bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics profiling utilized a nine immune‐related long noncoding RNA signature as a prognostic target for pancreatic cancer
Authors: Wei Chunmi , Liang Qingyu , Li Xue , Li Hongyu , Liu Yi , Huang Xiangming , Chen Xiujie , Guo Yongxin , Li Jianjun 
Published: April 2019

AbstractPurposeTo identify an immune‐related long noncoding RNA (lncRNA) signature with potential prognostic value for patients with pancreatic cancer.MethodsPancreatic cancer samples with available clinical information and whole genomic mRNA expression data obtained from The Cancer Genome Atlas (TCGA) were enrolled in our research. The immune score of each sample was calculated according to the expression level of immune‐related genes and used to identify the most promising immune‐related lncRNAs. According to the risk score developed from screened immune‐related lncRNAs, the high‐ and low‐risk groups were separated on the basis of the median risk score. The prediction reliability was further evaluated in the validation set and combination set. Both gene set enrichment analysis (GSEA) and principal component analysis (PCA) were performed for functional annotation, and the microenvironment cell population record was applied to evaluate the immune composition and purity of the tumor.ResultsA cohort of 176 samples was included in this study. A total of 163 immune‐related lncRNAs were collected according to Pearson correlation analyses between immune score and lncRNA expression |R| > 0.5, P < 0.01). Nine immune‐related lncRNAs (AL138966.2, AL133520.1, AC142472.1, AC127024.5, AC116913.1, AC083880.1, AC124016.1, AC008443.5, and AC092171.5) with the most significant prognostic values (P < 0.01) were identified. In the training set, it was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group (P < 0.001); meanwhile, similar results were found in the validation set, combination set and various stratified sets (P < 0.05, P < 0.001, P < 0.05, respectively). Moreover, the signature was identified as an independent prognostic factor and significantly associated with the OS of pancreatic cancer. The area under curve (AUC) of the receiver operating characteristic curve (ROC curve) for the nine lncRNA signature in predicting the 2‐year survival rate was 0.703. In addition, the low‐risk and high‐risk groups displayed different distributed patterns in PCA and different immune statuses in the GSEA. The signature indicated decreased purity of the tumor by implying a lower proportion of cancer cells along with an increasing enrichment of fibroblasts, myeloid dendritic cells, and monocytic lineage cells.ConclusionsOur research suggests that the immune‐related lncRNA signature possesses latent prognostic value for patients with pancreatic cancer and may provide new information for immunological research and treatment in pancreatic cancer.
miR‐144 reverses cisplatin resistance in cervical cancer via targeting LHX2
Authors: Shi Fan , Su Jin , Liu Zi , Wang Jiquan , Wang Tao 
Published: April 2019

AbstractMounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR‐144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR‐144 and LIM homeobox 2 (LHX2) expression in CDDP‐resistant and the parental cells was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot analysis, respectively. The functions of miR‐144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase‐3/7, the cleaved‐caspase‐3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR‐144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR‐144 could directly bind to the 3′ untranslated region (3′‐UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR‐144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR‐144 in resistance of cervical cancer cells. Taken together, miR‐144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.
Muscle wasting and function after muscle activation and early protocol‐based physiotherapy: an explorative trial
Authors: Wollersheim Tobias , Grunow Julius J. , Carbon Niklas M. , Haas Kurt , Malleike Johannes , Ramme Sara F. , Schneider Joanna , Spies Claudia D. , Märdian Sven , Mai Knut , Spuler Simone , Fielitz Jens , Weber‐Carstens Steffen 
Published: April 2019

