bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure–Activity and Structure–Toxicity Relationships of Peptoid‐Based Histone Deacetylase Inhibitors with Dual‐Stage Antiplasmodial Activity
Authors: Mackwitz Marcel K. W. , Hesping Eva , Antonova‐Koch Yevgeniya , Diedrich Daniela , Woldearegai Tamirat Gebru , Skinner‐Adams Tina , Clarke Mary , Schöler Andrea , Limbach Laura , Kurz Thomas , Winzeler Elizabeth A. , Held Jana , Andrews Katherine T. , Hansen Finn K. 
Published: January 2019

AbstractNovel malaria intervention strategies are of great importance, given the development of drug resistance in malaria‐endemic countries. In this regard, histone deacetylases (HDACs) have emerged as new and promising malaria drug targets. In this work, we present the design, synthesis, and biological evaluation of 20 novel HDAC inhibitors with antiplasmodial activity. Based on a previously discovered peptoid‐based hit compound, we modified all regions of the peptoid scaffold by using a one‐pot multicomponent pathway and submonomer routes to gain a deeper understanding of the structure–activity and structure–toxicity relationships. Most compounds displayed potent activity against asexual blood‐stage P. falciparum parasites, with IC50 values in the range of 0.0052–0.25 μm and promising selectivity over mammalian cells (SIPf3D7/HepG2: 170–1483). In addition, several compounds showed encouraging sub‐micromolar activity against P. berghei exo‐erythrocytic forms (PbEEF). Our study led to the discovery of the hit compound N‐(2‐(benzylamino)‐2‐oxoethyl)‐N‐(4‐(hydroxycarbamoyl)benzyl)‐4‐isopropylbenzamide (2 h) as a potent and parasite‐specific dual‐stage antiplasmodial HDAC inhibitor (IC50 Pf3D7=0.0052 μm, IC50 PbEEF=0.016 μm).
Enhanced semantic similarity measure based on two‐level retrieval model
Authors: Ben Djemaa Raoudha , Nabli Hajer , Amous Ben Amor Ikram 
Published: January 2019

SummaryWith the rapid spread of services in the Cloud computing environment, it is difficult for users to find the right service. Therefore, the necessity of a search engine with semantic focused crawler becomes a fundamental requirement. However, the huge size and varied functionalities of Cloud services on the Web, together with the lack of standardized and coherent description of services available, have a great effect for crawlers in order to provide effective Cloud services. To solve these issues, we propose a Cloud service discovery crawler that employs a two‐level semantic similarity measure based on both TF‐IDF and LDA models. Moreover, in order to automatically discover and categorize Cloud services, we present a Cloud Service Ontology (CSOnt) that contains a set of concepts defining Cloud service categories. Experimental results show that the proposed method enhances the performance of the focused crawlers and presents an efficient way to parse the Web and collect Web pages relevant to Cloud services.
Conjugated Carbon Nitride as an Emerging Luminescent Material: Quantum Dots, Thin Films and Their Applications in Imaging, Sensing, Optoelectronic Devices and Photoelectrochemistry
Authors: Xu Jingsan , Shalom Menny 
Published: January 2019

AbstractOver the past few years, graphitic/polymeric carbon nitride (CN) has attracted widespread attention due to its interesting electronic properties, which have been exploited in various applications, including, for example, in photo‐ and electrocatalysis, heterogeneous catalysis, CO2 reduction and water splitting. Its unique and tunable optical, chemical, and catalytic properties, alongside its low price and remarkably high stability to oxidation and harsh chemical environments, make it a very attractive material for optoelectronic devices as well as imaging and sensing‐related applications. In this Minireview, we will focus on the optical and photophysical properties of CN films and quantum dots and their potential applications in sensors, LEDs, solar cells and other photoelectronic devices. The synthetic approaches which determine the final chemical and photophysical properties of the CN materials are thoroughly elaborated.
Advancing Ethics and Policy for Healthy‐Volunteer Research through a Model‐Organism Framework
Authors: Fisher Jill A. , Walker Rebecca L. 
Published: January 2019

