bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular determinants for dsDNA translocation by the transcription-repair coupling and evolvability factor Mfd
Authors: Brugger Christiane , Zhang Cheng , Suhanovsky Margaret M. , Kim David D. , Sinclair Amy N. , Lyumkis Dmitry , Deaconescu Alexandra M. 
Published: July 2020

AbstractMfd couples transcription to nucleotide excision repair, and acts on RNA polymerases when elongation is impeded. Depending on impediment severity, this action results in either transcription termination or elongation rescue, which rely on ATP-dependent Mfd translocation on DNA. Due to its role in antibiotic resistance, Mfd is also emerging as a prime target for developing anti-evolution drugs. Here we report the structure of DNA-bound Mfd, which reveals large DNA-induced structural changes that are linked to the active site via ATPase motif VI. These changes relieve autoinhibitory contacts between the N- and C-termini and unmask UvrA recognition determinants. We also demonstrate that translocation relies on a threonine in motif Ic, widely conserved in translocases, and a family-specific histidine near motif IVa, reminiscent of the “arginine clamp” of RNA helicases. Thus, Mfd employs a mode of DNA recognition that at its core is common to ss/ds translocases that act on DNA or RNA.
Molecular engineering of safe and efficacious oral basal insulin
Authors: Hubálek Frantisek , Refsgaard Hanne H. F. , Gram-Nielsen Sanne , Madsen Peter , Nishimura Erica , Münzel Martin , Brand Christian Lehn , Stidsen Carsten Enggaard , Claussen Christian Hove , Wulff Erik Max , Pridal Lone , Ribel Ulla , Kildegaard Jonas , Porsgaard Trine , Johansson Eva , Steensgaard Dorte Bjerre , Hovgaard Lars , Glendorf Tine , Hansen Bo Falck , Jensen Maja Kirkegaard , Nielsen Peter Kresten , Ludvigsen Svend , Rugh Susanne , Garibay Patrick W. , Moore Mary Courtney , Cherrington Alan D. , Kjeldsen Thomas 
Published: July 2020

AbstractRecently, the clinical proof of concept for the first ultra-long oral insulin was reported, showing efficacy and safety similar to subcutaneously administered insulin glargine. Here, we report the molecular engineering as well as biological and pharmacological properties of these insulin analogues. Molecules were designed to have ultra-long pharmacokinetic profile to minimize variability in plasma exposure. Elimination plasma half-life of ~20 h in dogs and ~70 h in man is achieved by a strong albumin binding, and by lowering the insulin receptor affinity 500-fold to slow down receptor mediated clearance. These insulin analogues still stimulate efficient glucose disposal in rats, pigs and dogs during constant intravenous infusion and euglycemic clamp conditions. The albumin binding facilitates initial high plasma exposure with a concomitant delay in distribution to peripheral tissues. This slow appearance in the periphery mediates an early transient hepato-centric insulin action and blunts hypoglycaemia in dogs in response to overdosing.
Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Authors: Guttenplan Kevin A. , Weigel Maya K. , Adler Drew I. , Couthouis Julien , Liddelow Shane A. , Gitler Aaron D. , Barres Ben A. 
Published: July 2020

AbstractReactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.
A transdisciplinary and community-driven database to unravel subduction zone initiation
Authors: Crameri Fabio , Magni Valentina , Domeier Mathew , Shephard Grace E. , Chotalia Kiran , Cooper George , Eakin Caroline M. , Grima Antoniette Greta , Gürer Derya , Király Ágnes , Mulyukova Elvira , Peters Kalijn , Robert Boris , Thielmann Marcel 
Published: July 2020

AbstractSubduction zones are pivotal for the recycling of Earth’s outer layer into its interior. However, the conditions under which new subduction zones initiate are enigmatic. Here, we constructed a transdisciplinary database featuring detailed analysis of more than a dozen documented subduction zone initiation events from the last hundred million years. Our initial findings reveal that horizontally forced subduction zone initiation is dominant over the last 100 Ma, and that most initiation events are proximal to pre-existing subduction zones. The SZI Database is expandable to facilitate access to the most current understanding of subduction zone initiation as research progresses, providing a community platform that establishes a common language to sharpen discussion across the Earth Science community.
Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers
Authors: Glodzik Dominik , Bosch Ana , Hartman Johan , Aine Mattias , Vallon-Christersson Johan , Reuterswärd Christel , Karlsson Anna , Mitra Shamik , Niméus Emma , Holm Karolina , Häkkinen Jari , Hegardt Cecilia , Saal Lao H. , Larsson Christer , Malmberg Martin , Rydén Lisa , Ehinger Anna , Loman Niklas , Kvist Anders , Ehrencrona Hans , Nik-Zainal Serena , Borg Åke , Staaf Johan 
Published: July 2020

