie möglich zu ermitteln. Weiterhin ist dann eine Beurteilung des Schweregrades zur Störung ebenso durchzuführen wie eine Abgrenzung gegenüber Aggravation und Simulation. Nachvollziehbar und unter Berücksichtigung geeigneter Instrumente ist die Überprüfung der Konsistenz vorzunehmen, die Diagnosen unter Berücksichtigung geltender ICD-Kriterien und Kodierungshilfen als Vollbeweis zu ermitteln. Dabei ist zu berücksichtigen, dass Erkrankungen der Stütz- und Bewegungsorgane sehr häufig mit psychischen Komorbiditäten einhergehen. Diese gilt es zu erfassen. Darüber hinaus sind Erkrankungen der seelischen Gesundheit, die mit Schmerzen einhergehen, ebenfalls von höchster Relevanz für das Fachgebiet der Orthopädie und Unfallchirurgie und deren Begutachtung. Hier sind es vor allen Dingen die somatoformen Störungen und die chronische Schmerzstörung mit somatischen und psychischen Faktoren, die differenzialdiagnostisch abzugrenzen sind.
Entwicklung und Evaluation des Fragebogens zur Erfassung Aversiver und Protektiver Kindheitserfahrungen (APK)
Authors: Ehrenthal Johannes C. , Schauenburg Henning , Wagner Frank E. , Dinger Ulrike , Volz Matthias
Published: April 2020

Ziel der Studie Erste Evaluation des neu entwickelten Fragebogens zur Erfassung Aversiver und Protektiver Kindheitserfahrungen (APK).

Methodik In einer Stichprobe von 128 Patienten in stationärer oder teilstationärer Psychotherapie wurden die Reliabilität des APK sowie konvergente und Kriteriumsvalidität untersucht.

Ergebnisse Der APK zeigte in seinen Gesamtskalen und in den meisten Subskalen eine hohe bis sehr hohe interne Konsistenz, deutliche Hinweise auf konvergente Validität, sowie Zusammenhänge mit Depressivität und Bindungsunsicherheit. Insbesondere die Skala zu protektiven Kindheitserfahrungen klärte eigenständige Varianz in Bezug auf Validitätsaspekte auf.

Schlussfolgerung Mit dem APK liegt ein erweitertes Instrument zur Traumadiagnostik vor. Neben der Erfassung aversiver Kindheitserfahrungen hat die Möglichkeit des gleichzeitigen Erfassens protektiver Kindheitserfahrungen für Forschung wie Praxis eine besondere Bedeutung.
Der dggö Ausschuss „Gesundheitswirtschaft und E-Health“ – Rechtliche Aspekte der Digitalisierung, Einsatz von eHealth-Systemen und die gesundheitsökonomische Evaluation von eHealth-Anwendungen
Authors: Ziese Gabriele , Mähs Mareike , Fachinger Uwe , Lux Thomas , Müller-Mielitz Stefan
Published: April 2020

Am 28. und 29. Oktober 2019 fand die 31. Sitzung des Ausschusses „Gesundheitswirtschaft und eHealth“ der Deutschen Gesellschaft für Gesundheitsökonomie dggö e. V. statt. Gastgeber der Veranstaltungen waren Herr Prof. Dr. Frerichs und Herr Prof. Dr. Fachinger am Institut für Gerontologie an der Universität Vechta.