ABSTRACTNonhuman animal research and phase I healthy‐volunteer clinical trials are both critical components of testing the safety of investigational drugs as part of the development of new pharmaceuticals. In addition, these types of research share important structural features, as both take place in confinement and both use subjects that are dissimilar to the target population. By mobilizing a model‐organism framework for phase I trials, we employ concepts and mechanisms typical to animal research to query gaps in the human subjects ethics and policy framework. By bringing these two research worlds together, we aim to illustrate how the model‐organism framework can enhance healthy volunteers’ welfare during trials, improve research oversight, and more critically assess the science value of current phase I trials.
Odor biosensor system based on image lock‐in measurement for odorant discrimination
Authors: Sukekawa Yuji , Nakamoto Takamichi 
Published: January 2019

AbstractThere has been so far few odor sensors with an array of the biosensor elements. However, an odor sensor constructed in this fashion is expected to have high performance in terms of the ability to discriminate between odorants. In this study, a parallel lock‐in measurement circuit was developed to acquire the fluorescent image of the cells even under an ambient light. Since that circuit can extract only the responses of the cells from the fluorescent image, its output represents a specific pattern corresponding to the odorant. Therefore, principal component analysis was applied to that output in order to confirm the availability of the odorant discrimination by using a fluorescent image. It was found that the output pattern from the developed circuit included information enough to discriminate between at least two types of odorants.
Control of identification area of structured identifier by set theory and connection techniques for modularized facility management functions
Authors: Amano Koji , Nishiyama Hiroyasu , Koizumi Minoru , Shimizu Katsuto , Sasaki Wataru , Tano Shunichi 
Published: January 2019

AbstractThis paper is to propose an information management technique, which is easy to understand by humans and easy to utile analysis program, in order to manage complicated machines and facilities. To manage the facilities, we show a modeling that partly defines the structure of the facilities by set theory, further defines the requirements for joining the subset of structured identifiers on consistency. In verification of the proposal and programming method, we show how to control the amount of information of structured identifier as uniquely identifier. As a result, we show our proposal is useful to address real problems in management software.
Transformation of mature mouse B cells into malignant plasma cells in vitro via introduction of defined genetic elements
Authors: Högstrand Kari , Lindvall Jessica M. , Sundblad Anne , Grandien Alf 
Published: January 2019

AbstractAn experimental system where defined alterations in gene function or gene expression levels in primary B cells would result in the development of transformed plasma cells in vitro would be useful in order to facilitate studies of the underlying molecular mechanisms of plasma cell malignancies. Here, such a system is described in which primary murine B cells rapidly become transformed into surface CD138+, IgM−/low, CD19− IgM‐secreting plasma cells as a result of expression of the transcription factors IRF4 and MYC together with simultaneous expression of BMI1, mutated p53 or silencing of p19Arf, and suppression of intrinsic apoptosis through expression of BCLXL. Analysis of gene expression patterns revealed that this combination of transforming genes resulted in expression of a number of genes previously associated with terminally differentiated B cells (plasma cells) and myeloma cells, whereas many genes associated with mature B cells and B‐cell lymphomas were not expressed. Upon transplantation, the transformed cells preferentially localized to the bone marrow, presenting features of a plasma cell malignancy of the IgM isotype. The present findings may also be applicable in the development of novel methods for production of monoclonal antibodies.
Self‐punishment promotes reconciliation with third parties by addressing the symbolic implications of wrongdoing
Authors: de Vel‐Palumbo Melissa , Wenzel Michael , Woodyatt Lydia 
Published: January 2019

AbstractSelf‐punishment is a highly costly—and potentially harmful—way transgressors can respond to a wrongdoing. In this research, we propose that people might punish themselves in part because it has a communicative social function. Three studies using hypothetical vignettes showed that self‐punishment facilitates reconciliation with third party observers by addressing the symbolic implications of wrongdoing. Specifically, self‐punishment establishes a moral value consensus and/or diminishes offender status/power, and through this, increases third party perceptions of justice and transgressor remorse, and the third party's willingness to reconcile. This effect was robust to manipulations designed to make third parties question the sincerity of the self‐punisher's intention. Self‐punishment thus serves a beneficial interpersonal function by repairing social bonds between transgressors and their peers.
How positive and negative contact experiences relate to identification and acculturation of persons with a migration background: Differentiating between majority, minority, and religious group identity
Authors: Sixtus Frederick , Wesche Jenny S. , Tsantila Katerina , Kerschreiter Rudolf 
Published: January 2019