AbstractHomologous recombination deficiency (HRD) is a defining characteristic inBRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. We investigated the frequency ofBRCA1promoter hypermethylation in 237 triple-negative breast cancers (TNBCs) from a population-based study using reported whole genome and RNA sequencing data, complemented with analyses of genetic, epigenetic, transcriptomic and immune infiltration phenotypes. We demonstrate thatBRCA1promoter hypermethylation is twice as frequent asBRCA1pathogenic variants in early-stage TNBC and that hypermethylated and mutated cases have similarly improved prognosis after adjuvant chemotherapy.BRCA1hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors withBRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. Hypermethylation may be an early event in tumor development that progress along a common pathway withBRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC.
Multiscale real time and high sensitivity ion detection with complementary organic electrochemical transistors amplifier
Authors: Romele Paolo , Gkoupidenis Paschalis , Koutsouras Dimitrios A. , Lieberth Katharina , Kovács-Vajna Zsolt M. , Blom Paul W. M. , Torricelli Fabrizio 
Published: July 2020

AbstractIons are ubiquitous biological regulators playing a key role for vital processes in animals and plants. The combined detection of ion concentration and real-time monitoring of small variations with respect to the resting conditions is a multiscale functionality providing important information on health states. This multiscale functionality is still an open challenge for current ion sensing approaches. Here we show multiscale real-time and high-sensitivity ion detection with complementary organic electrochemical transistors amplifiers. The ion-sensing amplifier integrates in the same device both selective ion-to-electron transduction and local signal amplification demonstrating a sensitivity larger than 2300 mV V−1 dec−1, which overcomes the fundamental limit. It provides both ion detection over a range of five orders of magnitude and real-time monitoring of variations two orders of magnitude lower than the detected concentration, viz. multiscale ion detection. The approach is generally applicable to several transistor technologies and opens opportunities for multifunctional enhanced bioelectronics.
Homologous repair deficiency score for identifying breast cancers with defective DNA damage response
Authors: Min Ahrum , Kim Kwangsoo , Jeong Kyeonghun , Choi Seongmin , Kim Seongyeong , Suh Koung Jin , Lee Kyung-Hun , Kim Sun , Im Seock-Ah 
Published: July 2020

AbstractBreast cancer (BC) in patients with germline mutations ofBRCA1/BRCA2are associated with benefit from drugs targeting DNA damage response (DDR), but they account for only 5–7% of overall breast cancer. To define the characteristics of these tumors and also to identify tumors without BRCA mutation but with homologous recombination deficiency (HRD) is clinically relevant. To define characteristic features of HRD tumors and analyze the correlations betweenBRCA1/BRCA2and BC subtypes, we analyzed 981 breast tumors from the TCGA database using the signature analyzer. The BRCA signature was strongly associated with the HRD score top 10% (score ≥ 57) population. This population showed a high level of mutations in DDR genes, includingBRCA1/BRCA2. HRD tumors were associated with high expression levels ofBARD1andBRIP1. Besides,BRCA1/2 mutations were dominantly observed in basal and luminal subtypes, respectively. A comparison of HRD features in BC revealed thatBRCA1exerts a stronger influence inducing HRD features thanBRCA2does. It reveals genetic differences betweenBRCA1andBRCA2and provides a basis for the identification of HRD and other BRCA-associated tumors.
Rapid antibiotic susceptibility testing of bacteria from patients’ blood via assaying bacterial metabolic response with surface-enhanced Raman spectroscopy
Authors: Han Yin-Yi , Lin Yi-Chun , Cheng Wei-Chih , Lin Yu-Tzu , Teng Lee-Jene , Wang Juen-Kai , Wang Yuh-Lin 
Published: July 2020

