bluuebunny/crossref_metadata_2025_split huggingface dataset:
A RNA producing DNA hydrogel as a platform for a high performance RNA interference system
Authors: Song Jaejung , Lee Minhyuk , Kim Taeyoung , Na Jeongkyeong , Jung Yebin , Jung Gyoo Yeol , Kim Sungjee , Park Nokyoung 
Published: October 2018

AbstractRNA interference (RNAi) is a mechanism in which small interfering RNA (siRNA) silences a target gene. Herein, we describe a DNA hydrogel capable of producing siRNA and interfering with protein expression. This RNAi-exhibiting gel (termed I-gel for interfering gel) consists of a plasmid carrying the gene transcribing siRNA against the target mRNA as part of the gel scaffold. The RNAi efficiency of the I-gel has been confirmed by green fluorescent protein (GFP) expression assay and RNA production quantification. The plasmid stability in the I-gel results in an 8-times higher transcription efficiency than that of the free plasmid. We further applied the I-gel to live cells and confirmed its effect in interfering with the GFP expression. The I-gel shows higher RNAi effect than plasmids in free form or complexed with Lipofectamine. This nanoscale hydrogel, which is able to produce RNA in a cell, provides a platform technology for efficient RNAi system.
Quantum effects on dislocation motion from ring-polymer molecular dynamics
Authors: Freitas Rodrigo , Asta Mark , Bulatov Vasily V. 
Published: October 2018

AbstractQuantum motion of atoms known as zero-point vibration was recently proposed to explain a long-standing discrepancy between theoretically computed and experimentally measured low-temperature plastic strength of iron and possibly other metals with high atomic masses. This finding challenges the traditional notion that quantum motion of atoms is relatively unimportant in solids comprised of heavy atoms. Here we report quantum dynamic simulations of quantum effects on dislocation motion within the exact formalism of Ring-Polymer Molecular Dynamics (RPMD). To extend the reach of quantum atomistic simulations to length and time scales relevant for extended defects in materials, we implemented RPMD in the open-source code LAMMPS thus making the RPMD method widely available to the community. We use our RPMD/LAMMPS approach for direct calculations of dislocation mobility and its effects on the yield strength of α-iron. Our simulation results establish that quantum effects are noticeable at temperatures below 50 K but account for only a modest (≈13% at T = 0 K) overall reduction in the Peierls barrier, at variance with the factor of two reduction predicted earlier based on the more approximate framework of harmonic transition state theory. Our results confirm that zero-point vibrations provide ample additional agitation for atomic motion that increases with decreasing temperature, however its enhancing effect on dislocation mobility is largely offset by an increase in the effective atom size, an effect known as quantum dispersion that has not been accounted for in the previous calculations.
Efficient quantum simulation of photosynthetic light harvesting
Authors: Wang Bi-Xue , Tao Ming-Jie , Ai Qing , Xin Tao , Lambert Neill , Ruan Dong , Cheng Yuan-Chung , Nori Franco , Deng Fu-Guo , Long Gui-Lu 
Published: October 2018

AbstractNear-unity energy transfer efficiency has been widely observed in natural photosynthetic complexes. This phenomenon has attracted broad interest from different fields, such as physics, biology, chemistry, and material science, as it may offer valuable insights into efficient solar-energy harvesting. Recently, quantum coherent effects have been discovered in photosynthetic light harvesting, and their potential role on energy transfer has seen the heated debate. Here, we perform an experimental quantum simulation of photosynthetic energy transfer using nuclear magnetic resonance (NMR). We show that an N-chromophore photosynthetic complex, with arbitrary structure and bath spectral density, can be effectively simulated by a system with log2N qubits. The computational cost of simulating such a system with a theoretical tool, like the hierarchical equation of motion, which is exponential in N, can be potentially reduced to requiring a just polynomial number of qubits N using NMR quantum simulation. The benefits of performing such quantum simulation in NMR are even greater when the spectral density is complex, as in natural photosynthetic complexes. These findings may shed light on quantum coherence in energy transfer and help to provide design principles for efficient artificial light harvesting.
Targeting of the Yersinia pestis F1 capsular antigen by innate-like B1b cells mediates a rapid protective response against bubonic plague
Authors: Levy Yinon , Vagima Yaron , Tidhar Avital , Aftalion Moshe , Gur David , Nili Uri , Chitlaru Theodore , Zauberman Ayelet , Mamroud Emanuelle 
Published: October 2018

