bluuebunny/crossref_metadata_2025_split huggingface dataset:
An early phase of instructive plasticity before the typical onset of sensory experience
Authors: Roy Arani , Wang Shen , Meschede-Krasa Benyamin , Breffle Jordan , Van Hooser Stephen D. 
Published: January 2020

AbstractWhile early experience with moving stimuli is necessary for the development of direction selectivity in visual cortex of carnivores, it is unclear whether experience exerts a permissive or instructive influence. To test if the specific parameters of the experienced stimuli could instructively sculpt the emergent responses, visually naive ferrets were exposed to several hours of experience with unusual spatiotemporal patterns. In the most immature ferrets, cortical neurons developed selectivity to these patterns, indicating an instructive influence. In animals that were 1–10 days more mature, exposure to the same patterns led to a developmentally-typical increase in direction selectivity. We conclude that visual development progresses via an early phase of instructive plasticity, when the specific patterns of neural activity shape the specific parameters of the emerging response properties, followed by a late phase of permissive maturation, when sensory-driven activity merely serves to enhance the response properties already seeded in cortical circuits.
MAP3Kinase-dependent SnRK2-kinase activation is required for abscisic acid signal transduction and rapid osmotic stress response
Authors: Takahashi Yohei , Zhang Jingbo , Hsu Po-Kai , Ceciliato Paulo H. O. , Zhang Li , Dubeaux Guillaume , Munemasa Shintaro , Ge Chennan , Zhao Yunde , Hauser Felix , Schroeder Julian I. 
Published: January 2020

AbstractAbiotic stresses, including drought and salinity, trigger a complex osmotic-stress and abscisic acid (ABA) signal transduction network. The core ABA signalling components are snf1-related protein kinase2s (SnRK2s), which are activated by ABA-triggered inhibition of type-2C protein-phosphatases (PP2Cs). SnRK2 kinases are also activated by a rapid, largely unknown, ABA-independent osmotic-stress signalling pathway. Here, through a combination of a redundancy-circumventing genetic screen and biochemical analyses, we have identified functionally-redundant MAPKK-kinases (M3Ks) that are necessary for activation of SnRK2 kinases. These M3Ks phosphorylate a specific SnRK2/OST1 site, which is indispensable for ABA-induced reactivation of PP2C-dephosphorylated SnRK2 kinases. ABA-triggered SnRK2 activation, transcription factor phosphorylation and SLAC1 activation require these M3Ks in vitro and in plants. M3K triple knock-out plants show reduced ABA sensitivity and strongly impaired rapid osmotic-stress-induced SnRK2 activation. These findings demonstrate that this M3K clade is required for ABA- and osmotic-stress-activation of SnRK2 kinases, enabling robust ABA and osmotic stress signal transduction.
A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders
Authors: Schou M. B. , Sæther S. G. , Drange O. K. , Brenner E. , Crespi J. , Eikenes L. , Mykland M. S. , Pintzka C. , Håberg A. K. , Sand T. , Vaaler A. , Kondziella D. 
Published: January 2020

AbstractThe clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age – and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab−) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab− patients. There were no differences in CSF analysis (n = 6 ab+/12 ab−), EEG (n = 7 ab+/19 ab−) or brain MRI (n = 7 ab+/17 ab−) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.
MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2
Authors: Wei Qiaofeng , Lv Fang , Zhang Hongju , Wang Xinfang , Geng Qin , Zhang Xiuying , Li Tongying , Wang Shujun , Wang Yajuan , Cui Yanhui 
Published: January 2020

Abstract
Objective: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA.
Methods: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay.
Results: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2.
Conclusion: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.
Effect of lentivirus-mediated CFTR overexpression on oxidative stress injury and inflammatory response in the lung tissue of COPD mouse model
Authors: Xu Xiaoli , Huang Huimin , Yin Xiangyi , Fang Hongmei , Shen Xiaoyue 
Published: January 2020

