bluuebunny/crossref_metadata_2025_split huggingface dataset:
A suite of phenotypic assays to ensure pipeline diversity when prioritizing drug-like Cryptosporidium growth inhibitors
Authors: Jumani Rajiv S. , Hasan Muhammad M. , Stebbins Erin E. , Donnelly Liam , Miller Peter , Klopfer Connor , Bessoff Kovi , Teixeira Jose E. , Love Melissa S. , McNamara Case W. , Huston Christopher D. 
Published: April 2019

AbstractCryptosporidiosis is a leading cause of life-threatening diarrhea in children, and the only currently approved drug is ineffective in malnourished children and immunocompromised people. Large-scale phenotypic screens are ongoing to identify anticryptosporidial compounds, but optimal approaches to prioritize inhibitors and establish a mechanistically diverse drug development pipeline are unknown. Here, we present a panel of medium-throughput mode of action assays that enable testing of compounds in several stages of theCryptosporidiumlife cycle. Phenotypic profiles are given for thirty-nine anticryptosporidials. Using a clustering algorithm, the compounds sort by phenotypic profile into distinct groups of inhibitors that are either chemical analogs (i.e. same molecular mechanism of action (MMOA)) or known to have similar MMOA. Furthermore, compounds belonging to multiple phenotypic clusters are efficacious in a chronic mouse model of cryptosporidiosis. This suite of phenotypic assays should ensure a drug development pipeline with diverse MMOA without the need to identify underlying mechanisms.
Optimizing reaction paths for methanol synthesis from CO2 hydrogenation via metal-ligand cooperativity
Authors: Chen Yizhen , Li Hongliang , Zhao Wanghui , Zhang Wenbo , Li Jiawei , Li Wei , Zheng Xusheng , Yan Wensheng , Zhang Wenhua , Zhu Junfa , Si Rui , Zeng Jie 
Published: April 2019

AbstractAs diversified reaction paths exist over practical catalysts towards CO2 hydrogenation, it is highly desiderated to precisely control the reaction path for developing efficient catalysts. Herein, we report that the ensemble of Pt single atoms coordinated with oxygen atoms in MIL-101 (Pt1@MIL) induces distinct reaction path to improve selective hydrogenation of CO2 into methanol. Pt1@MIL achieves the turnover frequency number of 117 h−1 in DMF under 32 bar at 150 °C, which is 5.6 times that of Ptn@MIL. Moreover, the selectivity for methanol is 90.3% over Pt1@MIL, much higher than that (13.3%) over Ptn@MIL with CO as the major product. According to mechanistic studies, CO2 is hydrogenated into HCOO* as the intermediate for Pt1@MIL, whereas COOH* serves as the intermediate for Ptn@MIL. The unique reaction path over Pt1@MIL not only lowers the activation energy for the enhanced catalytic activity, but also contributes to the high selectivity for methanol.
Synthesizing a ν=2/3 fractional quantum Hall effect edge state from counter-propagating ν=1 and ν=1/3 states
Authors: Cohen Yonatan , Ronen Yuval , Yang Wenmin , Banitt Daniel , Park Jinhong , Heiblum Moty , Mirlin Alexander D. , Gefen Yuval , Umansky Vladimir 
Published: April 2019

AbstractTopological edge-reconstruction occurs in hole-conjugate states of the fractional quantum Hall effect. The frequently studied filling factor, ν = 2/3, was originally proposed to harbor two counter-propagating modes: a downstream v = 1 and an upstream v = 1/3. However, charge equilibration between these two modes always led to an observed downstream v = 2/3 charge mode accompanied by an upstream neutral mode. Here, we present an approach to synthetize a v = 2/3 edge mode from its basic counter-propagating charged constituents, allowing a controlled equilibration between the two counter-propagating charge modes. This platform is based on a carefully designed double-quantum-well, which hosts two populated electronic sub-bands (lower and upper), with corresponding filling factors, vl and vu. By separating the 2D plane to two gated intersecting halves, each with different fillings, counter-propagating chiral modes can be formed along the intersection line. Equilibration between these modes can be controlled with the top gates’ voltage and the magnetic field.
Current forest carbon fixation fuels stream CO2 emissions
Authors: Campeau A. , Bishop K. , Amvrosiadi N. , Billett M. F. , Garnett M. H. , Laudon H. , Öquist M. G. , Wallin M. B. 
Published: April 2019