AbstractBackgroundEarly mobilization improves physical independency of critically ill patients at hospital discharge in a general intensive care unit (ICU)‐cohort. We aimed to investigate clinical and molecular benefits or detriments of early mobilization and muscle activating measures in a high‐risk ICU‐acquired weakness cohort.MethodsFifty patients with a SOFA score ≥9 within 72 h after ICU admission were randomized to muscle activating measures such as neuromuscular electrical stimulation or whole‐body vibration in addition to early protocol‐based physiotherapy (intervention) or early protocol‐based physiotherapy alone (control). Muscle strength and function were assessed by Medical Research Council (MRC) score, handgrip strength and Functional Independence Measure at first awakening, ICU discharge, and 12 month follow‐up. Patients underwent open surgical muscle biopsy on day 15. We investigated the impact of muscle activating measures in addition to early protocol‐based physiotherapy on muscle strength and function as well as on muscle wasting, morphology, and homeostasis in patients with sepsis and ICU‐acquired weakness. We compared the data with patients treated with common physiotherapeutic practice (CPP) earlier.ResultsICU‐acquired weakness occurs within the entire cohort, and muscle activating measures did not improve muscle strength or function at first awakening (MRC median [IQR]: CPP 3.3 [3.0–4.3]; control 3.0 [2.7–3.4]; intervention 3.0 [2.1–3.8];P > 0.05 for all), ICU discharge (MRC median [IQR]: CPP 3.8 [3.4–4.4]; control 3.9 [3.3–4.0]; intervention 3.6 [2.8–4.0];P > 0.05 for all), and 12 month follow‐up (MRC median [IQR]: control 5.0 [4.3–5.0]; intervention 4.8 [4.3–5.0];P = 0.342 for all). No signs of necrosis or inflammatory infiltration were present in the histological analysis. Myocyte cross‐sectional area in the intervention group was significantly larger in comparison with the control group (type I +10%; type IIa +13%; type IIb +3%;P < 0.001 for all) and CPP (type I +36%; type IIa +49%; type IIb +65%;P < 0.001 for all). This increase was accompanied by an up‐regulated gene expression for myosin heavy chains (fold change median [IQR]:MYH12.3 [1.1–2.7];MYH20.7 [0.2–1.8];MYH45.1 [2.2–15.3]) and an unaffected gene expression forTRIM63,TRIM62, andFBXO32.ConclusionsIn our patients with sepsis syndrome at high risk for ICU‐acquired weakness muscle activating measures in addition to early protocol‐based physiotherapy did not improve muscle strength or function at first awakening, ICU discharge, or 12 month follow‐up. Yet it prevented muscle atrophy.
Inconsistency in the frequency of rainfall events in the Indian summer monsoon season
Authors: Prathipati Vinay K. , C. V. Naidu , Konatham Prasanna 
Published: April 2019

AbstractIn global warming, India is adversely affected by weather extremes. Summer monsoon contributes about 70% of annual mean rainfall to India by mode of an ensemble of synoptic disturbances and intense events. These events bring extreme amounts of rainfall in very few days. We have studied the anomalies of rainfall events for wet days (>0 mm rainfall), dry days (=0 mm), little rainfall days (>0 to <20 mm), moderate rainfall days (≥20 mm to <60 mm), heavy rainfall days (≥ 60 to <100 mm) and very heavy rainfall days (≥ 100 mm) during the period, 1901–1930; 1931–1960; 1961–1990 and 1991–2015 using India Meteorological Department (IMD) rainfall data. In the present scenario, even though an extensive increase in frequency of lows forming in the Bay of Bengal is observed, only a few are intensified into depressions and above stages. Alternatively, monsoon circulation is trailing its strength; therefore extreme (heavy and very heavy rainfall) events came into existence to balance the mean rainfall activity. The rise in these events may be due to an increasing inconsistency of the strength of low‐level jet, an increase of sea surface temperature over the Arabian Sea and dynamic flow of moisture supply to inland from neighbourhood seas. An increase in the frequency of extreme rainfall events is seen over Konkan & Goa, Madhya Maharashtra, Jammu & Kashmir, central Northeast India (CNEI) and west central India (WCI) in the recent years (25 years) compared to previous 9 decades. Whereas, a decrease in the frequencies of little and moderate rainfall events are observed over the parts of the Western Ghats, Northeast India, WCI and CNEI. There is an increasing trend in the inconsistency of daily rainfall activity due to an increase in the frequency of extreme events in the global warming era.
Correlating Infant Fecal Microbiota Composition and Human Milk Oligosaccharide Consumption by Microbiota of 1‐Month‐Old Breastfed Infants
Authors: Borewicz Klaudyna , Gu Fangjie , Saccenti Edoardo , Arts Ilja C.W. , Penders John , Thijs Carel , van Leeuwen Sander S. , Lindner Cordula , Nauta Arjen , van Leusen Ellen , Schols Henk A. , Smidt Hauke 
Published: April 2019