Abstract
We aimed to investigate the regulatory mechanism of lentivirus-mediated overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) in oxidative stress injury and inflammatory response in the lung tissue of mouse model of chronic obstructive pulmonary disease (COPD). COPD mouse model induced by cigarette smoke was established and normal mice were used as control. The mice were assigned into a normal group (control), a model group (untreated), an oe-CFTR group (injection of lentivirus overexpressing CFTR), and an oe-NC group (negative control, injection of lentivirus expressing irrelevant sequences). Compared with the oe-NC group, the oe-CFTR group had higher CFTR expression and a better recovery of pulmonary function. CFTR overexpression could inhibit the pulmonary endothelial cell apoptosis, reduce the levels of glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA) and increase the values of superoxide dismutase (SOD), GSH peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). The overexpression also led to reductions in the white blood cell (WBC) count in alveolus pulmonis, the concentrations of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-α, and the protein expressions of NF-κB p65, ERK, JNK, p-EPK, and p-JNK related to MAPK/NF-κB p65 signaling pathway. In conclusion, CFTR overexpression can protect lung tissues from injuries caused by oxidative stress and inflammatory response in COPD mouse model. The mechanism behind this may be related to the suppression of MAPK/NF-κB p65 signaling pathway.
EpiCO (epirubicin, cyclophosphamide and vincristine) as treatment for extrapulmonary high-grade neuroendocrine neoplasms
Authors: Munker Stefan , Vogelhuber Martin , Bornschein Jan , Stroszczynski Christian , Evert Matthias , Schlitt Hans , Herr Wolfgang , Teufel Andreas 
Published: January 2020

AbstractHigh-grade neuroendocrine neoplasms (NEN) comprise a rare entity. Due to the lack of randomized controlled trials, therapy recommendations were mainly extrapolated from its pulmonary analogue, small cell lung cancer and mostly validated in small retrospective case series. The multicentric Nordic NEC Study of gastro-entero-pancreatic (GEP) and cancer of unknown primary (CUP) high-grade neuroendocrine neoplasms showed a significant disease control upon treatment with etoposide and platinum-based chemotherapies 1. Such a combination with etoposide and a platinum (CE) compound is currently considered standard first-line treatment for high-grade GEP/CUP NEN. High-grade mixed-neuroendocrine-non-neuroendocrine neoplasms (MiNEN) formerly termed mixed adeno-neuroendocrine carcinomas (MANEC) also have a poor prognosis and are generally treated like other high-grade NEN. The CE protocol has significant activity in high-grade NEN and MiNEN, but the response is short-lived in most cases with response rates around 50–60 %. Second-line treatment alternatives are not established so far. The need for additional treatment options is evident.Combination chemotherapy with doxorubicin, cyclophosphamide and vincristine (CAV) showed efficacy in small cell lung carcinoma (SCLC) and was considered standard first-line therapy before the era of etoposide and platinum combinations. Due to a better toxicity profile, doxorubicin was replaced by epirubicin, resulting in the combination of epirubicin, cyclophosphamide and vincristine (abbreviated as EpiCO or CEV).In analogy to SCLC, selected patients with high-grade NEN were treated with the EpiCO regimen in second line (or in one patient first line) at our center. In this report we present the retrospective series of 5 cases with metastatic high-grade GEP/CUP NEN/MiNEN who received chemotherapy according to this protocol.
Persea Americana Seeds Cause Ileal Smooth Muscle Relaxation Via Stimulation of α-1 Adrenoceptors
Authors: Oridupa Olayinka Ayotunde , Oshinloye Adedunke Omobolanle , Obisesan Ayobami Deborah , Olateju Opeyemi Mordiyah , Adenuga Victor Adedotun 
Published: January 2020

AbstractThe effect of methanol extract of P. americana seeds on isolated ileal smooth muscle was studied for isometric response using 10 adult rabbits of both sexes. Reactivity and agonist-antagonist responses of rabbit ileum to the extract were determined in this study. The affinity, effective concentration to give 50% response (EC50) and maximum response were calculated from the concentration response curves (CRC) obtained. The result for the reactivity study showed the seed extract of P. americana caused concentration dependent relaxation of isolated rabbit ileum with threshold responses at concentration of 1×10−9 mg/ml and 120 mg/ml respectively. The extract-antagonist study showed an upward and right shift in CRC in the presence of phenoxybenzamine, a non-selective adrenergic antagonist, with the EC50 increased from 5.01 mg/ml to 12.59 mg/ml and affinity decreased from 0.20 to 0.08. Extract-antagonist study also showed a right and upward shift in the CRC with a greater magnitude in the presence of prazosin, an α1-adrenergic antagonist, with EC50 increased from 0.32 mg/ml to 25.12 mg/ml and a consequential decrease in the affinity from 3.13 to 0.04. In the presence of propranolol, a β-adrenergic antagonist, a downward and left shift in the CRC was observed with the EC50 and PA2 remaining constant at 0.1 mg/ml and 10 respectively. P. americana concentration-dependently reduced or inhibited gastric motility, increasing transit time which is important for food absorption, thus a pro-nutritive and antispasmodic effect. The interaction with α1-adrenoceptors is beneficially in heart failure management. The plant can be developed as a drug candidate for management of hypertension.
Suppressive Effects of Hot-water Extract of Magnolia obovata on Clostridium perfringens Enterotoxin-induced Cytotoxicity in Human Intestinal Caco-2 Cells
Authors: Kawahara Takeshi , Fujii Kotomi , Nakajima Kouki , Fujii Rikuri , Inagaki Shuichiro , Hara Kunio , Yasui Hisako 
Published: January 2020