AbstractStream CO2 emissions contribute significantly to atmospheric climate forcing. While there are strong indications that groundwater inputs sustain these emissions, the specific biogeochemical pathways and timescales involved in this lateral CO2 export are still obscure. Here, via an extensive radiocarbon (14C) characterisation of CO2 and DOC in stream water and its groundwater sources in an old-growth boreal forest, we demonstrate that the 14C-CO2 is consistently in tune with the current atmospheric 14C-CO2 level and shows little association with the 14C-DOC in the same waters. Our findings thus indicate that stream CO2 emissions act as a shortcut that returns CO2 recently fixed by the forest vegetation to the atmosphere. Our results expose a positive feedback mechanism within the C budget of forested catchments, where stream CO2 emissions will be highly sensitive to changes in forest C allocation patterns associated with climate and land-use changes.
The neural development of empathy is sensitive to caregiving and early trauma
Authors: Levy Jonathan , Goldstein Abraham , Feldman Ruth 
Published: April 2019

AbstractEmpathy is a core human social ability shaped by biological dispositions and caregiving experiences; yet the mechanisms sustaining maturation of the neural basis of empathy are unknown. Here, we followed eighty-four children, including 42 exposed to chronic war-related adversity, across the first decade of life, and assessed parenting, child temperament, and anxiety disorders as contributors to the neural development of empathy. At preadolescence, participants underwent magenetoencephalography while observing others’ distress. Preadolescents show a widely-distributed response in structures implicating the overlap of affective (automatic) and cognitive (higher-order) empathy, which is predicted by mother-child synchrony across childhood. Only temperamentally reactive young children growing in chronic adversity, particularly those who later develop anxiety disorders, display additional engagement of neural nodes possibly reflecting hyper-mentalizing and ruminations over the distressing stimuli. These findings demonstrate how caregiving patterns fostering interpersonal resonance, reactive temperament, and chronic adversity combine across early development to shape the human empathic brain.
Conductivity and lithiophilicity gradients guide lithium deposition to mitigate short circuits
Authors: Pu Jun , Li Jiachen , Zhang Kai , Zhang Tao , Li Chaowei , Ma Haixia , Zhu Jia , Braun Paul V. , Lu Jun , Zhang Huigang 
Published: April 2019

AbstractLithium metal anodes hold great promise to enable high-energy battery systems. However, lithium dendrites at the interface between anode and separator pose risks of short circuits and fire, impeding the safe application. In contrast to conventional approaches of suppressing dendrites, here we show a deposition-regulating strategy by electrically passivating the top of a porous nickel scaffold and chemically activating the bottom of the scaffold to form conductivity/lithiophilicity gradients, whereby lithium is guided to deposit preferentially at the bottom of the anode, safely away from the separator. The resulting lithium anodes significantly reduce the probability of dendrite-induced short circuits. Crucially, excellent properties are also demonstrated at extremely high capacity (up to 40 mAh cm−2), high current density, and/or low temperatures (down to −15 °C), which readily induce dendrite shorts in particular. This facile and viable deposition-regulating strategy provides an approach to preferentially deposit lithium in safer positions, enabling a promising anode for next-generation lithium batteries.
Implementation of distortion symmetry for the nudged elastic band method with DiSPy
Authors: Munro Jason M. , Liu Vincent S. , Gopalan Venkatraman , Dabo Ismaila 
Published: April 2019

