bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical findings in a patient with FARS2 mutations and early‐infantile‐encephalopathy with epilepsy
Authors: Raviglione Federico , Conte Giorgio , Ghezzi Daniele , Parazzini Cecilia , Righini Andrea , Vergaro Raffaella , Legati Andrea , Spaccini Luigina , Gasperini Serena , Garavaglia Barbara , Mastrangelo Massimo
Published: August 2016

The FARS2 gene encodes the mitochondrial phenylalanyl‐tRNA synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14, a clinical condition characterized by infantile onset epilepsy and encephalopathy. Mutations in FARS2 have been reported in only few patients, but a detailed description of seizures, electroencephalographic patterns, magnetic resonance imaging findings, and long‐term follow‐up is still needed. We provide a clinical report of a child with FARS2‐related disease manifesting drug‐resistant infantile spasms associated with focal seizures. By comparative genomic hybridization analysis we identified a heterozygous microdeletion in the short arm of chromosome 6, inherited from the mother, that encompasses the first coding exon of FARS2. By sequencing of the FARS2 gene we identified a variant c.1156C>G; p.(R386G), inherited from the father. By using standard spectrophotometric techniques in skin fibroblasts, we found a combined abnormality of complexes I and IV of the mitochondrial respiratory chain. The main clinical features of the patient included axial hypotonia, mild distal hypertonia, and psychomotor delay. The magnetic resonance imaging showed microcephaly, frontal cerebral atrophy, and signal changes of dentate nuclei. At the age of 3 years and 6 months, the patient was still under treatment with vigabatrin and he has been seizure free for the last 23 months. © 2016 Wiley Periodicals, Inc.
The pain–depression dyad and the association with sleep dysfunction in chronic rhinosinusitis
Authors: Cox Daniel R. , Ashby Shaelene , Mace Jess C. , DelGaudio John M. , Smith Timothy L. , Orlandi Richard R. , Alt Jeremiah A.
Published: August 2016

Background

Depression, pain, and sleep disturbance is a symptom cluster often found in patients with chronic illness, exerting a large impact on quality of life (QOL). A wealth of literature exists demonstrating a significant association between depression, pain, and sleep dysfunction in other chronic diseases. This relationship has not been described in patients with chronic rhinosinusitis (CRS).

Methods

Sixty‐eight adult patients with CRS were prospectively enrolled. Patients at risk for depression were identified using the Patient Health Questionnaire‐2 (PHQ‐2) using a cut‐off score of ≥1. Pain experience was measured using the Brief Pain Inventory Short Form (BPI‐SF) and the Short Form McGill Pain Questionnaire (SF‐MPQ). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI).

Results

Forty‐seven patients were at risk for depression. Significant positive correlations were found between total PSQI scores and all pain measures (R = 0.38‐0.61, p ≤ 0.05) and between total PSQI scores and PHQ‐2 scores (R = 0.46, p < 0.05). For patients at risk for depression, significant, positive correlations were found between pain measures, the total PSQI score, and the 3 PSQI subdomains (sleep latency, sleep quality, and daytime dysfunction; R = 0.31‐0.61, p < 0.05). The relationship between pain and sleep dysfunction scores was not seen in the absence of depression.

Conclusion

Depression, pain, and sleep dysfunction are interrelated in patients with CRS. In the absence of depression, significant correlations between pain and sleep are not observed, suggesting that depression plays a key role in this interaction. Further research is needed to investigate the complex relationship between depression, pain, and sleep dysfunction in CRS.
A recurrent mutation in KCNA2 as a novel cause of hereditary spastic paraplegia and ataxia
Authors: Helbig Katherine L. , Hedrich Ulrike B.S. , Shinde Deepali N. , Krey Ilona , Teichmann Anne‐Christin , Hentschel Julia , Schubert Julian , Chamberlin Adam C. , Huether Robert , Lu Hsiao‐Mei , Alcaraz Wendy A. , Tang Sha , Jungbluth Chelsy , Dugan Sarah L. , Vainionpää Leena , Karle Kathrin N. , Synofzik Matthis , Schöls Ludger , Schüle Rebecca , Lehesjoki Anna‐Elina , Helbig Ingo , Lerche Holger , Lemke Johannes R.
Published: August 2016

The hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders with over 50 known causative genes. We identified a recurrent mutation in KCNA2 (c.881G>A, p.R294H), encoding the voltage‐gated K+‐channel, KV1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow‐up analysis of > 2,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two‐electrode voltage‐clamp recordings of Xenopus laevis oocytes expressing mutant KV1.2 channels showed loss of function with a dominant‐negative effect. Our findings highlight the phenotypic spectrum of a recurrent KCNA2 mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. Ann Neurol 2016
Dehydrogenation of Formic Acid at Room Temperature: Boosting Palladium Nanoparticle Efficiency by Coupling with Pyridinic‐Nitrogen‐Doped Carbon
Authors: Bi Qing‐Yuan , Lin Jian‐Dong , Liu Yong‐Mei , He He‐Yong , Huang Fu‐Qiang , Cao Yong
Published: August 2016