AbstractThe physiological functions of the leaves of Japanese big-leaf magnolia (Magnolia obovata) against enterotoxins produced by foodborne pathogens remain unclear. In this study, we evaluated the protective effects of M. obovata leaf extract (MLE) against the cytotoxicity of Clostridium perfringens enterotoxin (CPE), which causes the symptoms of C. perfringens type A food poisoning. The protective effects of MLE against CPE-induced cytotoxicity were evaluated in human intestinal epithelial Caco-2 cells. Pre-treatment with MLE significantly suppressed the cytotoxicity induced by CPE in undifferentiated and differentiated human intestinal Caco-2 cells at a pH range of 4.0 – 7.0. This CPE-suppressive effect was due to a hydrophilic sugar-containing compound without phenolic and protein structures but not the hydrophobic biologically active neolignans, honokiol and magnolol. MLE had a protective effect against cytotoxicity caused by type A C. perfringens. Our results provide novel insight regarding the usage of M. obovata in managing food poisoning.
Synthetic Approaches to Unsymmetrically Substituted 5,7-Dihydroxycoumarins
Authors: Fatykhov Ramil F. , Chupakhin Oleg N. , Inyutina Anna K. , Khalymbadzha Igor A. 
Published: January 2020

The chemical equivalence of the hydroxy groups in the 5,7-dihydroxycoumarin core has challenged synthetic chemists to develop short and efficient strategies for the selective modification of one of the hydroxy groups leaving the second intact. Over the past 100 years, chemists have proposed various approaches to distinguishing between these two groups according to their reactivity. While the early syntheses included simple nonselective reactions of both hydroxy groups and the subsequent separation of mixtures of the 5-O- and 7-O-isomers formed, recent sophisticated approaches often include the introduction of protective groups for selective directing reactions or the completely controlled construction of the 5,7-dihydroxycoumarin framework by Horner–Wadsworth–Emmons reaction. This review discusses in detail approaches towards unsymmetrically substituted 5,7-dihydroxycoumarins as well as factors influencing 5-O vs. 7-O regioselectivity of reactions of 5,7-dihydroxycoumarins. This review covers all the literature since 1921 with an emphasis on recent works. This critical review may facilitate the synthesis of new drug candidates as well as the total synthesis of natural products.1	Introduction2	O-Modification of 5,7-Dihydroxycoumarins2.1	Alkylation/Alkenylation2.2	Acylation2.3	Sulfonylation2.4	Silylation2.5	Acylation Followed by Alkylation3	Other Approaches3.1	Synthesis from Substituted Phloroglucinol3.2	Synthesis from Derivatives of 2-Acylphloroglucinol4	Conclusion
Spectrum of Lysosomal Storage Disorders at Tertiary Centre: Retrospective Case-Record Analysis
Authors: Singh Ankur , Prasad Rajniti , Mishra Om Prakash 
Published: January 2020

AbstractLysosomal storage disorders (LSDs) are relatively common slow progressive inborn error of metabolism encountered by clinicians. This work intends to highlight the more common LSDs, their clinical presentation, outcome, and mutation (wherever feasible) collected from the genetic clinic at tertiary care center in Eastern Uttar Pradesh. The data for analysis were collected retrospectively from genetic records from a follow-up clinic. All cases < 18 years of age were analyzed. Cases with LSDs with confirmed enzyme results were enrolled in this study. Clinical profile, screening test results, and outcome were collected. There were 32 cases including 27 males and 5 females in this cohort: 8 Gaucher disease (GD) patient and 24 non-GD patients. GD (type 1) is the commonest LSD in GD group. Anemia, thrombocytopenia, splenomegaly, and hepatomegaly were the consistent finding in patients with GD (type 1). L483P mutation was reported in two GD patients. One GD patient is on enzyme replacement therapy for 2 years and is currently doing well. The commonest disorders in non-GD were mucopolysaccharidosis (MPS) (n = 11), metachromatic leukodystrophy (n = 4), I-cell disease (n = 3), Niemann-Pick A/B (n = 3). MPS-II is the commonest MPS among non-GD group.
Revision Multiligament Knee Reconstruction Surgery
Authors: Stuart Michael B. , Woodmass Jarret M. , Krych Aaron J. , Levy Bruce A. , Stuart Michael J. 
Published: January 2020

