bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy
Authors: Klouwer Femke C. C. , Koot Bart G. P. , Berendse Kevin , Kemper Elles M. , Ferdinandusse Sacha , Koelfat Kiran V. K. , Lenicek Martin , Vaz Frédéric M. , Engelen Marc , Jansen Peter L. M. , Wanders Ronald J. A. , Waterham Hans R. , Schaap Frank G. , Poll‐The Bwee Tien 
Published: February 2019

AbstractIntroductionCurrently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C27‐bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. It was noted that, in patients with advanced liver disease, caution is needed because of possible hepatotoxicity.MethodsAn extension study of the previously conducted pretest‐posttest design study was conducted including 17 patients with a ZSD. All patients received oral CA for an additional period of 12 months, encompassing a total of 21 months of treatment. Multiple clinically relevant parameters and markers for bile acid synthesis were assessed after 15 and 21 months of treatment.ResultsBile acid synthesis was still suppressed after 21 months of CA treatment, accompanied with reduced levels of C27‐bile acid intermediates in plasma. These levels significantly increased again after discontinuation of CA. No significant changes were found in liver tests, liver elasticity, coagulation parameters, fat‐soluble vitamin levels or body weight.ConclusionsAlthough CA treatment did lead to reduced levels of toxic C27‐bile acid intermediates in ZSD patients without severe liver fibrosis or cirrhosis, no improvement of clinically relevant parameters was observed after 21 months of treatment. We discuss the implications for CA therapy in ZSD based on these results.
The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy
Authors: Coughlin Curtis R. , Swanson Michael A. , Spector Elaine , Meeks Naomi J. L. , Kronquist Kathryn E. , Aslamy Mezhgan , Wempe Michael F. , van Karnebeek Clara D. M. , Gospe Sidney M. , Aziz Verena G. , Tsai Becky P. , Gao Hanlin , Nagy Peter L. , Hyland Keith , van Dooren Silvy J. M. , Salomons Gajja S. , Van Hove Johan L. K. 
Published: February 2019

AbstractPyridoxine dependent epilepsy (PDE) is a treatable epileptic encephalopathy characterized by a positive response to pharmacologic doses of pyridoxine. Despite seizure control, at least 75% of individuals have intellectual disability and developmental delay. Current treatment paradigms have resulted in improved cognitive outcomes emphasizing the importance of an early diagnosis. As genetic testing is increasingly accepted as first tier testing for epileptic encephalopathies, we aimed to provide a comprehensive overview of ALDH7A1 mutations that cause PDE. The genotypes, ethnic origin and reported gender was collected from 185 subjects with a diagnosis of PDE. The population frequency for the variants in this report and the existing literature were reviewed in the Genome Aggregation Database (gnomAD). Novel variants identified in population databases were also evaluated through in silico prediction software and select variants were over‐expressed in an E.coli‐based expression system to measure α‐aminoadipic semialdehyde dehydrogenase activity and production of α‐aminoadipic acid. This study adds 47 novel variants to the literature resulting in a total of 165 reported pathogenic variants. Based on this report, in silico predictions, and general population data, we estimate an incidence of approximately 1:64,352 live births. This report provides a comprehensive overview of known ALDH7A1 mutations that cause PDE, and suggests that PDE may be more common than initially estimated. Due to the relative high frequency of the disease, the likelihood of under‐diagnosis given the wide clinical spectrum and limited awareness among clinicians as well as the cognitive improvement noted with early treatment, newborn screening for PDE may be warranted.
An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency
Authors: O'Callaghan Benjamin , Bosch Annet M. , Houlden Henry 
Published: February 2019