AbstractBadea, Jetten, Iyer, and Er‐Rafiy proposed a model that specifies immigrants’ experienced rejection by majority and minority groups and social identification with these groups as predictors of their acculturation attitudes. The present research tested an extended version of this model by assessing (i) both positive and negative contact experiences with majority and minority groups, (ii) social identification with these groups and religious groups, and (iii) acculturation attitudes. We surveyed individuals with Greek (N = 186) and Turkish (N = 138) migration background living in Germany. The proposed model yielded a good fit with the empirical data and showed that positive and negative contact with majority and minority groups predicted minority members’ acculturation attitudes, mediated via identification with the majority, minority, and religious group. Our findings support the extended model and contribute to a broader understanding of contact–identification–acculturation links in the context of migration.
Statistics and spectra of turbulence under different roughness in the near‐neutral atmospheric surface layer
Authors: Li Xuebo , Bo Tianli 
Published: January 2019

AbstractAccurate knowledge of the contacts between surface roughness and the resultant wind speed are important for climatic models, wind power meteorology, agriculture and erosion hazards especially on sand saltation in arid and semi‐arid environments, where vegetation cover is scarce. In this study, synchronous measurements of three‐dimensional wind speed below 5 m are carried out in three different surface roughness conditions in Minqin, China, and the difference in the turbulence statistics and the structure of the very large‐scale motions (VLSMs) were revealed. The results show that the slope of the mean wind profile (MVP), the turbulent kinetic energy (TKE) and Reynolds stress increase with the surface roughness. The roughness seems to suppress the ejection events and the surface roughness will not only weaken the energy of the VLSMs, but also reduce the scale values of VLSMs near the wall. These influences may cause some changes regarding the dust transportation in streamwise and vertical directions during the sand and dust storm (SDS). That is, the decrease of the mean velocity near the ground will reduce the dust transportation in the streamwise direction and influence of the roughness on the ejection and sweep events will change the dust transportation in the vertical direction. Furthermore, the increase of roughness will weaken the scale and energy of VLSMs, which will lead to the decrease of the capacity of dust transportation. © 2019 John Wiley & Sons, Ltd.
Effect of domestic cooking on rice protein digestibility
Authors: Liu Kunlun , Zheng Jiabao , Chen Fusheng 
Published: January 2019

AbstractThe effects of washing, soaking, and common domestic cooking methods (normal cooking, high‐pressure cooking, and microwave cooking) on protein content, in vitro protein digestibility, and amino acid composition of japonica and indica rice were investigated. All processes in rice domestic cooking did not affect protein content. However, the gastric and gastrointestinal protein digestibilities decreased significantly after cooking. Protein solubility methods were used to observe the formation of disulfide bonds and hydrophobicity interactions after cooking. Disulfide bonds and hydrophobicity interactions were formed during cooking, and the cooking‐induced disulfide bond cross‐linking decreased the protein digestibility observably. Moreover, the solubility of 13 kDa prolamin subunit sharply decreased after cooking due to intramolecular disulfide bond cross‐linking. Therefore, cooking‐induced formation of intramolecular disulfide linkages might stabilize and strengthen the structure of protein body‐I, which exhibited strong resistance to proteases, particularly pepsin. Cooking had limited effect on amino acids.
Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions
Authors: Stenzinger Albrecht , Allen Jeffrey D. , Maas Jörg , Stewart Mark D. , Merino Diana M. , Wempe Madison M. , Dietel Manfred 
Published: January 2019

AbstractCharacterization of tumors utilizing next‐generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence‐based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.
Late Miocene increase in sediment accommodation rates in the southern North Sea Basin
Authors: Jef Deckers , Louwye Stephen 
Published: January 2019

Boreholes provided with biostratigraphic data indicate major changes in the Miocene sediment accommodation rates in the northern Campine Block, located in the southern North Sea Basin. Low sediment accommodation rates took place during the early to middle Miocene and abruptly increased into the late Miocene. Two processes likely explain these observations. First, the long‐time (±10 Myr) slow sedimentation of fine sands with a high—in part authigenic—glauconite content (of up to almost 50%) suggests that the southern North Sea area was sediment starved during the early to middle Miocene. Sediment starvation ended with the start of the late Miocene when the area became covered by west‐prograding clinoform sets of coarser sands with mainly reworked glauconite as part of the proto‐Rhine system. The latter sands filled the accommodation space that was left after early to middle Miocene sediment starvation. Second, accelerated subsidence during the late Miocene created additional accommodation space to be filled compared with the early to middle Miocene. A mechanism that explains well the regional accelerated subsidence is lithospheric folding or buckling. The timing and geometry of accelerated rates of subsidence in the southern North Sea area are indeed consistent with deformation that was thought to have been related to lithospheric folding in areas further south (in the direction of the Alps) under NW‐Alpine compression.
Brain network dynamics in schizophrenia: Reduced dynamism of the default mode network
Authors: Kottaram Akhil , Johnston Leigh A. , Cocchi Luca , Ganella Eleni P. , Everall Ian , Pantelis Christos , Kotagiri Ramamohanarao , Zalesky Andrew 
Published: January 2019