AbstractThe nudged elastic band (NEB) method is a commonly used approach for the calculation of minimum energy pathways of kinetic processes. However, the final paths obtained rely heavily on the nature of the initially chosen path. This often necessitates running multiple calculations with differing starting points in order to obtain accurate results. Recently, it has been shown that the NEB algorithm can only conserve or raise the distortion symmetry exhibited by an initial pathway. Using this knowledge, symmetry-adapted perturbations can be generated and used as a tool to systematically lower the initial path symmetry, enabling the exploration of other low-energy pathways that may exist. Here, the group and representation theory details behind this process are presented and implemented in a standalone piece of software (DiSPy). The method is then demonstrated by applying it to the calculation of ferroelectric switching pathways in LiNbO3. Previously reported pathways are more easily obtained, with new paths also being found which involve a higher degree of atomic coordination.
Investigation of chloride-induced depassivation of iron in alkaline media by reactive force field molecular dynamics
Authors: DorMohammadi Hossein , Pang Qin , Murkute Pratik , Árnadóttir Líney , Isgor O. Burkan 
Published: April 2019

AbstractThe passivity of iron in alkaline media enables the use of carbon steel as reinforcement in concrete, which makes up the majority of modern infrastructure. However, chlorides, mainly from deicing chemicals or marine salts, can break down the iron passive film and cause active corrosion. Despite recent advances in nanoscale characterization of iron passivity, significant gaps exist in our understanding of the dynamic processes that lead to the chloride-induced breakdown of passive films. In this study, chloride-induced depassivation of iron in pH 13.5 NaOH solution is studied using reactive force field molecular dynamics. The depassivation process initiates by local acidification of the electrolyte near the film surface, followed by iron dissolution into the electrolyte, and iron vacancy formation in the passive film. Chlorides do not penetrate the passive film, but mainly act as a catalyst for the formation of iron vacancies, which diffuse toward the metal/oxide interface, suggesting a depassivation mechanism consistent with the point-defect model.
Magnetic states of coupled spin tubes with frustrated geometry in CsCrF4
Authors: Hagihala Masato , Hayashida Shohei , Avdeev Maxim , Manaka Hirotaka , Kikuchi Hodaka , Masuda Takatsugu 
Published: April 2019

AbstractWhen a theoretical model is realized in nature, small perturbation terms play important roles in the selection of the ground state in geometrically frustrated magnets. In case of a triangular spin tube, the two-dimensional network of the inter-tube interaction forms characteristic lattices. Among them Kagome-Triangular (KT) lattice is known to exhibit an enriched phase diagram including various types of non-trivial structures: non-coplanar cuboc structure, coplanar 120° structure with the two-dimensional propagation vector of $${\boldsymbol{k}}_{2\mathrm{D}}$$

k

2
D

= (0, 0), $$\sqrt 3 \times \sqrt 3$$

3

×

3

structure with $${\boldsymbol{k}}_{2{\mathrm{D}}}$$

k

2

D

= (1/3, 1/3), and incommensurate structure. We investigate the magnetic state in the model material CsCrF4 by using neutron diffraction technique. Combination of representation analysis and Rietveld refinement reveals that a very rare structure, i.e., a quasi-120° structure with $${\boldsymbol{k}}_{2{\mathrm{D}}}$$

k

2

D

= (1/2, 0), is realized at the base temperature. The classical calculation of the phase diagram elucidates that CsCrF4 is the first experimental realization of the KT lattice having ferromagnetic Kagome bond. A single-ion anisotropy and Dzyaloshinskii-Moriya interaction play key roles in the selection of the ground state. Furthermore, a successive phase transition having an intermediate state represented by $${\boldsymbol{k}}_{2{\mathrm{D}}}$$

k

2

D

= (1/3, 1/3) is observed. The intermediate state is a partially ordered 120° structure which is induced by thermal fluctuation.
Mistletoe extract Fraxini inhibits the proliferation of liver cancer by down-regulating c-Myc expression
Authors: Yang Peiying , Jiang Yan , Pan Yong , Ding Xiaoping , Rhea Patrea , Ding Jibin , Hawke David H. , Felsher Dean , Narla Goutham , Lu Zhimin , Lee Richard T. 
Published: April 2019

