bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2)
Authors: Chaikuad Apirat , Koschade Sebastian E. , Stolz Alexandra , Zivkovic Katarina , Pohl Christian , Shaid Shabnam , Ren Huiyu , Lambert Lester J. , Cosford Nicholas D.P. , Brandts Christian H. , Knapp Stefan 
Published: February 2019

Abstract
Autophagy is essential for cellular homeostasis and when deregulated this survival mechanism has been associated with disease development. Inhibition of autophagy initiation by inhibiting the kinase ULK1 (Unc-51-like autophagy activating kinase 1) has been proposed as a potential cancer therapy. While inhibitors and crystal structures of ULK1 have been reported, little is known about the other closely related kinase ULK2 (Unc-51-like autophagy activating kinase 2). Here, we present the crystal structure of ULK2 in complex with ATP competitive inhibitors. Surprisingly, the ULK2 structure revealed a dimeric assembly reminiscent of dimeric arrangements of auto-activating kinases suggesting a role for this association in ULK activation. Screening of a kinase focused library of pre-clinical and clinical compounds revealed several potent ULK1/2 inhibitors and good correlation of inhibitor-binding behavior with both ULK kinases. Aurora A was identified as a major off-target of currently used ULK1 inhibitors. Autophagic flux assays demonstrated that this off-target activity by strongly inducing autophagy in different cellular systems conferred an additional layer of complexity in the interpretation of cellular data. The data presented here provide structural models and chemical starting points for the development of ULK1/2 dual inhibitors with improved selectivity for future exploitation of autophagy inhibition.
The role of VPS4 in ESCRT-III polymer remodeling
Authors: Caillat Christophe , Maity Sourav , Miguet Nolwenn , Roos Wouter H. , Weissenhorn Winfried 
Published: February 2019

Abstract
The endosomal sorting complex required for transport-III (ESCRT-III) and VPS4 catalyze a variety of membrane-remodeling processes in eukaryotes and archaea. Common to these processes is the dynamic recruitment of ESCRT-III proteins from the cytosol to the inner face of a membrane neck structure, their activation and filament formation inside or at the membrane neck and the subsequent or concomitant recruitment of the AAA-type ATPase VPS4. The dynamic assembly of ESCRT-III filaments and VPS4 on cellular membranes induces constriction of membrane necks with large diameters such as the cytokinetic midbody and necks with small diameters such as those of intraluminal vesicles or enveloped viruses. The two processes seem to use different sets of ESCRT-III filaments. Constriction is then thought to set the stage for membrane fission. Here, we review recent progress in understanding the structural transitions of ESCRT-III proteins required for filament formation, the functional role of VPS4 in dynamic ESCRT-III assembly and its active role in filament constriction. The recent data will be discussed in the context of different mechanistic models for inside-out membrane fission.
Coenzyme A: a protective thiol in bacterial antioxidant defence
Authors: Gout Ivan 
Published: February 2019

Abstract
Coenzyme A (CoA) is an indispensable cofactor in all living organisms. It is synthesized in an evolutionarily conserved pathway by enzymatic conjugation of cysteine, pantothenate (Vitamin B5), and ATP. This unique chemical structure allows CoA to employ its highly reactive thiol group for diverse biochemical reactions. The involvement of the CoA thiol group in the production of metabolically active CoA thioesters (e.g. acetyl CoA, malonyl CoA, and HMG CoA) and activation of carbonyl-containing compounds has been extensively studied since the discovery of this cofactor in the middle of the last century. We are, however, far behind in understanding the role of CoA as a low-molecular-weight thiol in redox regulation. This review summarizes our current knowledge of CoA function in redox regulation and thiol protection under oxidative stress in bacteria. In this context, I discuss recent findings on a novel mode of redox regulation involving covalent modification of cellular proteins by CoA, termed protein CoAlation.
It's all about the T: transcription termination in archaea
Authors: Maier Lisa-Katharina , Marchfelder Anita 
Published: February 2019