AbstractBlood stream infection is one of the major public health issues characterized with high cost and high mortality. Timely effective antibiotics usage to control infection is crucial for patients’ survival. The standard microbiological diagnosis of infection however can last days. The delay in accurate antibiotic therapy would lead to not only poor clinical outcomes, but also to a rise in antibiotic resistance due to widespread use of empirical broad-spectrum antibiotics. An important measure to tackle this problem is fast determination of bacterial antibiotic susceptibility to optimize antibiotic treatment. We show that a protocol based on surface-enhanced Raman spectroscopy can obtain consistent antibiotic susceptibility test results from clinical blood-culture samples within four hours. The characteristic spectral signatures of the obtained spectra of Staphylococcus aureus and Escherichia coli—prototypic Gram-positive and Gram-negative bacteria—became prominent after an effective pretreatment procedure removed strong interferences from blood constituents. Using them as the biomarkers of bacterial metabolic responses to antibiotics, the protocol reported the susceptibility profiles of tested drugs against these two bacteria acquired from patients’ blood with high specificity, sensitivity and speed.
Yang-Mills structure for electron–phonon interactions in vanadium dioxide
Authors: Booth Jamie M. , Russo Salvy P. 
Published: July 2020

AbstractThis work presents a method of grouping the electron spinors and the phonon modes of metal oxide crystals such as vanadium dioxide into an SU(2) gauge theory. The gauge “charge” is the electron spin, which is assumed to couple to the transverse acoustic phonons on the basis of spin ordering phenomena in $${\text{M}}_{{1}}$$M1- and $${\text{M}}_{{2}}$$M2-$${\text{VO}}_{{2}}$$VO2, while the longitudinal mode is neutral. A generalization of the Peierls Mechanism is presented based on the discrete gauge invariance of crystals and the corresponding Ward-Takahashi identity. The introduction of a band index results in violation of this discrete Ward-Takahashi identity for interband transitions, resulting in scattering from the longitudinal component. Thus both the spinors and the bosons acquire mass and an electronic band gap and optical phonon modes result: a symmetry-breaking metal-insulator transition, which can manifest concurrent spin-ordering.
Temperature-dependent charge-carrier transport between Si-δ-doped layers and AlGaAs/InGaAs/AlGaAs quantum well with various space layer thicknesses measured by Hall-effect analysis
Authors: Su Wilson Yeung-Sy , Lu Victor Chien-Pin , Wu Chii-Bin , Wang Jyh-Shyang , Shen Ji-Lin , Chiu Kuan-Cheng 
Published: July 2020

AbstractTemperature (T = 40 ~ 300 K) dependence of Hall-effect analysis on the dual Si-δ-doped AlGaAs/InGaAs/AlGaAs quantum-well (QW) structures with various space layer thicknesses (tS = 5, 10 and 15 nm) was performed. An interesting hysteresis behavior of electron sheet concentration [n2D(T)] was observed for tS = 10 and 15 nm but not for tS = 5 nm. A model involving two different activation barriers encountered respectively by electrons in the active QW and by electrons in the δ-doped layers is proposed to account for the hysteresis behavior. However, for small enough tS (= 5 nm ≤ 2.5 s, where s = 2.0 nm is the standard deviation of the Gaussian fit to the Si-δ-doped profile), the distribution of Si dopants near active QW acted as a specific form of “modulation doping” and can not be regarded as an ideal δ-doping. These Si dopants nearby the active QW effectively increase the magnitude of n2D, and hence no hysteresis curve was observed. Finally, effects from tS on the T-dependence of electron mobility in active QW channel are also discussed.
Transport pathways across the West African Monsoon as revealed by Lagrangian Coherent Structures
Authors: Niang Coumba , Mancho Ana Maria , García-Garrido Víctor José , Mohino Elsa , Rodriguez-Fonseca Belén , Curbelo Jezabel 
Published: July 2020

AbstractThe West African Monsoon (WAM) system is the main source of rainfall in the agriculturally based region of the Sahel. Understanding transport across the WAM is of crucial importance due to the strong impact of humidity and dust pathways on local cloud formation. However, the description of this transport is challenging due to its 3D complex nature. Lagrangian Coherent Structures (LCS) simplify transport description across the WAM by providing a geometrical partition of the troposphere into domains. Air parcels within each domain have similar dynamical characteristics. LCS make it possible to achieve an integrated vision of transport pathways across this system. Using this approach we unveil new connections in the WAM system. In particular, we identify transport pathways between the Tropical Easterly Jet (TEJ) and the African Easterly Jet (AEJ). Furthermore, the clockwise circulation associated with the divergent upper part of the Sahara heat low is clearly delimitated. Additionally, we show the presence of mixing regions in the AEJ and the lower part of the TEJ that are linked to pathways to sources of dust and humidity.
Defect spectroscopy on the dielectric material aluminum oxide
Authors: Oing Dennis , Geller Martin , Stahl Lucas , Kerski Jens , Lorke Axel , Wöhrl Nicolas 
Published: July 2020