ScopeUnderstanding the biological functions of human milk oligosaccharides (HMOs) in shaping gastrointestinal (GI) tract microbiota during infancy is of great interest. A link between HMOs in maternal milk and infant fecal microbiota composition is examined and the role of microbiota in degrading HMOs within the GI tract of healthy, breastfed, 1‐month‐old infants is investigated.Methods and resultsMaternal breast milk and infant feces are from the KOALA Birth Cohort. HMOs are quantified in milk and infant fecal samples using liquid chromatography‐mass spectrometry. Fecal microbiota composition is characterized using Illumina HiSeq 16S rRNA gene amplicon sequencing. The composition is associated with gender, delivery mode, and milk HMOs: Lacto‐N‐fucopentaose I and 2′‐fucosyllactose. Overall, Bifidobacterium, Bacteroides, Escherichia–Shigella, and Parabacteroides are predominating genera. Three different patterns in infant fecal microbiota structure are detected. GI degradation of HMOs is strongly associated with fecal microbiota composition, and there is a link between utilization of specific HMOs and relative abundance of various phylotypes (operational taxonomic units).ConclusionsHMOs in maternal milk are among the important factors shaping GI tract microbiota in 1‐month‐old breastfed infants. An infant's ability to metabolize different HMOs strongly correlates with fecal microbiota composition and specifically with phylotypes within genera Bifidobacterium, Bacteroides, and Lactobacillus.
Techno‐economic analysis of FiWi access networks based on optimized source packet traffic
Authors: Breskovic Damir , Begusic Dinko 
Published: April 2019

SummaryFiber wireless access networks (FiWi) are capable of providing broadband 100 Mbit/s services with acceptable costs and can be considered as a competitive alternative to fiber to the home (FTTH). Techno‐economic analysis of viable FiWi architectures is needed in order to obtain the most suitable solution taking into account both technical and economical viewpoints. In this paper, a new approach to techno‐economic analysis of the FiWi networks is proposed. The proposed approach is based on the net present value calculation with the source packet traffic generation rate and traffic intensity as input parameters. As a precondition to net present value calculation, a traffic optimization procedure that assures the quality of experience is performed. Case study results indicate the usability of the proposed method.
From fluorescent proteins to fluorogenic RNAs: Tools for imaging cellular macromolecules
Authors: Truong Lynda , Ferré‐D'Amaré Adrian R. 
Published: April 2019

AbstractThe explosion in genome‐wide sequencing has revealed that noncoding RNAs are ubiquitous and highly conserved in biology. New molecular tools are needed for their study in live cells. Fluorescent RNA–small molecule complexes have emerged as powerful counterparts to fluorescent proteins, which are well established, universal tools in the study of proteins in cell biology. No naturally fluorescent RNAs are known; all current fluorescent RNA tags are in vitro evolved or engineered molecules that bind a conditionally fluorescent small molecule and turn on its fluorescence by up to 5000‐fold. Structural analyses of several such fluorescence turn‐on aptamers show that these compact (30–100 nucleotides) RNAs have diverse molecular architectures that can restrain their photoexcited fluorophores in their maximally fluorescent states, typically by stacking between planar nucleotide arrangements, such as G‐quadruplexes, base triples, or base pairs. The diversity of fluorogenic RNAs as well as fluorophores that are cell permeable and bind weakly to endogenous cellular macromolecules has already produced RNA–fluorophore complexes that span the visual spectrum and are useful for tagging and visualizing RNAs in cells. Because the ligand binding sites of fluorogenic RNAs are not constrained by the need to autocatalytically generate fluorophores as are fluorescent proteins, they may offer more flexibility in molecular engineering to generate photophysical properties that are tailored to experimental needs.
Side chain rotameric changes and backbone dynamics enable specific cladosporin binding in Plasmodium falciparum lysyl‐tRNA synthetase
Authors: Chhibber‐Goel Jyoti , Sharma Amit 
Published: April 2019

