bluuebunny/crossref_metadata_2025_split huggingface dataset:
An accurate TMT-based approach to quantify and model lysine susceptibility to conjugation via N-hydroxysuccinimide esters in a monoclonal antibody
Authors: Hill Jennifer J. , Tremblay Tammy-Lynn , Corbeil Christopher R. , Purisima Enrico O. , Sulea Traian 
Published: November 2018

AbstractConjugation of small molecules to proteins through N-hydroxysuccinimide (NHS) esters results in a random distribution of small molecules on lysine residues and the protein N-terminus. While mass spectrometry methods have improved characterization of these protein conjugates, it remains a challenge to quantify the occupancy at individual sites of conjugation. Here, we present a method using Tandem Mass Tags (TMT) that enabled the accurate and sensitive quantification of occupancy at individual conjugation sites in the NIST monoclonal antibody. At conjugation levels relevant to antibody drug conjugates in the clinic, site occupancy data was obtained for 37 individual sites, with average site occupancy data across 2 adjacent lysines obtained for an additional 12 sites. Thus, altogether, a measure of site occupancy was obtained for 98% of the available primary amines. We further showed that removal of the Fc-glycan on the NIST mAb increased conjugation at two specific sites in the heavy chain, demonstrating the utility of this method to identify changes in the susceptibility of individual sites to conjugation. This improved site occupancy data allowed calibration of a bi-parametric linear model for predicting the susceptibility of individual lysines to conjugation from 3D-structure based on their solvent exposures and ionization constants. Trained against the experimental data for lysines from the Fab fragment, the model provided accurate predictions of occupancies at lysine sites from the Fc region and the protein N-terminus (R2 = 0.76). This predictive model will enable improved engineering of antibodies for optimal labeling with fluorophores, toxins, or crosslinkers.
Spatial analysis of the geographical distribution of thyroid cancer cases from the first-round thyroid ultrasound examination in Fukushima Prefecture
Authors: Nakaya Tomoki , Takahashi Kunihiko , Takahashi Hideto , Yasumura Seiji , Ohira Tetsuya , Ohto Hitoshi , Ohtsuru Akira , Midorikawa Sanae , Suzuki Shinichi , Shimura Hiroki , Yamashita Shunichi , Tanigawa Koichi , Kamiya Kenji 
Published: November 2018

AbstractFollowing the Fukushima Daiichi Nuclear Power Plant (FNPP) accident on 11 March 2011, there have been concerns regarding the health impacts of the ensuing radioactive environmental contamination, which was spatially heterogeneous. This study aimed to assess the geographical variability of thyroid cancer prevalence among children and adolescents in Fukushima Prefecture. We computed the sex- and age-standardised prevalence ratio using 115 diagnosed or suspected thyroid cancer cases among approximately 300,000 examinees at the first-round ultrasound examination during 2011–2015 from 59 municipalities in the prefecture, under the Fukushima Health Management Survey. We applied flexibly shaped spatial scan statistics and the maximised excess events test on the dataset to detect locally anomalous high-prevalence regions. We also conducted Poisson regression with selected regional indicators. Furthermore, approximately 200 examinees showed positive ultrasound examination results but did not undergo confirmatory testing; thus, we employed simulation-based sensitivity tests to evaluate the possible effect of such undiagnosed cases in the statistical analysis. In conclusion, this study found no significant spatial anomalies/clusters or geographic trends of thyroid cancer prevalence among the ultrasound examinees, indicating that the thyroid cancer cases detected are unlikely to be attributable to regional factors, including radiation exposure resulting from the FNPP accident.
Circulating small non-coding RNAs associated with age, sex, smoking, body mass and physical activity
Authors: Rounge Trine B. , Umu Sinan U. , Keller Andreas , Meese Eckart , Ursin Giske , Tretli Steinar , Lyle Robert , Langseth Hilde 
Published: November 2018