The use of formic acid (FA) to produce molecular H2 is a promising means of efficient energy storage in a fuel‐cell‐based hydrogen economy. To date, there has been a lack of heterogeneous catalyst systems that are sufficiently active, selective, and stable for clean H2 production by FA decomposition at room temperature. For the first time, we report that flexible pyridinic‐N‐doped carbon hybrids as support materials can significantly boost the efficiency of palladium nanoparticle for H2 generation; this is due to prominent surface electronic modulation. Under mild conditions, the optimized engineered Pd/CN0.25 catalyst exhibited high performance in both FA dehydrogenation (achieving almost full conversion, and a turnover frequency of 5530 h−1 at 25 °C) and the reversible process of CO2 hydrogenation into FA. This system can lead to a full carbon‐neutral energy cycle.
The speed control effect of highway tunnel sidewall markings based on color and temporal frequency
Authors: Wan Hongliang , Du Zhigang , Yan Qixiang
Published: August 2016

The low‐luminance monotonous environment in the middle section of highway tunnels offers few reference points and is prone to cause severe visual illusion. Thus, drivers tend to underestimate their driving speed, which can induce speeding behaviors that result in rear‐end collisions. Therefore, discovering low‐cost methods of traffic engineering that reduce this visual illusion and ensure a steady driving speed is an important challenge for current highway tunnel operations. This study analyzes the effects of sidewall markings in typical highway tunnels, specifically observing how their colors and temporal frequencies affect the driver's speed perception in a low‐luminance condition. A three‐dimensional model of the middle section of highway tunnels was built in a driving simulator. Psychophysical tests of speed perception were carried out by the method of limits. The precision of the simulation model was then checked by comparing the results to field test data. The simulation tests studied the stimulus of subjectively equal speed and reaction time in relation to sidewall markings in different colors (red–white combined, yellow–white combined, and blue–white combined). Furthermore, based on the optimal color, the effects of sidewall marking with different temporal frequencies (0.4, 0.8, 1.2, 2, 4, 8, 12, 16, and 32 Hz) on the speed perception of drivers were also analyzed. The test results reveal that the color and temporal frequency of sidewall marking have a significant impact on the driver's stimulus of subjectively equal speed and reaction time. The subjects have the highest speed overestimation and an easy speed judgment with the red–white combined sidewall marking. Within the temporal frequency range of 4.45–7.01 Hz, the subjects have a certain degree of speed overestimation (less than 20%), and the speed perception is sensitive to the temporal frequency changes. Copyright © 2016 John Wiley & Sons, Ltd.
The impact of stratification by implausible energy reporting status on estimates of diet‐health relationships
Authors: Tooze Janet A. , Freedman Laurence S. , Carroll Raymond J. , Midthune Douglas , Kipnis Victor
Published: August 2016

The food frequency questionnaire (FFQ) is known to be prone to measurement error. Researchers have suggested excluding implausible energy reporters (IERs) of FFQ total energy when examining the relationship between a health outcome and FFQ‐reported intake to obtain less biased estimates of the effect of the error‐prone measure of exposure; however, the statistical properties of stratifying by IER status have not been studied. Under certain assumptions, including nondifferential error, we show that when stratifying by IER status, the attenuation of the estimated relative risk in the stratified models will be either greater or less in both strata (implausible and plausible reporters) than for the nonstratified model, contrary to the common belief that the attenuation will be less among plausible reporters and greater among IERs. Whether there is more or less attenuation depends on the pairwise correlations between true exposure, observed exposure, and the stratification variable. Thus exclusion of IERs is inadvisable but stratification by IER status can sometimes help. We also address the case of differential error. Examples from the Observing Protein and Energy Nutrition Study and simulations illustrate these results.
Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin
Authors: Pan Dong‐qi , Jiang Min , Liu Ting‐Ting , Wang Qi , Shi Jie‐hua
Published: August 2016

The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV–vis absorption spectroscopy (UV–vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT‐IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady‐state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >1010 L mol−1 sec−1. This result indicates that the ENPL–BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (ΔG0), enthalpic change (ΔH0) and entropic change (ΔS0). The binding of ENPL with BSA is an enthalpy‐driven process due to |ΔH°| > |TΔS°| in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub‐domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its α‐helical secondary structure.
Role of omentectomy as part of radical surgery for gastric cancer
Authors: Jongerius E J , Boerma D , Seldenrijk K A , Meijer S L , Scheepers J J G , Smedts F , Lagarde S M , Balague Ponz O , van Berge Henegouwen M I , van Sandick J W , Gisbertz S S
Published: August 2016

Background

A complete omentectomy is recommended as part of radical (sub)total gastrectomy for gastric cancer, but there is little evidence to suggest any survival benefit. The aim of this study was to evaluate the incidence of, and risk factors for, metastases in the greater omentum in patients undergoing gastrectomy for gastric cancer.