Abstract
One of the most fundamental biological processes driving all life on earth is transcription. The, at first glance, relatively simple cycle is divided into three stages: initiation at the promoter site, elongation throughout the open reading frame, and finally termination and product release at the terminator. In all three processes, motifs of the template DNA and protein factors of the transcription machinery including the multisubunit polymerase itself as well as a broad range of associated transcription factors work together and mutually influence each other. Despite several decades of research, this interplay holds delicate mechanistic and structural details as well as interconnections yet to be explored. One of the surprising characteristics of archaeal biology is the use of eukaryotic-like information processing systems against a backdrop of a bacterial-like genome. Archaeal genomes usually comprise main chromosomes alongside chromosomal plasmids, and the genetic information is encoded in single transcriptional units as well as in multicistronic operons alike their bacterial counterparts. Moreover, archaeal genomes are densely packed and this necessitates a tight regulation of transcription and especially assured termination events in order to prevent read-through into downstream coding regions and the accumulation of antisense transcripts.
STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer
Authors: Liu Chao , Shi Jiaqi , Li Qingwei , Li Zhiwei , Lou Changjie , Zhao Qi , Zhu Yuanyuan , Zhan Fei , Lian Jie , Wang Bojun , Guan Xin , Fang Lin , Li Zengxun , Wang Yifei , Zhou Bodong , Yao Yuanfei , Zhang Yanqiao 
Published: February 2019

Abstract
Forkhead box protein M1 (FOXM1) was identified as an oncogenic transcription factor and master regulator of tumor progression and metastasis. FOXM1 expression often correlates with poor prognosis and chemotherapy resistance. In the present study, we investigated the association of FOXM1 expression and chemoresistance in pancreatic cancer. Elevated FOXM1 protein levels were associated with gemcitabine chemoresistance in patients with pancreatic cancer. In gemcitabine resistance cell line models of pancreatic cancer, FOXM1 expression increased, which induced gemcitabine chemoresistance in vitro. In pancreatic cancer cells treated with gemcitabine, FOXM1 affected nuclear factor κB (NF-κB) signaling activity. Immunohistochemical analysis demonstrated a negative association of FOXM1 expression and the level of phosphorylated signal transducer and activator of transcription 1 (pSTAT1) in human pancreatic cancer tissues. Dual-luciferase reporter assays and chromatin-immunoprecipitation assays demonstrated that pSTAT1 directly binds to the FOXM1 promoter to down-regulate its transcription. Interferon γ (IFNγ) promoted gemcitabine-induced cell apoptosis and inhibited cell proliferation in vitro and in vivo by FOXM1 inhibition. These data suggested that FOXM1 enhances chemoresistance to gemcitabine in pancreatic cancer. IFNγ could be used to down-regulate the expression of FOXM1 through STAT1 phosphorylation, thereby increasing the sensitivity of pancreatic cancer cells to gemcitabine. These studies suggested the sensitization by IFNγ in pancreatic ductal adenocarcinoma (PDAC) chemotherapy, which requires further clinical studies.
The Effect of Kalman-Weighted Averaging and Artifact Rejection on Residual Noise During Auditory Brainstem Response Testing
Authors: Norrix Linda W. , Thein Julie , Velenovsky David 
Published: February 2019

Purpose
Low residual noise (RN) levels are critically important when obtaining electrophysiological recordings of threshold auditory brainstem responses. In this study, we examine the effectiveness and efficiency of Kalman-weighted averaging (KWA) implemented on the Vivosonic Integrity System and artifact rejection (AR) implemented on the Intelligent Hearing Systems SmartEP system for obtaining low RN levels.

Method
Sixteen adults participated. Electrophysiological measures were obtained using simultaneous recordings by the Vivosonic and Intelligent Hearing Systems for subjects in 2 relaxed conditions and 4 active motor conditions. Three averaging times were used for the relaxed states (1, 1.5, and 3 min) and for the active states (1.5, 3, and 6 min). Repeated-measures analyses of variance were used to examine RN levels as a function of noise reduction strategy (i.e., KWA, AR) and averaging time.

Results
Lower RN levels were obtained using KWA than AR in both the relaxed and active motor states. Thus, KWA was more effective than was AR under the conditions examined in this study. Using KWA, approximately 3 min of averaging was needed in the relaxed condition to obtain an average RN level of 0.025 μV. In contrast, in the active motor conditions, approximately 6 min of averaging was required using KWA. Mean RN levels of 0.025 μV were not attained using AR.