AbstractCladosporin (CLD) is a fungal metabolite that kills the malaria parasite via inhibiting its cytoplasmic lysyl‐tRNA synthetase (KRS) and abrogating protein translation. Here we provide structural and drug selectivity analyses on CLD interacting residues in apo and holo KRSs from Plasmodium falciparum, Homo sapiens, Cryptosporidium parvum, and Mycobacterium ulcerans. We show that both gross and subtle alterations in protein backbone and sidechains drive the active site structural plasticity that allows integration of CLD in KRSs. The ligand‐induced fit of CLD in PfKRS is marked by closure and stabilization of three disordered loops and one alpha helix. However, these structural rearragements are not evident in KRS‐CLD complexes from H. sapiens, C. parvum, or M. ulcerans. Strikingly, CLD fits into the MuKRS active site due to a remarkable rotameric alteration in its clash‐prone methionine residue that provides accommodation for the methyl moiety in CLD. Although the high concentrations of drugs used for Hs, Cp, and MuKRS‐CLD complexes in co‐crystallization studies enable elucidation of a structural framework for understanding drug binding in KRSs, we propose that these data should be concurrently assessed via biochemical studies of potency and drug selectivity given the poor cell‐based activity of CLD against human and bacterial cells. Our comprehensive analyses of KRS‐CLD interactions, therefore, highlight vital issues in structure‐based drug discovery studies.
A hyperthermophilic protein G variant engineered via directed evolution prevents the formation of toxic SOD1 oligomers
Authors: Dagan Bar , Oren Ofek , Banerjee Victor , Taube Ran , Papo Niv 
Published: April 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by selective death of motor neurons in the brainstem, motor cortex, and spinal cord, leading to muscle atrophy and eventually to death. It is currently held that various oligomerization‐inducing mutations in superoxide dismutase 1 (SOD1), an amyloid‐forming protein, may be implicated in the familial form of this fast‐progressing highly lethal neurodegenerative disease. A possible therapeutic approach could therefore lie in developing inhibitors to SOD1 mutants. By screening a focused mutagenesis library, mutated randomly in specific “stability patch” positions of the B1 domain of protein G (HTB1), we previously identified low affinity inhibitors of aggregation of SOD1G93A and SOD1G85R mutants. Herein, with the aim to generate a more potent inhibitor with higher affinity to SOD1 mutants, we employed an unbiased, random mutagenesis approach covering the entire sequence space of HTB1 to optimize as yet undefined positions for improved interactions with SOD1. Using affinity maturation screens in yeast, we identified a variant, which we designated HTB1M3, that bound strongly to SOD1 misfolded mutants but not to wild‐type SOD1. In‐vitro aggregation assays indicated that in the presence of HTB1M3 misfolded SOD1 assembled into oligomeric species that were not toxic to NSC‐34 neuronal cells. In addition, when NSC‐34 cells were exposed to misfolded SOD1 mutants, either soluble or preaggregated, in the presence of HTB1M3, this inhibitor prevented the prion‐like propagation of SOD1 from one neuronal cell to another by blocking the penetration of SOD1 into the neuronal cells.
Viral infection in primary antibody deficiency syndromes
Authors: Jones Timothy P.W. , Buckland Matthew , Breuer Judith , Lowe David M. 
Published: April 2019

SummaryPatients with primary antibody deficiency syndromes such as X‐linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID) are at increased risk of severe and invasive infection. Viral infection in these populations has been of increasing interest as evidence mounts that viruses contribute significant morbidity and mortality: this is mediated both directly and via aberrant immune responses. We explain the importance of the humoral immune system in defence against viral pathogens before highlighting several significant viral syndromes in patients with antibody deficiency.We explore historical cases of hepatitis C via contaminated immunoglobulin products, the predisposition to invasive enteroviral infections, prolonged excretion of vaccine‐derived poliovirus, the morbidity of chronic norovirus infection, and recent literature revealing the importance of respiratory viral infections. We discuss evidence that herpesviruses may play a role in driving the inflammatory disease seen in a subset of patients. We explore the phenomenon of within‐host evolution during chronic viral infection and the potential emergence of new pathogenic strains. We highlight novel and emerging viruses identified via deep sequencing techniques. We describe the treatment strategies that have been attempted in all these scenarios and the urgent outstanding questions for research.
Full‐complexity polytopic robust control invariant sets for uncertain linear discrete‐time systems
Authors: Liu Chengyuan , Tahir Furqan , Jaimoukha Imad M. 
Published: April 2019