AbstractThe generation of adaptive immunity by vaccination is usually a prolonged process that requires multiple dosing over several months. Hence, vaccines are administered for disease prevention a relatively long time prior to possible infection as opposed to post-exposure prophylaxis, which typically requires rapid intervention such as antibiotic therapy. The emergence of pathogens resistant to common antibiotic treatments has prompted the search for alternative therapeutic strategies. We previously demonstrated that vaccination of mice with the F1 capsular antigen ofYersinia pestiselicits specific and effective yet, unexpectedly, rapid anti-plague immunity. Here, we show by applying genetic and immunological approaches that the F1 antigen is targeted by peritoneal innate-like B1b cells that generate a prompt T-independent (TI) anti-F1 humoral response. The rapid F1-mediated defense response was diminished inXid(Btkm) mice in which B1 cell numbers and activity are limited. Binding of fluorophore-labeled F1 to peritoneal B1b cells was detected as soon as 6 h post vaccination, emphasizing the high speed of this process. By assessing the ability to achieve rapid immunity with monomerized F1, we show that the natural polymeric structure of F1 is essential for (i) rapid association with peritoneal B1b cells, (ii) early induction of anti-F1 titers and (iii) rapid TI immunity in the mouse model of bubonic plague. These observations shed new light on the potential of novel as well as well-known protective antigens in generating rapid immunity and could be implemented in the rational design of future vaccines.
Estimating the potential yield and ETc of winter wheat across Huang-Huai-Hai Plain in the future with the modified DSSAT model
Authors: Tang Xiaopei , Song Ni , Chen Zhifang , Wang Jinglei , He Jianqiang 
Published: October 2018

AbstractThe DSSAT model, integrated the calibrated Hargreaves ET model and dynamic crop coefficient, was run with the generated weather data by SDSM4.2 and CanESM2 to predict the potential yield and crop water requirement (ETC) of winter wheat in the Huang-Huai-Hai Plain in China under RCP4.5 and RCP8.5 scenarios. The results showed that the spatial distribution of potential yield in the future under RCP4.5 and RCP8.5 were similar, characterized by an increasing trend from the northwest inland to the southeast coast. The spatial distribution of ETCdecreased gradually from the Shandong Peninsula to the surrounding area, and the minimum ETCwas observed in the southern part of Huang-Huai-Hai Plain. The potential yield, ETC,and effective precipitation during winter wheat growing seasons might increase in the future under RCP4.5, while irrigation water requirements (IWR) would decrease. Under RCP8.5, the effective precipitation during the wheat growing seasons decreased first and then increased. However, the potential yield, ETC, and IWR of winter wheat increased first and then decreased. This study can provide some scientific evidence to mitigate the negative effects of climate change on agricultural production and water use in the Huang-Huai-Hai Plain.
Influence of the Occipital Orientation on Cervical Sagittal Alignment: A Prospective Radiographic Study on 335 Normal Subjects
Authors: Zhu Weiguo , Sha Shifu , Liu Zhen , Li Yang , Xu Leilei , Zhang Wen , Qiu Yong , Zhu Zezhang 
Published: October 2018

AbstractCervical sagittal alignment is considered to have a special role in the pathogenesis and evaluation of cervical diseases. Previous studies have demonstrated that cervical sagittal alignment is correlated with thoracolumbar and pelvic alignments. As the direct anatomical structures connect to the cervical region, however, no parameters in the occiput have been reported to be intimately related to the alignment of the cervical spine. A retrospective radiographic study of 335 individuals (182 males and 153 females) between 18 and 60 years of age was performed between January 2007 and January 2016. The occipital incidence (OI), occipital slope (OS), occipital tilt (OT), C0-C2 angle, C2-C7 angle, C0-C7 angle, T1 slope and thoracic kyphosis were measured in every individual. The mean values of the occipital parameters of the cohort were 34.6° ± 3.1° for OI, 23.4° ± 7.4° for OS, and 11.8° ± 3.3° for OT. OI was constant throughout three age groups. No significant differences were noted between males and females. In addition, strong correlations were found between the occipital parameters and cervical parameters. The occipital orientation was an important factor that influenced the cervical sagittal alignment.
Understanding molecular consequences of putative drug resistant mutations in Mycobacterium tuberculosis
Authors: Portelli Stephanie , Phelan Jody E. , Ascher David B. , Clark Taane G. , Furnham Nicholas 
Published: October 2018