AbstractMistletoe (Viscum album) is a type of parasitic plant reported to have anticancer activity including in hepatocellular carcinoma (HCC). However, the mechanism of mistletoe’s anticancer activity, and its effectiveness in treating HCC are not fully understood. We report here that mistletoe extracts, including Fraxini (grown on ash trees) and Iscador Q and M (grown on oak and maple trees), exert strong antiproliferative activity in Hep3B cells, with median inhibitory concentrations (IC50) of 0.5 µg/mL, 7.49 µg/mL, and 7.51 µg/mL, respectively. Results of Reversed Phase Proteomic Array analysis (RPPA) suggests that Fraxini substantially down-regulates c-Myc expression in Hep3B cells. Fraxini-induced growth inhibition (at a concentration of 1.25 μg/ml) was less pronounced in c-Myc knockdown Hep3B cells than in control cells. Furthermore, in the Hep3B xenograft model, Fraxini-treated (8 mg/kg body weight) mice had significantly smaller tumors (34.6 ± 11.9 mm3) than control mice (161.6 ± 79.4 mm3, p < 0.036). Similarly, c-Myc protein expression was reduced in Fraxini treated Hep3B cell xenografts compared to that of control mice. The reduction of c-Myc protein levels in vitro Hep3B cells appears to be mediated by the ubiquitin-proteasome system. Our results suggest the importance of c-Myc in Fraxini’s antiproliferative activity, which warrants further investigation.
Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway
Authors: Lübbehüsen Christoph , Lüke Julian , Seeling Carolin , Mellert Kevin , Marienfeld Ralf , von Baer Alexandra , Schultheiss Markus , Möller Peter , Barth Thomas F. E. 
Published: April 2019

AbstractThe giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that is composed of mononuclear stroma cells, scattered macrophages, and multinucleated osteoclast-like giant cells which cause pathologic osteolysis. The stroma cells represent the neoplastic population of the tumor and are characterized by the H3F3A mutation G34W. This point mutation is regarded as the driver mutation of GCTB. We have established three new stable H3F3A mutated GCTB cell lines: U-GCT1, U-GCT2, and U-GCT3M. MK-1775 is a Wee1-kinase inhibitor which has been used for blocking of sarcoma growth. In the cell lines we detected Wee1, Cdk1, Cyclin B1, H3K36me3, and Rrm2 as members of the Wee1 pathway. We analyzed the effect of MK-1775 and gemcitabine, alone and in combination, on the growth of the cell lines. The cell lines showed a significant reduction in cell proliferation when treated with MK-1775 or gemcitabine. The combination of both agents led to a further significant reduction in cell proliferation compared to the single agents. Immunohistochemical analysis of 13 GCTB samples revealed that Wee1 and downstream-relevant members are present in GCTB tissue samples. Overall, our work offers valuable new tools for GCTB studies and presents a description of novel biomarkers and molecular targeting strategies.
Body mass index in young men and risk of inflammatory bowel disease through adult life: A population-based Danish cohort study
Authors: Mendall Michael A. , Jensen Camilla B. , Sørensen Thorkild I. A. , Ängquist Lars H. , Jess Tine 
Published: April 2019

AbstractBody mass index (BMI) is associated with increased future risk of inflammatory bowel disease(IBD) particularly Crohn’s disease(CD), where associations with high and low BMI have been observed. Most studies are based on adult women. We aimed to explore the impact of BMI in men entering adult life on their long-term risk of developing IBD. A total of 377,957 men born during 1939–1959, with BMI measured at draft boards at mean age 19, were followed from 1977, or time of examination, to end of 2015. Risk of IBD was assessed using Cox regression. During 13 million person-years of follow-up, 1,523 developed CD and 3,323 UC. Using normal weight as reference, for CD the following HRs were observed: BMI < 18.5, 1.35; 95% CI, 1.12–1.62, BMI 25–29.9; 0.83; 95% CI, 0.68–1.02. and BMI > 30 1.20; 95% CI, 0.75–1.90). The increased risk of CD in underweight was maintained up until age 60 not explained by known effects of smoking. For UC, minor inverse associations were observed. Restricted cubic splines revealed a U-shape association between BMI and CD, but not UC. Low BMI of men entering adult life is associated with an increased incidence of CD and UC up to 40 years later.
Comparative transcriptome analysis reveals the genetic basis of coat color variation in Pashmina goat
Authors: Bhat Basharat , Singh Ashutosh , Iqbal Zaffar , Kaushik Jai K. , Rao A. R. , Ahmad Syed Mudasir , Bhat Hina , Ayaz Aadil , Sheikh F. D. , Kalra Shalini , Shanaz Syed , Mir Masood Salim , Agarwal Pawan Kumar , Mohapatra Trilochan , Ganai Nazir A. 
Published: April 2019