Conclusions
When patients are not physiologically quiet, low RN levels are more likely to be obtained and more efficiently obtained using KWA than AR. However, even when using KWA, in active motor states, 6 min of averaging or more may be required to obtain threshold responses. Averaging time needed and whether a low RN level can be attained will depend on the level of motor activity exhibited by the patient.
Enhanced Speechreading Performance in Young Hearing Aid Users in China
Authors: Lei Jianghua , Gong Huina , Chen Liang 
Published: February 2019

Purpose
The study was designed primarily to determine if the use of hearing aids (HAs) in individuals with hearing impairment in China would affect their speechreading performance.

Method
Sixty-seven young adults with hearing impairment with HAs and 78 young adults with hearing impairment without HAs completed newly developed Chinese speechreading tests targeting 3 linguistic levels (i.e., words, phrases, and sentences).

Results
Groups with HAs were more accurate at speechreading than groups without HA across the 3 linguistic levels. For both groups, speechreading accuracy was higher for phrases than words and sentences, and speechreading speed was slower for sentences than words and phrases. Furthermore, there was a positive correlation between years of HA use and the accuracy of speechreading performance; longer HA use was associated with more accurate speechreading.

Conclusions
Young HA users in China have enhanced speechreading performance over their peers with hearing impairment who are not HA users. This result argues against the perceptual dependence hypothesis that suggests greater dependence on visual information leads to improvement in visual speech perception.
Investigating Listening Effort in Classrooms for 5- to 7-Year-Old Children
Authors: Prodi Nicola , Visentin Chiara , Peretti Alessandro , Griguolo Jacopo , Bartolucci Giovanni Battista 
Published: February 2019

Purpose
This study aims to investigate the listening effort made by young children in real classrooms during a prolonged speech reception task in the presence of background noise.

Method

The experiment was proposed to 117 typically developing kindergarten and primary school pupils, aged 5–7 years old. An ecological experimental approach was followed, and speech-in-noise tests were presented in the classrooms to groups made up of the whole class. The speech material of the Word Intelligibility by Picture Identification Test in the Italian language (
Arslan, Genovese, Orzan, & Turrini, 1997
) was presented in 2 listening conditions (quiet classroom [no noise added] and working classroom [with stationary noise]) and was repeated twice during the experiment. Data on the number of correctly recognized words and the single-task response time (RT) were collected; the quantity of the latter was considered informative on listening effort.

Results
It was found that when background noise was present, the pupils' performance decreased, and greater RTs were required compared to the “quiet classroom” condition. When the RTs were analyzed over the course of the experiment, there were no changes in the quiet condition, whereas in the working classroom, a significant increase was found for the 6- and 7-year-old pupils. On the contrary, the youngest pupils (5-year-olds) showed a decrease in the RT results over the test repetitions.

Conclusions
The RT measured with a single-task paradigm was found to be a viable approach for investigating the listening effort in 6- to 7-year-old pupils. For this age range, the metric was sensitive to changes both in the listening conditions and within the same listening condition across the time of exposure. More research is needed to assess the feasibility of the experimental paradigm with the 5-year-old children.
Two‐step, piecewise‐linear SAR ADC with programmable transfer function
Authors: Sengupta S. , Johnston M.L. 
Published: February 2019

A 7‐bit successive approximation register (SAR) analogue‐to‐digital converter (ADC) with programmable transfer functions is presented. Building upon prior art, a two‐step successive approximation technique is used to implement a piecewise‐linear approximation of the desired transfer function. However, unlike previous implementations of SAR‐based non‐linear ADCs, the proposed work demonstrates programmability of arbitrary non‐linear transfer functions, thus making it suitable for a wide range of low‐bandwidth applications. Simulation results from a proof‐of‐concept design in a standard 180 nm CMOS process are presented to validate the proposed idea.
Slim dual‐polarised antenna with omnidirectional patterns for WLAN applications
Authors: Sun Li , Li Yulian 
Published: February 2019