Methods

This was a multicentre prospective cohort study (OMEGA trial) of consecutive patients with gastric cancer undergoing (sub)total gastrectomy with complete en bloc omentectomy and modified D2 lymphadenectomy. After resection, the omentum was separated from the gastrectomy specimen distal to the gastroepiploic vessels and sent separately for pathological examination. The primary endpoint was the presence of metastases in the greater omentum.

Results

Of 100 included patients, five (5·0 per cent) had metastases in the greater omentum. Pathology results showed advanced tumours in all five (pT4b N1 M1, pT4b N2 M1, ypT4a N1 M1, ypT3 N2 M0, ypT3 N3 M0). The resection was microscopically non-radical at the proximal (3) or distal (2) resection margin in all of these patients. Metastases in the greater omentum correlated significantly with a microscopically non-radical resection, tumour expansion in the oesophagus or duodenum, linitis plastica or a proximal gastric tumour with diameter of at least 5 cm, stage III–IV disease and (y)pM1 category.

Conclusion

In resectable gastric cancer, the incidence of metastases in the greater omentum is low, and when present associated with advanced disease and non-radical features. Thus, omentectomy as part of a radical gastrectomy may be omitted. Registration number: NCT02050659 (http://www.clinicaltrials.gov).
Long-term survival of patients undergoing liver resection for very large hepatocellular carcinomas
Authors: Chang Y J , Chung K P , Chang Y J , Chen L J
Published: August 2016

Background

This study aimed to assess long-term survival after liver resection for huge hepatocellular carcinoma (HCC).

Methods

Patients with stage I–III HCC who underwent hepatectomy from 2002 to 2010 were identified retrospectively from prospective national databases and followed until December 2012. Patients were assigned into four groups according to tumour size: less than 3·0 cm (small), 3·0–4·9 cm (medium), 5·0–10·0 cm (large) and over 10·0 cm (huge). The primary endpoint was overall survival. The Kaplan–Meier method and Cox proportional hazards model were used for survival analysis.

Results

A total of 11 079 patients with HCC (mean(s.d.) age 59·7 (12·0) years) were eligible for this study. Median follow-up was 72·5 months. Patients with huge HCC had the worst prognosis; overall survival rates for patients with small, medium, large and huge HCC were 72·0, 62·1, 50·8 and 35·0 per cent respectively at 5 years, and 52·6, 41·8, 35·8 and less than 20·0 per cent at 10 years (P < 0·001). Multivariable analysis showed that tumour size affected long-term survival (hazard ratio (HR) 1·31, 1·55 and 2·38 for medium, large and huge HCC respectively versus small HCC). Prognostic factors for huge HCC were surgical margin larger than 0·2 cm (HR 0·70; P = 0·025), poor differentiation (HR 1·34; P = 0·004), multiple tumours (HR 1·64; P < 0·001), vascular invasion (HR 1·52; P = 0·008), cirrhosis (HR 1·37; P = 0·013) and the use of nucleoside analogues (HR 0·69; P = 0·004).

Conclusion

Huge HCCs have a worse prognosis than smaller HCCs after liver resection. A wide resection margin and antiviral therapy with nucleoside analogues may be associated with favourable long-term survival.
Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection
Authors: Ikeda A , Konishi T , Ueno M , Fukunaga Y , Nagayama S , Fujimoto Y , Akiyoshi T , Yamaguchi T
Published: August 2016

Background

The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting.

Methods

Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications.

Results

Of 540 patients offered participation in the trial in 2013–2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups.

Conclusion

Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 (http://www.umin.ac.jp/ctr/).
Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC‐QTOF‐MS/MS and LC‐TQ‐MS/MS
Authors: Liu Yu‐Cai , Zhu He , Shakya Shailendra , Wu Jun‐Wen
Published: August 2016

Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC‐QTOF‐MS/MS and LC‐TQ‐MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action.
Development and validation of an LC–MS/MS method for the determination of hinokiflavone in rat plasma and its application to a pharmacokinetic study
Authors: Yin Ruofeng , Xiong Kun , Wen Simin , Wang Yuanyi , Xu Feng
Published: August 2016