AbstractGenomic studies of Mycobacterium tuberculosis bacteria have revealed loci associated with resistance to anti-tuberculosis drugs. However, the molecular consequences of polymorphism within these candidate loci remain poorly understood. To address this, we have used computational tools to quantify the effects of point mutations conferring resistance to three major anti-tuberculosis drugs, isoniazid (n = 189), rifampicin (n = 201) and D-cycloserine (n = 48), within their primary targets, katG, rpoB, and alr. Notably, mild biophysical effects brought about by high incidence mutations were considered more tolerable, while different structural effects brought about by haplotype combinations reflected differences in their functional importance. Additionally, highly destabilising mutations such as alr Y388, highlighted a functional importance of the wildtype residue. Our qualitative analysis enabled us to relate resistance mutations onto a theoretical landscape linking enthalpic changes with phenotype. Such insights will aid the development of new resistance-resistant drugs and, via an integration into predictive tools, in pathogen surveillance.
All-optical fiber optic coherent amplifier
Authors: Goodarzi A. , Ghanaatshoar M. , Mozafari M. 
Published: October 2018

AbstractA fiber optic-based all-optical amplifier is designed by using the coherent perfect absorption phenomenon. For this purpose, we use a deposited chromium thin layer as an absorbent material on the cross-section of a PM fiber. By placing another fiber in front of the deposited one, we show that by controlling the relative phase between the two counter-propagating beams, total absorbance can be controlled. In the interaction of two beams with unequal intensities, absorption control can be associated with amplification for the weaker beam. By using this mechanism, the effect of an external phase-shifting parameter can be amplified. Furthermore, it is possible to amplify a small signal riding on a CW background through this all-optical procedure.
Dynamical and Thermodynamical Influences of the Maritime Continent on ENSO Evolution
Authors: Zhang Tuantuan , Huang Bohua , Yang Song , Chen Junwen , Jiang Xingwen 
Published: October 2018

AbstractEl Niño-Southern Oscillation (ENSO) exerts tremendous influences on the global climate. Through dynamic lifting and thermal forcing, the Maritime Continent (MC) plays an important role in affecting global atmospheric circulation. In spite of the extensive studies on ENSO mechanisms, the influence of MC on the characteristics of ENSO life cycle remains unclear. Our coupled model experiments reveal that the absence of the MC land contributes to a strong ENSO asymmetry and a weakened nonlinear atmospheric response to the combined seasonal and interannual SST variations (i.e. the combination mode) that prolongs the warm events, resulting in a reduction of ENSO frequency. On the other hand, our experiments suggest that the global climate model applied (NCAR CESM) overestimates the MC topographic uplifting effect on ENSO simulation. Overall, this study provides a new physical insight into the nature of the MC influence on ENSO evolution.
Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models
Authors: Brooks Harold B. , Meier Timothy I. , Geeganage Sandaruwan , Fales Kevin R. , Thrasher Kenneth J. , Konicek Susan A. , Spencer Charles D. , Thibodeaux Stefan , Foreman Robert T. , Hui Yu-Hua , Roth Kenneth D. , Qian Yue-Wei , Wang Tao , Luo Shuang , Torrado Alicia , Si Chong , Toth James L. , Mc Cowan Jefferson R. , Frimpong Kwame , Lee Matthew R. , Dally Robert D. , Shepherd Timothy A. , Durham Timothy B. , Wang Yong , Wu Zhipei , Iversen Philip W. , Njoroge F. George 
Published: October 2018