AbstractRiboflavin transporter deficiency (RTD) is a rare neurological condition that encompasses the Brown‐Vialetto‐Van Laere and Fazio‐Londe syndromes since the discovery of pathogenic mutations in the SLC52A2 and SLC52A3 genes that encode human riboflavin transporters RFVT2 and RFVT3. Patients present with a deteriorating progression of peripheral and cranial neuropathy that causes muscle weakness, vision loss, deafness, sensory ataxia, and respiratory compromise which when left untreated can be fatal. Considerable progress in the clinical and genetic diagnosis of RTDs has been made in recent years and has permitted the successful lifesaving treatment of many patients with high dose riboflavin supplementation. In this review, we first outline the importance of riboflavin and its efficient transmembrane transport in human physiology. Reports on 109 patients with a genetically confirmed diagnosis of RTD are then summarized in order to highlight commonly presenting clinical features and possible differences between patients with pathogenic SLC52A2 (RTD2) or SLC52A3 (RTD3) mutations. Finally, we focus attention on recent work with different models of RTD that have revealed possible pathomechanisms contributing to neurodegeneration in patients.
A review on analytical methods for natural berberine alkaloids
Authors: Wang Jiahui , Jiang Yanyan , Wang Bing , Zhang Ning 
Published: February 2019

AbstractBerberine alkaloids, a group of protoberberine alkaloids under the classification of isoquinoline alkaloids, include berberine, coptisine, palmatine, columbamine, dehydrocorydaline, jatrorrhizine, and epiberberine from natural sources. Studies have shown that berberine alkaloids have various pharmacological functions, such as antibacterial, antiviral, blood pressure‐lowering, hypoglycaemic, antiarrhythmia, and anticancer effects. Therefore, it is worthwhile to develop analytical methods to investigate the pharmacokinetics and activity mechanisms of berberine alkaloids and to study berberine alkaloids more comprehensively. Current analytical methods for berberine alkaloids include liquid chromatography, thin‐layer chromatography, ultraviolet spectroscopy, capillary electrophoresis, and gas chromatography. The most widely used detection method is mass spectrometry. In order to provide a systematic and comprehensive summary and to serve as a reference for the future pharmacokinetics studies and analysis of berberine alkaloids, analytical methods for natural berberine alkaloids that have been used in the past ten years are reviewed here.
Separation of betacyanins from flowers of Amaranthus cruentus L. in a polar solvent system by high‐speed counter‐current chromatography
Authors: Spórna‐Kucab Aneta , Kumorkiewicz Agnieszka , Szmyr Natalia , Szneler Edward , Wybraniec Sławomir 
Published: February 2019

AbstractBetacyanin extract of Amaranthus cruentus L. flowers was fractionated by semi‐preparative high‐speed counter‐current chromatography in a highly polar solvent system: propan‐1‐ol/acetonitrile/(NH4)2SO4satd. soln/H2O (1.0:0.5:1.2:1.0, v/v/v/v) in tail‐to‐head mode with 76% retention of the stationary phase. The crude extract as well as the fractions containing betacyanins were analyzed by liquid chromatography with tandem mass spectrometry as well as by high‐resolution ion‐trap time‐of‐flight mass spectrometry detection technique for the molecular formulae and multi‐step fragmentation pattern elucidation. Four betacyanins; namely, amaranthin, betanin, 6′‐O‐formyl‐amaranthin, and 6′‐O‐malonyl‐amaranthin as well as their diastereomeric forms differing in the configuration of the C‐15 carbon atom were identified in the fractions. Amaranthin was the dominant pigment in the extract and was additionally analyzed by nuclear magnetic resonance correlation techniques after the counter‐current chromatographic and high‐performance liquid chromatographic isolation. Betacyanins were highly enriched during a single high‐speed counter‐current chromatographic step; therefore, the tentative identification of new compounds for the whole Amaranthaceae family, 6′‐O‐formyl‐amaranthin and 6′‐O‐malonyl‐amaranthin was possible. Different elution profiles of the pigments observed in the counter‐current chromatographic system in comparison to high‐performance liquid chromatography system confirm a complementarity of both the techniques especially in the separation of diastereomeric pairs of betacyanins.
The Synthesis of Urchin‐Like Serried Hydroxyapatite (USHA) and its Reinforcing Effect for Dental Resin Composites
Authors: Qian Li , Wang Ruili , Li Wei , Chen Hongyan , Jiang Xiaoze , Zhu Meifang 
Published: February 2019