AbstractComplex human behavior emerges from dynamic patterns of neural activity that transiently synchronize between distributed brain networks. This study aims to model the dynamics of neural activity in individuals with schizophrenia and to investigate whether the attributes of these dynamics associate with the disorder's behavioral and cognitive deficits. A hidden Markov model (HMM) was inferred from resting‐state functional magnetic resonance imaging (fMRI) data that was temporally concatenated across individuals with schizophrenia (n = 41) and healthy comparison individuals (n = 41). Under the HMM, fluctuations in fMRI activity within 14 canonical resting‐state networks were described using a repertoire of 12 brain states. The proportion of time spent in each state and the mean length of visits to each state were compared between groups, and canonical correlation analysis was used to test for associations between these state descriptors and symptom severity. Individuals with schizophrenia activated default mode and executive networks for a significantly shorter proportion of the 8‐min acquisition than healthy comparison individuals. While the default mode was activated less frequently in schizophrenia, the duration of each activation was on average 4–5 s longer than the comparison group. Severity of positive symptoms was associated with a longer proportion of time spent in states characterized by inactive default mode and executive networks, together with heightened activity in sensory networks. Furthermore, classifiers trained on the state descriptors predicted individual diagnostic status with an accuracy of 76–85%.
Gray matter volume covariance networks associated with dual‐task cost during walking‐while‐talking
Authors: Tripathi Susmit , Verghese Joe , Blumen Helena M. 
Published: January 2019

AbstractWe studied gray matter volume covariance networks associated with normal pace walking (NPW) speed and dual‐task costs (DTCs) during walking‐while‐talking (WWT)—a mobility stress test that involves walking while reciting alternate letters of the alphabet. Using a multivariate covariance‐based analytic approach, we identified gray matter networks associated with NPW speed (mean 102.1 cm/s ±22.5 cm/s) and DTC (percent difference in gait speed between NPW and WWT, mean 25.9% ± 18.8%) in 139 older adults without dementia (M = 75.3 ± 6.1 years). The gray matter network associated with NPW was primarily composed of supplementary motor area, precuneus cortex, and the middle frontal gyrus. Greater expression of this NPW network was associated with better processing speed (trail‐making test A [r = −0.30, p = 0.005]) and executive function (trail‐making test B − A [r = −0.43, p < 0.0001]). The gray matter network associated with DTC was primarily composed of medial prefrontal, cingulate, and thalamic regions. Greater expression of this DTC network was associated with better episodic memory performance on the free and cued selective reminding test (r = 0.30, p = 0.007). These results suggest that NPW speed and DTC are supported by different networks, and are associated with different cognitive domains.
The role of shape and specificity in young children's object substitution
Authors: Burns‐Nader Sherwood , Scofield Jason , Jones Caroline 
Published: January 2019

AbstractChildren often substitute one object for another during play. They may substitute a stick for a sword or a box for a car, often favouring substitutes that are shaped like the needed object. The current study looked at the roles of shape and specificity, the degree to which a possible substitute resembles something else, in children's object substitutions. We asked whether children would favour generic, similarly shaped substitutes (those with low specificity) over specific ones and whether generic objects would elicit a great variety of potential substitutes than their specific counterparts. Three‐, 4‐, and 5‐year‐olds (N = 66) saw objects that varied by shape (round versus rectangular) and by specificity (generic versus specific) and were asked to help a story character find a series of objects. Children were also given an object and asked to generate a list of possible things for which the object could be substituted. Overall, children, especially 5‐year‐olds, strongly favoured the generic, same‐shaped substitutes over other objects and regularly used them for multiple substitutions. Children did not generate a longer list of potential substitutes when given a generic object. Findings suggest that children may pass over specific objects in favour generic ones when making object substitutions during play.Highlights

Researchers examined the roles of shape and specificity in young children's choice of object substitutions.
Children were asked to help a story character find four objects using four substitutes that varied in shape and specificity.
Children used generic shapes to be used as multiple needed objects more than those designed to look like something specific.