AbstractA method for defect characterization is presented that allows to measure the activation energy, capture cross-section, and defect density in dielectric materials. This is exemplarily performed on aluminum oxide thin films deposited on hydrogen-terminated diamond. During the measurement, samples were illuminated using a 405 nm laser, charging the defects while simultaneously measuring the surface conductivity of the diamond at different temperatures. By applying the standard boxcar evaluation known from deep-level transient spectroscopy, we found five different defect levels in $$\hbox {Al}_2\hbox {O}_3$$Al2O3. One can be identified as substitutional silicon in aluminum oxide, while the others are most likely connected to either aluminum interstitials or carbon and nitrogen impurities.
Clinicomicrobiological profile, visual outcome and mortality of culture-proven endogenous endophthalmitis in Taiwan
Authors: Hsieh Ming-Chieh , Chen San-Ni , Cheng Chieh-Yin , Li Kun-Hsien , Chuang Chih-Chun , Wu Jian-Sheng , Lee Sheng-Ta , Chiu Shin-Lin 
Published: July 2020

AbstractThis is a retrospective study in consecutive cases with cultured-proven endogenous endophthalmitis (EE) treated at the largest tertiary medical center in middle Taiwan in the past 10 years. 83 eyes of 70 patients were enrolled. The mean interval between systemic diseases to the diagnosis of EE was 8.84 ± 6.94 days. The mean initial visual acuity (VA) in the logarithm of minimal angle of resolution (logMAR) was 1.63 ± 0.87. Type 2 diabetes mellitus was the most common predisposing medical illness (N = 53, 63.86%). The most common infectious sources were intra-abdominal abscess (N = 36, 43.37%), and the second most reason was urinary tract infection. The causative pathogen was Gram-negative predominant (N = 64, 77.11%). After aggressive treatment, 34.94% of eyes regain useful vision, and only six eyes underwent enucleation or evisceration. The binary multivariate logistic regression model revealed that female gender (95% CI 1.002–19.036, p = 0.05, OR 4.37), initial VA logMAR (95% CI 0.089–0.550, p = 0.01, OR 0.22), and more intravitreal injections (95% CI 0.368–0.927, p = 0.023, OR 0.58) were independent risk factors influencing final outcomes. Based on the results mentioned above, early diagnosis is recommended to gain better outcomes. The mean interval between systemic diseases to the diagnosis of EE was 8.84 ± 6.94 days in our sample population, clinicians should maintain a higher index of suspicion during this period when encountering patients with bacteremia or fungemia.
Graphene/PbS quantum dot hybrid structure for application in near-infrared photodetectors
Authors: Jeong Hyun , Song Jung Hoon , Jeong Sohee , Chang Won Seok 
Published: July 2020

AbstractA graphene-PbS quantum dot (QD) composite for application in high-performance near-infrared (NIR) photodetectors (PDs) is proposed in this study. A single-layer graphene flake and oleic acid-capped PbS QD composite is fabricated through the conventional sonication process, in hexane solution. Field emission scanning electron microscopy images of the graphene-PbS QD composite dispersed on a glass substrate confirm that the composite contains both aggregated graphene flakes and single-layer graphene with wrinkles; Transmission electron microscopy images reveal close packing with uniform size. The increased absorbance and quenched photoluminescence intensity of the graphene-PbS QD composite supports enhanced photoinduced charge transfer between graphene and the PbS QDs. Moreover, the specific Raman mode of the PbS QDs, embedded in the spectrum, is enhanced by combination with graphene, which can be interpreted by SERS as relevant to the photoinduced charge transfer between the Pbs QDs and graphene. For device application, a PD structure comprised by graphene-PbS QDs is fabricated. The photocurrent of the PD is measured using a conventional probe station with a 980-nm NIR laser diode. In the fabricated PD comprising graphene-PbS QDs, five-times higher photocurrent, 22% faster rise time, and 47% faster decay time are observed, compared to that comprising PbS QDs alone. This establishes the potential of the graphene-PbS QD composite for application in ultrathin, flexible, high-performance NIR PDs.
Silicon changes C:N:P stoichiometry of sugarcane and its consequences for photosynthesis, biomass partitioning and plant growth
Authors: Frazão Joaquim José , Prado Renato de Mello , de Souza Júnior Jonas Pereira , Rossatto Davi Rodrigo 
Published: July 2020