Hinokiflavone has drawn a lot of attention for its multiple biological activities. In this study, a sensitive and selective method for determination of hinokiflavone in rat plasma was developed for the first time, using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Amentoflavone was used as an internal standard. Separation was achieved on a Hypersil Gold C18 column with isocratic elution using methanol–water (65:35, v/v) as mobile phase at a flow rate of 0.3 mL/min. A triple quadrupole mass spectrometer operating in the negative electrospray mode with selected reaction monitoring was used to detect the transitions of m/z 537 → 284 for hinokiflavone and m/z 537 → 375 for IS. The LOQ was 0.9 ng/mL with a linear range of 0.9–1000 ng/mL. The intra‐ and inter‐day accuracy (RE%) ranged from −3.75 to 6.91% and from −9.20 to 2.51% and the intra‐ and inter‐day precision (RSD) was between 0.32–14.11 and 2.85–10.04%. The validated assay was successfully applied to a pharmacokinetic study of hinokiflavone in rats. The half‐life of drug elimination at the terminal phase was 6.10 ± 1.86 h, and the area under the plasma concentration‐time curve from time zero to the time of last measurable concentration and to infinity values obtained were 2394.42 ± 466.86 and 2541.93 ± 529.85 h ng/mL, respectively.
Herbert Haviland Field (1868–1921): Bibliographer of Zoology
Authors: Burke Colin B. , Buckland Michael K.
Published: August 2016

EDITOR'S SUMMARY

Before the field of bioinformatics was imagined, zoologist Herbert Haviland Field advanced the Concilium Bibliographicum, a comprehensive bibliographic resource for zoology. Born in New York to a wealthy family, Field pursued his early interest in science and earned multiple degrees but was frustrated by the difficulty of searching publications. Field developed a vision and plan for the Concilium, garnering financial support from donors and his family's resources and implementing the young Universal Decimal Classification for the project. Despite contacts with scientists throughout Europe, reliable funding for the Concilium eluded him. At the start of World War I, Field shifted his attention to relief missions, eventually using his international social position and language skills in commerce, the intelligence field and ultimately peace efforts. Attempts to rebuild the Concilium after the war failed, and Field died of influenza in 1921 at age 53, falling short of his goal to use the best technology of the day to improve information access.
Data and Copyright
Authors: Kristof Cindy
Published: August 2016

EDITOR'S SUMMARY

Raw data is not open to copyright, but databases, as compilations of data, have been treated differently. Early legal interpretations respected the compiler's work under the “sweat of the brow” doctrine, until the Supreme Court ruled in 1991 that a modicum of creativity was required to earn copyright protection. The Court also ruled the International News Service infringed on the rights of the Associated Press (AP) by telegraphing news gathered by its competitor, and that the AP's work was protected under state law through the “misappropriation doctrine.” The case was the basis of a 1997 case in which the National Basketball Association sued Motorola for transmitting real time game data by pager, making the defendant a competitor in providing the service. Databases must select, coordinate and arrange data with some creativity to earn copyright protection, and database producers use carefully worded contracts to protect their works. Librarians must be aware of copyright and contract details for databases and the scholarly use of data therein.
Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small‐Molecule Inhibitor of Eg5
Authors: Möckel Martin M. , Hund Corinna , Mayer Thomas U.
Published: August 2016

Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small‐molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical‐genetics approach to render kinesin motor proteins sensitive to inhibition by the well‐characterized small molecule S‐Trityl‐l‐cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single‐molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild‐type Kif4A along microtubules. Thus, our proof‐of‐concept study revealed that this chemical‐genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small‐molecule inhibitors are not yet available.
A Doubly Biomimetic Synthetic Transformation: Catalytic Decarbonylation and Halogenation at Room Temperature by Vanadium Pentoxide
Authors: Rana Sujoy , Pandey Bhawana , Dey Aniruddha , Haque Rameezul , Rajaraman Gopalan , Maiti Debabrata
Published: August 2016

The halogenation of the C−H bond by metal‐oxo‐peroxo species and the decarbonylation of aldehydes by metal‐peroxo species are performed routinely in biological systems. However, metal‐mediated decarbonylative halogenation is unknown in nature. In this work, we have shown that widely available V2O5 and VO(acac)2 (acac=acetylacetonate) can catalyze decarbonylative halogenation through the generation of an intermediate vanadium‐oxo‐peroxo species, which was characterized by using 51 V NMR, UV/Vis, and resonance Raman spectroscopy. Further detection of formic acid from the reaction mixture confirmed the biomimetic aspects of decarbonylative halogenation. A detailed experimental and DFT study indicated a concerted mechanism for this decarbonylative halogenation performed under simple and mild reaction conditions.
“Release and Catch” Effect of Perfluoroalkylsulfonylimide‐Functionalized Imidazole/Pyridine on Brønsted Acids in Organic Systems
Authors: You Li , Ren Xiao‐Fei , Wang Yun , Ma Zhong‐Hua , Gu Yanlong , Ma Jing‐Zhong
Published: August 2016