AbstractThe genetics of coat color variation remains a classic area. Earlier studies have focused on a limited number of genes involved in color determination; however, the complete set of trait determinants are still not well known. In this study, we used high-throughput sequencing technology to identify and characterize intricate interactions between genes that cause complex coat color variation in Changthangi Pashmina goats, producer of finest and costly commercial animal fiber. We systematically identified differentially expressed mRNAs and lncRNAs from black, brown and white Pashmina goat skin samples by using RNA-sequencing technique. A pairwise comparison of black, white and brown skin samples yielded 2479 significantly dysregulated genes (2422 mRNA and 57 lncRNAs). Differentially expressed genes were enriched in melanin biosynthesis, melanocyte differentiation, developmental pigmentation, melanosome transport activities GO terms. Our analysis suggested the potential role of lncRNAs on color coding mRNAs in cis and trans configuration. We have also developed online data repository as a component of the study to provide a central location for data access, visualization and interpretation accessible through http://pcd.skuastk.org/.
A concept for single-shot volumetric fluorescence imaging via orthogonally polarized excitation lattices
Authors: Ströhl Florian , Kaminski Clemens F. 
Published: April 2019

AbstractThe deconvolution of widefield fluorescence images provides only guesses of spatial frequency information along the optical axis due to the so called missing cone in the optical transfer function. Retaining the single-shot imaging speed of deconvolution microscopy while gaining access to missing cone information is thus highly desirable for microscopy of volumetric samples. Here, we present a concept that superimposes two orthogonally polarized excitation lattices with a phase-shift of p between them. In conjunction with a non-iterative image reconstruction algorithm this permits the restoration of missing cone information. We show how fluorescence anisotropy could be used as a method to encode and decode the patterns simultaneously and develop a rigorous theoretical framework for the method. Through in-silico experiments and imaging of fixed biological cells on a structured illumination microscope that emulates the proposed setup we validate the feasibility of the method.
Survey on Heavy Metals Contamination and Health Risk Assessment in Commercially Valuable Asian Swamp Eel, Monopterus albus from Kelantan, Malaysia
Authors: Sow Ai Yin , Ismail Ahmad , Zulkifli Syaizwan Zahmir , Amal Mohammad Noor , Hambali Kamarul Ariffin 
Published: April 2019

AbstractThis work investigates the metals concentration in the tissues of Asian swamp eel, Monopterus albus. Five selected tissues, including liver, gill, bone, skin, and muscle were examined for the concentration of Zn, Cu, Cd, Pb, and Ni. The concentrations of Cd and Pb were found high in the muscle tissues of the eels. Additionally, high amounts of Zn and Cu metals were observed in the liver, whereas the Cd, Pb, and Ni metals were highly detected in gill. The accumulation of Zn, Cu, Cd, Pb, and Ni in both skin and bone of the eel seems to vary between seasons. Low levels of Zn, Cu, and Ni were identified in the muscle tissues of the eels. This study revealed that the concentration of Cd and Pb in the muscle tissues of Asian swamp eels exceeded the permissible limits by the US EPA, suggesting the consumption of the muscle may be hazardous and can severely affect one’s health.
K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation
Authors: Tamanaha-Nakasone Ayumi , Uehara Karina , Tanabe Yasuka , Ishikawa Haruna , Yamakawa Natsuko , Toyoda Zensei , Kurima Kiyoto , Kina Shinichiro , Tsuneki Masayuki , Okubo Yuko , Yamaguchi Sayaka , Utsumi Daisuke , Takahashi Kenzo , Arakawa Hirofumi , Arasaki Akira , Kinjo Takao 
Published: April 2019

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.