AbstractSmall non-coding RNAs (sncRNA) are regulators of cell functions and circulating sncRNAs from the majority of RNA classes are potential non-invasive biomarkers. Understanding how common traits influence ncRNA expression is essential for assessing their biomarker potential. In this study, we identify associations between sncRNA expression and common traits (sex, age, self-reported smoking, body mass, self-reported physical activity). We used RNAseq data from 526 serum samples from the Janus Serum Bank and traits from health examination surveys. Ageing showed the strongest association with sncRNA expression, both in terms of statistical significance and number of RNAs, regardless of RNA class. piRNAs were abundant in the serum samples and they were associated to sex. Interestingly, smoking cessation generally restored RNA expression to non-smoking levels, although for some sncRNAs smoking-related expression levels persisted. Pathway analysis suggests that smoking-related sncRNAs target the cholinergic synapses and may therefore potentially play a role in smoking addiction. Our results show that common traits influence circulating sncRNA expression. It is clear that sncRNA biomarker analyses should be adjusted for age and sex. In addition, for specific sncRNAs, analyses should also be adjusted for body mass, smoking, physical activity and technical factors.
Sleep deprivation alters the time course but not magnitude of locomotor sensitization to cocaine
Authors: Bjorness Theresa E. , Greene Robert W. 
Published: November 2018

AbstractRepeated exposure to drugs of abuse progressively increases the response to the same stimuli, a process known as sensitization. Behavioral sensitization to cocaine administration is often measured in non-human subjects via locomotor activity which is easily quantifiable. The effects of four hours of sleep deprivation on repeated cocaine (five daily and one challenge) showed attenuated hyperactivity on the first day only, compared to the non-deprived group. Both groups reached the same final level of sensitization, indicating that sleep deprivation altered the time course, but not magnitude of locomotor sensitization.
A quantitative reverse transcription-polymerase chain reaction for detection of Getah virus
Authors: Sam Sing-Sin , Teoh Boon-Teong , Chee Cheah-Mun , Mohamed-Romai-Noor Noor-Adila , Abd-Jamil Juraina , Loong Shih-Keng , Khor Chee-Sieng , Tan Kim-Kee , AbuBakar Sazaly 
Published: November 2018

AbstractGetah virus (GETV), a mosquito-borne alphavirus, is an emerging animal pathogen causing outbreaks among racehorses and pigs. Early detection of the GETV infection is essential for timely implementation of disease prevention and control interventions. Thus, a rapid and accurate nucleic acid detection method for GETV is highly needed. Here, two TaqMan minor groove binding (MGB) probe-based quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays were developed. The qRT-PCR primers and TaqMan MGB probe were designed based on the conserved region of nsP1 and nsP2 genes of 23 GETV genome sequences retrieved from GenBank. Only the qRT-PCR assay using nsP2-specific primers and probe detected all two Malaysia GETV strains (MM2021 and B254) without cross-reacting with other closely related arboviruses. The qRT-PCR assay detected as few as 10 copies of GETV RNA, but its detection limit at the 95% probability level was 63.25 GETV genome copies (probit analysis, P ≤ 0.05). Further validation of the qRT-PCR assay using 16 spiked simulated clinical specimens showed 100% for both sensitivity and specificity. In conclusion, the qRT-PCR assay developed in this study is useful for rapid, sensitive and specific detection and quantification of GETV.
Quantum Annealing for Prime Factorization
Authors: Jiang Shuxian , Britt Keith A. , McCaskey Alexander J. , Humble Travis S. , Kais Sabre 
Published: November 2018

AbstractWe have developed a framework to convert an arbitrary integer factorization problem to an executable Ising model by first writing it as an optimization function then transforming the k-bit coupling (k ≥ 3) terms to quadratic terms using ancillary variables. Our resource-efficient method uses $${\mathscr{O}}({\mathrm{log}}^{2}(N))$$
O
(

log

2

(
N
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binary variables (qubits) for finding the factors of an integer N. We present how to factorize 15, 143, 59989, and 376289 using 4, 12, 59, and 94 logical qubits, respectively. This method was tested using the D-Wave 2000Q for finding an embedding and determining the prime factors for a given composite number. The method is general and could be used to factor larger integers as the number of available qubits increases, or combined with other ad hoc methods to achieve better performances for specific numbers.
Enhancement of photoluminescence efficiency in GeSe ultrathin slab by thermal treatment and annealing: experiment and first-principles molecular dynamics simulations
Authors: Mao Yuliang , Mao Xin , Zhao Hongquan , Zhang Nandi , Shi Xuan , Yuan Jianmei 
Published: November 2018