A “release and catch” method was developed by utilising the scavenging effect of a fluorous zwitterion on a homogeneous triflic acid (TfOH) catalyst in Michael addition and Rupe rearrangement. Both TfOH and the zwitterion were recycled with >90 % recovery using toluene. The zwitterions were designed by functionalising imidazole/pyridine with the perfluoroalkylsulfonylimide group. The “caught” TfOH was delivered to ethyl acetate and re‐used. The smooth delivery was primarily because of the fluorous tail of the zwitterion, the hydrophobicity of which probably weakened the ability of the zwitterion to form H bonds, so that retro‐ion‐exchange occurred towards the formation of the acid and zwitterion. The method was universal for other strong Brønsted acids such as H2SO4 and p‐MeC6H4SO3H. The method combined the significant advantages of homogeneous catalysis and heterogeneous isolation. Based on the H0 acidity function and the 31P NMR chemical shift of Et3P=O adducts, it is reasonable to deduce that the decrease of the acid strength of the formed composites of Brønsted acids and the zwitterion drove the scavenging effect.
Recycling Homogeneous Catalysts Simply by Organic Solvent Nanofiltration: New Ways to Efficient Catalysis
Authors: Dreimann Jens M. , Skiborowski Mirko , Behr Arno , Vorholt Andreas J.
Published: August 2016

Organic solvent nanofiltration is a convenient method for the recovery of homogeneous transition metal catalysts. The long chain olefin 1‐dodecene is hydroformylated continuously, and the commercially available catalyst complex is separated efficiently using a commercially available nanofiltration membrane. An advantage of this method is that both reaction and separation take place in a single liquid phase. Only continuous operation shows interactions of reaction and separation in the long run. Low energy demand, high scalability as well as transferability to other reactions make this method promising for new industrial applications.
A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study
Authors: van der Meer Margarethe , Rechkemmer Yvonne , Frank Uta , Breitgoff Frauke D. , Hohloch Stephan , Su Cheng‐Yong , Neugebauer Petr , Marx Raphael , Dörfel María , van Slageren Joris , Sarkar Biprajit
Published: August 2016

Quinonoid ligands are excellent bridges for generating redox‐rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed‐valent form have been isolated and characterized by single crystal X‐ray diffraction. The complex displays a large comproportionation constant for the mixed‐valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi‐frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed‐valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis.
Molecular E(CN)3 (E=Sb, Bi) Species Synthesized from Ionic Liquids as Solvates
Authors: Arlt Sören , Harloff Jörg , Schulz Axel , Stoffers Alrik , Villinger Alexander
Published: August 2016

The heavy pnictogen tricyanides, E(CN)3 (E=Sb, Bi), were synthesized from EF3 and Me3SiCN in ionic liquids, for example, 1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate ([BMIm][OTf]), which prevents the oligomerization of the molecular E(CN)3 species by formation of [BMIm][E(CN)3(OTf)] salts in solution. Recrystallization of [BMIm][E(CN)3(OTf)] from THF led to the isolation and full characterization of the molecular species E(CN)3⋅2 THF.
N‐Heteroarylation of Optically Pure α‐Amino Esters using the Pd‐PEPPSI‐IPentCl‐o‐picoline Pre‐Catalyst
Authors: Sharif Sepideh , Mitchell David , Rodriguez Michael J. , Farmer Jennifer L. , Organ Michael G.
Published: August 2016

A robust, mild, and efficient method for the Pd‐catalyzed N‐heteroarylation of optically pure α‐amino esters was developed. Dichloro[1,3‐bis(2,6‐di‐3‐pentylphenyl)imidazol‐2‐ylidene](o‐picoline)palladium(II) (Pd‐PEPPSI‐IPentCl‐o‐picoline; PEPPSI=pyridine enhanced pre‐catalyst preparation, stabilization, and initiation) was shown to effectively couple a variety of amino acids as thetert‐butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester. Control experiments revealed that racemization is base‐mediated, with no evidence of Pd‐mediated β‐hydride elimination when using Pd‐PEPPSI‐IPentCl, and that racemization occurs only after the product is formed, that is, the non‐arylated starting amino ester does not deprotonate under our reaction conditions. Studies also revealed that increasing the steric bulk of the ester moiety on the amino acid (e.g., ethyl totert‐butyl) drastically slows racemization of the product.
Synthesis of mesoporous silica materials (MCM‐41) using silica fume as the silica source in a binary surfactant system assisted by post‐hydrothermal treatment and its Pb2+ removal properties
Authors: Zhu Wenjie , Wu Di , Li Xitong , Yu Jie , Zhou Yang , Luo Yongming , Ma Wenhui
Published: August 2016