A slim dual‐polarised antenna with omnidirectional patterns is proposed for wireless local area network (WLAN) applications. The antenna is a composition of a modified J‐type antenna for vertical polarisation and two crossed‐loop antennas for horizontal polarisation. For improving the isolation between the two polarisations, a rectangular loop is partially added in the middle of one of the loop antenna, connecting the end of the J‐type antenna. The rectangular loop also acts as tuning the impedance of the antenna. For achieving omnidirectional patterns of the horizontal polarisation, a series circular feeding network is designed to excite the loop antennas. The antenna is fabricated by copper and the circular network is printed on a substrate. Measurement results show the 10 dB return losses of the two ports are covering the whole 2.4 GHz WLAN band, with the isolation better than 20 dB. The gains vary <2.2 dB in the horizontal plane for both the polarisations. With the advantages of slim structure, lightweight, and easy fabrication, the proposed antenna is convenient to use in the WLAN routers.
Formation of wind-captured disks in supergiant X-ray binaries
Authors: El Mellah I. , Sander A. A. C. , Sundqvist J. O. , Keppens R. 
Published: February 2019

Context. In supergiant X-ray binaries (SgXB), a compact object captures a fraction of the wind of an O/B supergiant on a close orbit. Proxies exist to evaluate the efficiency of mass and angular momentum accretion, but they depend so dramatically on the wind speed that given the current uncertainties, they only set loose constraints. Furthermore, these proxies often bypass the impact of orbital and shock effects on the flow structure.
Aims. We study the wind dynamics and angular momentum gained as the flow is accreted. We identify the conditions for the formation of a disk-like structure around the accretor and the observational consequences for SgXB.
Methods. We used recent results on the wind launching mechanism to compute 3D streamlines, accounting for the gravitational and X-ray ionizing influence of the compact companion on the wind. Once the flow enters the Roche lobe of the accretor, we solved the hydrodynamics equations with cooling.
Results. A shocked region forms around the accretor as the flow is beamed. For wind speeds on the order of the orbital speed, the shock is highly asymmetric compared to the axisymmetric bow shock obtained for a purely planar homogeneous flow. With net radiative cooling, the flow always circularizes for sufficiently low wind speeds.
Conclusions. Although the donor star does not fill its Roche lobe, the wind can be significantly beamed and bent by the orbital effects. The net angular momentum of the accreted flow is then sufficient to form a persistent disk-like structure. This mechanism could explain the proposed limited outer extension of the accretion disk in Cygnus X-1 and suggests the presence of a disk at the outer rim of the neutron star magnetosphere in Vela X-1 and has dramatic consequences on the spinning up of the accretor.
Theoretical investigation of energy levels and transition data for S II, Cl III, Ar IV
Authors: Rynkun P. , Gaigalas G. , Jönsson P. 
Published: February 2019

Aims. The aim of this work is to present accurate and extensive results of energy spectra and transition data for the S II, Cl III, and Ar IV ions. These data are useful for understanding and probing physical processes and conditions in various types of astrophysical plasmas.Methods. The multiconfiguration Dirac–Hartree–Fock (MCDHF) and relativistic configuration interaction (RCI) methods, which are implemented in the general-purpose relativistic atomic structure package GRASP2K, are used in the present work. In the RCI calculations the transverse-photon (Breit) interaction, the vacuum polarization, and the self-energy corrections are included.Results. Energy spectra are presented comprising the 134, 87, and 103 lowest states in S II, Cl III, and Ar IV, respectively. Energy levels are in very good agreement with NIST database recommended values and associated with smaller uncertainties than energies from other theoretical computations. Electric dipole (E1), magnetic dipole (M1), and electric quadrupole (E2) transition data are computed between the above states together with the corresponding lifetimes. Based on internal validation, transition rates for the majority of the stronger transitions are estimated to have uncertainties of less than 3%.
Ingénierie écologique appliquée aux eﬀuents vinicoles : exemple du dispositif de BlueSET Phytostation® dans la cave « Les Vignerons de Buzet »
Authors: Rochard J. , Wang R. , Alary A. , Lecuona Y. , Philippe P. 
Published: February 2019