AbstractFailed multiligament knee reconstruction is a challenging problem due to recurrent pathologic laxity that is often associated with limb malalignment, meniscus deficiency, articular cartilage insufficiency, decreased motion, compromised bone stock, and a paucity of graft sources. Revision surgical indications and techniques require a comprehensive evaluation of the patient, injury and treatment factors along with a focused physical examination and advanced imaging. A stepwise treatment approach can be effective in the evaluation of revision surgery and also in setting realistic patient goals.
Analysis of a 6-DOF parallel robot motion simulation
Authors: Miclosina C O , Cojocaru V , Korka Z I 
Published: January 2020

Abstract
The paper presents the geometrical model of a parallel topology robot of MSSM type, operated as a flight simulator. Certain strokes of the driving kinematical joints lead to the simulation of real limit situations, which are dangerous for the human operator, such as a sudden pitch movement. The variations of different motion parameters are analyzed. SolidWorks software was used in the modeling and simulation processes.
PLC programming to optimize water flow in secondary cooling zone
Authors: Tirian G O , Chioncel C P , Holubeck R , Cinkar K 
Published: January 2020

Abstract
In the paper was made PLC programming, with which an adaptive system was implemented, was used the Simatic Manager Step 7 software, which is specific to the chosen PLC Simatic S7-300. Input data, computation relationships and correlations between the different sizes were retrieved and processed from the database of the two human operators, commanding the opening of the valve automatically. With this software, it was possible to eliminate the human factor in controlling parameters specific to the continuous casting secondary cooling zone.
The kinematic and kinetostatic study of the shaker mechanism with SolidWorks Motion
Authors: Nedelcu D , Gillich G R , Bloju A , Padurean I 
Published: January 2020

Abstract
The objective of the paper is to calculate the kinematic and dynamic behaviour of the shaker mechanism and compare the theoretical with the following SolidWorks Motion results: the positional analysis, kinematic analysis of velocities, kinematic analysis of accelerations and kinetostatic analysis.
Principles of development of product lifecycle management system for threaded connections based on the Python programming language
Authors: Kopei V B , Onysko O R , Panchuk V G 
Published: January 2020

Abstract
The principles of the development of PLM-system for threaded connections of oil and gas equipment are described. In order to ensure efficiency, the PLM-system must be isomorphic to other complex systems and have their laws, in particular, the emergence and “requisite variety”. The proposed system belongs to the class of hybrid multi-agent intelligent systems that combine various methods of knowledge representation and decision making. The system contains a knowledge base with inference rules, an inference engine, a code editor, simulation models of threaded connections, the results of their simulations, and other components. The knowledge base contains facts, in which the factors that affect the reliability and durability of threaded connections, are connected by cause-effect relations “is the cause” and “is the effect”. Facts can have such properties as an information source, dependence of quantities, a simulation model, etc. The rules of inference allow you to get new facts from the knowledge base and simulation models. All system components or their software interfaces are developed in a high-level general-purpose programming language Python, which simplifies the implementation of the system and the integration of components with different types. In particular, any Python package can be easily connected to the system. Classes and individuals of ontology are declaratively described by Python classes and objects, attributes and relationships are Python-attributes. For easy editing, the system code is divided into parts, which are combined before execution.
Investigation of the technological damageability of castings at the stage of design and technological preparation of the machine Life Cycle
Authors: Kusyi Y M , Kuk A M 
Published: January 2020

Abstract
Solution of the problem of machines reliability requires new approaches which at the present stage of machine-building industry development is realized by implementing PLM - conceps (Product Lifecycle Management). The PLM - concepts are the system of management of the machine parts life with design of the functionally-oriented technologies of production by means of parallel engineering.
Complex conditions of the products exploitation and complex technological processes of treatment require their profound theoretical and experimental investigation. An important task in the mechanical treatment and operation of products from the standpoint of their reliability is to predict their behavior at a certain point of time.
The LM-hardness method developed under the guidance of academician A.A. Lebedev to control the samples structure quality and materials damageability in the investigated part of the samples is proposed. According to the LM-hardness method derivatives of the physical parameters absolute values, for example, dissipation of the obtained control results carried out by the same devices in identical conditions serve as the evaluation criterion.
Homogeneity is a parameter that integrally describes the material state when processing the results of hardness control. The homogeneity is described by the Weibull coefficient m and the known Gumbel formula.
In our researches we propose to evaluate the analysis of the material structure state both by means of the Weibull coefficient m, and its technological damageability W, which is inversely proportional to the Weibull coefficient.
The experimental researches were carried out on aluminium alloy castings in sand moulds.Distribution of the technological damages W by the height of castings is established on the basis of performed researches at the stage of process engineering. The influence of the parameters of the “Sandvik” company tool design in treatment, using the “HAAS” treatment equipment on the change of the Weibull coefficient m is analyzed.