Mesoporous silica materials (MCM‐41) were successfully prepared by substituting silica fume for silicate in different surfactant systems. The effects of binary surfactant systems and post‐hydrothermal treatment on the morphology and structural properties of MCM‐41 were investigated based on X‐ray diffraction (XRD), N2 sorption/desorption, and transmission electron microscopy analyses (TEM). The results confirmed that polyethylene glycol (PEG‐6000) is an effective additive template in a binary surfactant system for the synthesis of mesoporous silica materials. Meanwhile, the hydrothermal stability of the mesoporous silica materials can be improved by post‐hydrothermal treatment and the optimal experimental parameters are a temperature of 140 °C and a treatment time of 48 h. The formation of high‐quality MCM‐41 is based on the balance between the ordered assembly of the inorganic anionic species and cationic surfactant, in accordance with the electrostatic interactions and hydrogen bonds between PEG‐6000 and the inorganic species. Meanwhile, Pb(II) removal from aqueous solution has also been examined using MCM‐41 as an adsorbent. The results of adsorption showed that the as‐synthesized MCM‐41 demonstrated a high capacity of Pb2+.
Application of fractionated bleached pulp fibres on sodium alginate films
Authors: Khan Ruhul A. , Salem Hayder J. , Korehei Reza , Martinez D. Mark , Olson James A.
Published: August 2016

Bleached NBSK (Northern Bleached Softwood Kraft) pulp was fractionated using a pilot pressure screen. Then the fractionated fibres were characterized using a Fibre Quality Analyzer (FQA) and Scanning Electron Microscope (SEM). It was found that the mean fibre length and width significantly decreased after fractionation. Aspect ratio (length divided by width) of the fractionated fibres was lower than NBSK fibres. The SEM analysis indicated that the diameter of the NBSK fibres was in the range of 100 to 200 μm, while the fractionated fibre diameters were found to be 10 to 40 nm. The fibre length of the fractions varied from a few hundred nanometres to a few micrometres. The fractionated fibres were incorporated into sodium alginate‐based biodegradable films during solution casting. It was found that the fractionated fibres significantly improved the mechanical properties of the sodium alginate films.
Charge Spreading in Deep Eutectic Solvents
Authors: Zahn Stefan , Kirchner Barbara , Mollenhauer Doreen
Published: August 2016

Ab initio molecular dynamic simulations reveal significantly reduced ion charges in several choline‐based deep eutectic solvents, which are cheap and eco‐friendly alternatives to ionic liquids. Increasing hydrogen bond strength between the anion and the organic compound enhances charge spreading from the anion to the organic compound while the positive charge is stronger located at the cation. Nonetheless, the negative charge transferred from chloride to urea in choline chloride urea mixtures is negligible. Thus, it seems questionable if charge delocalization occurring through hydrogen bonding between the halide anion and the organic compound is responsible for the deep eutectic melting point.
Magnetically Assembled SERS Substrates Composed of Iron–Silver Nanoparticles Obtained by Laser Ablation in Liquid
Authors: Scaramuzza Stefano , Badocco Denis , Pastore Paolo , Coral Diego F. , Fernández van Raap Marcela B. , Amendola Vincenzo
Published: August 2016

The widespread application of surface‐enhanced Raman scattering (SERS) would benefit from simple and scalable self‐assembly procedures for the realization of plasmonic arrays with a high density of electromagnetic hot‐spots. To this aim, the exploitation of iron‐doped silver nanoparticles (NPs) synthesized by laser ablation of a bulk bimetallic iron–silver target immersed in ethanol is described. The use of laser ablation in liquid is key to achieving bimetallic NPs in one step with a clean surface available for functionalization with the desired thiolated molecules. These iron–silver NPs show SERS performances, a ready response to external magnetic fields and complete flexibility in surface coating. All these characteristics were used for the magnetic assembly of plasmonic arrays which served as SERS substrates for the identification of molecules of analytical interest. The magnetic assembly of NPs allowed a 28‐fold increase in the SERS signal of analytes compared to not‐assembled NPs. The versatility of substrate preparation and the SERS performances were investigated as a function of NPs surface coating among different thiolated ligands. These results show a simple procedure to obtain magnetically assembled regenerable plasmonic arrays for repeated SERS investigation of different samples, and it can be of inspiration for the realization of other self‐assembled and reconfigurable magnetic–plasmonic devices.
Computational Insight to Improve the Thermal Isomerisation Performance of Overcrowded Alkene‐Based Molecular Motors through Structural Redesign
Authors: Oruganti Baswanth , Wang Jun , Durbeej Bo
Published: August 2016