AbstractSilicon (Si) application has improved yield and stress tolerance in sugarcane crops. In this respect, C:N:P stoichiometry makes it possible to identify flows and interaction between elements in plants and their relationship with growth. However, few studies have investigated the influence of Si on physiological variables and C:N:P stoichiometry in sugarcane. As such, this study aimed to assess the effect of increasing Si concentrations on the growth and stoichiometric composition of sugarcane plants in the early growth stage. The experiment was conducted in pots, using four Si concentrations (0, 0.8, 1.6 and 3.2 mM). Biomass production, the concentration and accumulation of C, N, P and Si as well as the relationship between them were assessed. Silicon application increased biomass production, the rate of photosynthesis, instantaneous carboxylation efficiency and C, N, P and Si accumulation, in addition to altering stoichiometric ratios (C:N, C:P, N:P and C:Si) in different parts of the plants. The decline in C concentration associated with greater N and P absorption indicates that Si favoured physiological processes, which is reflected in biomass production. Our results demonstrate that Si supply improved carbon use efficiency, directly influencing sugarcane yield as well as C and nutrient cycling.
Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin
Authors: Hsin Chih-hsuan , Stoffel Marc S. , Gazzaz Malaz , Schaeffeler Elke , Schwab Matthias , Fuhr Uwe , Taubert Max 
Published: July 2020

AbstractEffects of different genotypes on the pharmacokinetics of probe substrates may support their use as phenotyping agents for the activity of the respective enzyme or transporter. Digoxin is recommended as a probe substrate to assess the activity of the transporter P-glycoprotein (P-gp) in humans. Current studies on the individual effects of three commonly investigated single nucleotide polymorphisms (SNPs) of theABCB1gene encoding P-gp (C1236T, G2677T/A, and C3435T) on digoxin pharmacokinetics are inconclusive. Since SNPs are in incomplete linkage disequilibrium, considering combinations of these SNPs might be necessary to assess the role of polymorphisms in digoxin pharmacokinetics accurately. In this study, the relationship between SNP combinations and digoxin pharmacokinetics was explored via a population pharmacokinetic approach in 40 volunteers who received oral doses of 0.5 mg digoxin. Concerning the SNPs 1236/2677/3435, the following combinations were evaluated: CGC, CGT, and TTT. Carriers of CGC/CGT and TTT/TTT had 35% higher apparent bioavailability compared to the reference group CGC/CGC, while no difference was seen in CGC/TTT carriers. No significant effect on renal clearance was observed. The population pharmacokinetic model supports the use of oral digoxin as a phenotyping substrate of intestinal P-gp, but not to assess renal P-gp activity.
A novel predictive model incorporating immune-related gene signatures for overall survival in melanoma patients
Authors: Liao Mengting , Zeng Furong , Li Yao , Gao Qian , Yin Mingzhu , Deng Guangtong , Chen Xiang 
Published: July 2020

AbstractMelanoma is the most invasive type of skin cancer, in which the immune system plays a vital role. In this study, we aimed to establish a prognostic prediction nomogram for melanoma patients that incorporates immune-related genes (IRGs). Ninety-seven differentially expressed IRGs between melanoma and normal skin were screened using gene expression omnibus database (GEO). Among these IRGs, a two-gene signature consisting of CCL8 and DEFB1 was found to be closely associated with patient prognosis using the cancer genome atlas (TCGA) database. Survival analysis verified that the IRGs score based on the signature gene expressions efficiently distinguished between high- and low-risk patients, and was identified to be an independent prognostic factor. A nomogram integrating the IRGs score, age and TNM stage was established to predict individual prognosis for melanoma. The prognostic performance was validated by the TCGA/GEO-based concordance indices and calibration plots. The area under the curve demonstrated that the nomogram was superior than the conventional staging system, which was confirmed by the decision curve analysis. Overall, we developed and validated a nomogram for prognosis prediction in melanoma based on IRGs signatures and clinical parameters, which could be valuable for decision making in the clinic.