AbstractAICARFT is a folate dependent catalytic site within the ATIC gene, part of the purine biosynthetic pathway, a pathway frequently upregulated in cancers. LSN3213128 is a potent (16 nM) anti-folate inhibitor of AICARFT and selective relative to TS, SHMT1, MTHFD1, MTHFD2 and MTHFD2L. Increases in ZMP, accompanied by activation of AMPK and cell growth inhibition, were observed with treatment of LY3213128. These effects on ZMP and proliferation were dependent on folate levels. In human breast MDA-MB-231met2 and lung NCI-H460 cell lines, growth inhibition was rescued by hypoxanthine, but not in the A9 murine cell line which is deficient in purine salvage. In athymic nude mice, LSN3213128 robustly elevates ZMP in MDA-MB-231met2, NCI-H460 and A9 tumors in a time and dose dependent manner. Significant tumor growth inhibition in human breast MDA-MB231met2 and lung NCI-H460 xenografts and in the syngeneic A9 tumor model were observed with oral administration of LSN3213128. Strikingly, AMPK appeared activated within the tumors and did not change even at high levels of intratumoral ZMP after weeks of dosing. These results support the evaluation of LSN3213128 as an antineoplastic agent.
N-Acetylglutamate Synthase Deficiency Due to a Recurrent Sequence Variant in the N-acetylglutamate Synthase Enhancer Region
Authors: Williams Monique , Burlina Alberto , Rubert Laura , Polo Giulia , Ruijter George J. G. , van den Born Myrthe , Rüfenacht Véronique , Haskins Nantaporn , van Zutven Laura J. C. M. , Tuchman Mendel , Saris Jasper J. , Häberle Johannes , Caldovic Ljubica 
Published: October 2018

AbstractN-acetylglutamate synthase deficiency (NAGSD, MIM #237310) is an autosomal recessive disorder of the urea cycle that results from absent or decreased production of N-acetylglutamate (NAG) due to either decreased NAGS gene expression or defective NAGS enzyme. NAG is essential for the activity of carbamylphosphate synthetase 1 (CPS1), the first and rate-limiting enzyme of the urea cycle. NAGSD is the only urea cycle disorder that can be treated with a single drug, N-carbamylglutamate (NCG), which can activate CPS1 and completely restore ureagenesis in patients with NAGSD. We describe a novel sequence variant NM_153006.2:c.-3026C > T in the NAGS enhancer that was found in three patients from two families with NAGSD; two patients had hyperammonemia that resolved upon treatment with NCG, while the third patient increased dietary protein intake after initiation of NCG therapy. Two patients were homozygous for the variant while the third patient had the c.-3026C > T variant and a partial uniparental disomy that encompassed the NAGS gene on chromosome 17. The c.-3026C > T sequence variant affects a base pair that is highly conserved in vertebrates; the variant is predicted to be deleterious by several bioinformatics tools. Functional assays in cultured HepG2 cells demonstrated that the c.-3026C > T substitution could result in reduced expression of the NAGS gene. These findings underscore the importance of analyzing NAGS gene regulatory regions when looking for molecular causes of NAGSD.
Current-driven production of vortex-antivortex pairs in planar Josephson junction arrays and phase cracks in long-range order
Authors: Estellés-Duart Francisco , Ortuño Miguel , Somoza Andrés M. , Vinokur Valerii M. , Gurevich Alex 
Published: October 2018

AbstractProliferation of topological defects like vortices and dislocations plays a key role in the physics of systems with long-range order, particularly, superconductivity and superfluidity in thin films, plasticity of solids, and melting of atomic monolayers. Topological defects are characterized by their topological charge reflecting fundamental symmetries and conservation laws of the system. Conservation of topological charge manifests itself in extreme stability of static topological defects because destruction of a single defect requires overcoming a huge energy barrier proportional to the system size. However, the stability of driven topological defects remains largely unexplored. Here we address this issue and investigate numerically a dynamic instability of moving vortices in planar arrays of Josephson junctions. We show that a single vortex driven by sufficiently strong current becomes unstable and destroys superconductivity by triggering a chain reaction of self-replicating vortex-antivortex pairs forming linear of branching expanding patterns. This process can be described in terms of propagating phase cracks in long-range order with far-reaching implications for dynamic systems of interacting spins and atoms hosting magnetic vortices and dislocations.
E-cadherin loss induces targetable autocrine activation of growth factor signalling in lobular breast cancer
Authors: Teo Katy , Gómez-Cuadrado Laura , Tenhagen Milou , Byron Adam , Rätze Max , van Amersfoort Miranda , Renes Jojanneke , Strengman Eric , Mandoli Amit , Singh Abhishek A. , Martens Joost H. , Stunnenberg Hendrik G. , van Diest Paul J. , Brunton Valerie G. , Derksen Patrick W. B. 
Published: October 2018