Synthetic overcrowded alkene‐based molecular motors achieve 360° unidirectional rotary motion of one motor half (rotator) relative to the other (stator) through sequential photochemical and thermal isomerisation steps. In order to facilitate and expand the use of these motors for various applications, it is important to investigate ways to increase the rates and efficiencies of the reactions governing the rotary motion. Here, we use computational methods to explore whether the thermal isomerisation performance of some of the fastest available motors of this type can be further improved by reducing the sizes of the motor halves. Presenting three new redesigned motors that combine an indanylidene rotator with a cyclohexadiene, pyran or thiopyran stator, we first use multiconfigurational quantum chemical methods to verify that the photoisomerisations of these motors sustain unidirectional rotary motion. Then, by performing density functional calculations, we identify both stepwise and concerted mechanisms for the thermal isomerisations of the motors and show that the rate‐determining free‐energy barriers of these processes are up to 25 kJ mol−1 smaller than those of the original motors. Furthermore, the thermal isomerisations of the redesigned motors proceed in fewer steps. Altogether, the results suggest that the redesigned motors are useful templates for improving the thermal isomerisation performance of existing overcrowded alkene‐based motors.
Evaluation of AMGEN clone 9G8A anti‐Epo antibody for application in doping control
Authors: Reichel Christian , Benetka Wolfgang , Lorenc Barbara , Thevis Mario
Published: August 2016

The two mouse monoclonal anti‐erythropoietin (EPO) antibodies clone AE7A5 (generated by using a 26 amino acid N‐terminal EPO‐peptide) and 9G8A (developed by immunizing mice with full length human EPO) are both directed against linear epitopes at the N‐terminus of EPO. While AE7A5 has been commercially available for many years, 9G8A was made for Amgen's internal research purposes. In the past, the commercial antibody was shown to cross‐react with several proteins unrelated to EPO (e.g. E. coli thioredoxin reductase, zinc­α2­glycoprotein, S. cerevisiae enolase, human neuron‐specific enolase, and human non‐neuronal enolase). However, it displayed high sensitivity for detecting recombinant EPO (rEPO) misuse by athletes on Western blots. We evaluated the potential use of clone 9G8A for doping control purposes. While 9G8A showed lower sensitivity than AE7A5 (ca 45% on isoelectric focusing (IEF)‐polyacrylamide gel electrophoresis (PAGE), ca 40% on sodium dodecyl sulfate (SDS)‐ and sarcosyl (SAR)‐PAGE), non‐specific binding of the five proteins was not observed. The cross‐reactivity of AE7A5 can be overcome by immunoaffinity purification of EPO before electrophoresis and Western blotting. Similar to AE7A5, clone 9G8A is also suited for Western double‐blotting. Copyright © 2016 John Wiley & Sons, Ltd.
The Dok‐3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor‐independent manner
Authors: Manno Birgit , Oellerich Thomas , Schnyder Tim , Corso Jasmin , Lösing Marion , Neumann Konstantin , Urlaub Henning , Batista Facundo D. , Engelke Michael , Wienands Jürgen
Published: August 2016

The SH2 domain‐containing inositol 5'‐phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen‐mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine‐based inhibitory motifs. Here, we demonstrate a coreceptor‐independent membrane recruitment and function of SHIP in B cells. In the absence of coreceptor ligation, SHIP translocates to sites of BCR activation through a concerted action of the protein adaptor unit Dok‐3/Grb2 and phosphorylated BCR signaling components. Our data reveal auto‐inhibitory SHIP activation by the activated BCR and suggest an unexpected negative‐regulatory capacity of immunoreceptor tyrosine‐based activation motifs in Igα and Igβ.
Regio‐ and Stereoselective Synthesis of Acetallic Tetrahydropyrans as Building Blocks for Natural Products Preparation, via a Tandem [4+3]‐Cycloaddition/Ozonolysis Process
Authors: Montaña Ángel M. , Corominas Albert , Chesa Juan F. , García Francisca , Font‐Bardia Mercè
Published: August 2016

A highly versatile synthetic pathway is presented for the preparation of polyfunctionalized acetallic tetrahydropyrans from conveniently substituted 1‐methoxy‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one derivatives, as intermediates in the total synthesis of natural and unnatural products with structural, functional and/or biological importance. This synthetic methodology involves two key steps: a [4 + 3] cycloaddition reaction between an oxyallyl cation and 2‐methoxyfuran as a diene, followed by oxidative and/or reductive ozonolysis of the cycloheptenone subunit. This sequence renders polyfunctionalized 2‐methoxytetrahydropyranic products capable of being easily opened under acidic conditions. The key steps, cycloaddition and subsequent ozonolysis were both fully studied under different reaction conditions and using several substrates in order to optimize yields and stereoselectivities and to study the scope of the methodology. It is noteworthy that both reactions proceed with high diastereoselectivity and, in the case of the oxidative ozonolysis, outstanding regioselectivity as well. A chemical library of 14 polyfunctionalized tetrahydrofurans, having five or seven stereocenters, has been prepared using the detailed approach.
Flexible Transparent Triboelectric Nanogenerators with Graphene and Indium Tin Oxide Electrode Structures
Authors: Zhou Jinhao , Chen Yuanfu , Song Xinbo , Zheng Binjie , Li Pingjian , Liu Jingbo , Qi Fei , Hao Xin , Zhang Wanli
Published: August 2016