SummaryThis paper presents an algorithm for the computation of full‐complexity polytopic robust control invariant (RCI) sets, and the corresponding linear state‐feedback control law. The proposed scheme can be applied for linear discrete‐time systems subject to additive disturbances and structured norm‐bounded or polytopic uncertainties. Output, initial condition, and performance constraints are considered. Arbitrary complexity of the invariant polytope is allowed to enable less conservative inner/outer approximations to the RCI sets whereas the RCI set is assumed to be symmetric around the origin. The nonlinearities associated with the computation of such an RCI set structure are overcome through the application of Farkas' theorem and a corollary of the elimination lemma to obtain an initial polytopic RCI set, which is guaranteed to exist under certain conditions. A Newton‐like update, which is recursively feasible, is then proposed to yield desirable large/small volume RCI sets.
Strong Charge Transfer at 2H–1T Phase Boundary of MoS2 for Superb High‐Performance Energy Storage
Authors: Ke Qingqing , Zhang Xiao , Zang Wenjie , Elshahawy Abdelnaby M. , Hu Yating , He Qiyuan , Pennycook Stephen J. , Cai Yongqing , Wang John 
Published: April 2019

AbstractTransition metal dichalcogenides exhibit several different phases (e.g., semiconducting 2H, metallic 1T, 1T′) arising from the collective and sluggish atomic displacements rooted in the charge‐lattice interaction. The coexistence of multiphase in a single sheet enables ubiquitous heterophase and inhomogeneous charge distribution. Herein, by combining the first‐principles calculations and experimental investigations, a strong charge transfer ability at the heterophase boundary of molybdenum disulfide (MoS2) assembled together with graphene is reported. By modulating the phase composition in MoS2, the performance of the nanohybrid for energy storage can be modulated, whereby remarkable gravimetric and volumetric capacitances of 272 F g−1 and 685 F cm−3 are demonstrated. As a proof of concept for energy application, a flexible solid‐state asymmetric supercapacitor is constructed with the MoS2‐graphene heterolayers, which shows superb energy and power densities (46.3 mWh cm−3 and 3.013 W cm−3, respectively). The present work demonstrates a new pathway for efficient charge flow and application in energy storage by engineering the phase boundary and interface in 2D materials of transition metal dichalcogenides.
Optically Stimulated Artificial Synapse Based on Layered Black Phosphorus
Authors: Ahmed Taimur , Kuriakose Sruthi , Mayes Edwin L. H. , Ramanathan Rajesh , Bansal Vipul , Bhaskaran Madhu , Sriram Sharath , Walia Sumeet 
Published: April 2019

AbstractThe translation of biological synapses onto a hardware platform is an important step toward the realization of brain‐inspired electronics. However, to mimic biological synapses, devices till‑date continue to rely on the need for simultaneously altering the polarity of an applied electric field or the output of these devices is photonic instead of an electrical synapse. As the next big step toward practical realization of optogenetics inspired circuits that exhibit fidelity and flexibility of biological synapses, optically‑stimulated synaptic devices without a need to apply polarity‑altering electric field are needed. Utilizing a unique photoresponse in black phosphorus (BP), here reported is an all‑optical pathway to emulate excitatory and inhibitory action potentials by exploiting oxidation‑related defects. These optical synapses are capable of imitating key neural functions such as psychological learning and forgetting, spatiotemporally correlated dynamic logic and Hebbian spike‑time dependent plasticity. These functionalities are also demonstrated on a flexible platform suitable for wearable electronics. Such low‐power consuming devices are highly attractive for deployment in neuromorphic architectures. The manifestation of cognition and spatiotemporal processing solely through optical stimuli provides an incredibly simple and powerful platform to emulate sophisticated neural functionalities such as associative sensory data processing and decision making.
Zeitliche Restriktionen als hochschulexterne Bedingungsfaktoren struktureller Studierbarkeit
Authors: Buß Imke 
Published: April 2019

ZusammenfassungDieses Kapitel fokussiert die Lebens- und Studiensituation, den Studienerfolg sowie die zeitlichen Restriktionen von vier unterschiedlichen Studierendengruppen: erwerbstätigen Studierenden, Studierenden mit Kind, Studierenden mit Pflegeaufgaben und behinderten Studierenden. Diese Analysen sind relevant, um das im Modell der strukturellen Studierbarkeit enthaltene Konzept der zeitlichen Restriktionen entwickeln zu können (siehe Abschnitt 3.5). Denn im Modell gehen nicht die einzelnen Studierendengruppen in die Analysen ein, sondern die Gemeinsamkeit der zeitlichen Restriktion.