AbstractThe effect of thermal treatment and annealing under different temperatures from 100 °C to 250 °C on the photoluminescence spectroscopy of the GeSe ultrathin slab is reported. After the thermal treatment and annealing under 200 °C, we found that the photoluminescence intensity of A exciton and B exciton in GeSe ultrathin slab is increased to twice as much as that in untreated case, while is increased by ~84% in the photoluminescence intensity of C exciton. Combined by our experimental work and theoretical simulations, our study confirms the significant role of thermal treatments and annealing in reducing surface roughness and removing the Se vacancy to form more compact and smoother regions in GeSe ultrathin slab. Our findings imply that the improved quality of GeSe surface after thermal treatments is an important factor for the photoluminescence enhancement.
Simple multi-wavelength imaging of birefringence:case study of silk
Authors: Honda Reo , Ryu Meguya , Li Jing-Liang , Mizeikis Vygantas , Juodkazis Saulius , Morikawa Junko 
Published: November 2018

AbstractPolarised light imaging microscopy, with the addition of a liquid crystal (LC) phase retarder, was used to determine the birefringence of silk fibres with high (∼1 μm) spatial resolution. The measurement was carried out with the silk fibres (the optical slow axis) and the slow axis of the LC-retarder set at parallel angles. The direct fit of the transmission data allowed for high fidelity determination of the birefringence Δn ≈ 1.63 × 10−2 (with ∼2% uncertainty) of the brown silk fibre, (Antheraea pernyi) averaged over the wavelength range λ = (425–625) nm. By measuring retardance at four separate wavelengths, it was possible to determine the true value of the birefringence of a thicker sample when an optical path may include a large number of wavelengths. The numerical procedures and required hardware are described for the do-it-yourself assembly of the imaging polariscope at a fractional budget compared to commercial units.
Cryopreservation of primary B cells minimally influences their signaling responses
Authors: Hermansen Johanne U. , Tjønnfjord Geir E. , Munthe Ludvig A. , Taskén Kjetil , Skånland Sigrid S. 
Published: November 2018

AbstractPhospho flow is a powerful approach to detect cell signaling aberrations, identify biomarkers and assess pharmacodynamics, and can be performed using cryopreserved samples. The effects of cryopreservation on signaling responses and the reproducibility of phospho flow measurements are however unknown in many cell systems. Here, B lymphocytes were isolated from healthy donors and patients with the B cell malignancy chronic lymphocytic leukemia and analyzed by phospho flow using phospho-specific antibodies targeting 20 different protein epitopes. Cells were analyzed both at basal conditions and after activation of cluster of differentiation 40 (CD40) or the B cell receptor. Pharmacodynamics of the novel pathway inhibitor ibrutinib was also assessed. At all conditions, fresh cells were compared to cryopreserved cells. Minimal variation between fresh and frozen samples was detected. Reproducibility was tested by running samples from the same donors in different experiments. The results demonstrate reproducibility across different phospho flow runs and support the use of cryopreserved samples in future phospho flow studies of B lymphocytes.
Extracellular Protein Fibulin-7 and Its C-Terminal Fragment Have In Vivo Antiangiogenic Activity
Authors: Ikeuchi Tomoko , de Vega Susana , Forcinito Patricia , Doyle Andrew D. , Amaral Juan , Rodriguez Ignacio R. , Arikawa-Hirasawa Eri , Yamada Yoshihiko 
Published: November 2018