AbstractThe novel urchin‐like serried hydroxyapatite (USHA) is synthesized by homogeneous hydrothermal precipitation method through adjusting the pH value and temperature. The silanized USHA is thereby used as the reinforcing filler for dental resin composites. The structure and morphology of various HA nanostructures are characterized with X‐ray diffraction, Fourier transform infrared spectroscopy, and field‐emission scanning electron microscope. Thermogravimetric analysis is used to analyze the grafting ratio of 3‐methacryloxypropyl trimethoxysilane on the surface of USHA. Mechanical performance of dental resin composites reinforced with silanized USHA at different filler loadings are measured by a universal mechanical testing machine. The neat resin matrix is served as the control group. Results demonstrate that the optimization of USHA morphology gave a better understanding of the effect of the pH value and temperature on its structure transformation. After trials, USHA with the complete globular structure and the serried whiskers is synthesized at pH value of 12.5 under 105 °C. When the USHA loading is 30 wt%, the corresponding dental composite significantly improved the mechanical properties in comparison with the neat resin, especially for the compressive strength.
Genome and transcriptome analysis of Bacillus velezensis BS‐37, an efficient surfactin producer from glycerol, in response to d‐/l‐leucine
Authors: Zhou Dayuan , Hu Fangxiang , Lin Junzhang , Wang Weidong , Li Shuang 
Published: February 2019

AbstractSurfactin is one of the most widely studied biosurfactants due to its many potential applications in different fields. In the present study, Bacillus velezensis BS‐37, initially identified as a strain of Bacillus subtilis, was used to efficiently produce surfactin with the addition of glycerol, an inexpensive by‐product of biodiesel production. After 36 hr of growth in glycerol medium, the total surfactin concentration reached more than 1,000 mg/L, which was two times higher than that in sucrose medium. Moreover, the addition of l‐ and d‐Leu to the culture medium had opposite effects on surfactin production by BS‐37. While surfactin production increased significantly to nearly 2,000 mg/L with the addition of 10 mM l‐Leu, it was dramatically reduced to about 250 mg/L with the addition of 10 mM d‐Leu. To systemically elucidate the mechanisms influencing the efficiency of this biosynthesis process, we sequenced the genome of BS‐37 and analyzed changes of the transcriptome in glycerol medium in response to d‐/l‐leucine. The RPKM analysis of the transcriptome of BS‐37 showed that the transcription levels of genes encoding modular surfactin synthase, the glycerol utilization pathway, and branched‐chain amino acid (BCAA) synthesis pathways were all at a relatively high level, which may offered an explanation why this strain can efficiently use glycerol to produce surfactin with a high yield. Neither l‐Leu nor d‐Leu had a significant effect on the expression of genes in these pathways, indicating that l‐Leu plays an important role as a precursor or substrate involved in surfactin production, while d‐Leu appears to act as a competitive inhibitor. The results of the present study provide new insights into the synthesis of surfactin and ways of its regulation, and enrich the genomic and transcriptomic resources available for the construction of high‐producing strains.
Miniaturization of a single‐ended mixer using T‐shaped Wilkinson power combiner for medical wireless communication applications
Authors: Yoon Ki‐Cheol , Kim Kwang Gi 
Published: February 2019

AbstractIn the modern day, wireless communications systems are widely used for medical services and medical information security. A wireless communication device for medical services is required for a high performance and small size technique. In this article, a proposed compact size of the single‐ended mixer using small size of the Wilkinson power divider with T‐shaped transmission line is presented. The compact size of the mixer used for small size is based on Wilkinson power divider using T‐shaped transmission line which is connected to amplifier circuit part. The electrical length of the transmission line for the conventional Wilkinson power divider was 90°. However, the electrical length of the T‐shaped transmission line was 30°. Therefore, the physical length was reduced by 1/2 times. The size of a proposed mixer was 22.21 × 18.32 mm2 at a center frequency of 2.165 GHz. It will be applied to a transceiver for wireless communication system of medical services.
Low field NMR for quality monitoring of 3D printed surimi from cod by‐products: Effects of the pH‐shift method compared with conventional washing
Authors: Gudjónsdóttir María , Napitupulu Romauli Juliana , Petty Kristinsson Holly T. 
Published: February 2019