AbstractDespite the fact that loss of E-cadherin is causal to the development and progression of invasive lobular carcinoma (ILC), options to treat this major breast cancer subtype are limited if tumours develop resistance to anti-oestrogen treatment regimens. This study aimed to identify clinically targetable pathways that are aberrantly active downstream of E-cadherin loss in ILC. Using a combination of reverse-phase protein array (RPPA) analyses, mRNA sequencing, conditioned medium growth assays and CRISPR/Cas9-based knock-out experiments, we demonstrate that E-cadherin loss causes increased responsiveness to autocrine growth factor receptor (GFR)-dependent activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signalling. Autocrine activation of GFR signalling and its downstream PI3K/Akt hub was independent of oncogenic mutations in PIK3CA, AKT1 or PTEN. Analyses of human ILC samples confirmed growth factor production and pathway activity. Pharmacological inhibition of Akt using AZD5363 or MK2206 resulted in robust inhibition of cell growth and survival of ILC cells, and impeded tumour growth in a mouse ILC model. Because E-cadherin loss evokes hypersensitisation of PI3K/Akt activation independent of oncogenic mutations in this pathway, we propose clinical intervention of PI3K/Akt in ILC based on functional E-cadherin inactivation, irrespective of activating pathway mutations.
Electrodeposited metal-organic framework films as self-assembled hierarchically superstructured supports for stable omniphobic surface coatings
Authors: Sablowski Jakob , Linnemann Julia , Hempel Simone , Hoffmann Volker , Unz Simon , Beckmann Michael , Giebeler Lars 
Published: October 2018

AbstractSuperhierarchically rough films are rapidly synthesised on metal substrates via electrochemically triggered self-assembly of meso/macroporous-structured metal-organic framework (MOF) crystals. These coatings are applied to immobilise a functional oil with low surface energy to provide stable coatings repellent to a wide range of hydrophobic as well as hydrophilic fluids. Such omniphobic surfaces are highly interesting for several applications such as anti-fouling, anti-icing, and dropwise condensation, and become easily scalable with the presented bottom-up fabrication approach. As investigated by environmental scanning electron microscopy (ESEM), the presented perfluorinated oil-infused Cu-BTC coating constitutes of a flat liquid-covered surface with protruding edges of octahedral superstructured MOF crystals. Water and non-polar diiodomethane droplets form considerably high contact angles and even low-surface-tension fluids, e.g. acetone, form droplets on the infused coating. The repellent properties towards the test fluids do not change upon extended water spraying in contrast to oil-infused porous copper oxide or native copper surfaces. It is discussed in detail, how the presented electrodeposited MOF films grow and provide a proficient surface morphology to stabilise the functional oil film due to hemiwicking.
Evaluation of different mucosal microbiota leads to gut microbiota-based prediction of type 1 diabetes in NOD mice
Authors: Hu Youjia , Peng Jian , Li Fangyong , Wong F. Susan , Wen Li 
Published: October 2018

AbstractType 1 diabetes (T1D) is a progressive autoimmune disease in which the insulin-producing beta cells are destroyed by auto-reactive T cells. Recent studies suggest that microbiota are closely associated with disease development. We studied gut, oral and vaginal microbiota longitudinally in non-obese diabetic (NOD) mice. We showed that the composition of microbiota is very different at the different mucosal sites and between young and adult mice. Gut microbiota are more diverse than oral or vaginal microbiota and the changes were more evident in the mice before and after onset of diabetes. Using alpha-diversity, Gram-positive/Gram-negative ratio as well as the relative abundance ofBacteroidetesandErysipelotrichaceaein the gut microbiota, at 8 weeks of age, we formulated a predictive algorithm for T1D development in a cohort of 63 female NOD mice. Using this algorithm, we obtained 80% accuracy of prediction of diabetes onset, in two independent experiments, totaling 29 mice, with Area Under the Curve of 0.776 by ROC analysis. Interestingly, we did not find differences in peripheral blood mononuclear cells of the mice at 8 weeks of age, regardless of later diabetes development. Our results suggest that the algorithm could potentially be used in early prediction of future T1D development.