AbstractAngiogenesis is crucial for tissue development and homeostasis; however, excessive angiogenesis can lead to diseases, including arthritis and cancer metastasis. Some antiangiogenic drugs are available, but side effects remain problematic. Thus, alternative angiogenesis inhibition strategies are needed. Fibulin-7 (Fbln7) is a newly discovered member of the fibulin protein family, a group of cell-secreted glycoproteins, that functions as a cell adhesion molecule and interacts with other extracellular matrix (ECM) proteins as well as cell receptors. We previously showed that a recombinant C-terminal Fbln7 fragment (Fbln7-C) inhibits tube formation by human umbilical vein endothelial cells (HUVECs) in vitro. In the present study, we examined the in vivo antiangiogenic activity of recombinant full-length Fbln7 (Fbln7-FL) and Fbln7-C proteins using a rat corneal angiogenesis model. We found that both Fbln7-FL and Fbln7-C inhibited neovascularization. Fbln7-C bound to vascular endothelial growth factor receptor 2 (VEGFR2), inhibiting VEGFR2 and ERK phosphorylation and resulting in reduced HUVEC motility. HUVEC attachment to Fbln7-C occurred through an interaction with integrin α5β1 and regulated changes in cellular morphology. These results suggest that Fbln7-C action may target neovascularization by altering cell/ECM associations. Therefore, Fbln7-C could have potential as a therapeutic agent for diseases associated with angiogenesis.
Sox2 is associated with cancer stem-like properties in colorectal cancer
Authors: Takeda Koki , Mizushima Tsunekazu , Yokoyama Yuhki , Hirose Haruka , Wu Xin , Qian Yamin , Ikehata Katsuya , Miyoshi Norikatsu , Takahashi Hidekazu , Haraguchi Naotsugu , Hata Taishi , Matsuda Chu , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi 
Published: November 2018

AbstractSox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.
A neutron tomography study: probing the spontaneous crystallization of randomly packed granular assemblies
Authors: Dhiman Indu , Kimber Simon A. J. , Mehta Anita , Chatterji Tapan 
Published: November 2018

AbstractWe study the spontaneous crystallization of an assembly of highly monodisperse steel spheres under shaking, as it evolves from localized icosahedral ordering towards a packing reaching crystalline ordering. Towards this end, real space neutron tomography measurements on the granular assembly are carried out, as it is systematically subjected to a variation of frequency and amplitude. As expected, we see a presence of localized icosahedral ordering in the disordered initial state (packing fraction ≈ 0.62). As the frequency is increased for both the shaking amplitudes (0.2 and 0.6 mm) studied here, there is a rise in packing fraction, accompanied by an evolution to crystallinity. The extent of crystallinity is found to depend on both the amplitude and frequency of shaking. We find that the icosahedral ordering remains localized and its extent does not grow significantly, while the crystalline ordering grows rapidly as an ordering transition point is approached. In the ordered state, crystalline clusters of both face centered cubic (FCC) and hexagonal close packed (HCP) types are identified, the latter of which grows from stacking faults. Our study shows that an earlier domination of FCC gives way to HCP ordering at higher shaking frequencies, suggesting that despite their coexistence, there is a subtle dynamical competition at play. This competition depends on both shaking amplitude and frequency, as our results as well as those of earlier theoretical simulations demonstrate. It is likely that this involves the very small free energy difference between the two structures.
Structural and chemical biology of deacetylases for carbohydrates, proteins, small molecules and histones
Authors: Bürger Marco , Chory Joanne 
Published: November 2018

AbstractDeacetylation is the removal of an acetyl group and occurs on a plethora of targets and for a wide range of biological reasons. Several pathogens deacetylate their surface carbohydrates to evade immune response or to support biofilm formation. Furthermore, dynamic acetylation/deacetylation cycles govern processes from chromatin remodeling to posttranslational modifications that compete with phosphorylation. Acetylation usually occurs on nitrogen and oxygen atoms and are referred to as N- and O-acetylation, respectively. This review discusses the structural prerequisites that enzymes must have to catalyze the deacetylation reaction, and how they adapted by formation of specific substrate and metal binding sites.
Parallel and functionally segregated processing of task phase and conscious content in the prefrontal cortex
Authors: Kapoor Vishal , Besserve Michel , Logothetis Nikos K. , Panagiotaropoulos Theofanis I. 
Published: November 2018