AbstractImplementation of three‐dimensional (3D) food printing and novel analytics can reduce food waste and increase utilization of seafood by‐products. Low field nuclear magnetic resonance (LF‐NMR) and chemometrics were used to investigate the printability and characteristics of surimi pastes from cod by‐products as affected by different processing methods (the pH‐shift method vs. conventional washing), addition of salt (0, 1.5, and 3%), length of cold storage (0, 4, and 7 days) until 3D printing, and steam cooking. The analysis revealed two to three water populations in the 3D printed samples. Increasing the salt concentration induced myofibrillar swelling in the conventionally prepared surimi, whereas a more salt‐induced gelling effect was observed in the pH‐shift processed surimi. Cooking had a decreasing effect on the T21 relaxation time and its corresponding apparent population (A21), corresponding to protein denaturation and water loss during cooking. Increasing the salt concentration to 3% had a protective effect towards water exchange between the A21 and A23 populations in the conventionally washed samples but more subtly in the pH‐shift samples. Similar trends in relaxation parameters were observed after 4 and 7 days of storage, although the intermediate population A22 seemed to be most affected by the storage. Overall LF‐NMR was an effective quality monitoring tool for the physicochemical changes occurring in the 3D printed surimi. The analysis showed both advantages and disadvantages of the two processing methods. However, it can clearly be concluded that increasing the salt content had a stabilizing effect on the surimi, and printing of fresh raw materials is recommended.
The views of people with joint hypermobility syndrome on its impact, management and the use of patient‐reported outcome measures. A thematic analysis of open‐ended questionnaire responses
Authors: Palmer Shea , Bridgeman Keely , Di Pierro Isabelle , Jones Rosanna , Phillips Caitlin , Wilson Megan 
Published: February 2019

AbstractIntroductionJoint hypermobility syndrome (JHS) has been reported to have widespread impacts on people with the condition. However, our understanding of those impacts is still developing and we do not know if they can be captured effectively using patient‐reported outcome measures. The aim of the present study was to explore written qualitative comments from previously administered questionnaires, to identify the impacts of JHS and any issues related to using patient‐reported outcome measures to assess those impacts.MethodsPrevious research administered a draft condition‐specific questionnaire and Short Form‐36 questionnaire to adult members of a patient organization in the UK, incorporating an open text box for further comments. Those comments were transcribed, anonymized and analysed using thematic analysis. A coding list, themes and subthemes were developed through double coding, parallel independent analysis and consensus.ResultsA total of 393 of 614 eligible questionnaires (64%) contained qualitative comments and were analysed (mean respondent age 41 years, mean Bristol Impact of Hypermobility questionnaire score 228/360, 95% women). Three main themes were identified: (a) “Impacts of living with JHS”; (b) “Management strategies for JHS”; and (c) “Measurement and research into JHS”. Participants highlighted a range of impacts of JHS, incorporating physical, social and psychological domains. Respondents described difficult journeys to diagnosis, and feeling unsupported and misunderstood by their peers and healthcare professionals. They detailed helpful strategies for managing their condition and provided useful comments on using questionnaires to assess JHS.ConclusionsThe study yielded valuable findings that can be used to directly inform the assessment and management of JHS.
Oxidation Chemistry of DNA and p53 Tumor Suppressor Gene
Authors: Jiang Di , Rusling James F. 
Published: February 2019