Le traitement des eﬀuents vinicoles est très souvent réalisé par des systèmes aérobies avec des bassins ouverts. Au-delà de la consommation d'énergie, ces dispositifs génèrent souvent des nuisances sonores, olfactives et visuelles, ce qui impose le plus souvent d'éloigner le dispositif de la cave. La coopérative « Les Vignerons de de Buzet », située dans le sud-ouest de la France, qui a déjà développé une démarche durable pour le vignoble et la cave, a souhaité intégrer une zone humide associée au traitement des eﬀuents de cave avec le procédé breveté de la société BlueSET spécialisée dans le génie écologique. Après une première étape de traitement en aérobie, le dispositif se compose d'un ensemble de bassins dans lesquels sont implantés majoritairement de plantes locales non invasives. Il a pour objectif de favoriser la biodiversité et de permettre aux visiteurs de profiter de manière didactique d'une zone de promenade écologique qui valorise l'image environnementale de la cave. Les résultats de la première année démontrent que les performances sont compatibles avec les normes de rejet locales.
Base-Metal-Catalyzed Olefin Isomerization Reactions
Authors: Liu Qiang , Liu Xufang , Li Bin 
Published: February 2019

The catalytic olefin isomerization reaction is a highly efficient and atom-economic transformation in organic synthesis that has attracted tremendous attention both in academia and industry. Recently, the development of Earth-abundant metal catalysts has received growing interest owing to their wide availability, sustainability, and ­environmentally benign nature, as well as the unique properties of non-precious metals. This review provides an overview of a broad range of base-metal-catalyzed olefin isomerization reactions categorized ­according to their different reaction mechanisms.1	Introduction2	Base-Metal-Catalyzed Olefin Isomerization Reactions3	Base-Metal-Catalyzed Cycloisomerization Reactions4	Conclusion
Complete Covalent Structure of Human Platelet Factor 4
Authors: Morgan Francis J , Begg Geoffrey S , Chesterman Colin N 
Published: February 2019

SummaryThe amino acid sequence of the subunit of human platelet factor 4 has been determined. Human platelet factor 4 consists of identical subunits containing 70 amino acids, each with a molecular weight of 7,756. The molecule contains no methionine, phenylalanine or tryptophan. The proposed amino acid sequence of PF4 is: Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gln-Cys-Leu-Cys-Val-Lys-Thr-Thr-Ser- Gln-Val-Arg-Pro-Arg-His-Ile-Thr-Ser-Leu-Glu-Val-Ile-Lys-Ala-Gly-Pro-His-Cys-Pro-Thr-Ala-Gin- Leu-Ile-Ala-Thr-Leu-Lys-Asn-Gly-Arg-Lys-Ile-Cys-Leu-Asp-Leu-Gln-Ala-Pro-Leu-Tyr-Lys-Lys- Ile-Ile-Lys-Lys-Leu-Leu-Glu-Ser. From consideration of the homology with p-thromboglobulin, disulphide bonds between residues 10 and 36 and between residues 12 and 52 can be inferred.
Plasmacytoid Urothelial Carcinoma of the Bladder: Case Report and Review of the Literature
Authors: Molina Barrera Ángela , Vásquez Franco Andrea , Aristizábal Andrés Felipe , Correa Galeano David , Cabrales Hessen Manuel 
Published: February 2019

Introduction Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histological variant, accounting for 1 to 3% of the invasive urothelial carcinomas, and it is typically aggressive. So far, it has not been well characterized, and the literature is based on reports and case series.
Case Report A 70-year-old male patient presenting with 4 months of constitutional and urinary symptoms, with an ultrasound finding of bilateral hydronephrosis and diffuse thickening of the bladder walls. In the cystoscopy, trigone of infiltrated appearance, a biopsy wass performed, whose immunohistochemistry revealed a PUC. The abdominopelvic image showed an infiltrative lesion that compromised the muscle of the bladder and extended to the perivesical fat, without adequate plane of cleavage with the prostate and a single hypogastric adenopathy suspected of malignancy. It was classified as cT3b vs cT4aN1M0 (chest computed tomography [CT] negative for malignancy), and the patient was submitted to a radical cystoprostatectomy, extended pelvic lymphadenectomy and non-continent urinary diversion with ileal conduit. The pathology revealed a diffuse PUC with prostatic stromal involvement and 22 of 39 lymph nodes positive for malignancy. Finally, the patient presented a series of postoperative complications and died.
Conclusion Plasmacytoid urothelial carcinoma of the bladder is a rare entity, characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis. Currently, an aggressive approach is recommended due to its high invasive potential.