AbstractThe role of lateral prefrontal cortex (LPFC) in mediating conscious perception has been recently questioned due to potential confounds resulting from the parallel operation of task related processes. We have previously demonstrated encoding of contents of visual consciousness in LPFC neurons during a no-report task involving perceptual suppression. Here, we report a separate LPFC population that exhibits task-phase related activity during the same task. The activity profile of these neurons could be captured as canonical response patterns (CRPs), with their peak amplitudes sequentially distributed across different task phases. Perceptually suppressed visual input had a negligible impact on sequential firing and functional connectivity structure. Importantly, task-phase related neurons were functionally segregated from the neuronal population, which encoded conscious perception. These results suggest that neurons exhibiting task-phase related activity operate in the LPFC concurrently with, but segregated from neurons representing conscious content during a no-report task involving perceptual suppression.
A giant trichobezoar extracted by laparoscopic and endoscopic cooperative surgery (LECS)
Authors: Kurosu Takahiro , Tanabe Satoshi , Hasegawa Rikiya , Yano Takafumi , Wada Takuya , Ishido Kenji , Azuma Mizutomo , Katada Chikatoshi , Koizumi Wasaburo , Moriya Hiromitsu , Yamashita Keishi 
Published: November 2018

AbstractA gastric bezoar is a mass that forms in the stomach. A giant gastric bezoar is particularly difficult to treat medically, and surgical therapy is selected. We describe our experience with a patient who had a giant gastric trichobezoar that was extracted by laparoscopic and endoscopic cooperative surgery (LECS) in accordance with the principles of LECS. The patient was a 32-year-old woman who presented at our hospital because of abdominal pain. Upper gastrointestinal endoscopy confirmed the presence of a giant gastric trichobezoar extending from the gastric cardia to the gastric angle. Because endoscopic removal was considered difficult, we extracted the giant gastric trichobezoar by LECS. The concurrent use of endoscopy was considered to allow a gastric bezoar to be extracted more safely and reliably than was previously possible.
Usefulness of the “newly designed” short-type single-balloon enteroscope for ERCP in patients with Roux-en-Y gastrectomy: a pilot study
Authors: Tanisaka Yuki , Ryozawa Shomei , Mizuide Masafumi , Kobayashi Masanori , Fujita Akashi , Minami Kazuhiro , Kobatake Tsutomu , Omiya Kumiko , Iwano Hirotoshi , Araki Ryuichiro 
Published: November 2018

Abstract
Background and aims In recent years, the short single-balloon enteroscope (SBE) has been used during endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy and has been reported to be useful. However, difficulties remain, and the procedures and devices need improvements. We assessed the usefulness and superiority of a new short SBE equipped with passive bending and high-force transmission by comparisons with outcomes using the conventional short SBE.
Methods This study evaluated short SBE-assisted ERCP-related procedures for Roux-en-Y gastrectomy between September 2011 and October 2017. Outcomes including the procedural success rate, which was the primary outcome, were assessed to compare the conventional short SBE (SIF-Y0004 [prototype]) and the new short SBE (SIF-H290S).
Results Of 74 procedures performed in 61 patients, 51 procedures in 39 patients involved the SIF-Y0004, and 23 procedures in 22 patients involved the SIF-H290S. The procedural success rates were 70.6 % for SIF-Y0004, and 95.7 % for SIF-H290S, representing better results for the new short SBE (P = 0.02). The new short SBE also had a superior diagnostic success rate (P = 0.047) and median time to reach the blind end (P < 0.001).
Conclusions Roux-en-Y gastrectomy patients treated with the new short SBE had better outcomes than those treated with conventional short SBE. More cases need to be studied; however, the new short SBE has the potential to improve ERCP outcomes in patients with surgically altered anatomy.
Metabolic Syndrome is a Risk Factor for Post-Operative Adhesions: Need for Novel Treatment Strategies
Authors: Pilpel Yair , Pines Guy , Birkenfeld Andreas , Bornstein Stefan , Miller Rafael 
Published: November 2018

AbstractMetabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.