AbstractThe chemistry of DNA and its repair selectivity control the influence of genomic oxidative stress on the development of serious disorders such as cancer and heart diseases. DNA is oxidized by endogenous reactive oxygen species (ROS) in vivo or in vitro as a result of high energy radiation, non‐radiative metabolic processes, and other consequences of oxidative stress. Some oxidations of DNA and tumor suppressor gene p53 are thought to be mutagenic when not repaired. For example, site‐specific oxidations of p53 tumor suppressor gene may lead to cancer‐related mutations at the oxidation site codon. This review summarizes the research on the primary products of the most easily oxidized nucleobase guanine (G) when different oxidation methods are used. Guanine is by far the most oxidized DNA base. The primary initial oxidation product of guanine for most, but not all, pathways is 8‐oxoguanine (8‐oxoG). With an oxidation potential much lower than G, 8‐oxoG is readily susceptible to further oxidation, and the products often depend on the oxidants. Specific products may control the types of subsequent mutations, but mediated by gene repair success. Site‐specific oxidations of p53 tumor suppressor gene have been reported at known mutation hot spots, and the codon sites also depend on the type of oxidants. Modern methodologies using LC–MS/MS for codon specific detection and identification of oxidation sites are summarized. Future work aimed at understanding DNA oxidation in nucleosomes and interactions between DNA damage and repair is needed to provide a better picture of how cancer‐related mutations arise.
Initiation and Overdriven Detonation of High Explosives Using Multipoint Initiation
Authors: Guo Junfeng , Zeng Qingxuan , Qin Guosheng , Li Mingyu 
Published: February 2019

AbstractHigh explosives (HE) with desirable safety and detonation performances are widely used in weapon system and aerospace engineering. Multipoint initiation is utilized to initiate TATB and thus create overdriven state. High‐pressure areas of colliding shock waves are observed by measuring steel dent value and the whole processes, involving multiple wave interactions and overdriven detonation formation, are reproduced using LS‐DYNA3D program. Results indicate that the quadruple point is at the center where four shock waves collide, and the double point is between two initiation points where two shock waves collide. When the height of donor explosive exceeds 5 mm, the retardation time of the quadruple point compared to the double point and the individual point are 180 ns and 260 ns, respectively. In addition, overdriven state may disappear when the height of UF‐TATB exceeds 9 mm, and the delay effect is negligible for initiating PBX‐9502 when the simultaneity of slapper detonators is within 100 ns.
Dimerization of a ubiquitin variant leads to high affinity interactions with a ubiquitin interacting motif
Authors: Manczyk Noah , Veggiani Gianluca , Gish Gerald D. , Yates Bradley P. , Ernst Andreas , Sidhu Sachdev S. , Sicheri Frank 
Published: February 2019

AbstractWe previously described structural and functional characterization of the first ubiquitin variant (UbV), UbV.v27.1, engineered by phage display to bind with high affinity to a specific ubiquitin interacting motif (UIM). We identified two substitutions relative to ubiquitin (Gly10Val/His68Tyr) that were critical for enhancing binding affinity but could only rationalize the mechanism of action of the Tyr68 substitution. Here, we extend our characterization and uncover the mechanism by which the Val10 substitution enhances binding affinity. We show that Val10 in UbV.v27.1 drives UbV dimerization through an intermolecular β‐strand exchange. Dimerization serves to increase the contact surface between the UIM and UbV and also affords direct contacts between two UIMs through an overall 2:2 binding stoichiometry. Our identification of the role of Val10 in UbV dimerization suggests a general means for the development of dimeric UbVs with improved affinity and specificity relative to their monomeric UbV counterparts. Statement: Previously, we used phage display to engineer a UbV that bound tightly and specifically to a UIM. Here, we discovered that tight binding is partly due to the dimerization of the UbV, which increases the contact surface between the UbV and UIM. We show that UbV dimerization is dependent on the Gly10Val substitution, and posit that dimerization may provide a general means for engineering UbVs with improved binding properties.
Atomic pseudopotentials for reproducing π‐orbital electron behavior in sp2 carbon atoms
Authors: Punter Alexander , Nava Paola , Carissan Yannick 
Published: February 2019

AbstractA pseudopotential system for an sp2 carbon atom is built and tested as a building block for various pseudohydrocarbon polyenes and polycyclic aromatic hydrocarbons. This pseudosystem has a central charge of Z = 1; it contains only one electron. It is employed in ab‐initio calculations in which several physical characteristics including the orbital energies and first ionization energy, as well as first excitation energy and UV spectra, are found to be well‐reproduced by the pseudosystem. Remarkably, not only are the π excitation energies in good agreement with the reference calculations, but also transition densities and intensities, confirming that the virtual space obtained with the pseudopotentials is of excellent quality. Finally, this approach is capable of reproducing the π electron systems of small or large, planar or nonplanar hydrocarbons at low computational cost.