Triboelectric generators, which can directly transform energy from our living environment into electricity, are self‐powered component for wearable devices. Flexible and transparent triboelectric generators (FTTGs) with high output power densities are urgently needed for wearable electronics. By introducing graphene (G) and indium tin oxide (ITO) as transparent electrodes and optimizing the electrode structure, a FTTG with polyimide (PI) and polyethylene terephthalate (PET) as friction layers and graphene (ITO) as top (bottom) electrode was obtained and it has a large output power density of 10.1 μW cm−2, which is over four times larger than previously reported FTTGs ca. 2 μW cm−2. Moreover, the output voltage of the graphene‐based FTTG is as large as 56 V, and it exhibits excellent cycling behavior. The effects of electrode structure on the performance of FTTG have been analyzed and corresponding mechanism has been discussed. Light‐emitting diodes (LED) can be easily powered by the FTTG, suggesting its potential application in harvesting electrical energy from human activities by using flexible and transparent devices.
Environmental data analysis based on the gamma distribution: compliance assessment using tolerance limits and exceedance fractions
Authors: Bebu Ionut , Mathew Thomas
Published: August 2016

The gamma distribution has found extensive applications in the modeling and analysis of environmental data. Furthermore, for groundwater monitoring and environmental monitoring, an upper tolerance limit (i.e., an upper confidence limit for a percentile) can be used for checking compliance and is recommended in some of the standards published by the U.S. EPA. In addition, estimation of the proportion of samples where the measurements exceed a threshold (proportion of non‐compliance, for example), referred to as an exceedance fraction, is of obvious interest. Thus the computation of an accurate upper tolerance limit, and an accurate upper confidence limit for the exceedance fraction, are important. The problems are somewhat challenging since environmental samples are typically not large, and large sample methods cannot be used. In the present investigation, we have succeeded in obtaining accurate solutions to the above problems using a small sample modification of the likelihood based method. The results are also applied for analyzing a data set on vinyl chloride concentrations in ground water monitoring wells.
Phototoxic target lipid model of single polycyclic aromatic hydrocarbons
Authors: Marzooghi Solmaz , Finch Bryson E. , Stubblefield William A. , Dmitrenko Olga , Neal Sharon L. , Di Toro Dominic M.
Published: August 2016

A phototoxic target lipid model (PTLM) is developed to predict phototoxicity of individual polycyclic aromatic hydrocarbons (PAHs) measured either as median lethal concentration (LC50) or median lethal time (LT50) for a 50% toxic response. The model is able to account for the differences in the physical/chemical properties of PAHs, test species sensitivities, and variations in light source characteristics, intensity, and length of exposure. The PTLM is based on the narcotic target lipid model (NTLM) of PAHs. Both models rely on the assumption that mortality occurs when the toxicant concentration in the target lipid of the organism reaches a threshold concentration. The PTLM is applied to observed LC50s and LT50s for 20 individual PAHs, 15 test species—including arthropods, fishes, amphibians, annelids, mollusks, and algae—exposed to simulated solar and various UV light sources, for exposure times varying from less than 1 h to 100 h, a total of 333 observations. The LC50 concentrations range from less than 0.1 µg/L to greater that 104 µg/L. The model has 2 fitting parameters that are constant and apply to all PAHs and organisms. The root mean square errors of prediction for log(LC50) and log(LT50) are 0.473 and 0.382, respectively. The results indicate that the PTLM can predict the phototoxicity of single PAHs over a wide range of exposure conditions and to organisms with a wide range of sensitivities. Environ Toxicol Chem 2017;36:926–937. © 2016 SETAC
Efficient unified rare variant association test by modeling the population genetic distribution in case‐control studies
Authors: Li Huilin , Chen Jinbo
Published: August 2016

Recent advancements in next‐generation DNA sequencing technologies have made it plausible to study the association of rare variants with complex diseases. Due to the low frequency, rare variants need to be aggregated in association tests to achieve adequate power with reasonable sample sizes. Hierarchical modeling/kernel machine methods have gained popularity among many available methods for testing a set of rare variants collectively. Here, we propose a new score statistic based on a hierarchical model by additionally modeling the distribution of rare variants under the case‐control study design. Results from extensive simulation studies show that the proposed method strikes a balance between robustness and power and outperforms several popular rare‐variant association tests. We demonstrate the performance of our method using the Dallas Heart Study.