bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Organocatalytic Multicomponent Synthesis of Enantiopure γ‐Butyrolactones via Tandem Knoevenagel‐Michael‐Lactonization Sequence
Authors: Khopade Tushar M. , Sonawane Amol D. , Arora Jyotsna S. , Bhat Ramakrishna G.
Published: August 2017

An expedient and straightforward protocol is developed for the synthesis of highly enantiopure synthesis of γ‐butyrolactones. For the first time, one pot enantioselective organocatalytic multicomponent reaction (OMCR) is explored to construct functionalized butyrolactones without the use of pre‐functionalized substrates and expensive transition metals. The protocol is proved to be reproducible on a gram scale. Density functional theory (DFT) calculations strongly support the mechanism and were in close agreement with the observed high stereoselectivity.

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Sorption enhanced reaction for high purity products in reversible reactions
Authors: Ni Fan , Caram Hugo S.
Published: August 2017

Reversible reactions (A + B = C + D) can be performed to near completion using an admixture of catalyst and sorbent that will selectively adsorb one of the reaction products. For an initially clean sorbent and a favorable adsorption isotherm and a long reactor, the adsorbed product, C, will propagate as a sharp, shock‐like front. While the adsorbed product will not move faster than this front, the second, nonadsorbed product, D, will, in principle, leave the reactor, uncontaminated. However, a parametric analysis of the two examples presented in this work, the water gas shift and the cracking of hydrogen sulfide, reveals an unexpectedly complex behavior. While assuming adsorption equilibrium the effect of the equilibrium constant, the reaction kinetics and adsorption isotherm on the reactant and product concentration profiles are simulated. It is found that desired behavior is favored by large equilibrium constants, rapid kinetics, and strong nonlinear adsorption. © 2017 American Institute of Chemical Engineers AIChE J, 63: 5452–5461, 2017
A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral T‐cell lymphomas
Authors: Boonstra Philip S. , Polk Avery , Brown Noah , Hristov Alexandra C. , Bailey Nathanael G. , Kaminski Mark S. , Phillips Tycel , Devata Sumana , Mayer Tera , Wilcox Ryan A.
Published: August 2017

The transcription factor GATA‐3, highly expressed in many cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphomas (PTCL), confers resistance to chemotherapy in a cell‐autonomous manner. As GATA‐3 is transcriptionally regulated by NF‐κB, we sought to determine the extent to which proteasomal inhibition impairs NF‐κB activation and GATA‐3 expression and cell viability in malignant T cells. Proteasome inhibition, NF‐κB activity, GATA‐3 expression, and cell viability were examined in patient‐derived cell lines and primary T‐cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NF‐κB activation, and GATA‐3 expression were observed preclinically in ixazomib‐treated cells. Therefore, an investigator‐initiated, single‐center, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NF‐κB activation and GATA‐3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NF‐κB/GATA‐3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.
A retrospective analysis of 538 sinonasal fungus ball cases treated at a single tertiary medical center in Korea (1996‐2015)
Authors: Yoon Young Hoon , Xu Jun , Park Soo Kyoung , Heo Jae Hyung , Kim Yong Min , Rha Ki‐Sang
Published: August 2017

Background

Sinonasal fungus ball (FB) is a type of noninvasive fungal rhinosinusitis affecting immunocompetent hosts. FB, previously considered rare, has been reported with increasing frequency. We reviewed our experience of 538 cases over the past 20 years.

Methods

We retrospectively examined clinical records including clinical presentations, radiological findings, management, and outcomes of FB patients who have undergone surgery for treatment. The number of FB patients who underwent endoscopic sinus surgery (ESS) was calculated annually. Causal relationships between structural variations and FB were also investigated.

Results

The number of FB patients who underwent sinus surgery has increased. The mean age was 58.3 years, and the gender ratio was approximately 2 (female): 1 (male). While the most common presenting symptoms of maxillary sinus FB patients were nasal symptoms, such as postnasal drip and nasal obstruction, sphenoid sinus FB patients presented with headache mostly. On computed tomography (CT) scans, the most common finding was intralesional hyperdensity (77.3%). There was no significant correlation between the presence of FB and structural variations (nasal septal deviation, concha bullosa, Haller cell). Median follow‐up period of the patients was 11 months. Recurrence or residual disease occurred in only 6 (1.1%) cases.

Conclusion

The number of FB patients who underwent surgery has increased steadily over the past 20 years. FB should be considered in patients with unilateral nasal symptoms and unexplained headaches. A preoperative CT scan is an essential tool in making diagnosis easier and faster. Endoscopic surgery is the treatment of choice, with a low morbidity and recurrence rate.
Dysregulation of LIMK‐1/cofilin‐1 pathway: A possible basis for alteration of neuronal morphology in experimental cerebral malaria
Authors: Simhadri Praveen Kumar , Malwade Ruchi , Vanka Ravisankar , Nakka Venkata Prasuja , Kuppusamy Gowthamarajan , Babu Phanithi Prakash
Published: August 2017

Objective

Loss of cognition even after survival is the salient feature of cerebral malaria (CM). Currently, the fate of neuronal morphology is not studied at the ultrastructural level in CM. Recent studies suggest that maintenance of neuronal morphology and dendritic spine density (actin dynamics in particular) are essential for proper cognitive function. LIMK‐1/cofilin‐1 signaling pathway is known to be involved in the maintenance of actin dynamics through regulation of cofilin‐1, and in executing learning and memory functions.

Methods

Using an experimental mouse model, we analyzed the behavioral parameters of asymptomatic mice with CM by performing a rapid murine coma and behavior scale experiment. We performed Golgi–Cox staining to assess neuronal morphology, dendritic spine density, and arborization in brain cortex subjected to Plasmodium berghei ANKA infection compared to asymptomatic, anemic, and control groups. We studied the neural gene expression pattern of LIMK‐1, cofilin‐1, and β‐actin in all the experimental groups by semiquantitative and quantitative polymerase chain reaction followed by immunoblotting and immunofluorescence.

Results

We observed significant loss of dendritic spine density, abnormal spine morphology, reduced dendritic arborization, and extensive dendritic varicosities in the cortical neurons of CM‐infected brain. Furthermore, these observations correlated with diminished protein levels of LIMK‐1, cofilin‐1, phospho‐cofilin‐1, and β‐actin in the whole brain lysates as well as formation of actin–cofilin rods in the brain sections of symptomatic mice with CM.

Interpretation

Overall, our findings suggest that the altered neuronal morphology and dysregulation of LIMK‐1/cofilin‐1 pathway could affect the cognitive outcome after experimental CM. Therefore, this study could help to establish newer therapeutic strategies addressing long‐term cognitive impairment after CM. Ann Neurol 2017;82:429–443
One‐Step Reforming of CO2 and CH4 into High‐Value Liquid Chemicals and Fuels at Room Temperature by Plasma‐Driven Catalysis
Authors: Wang Li , Yi Yanhui , Wu Chunfei , Guo Hongchen , Tu Xin
Published: August 2017

The conversion of CO2 with CH4 into liquid fuels and chemicals in a single‐step catalytic process that bypasses the production of syngas remains a challenge. In this study, liquid fuels and chemicals (e.g., acetic acid, methanol, ethanol, and formaldehyde) were synthesized in a one‐step process from CO2 and CH4 at room temperature (30 °C) and atmospheric pressure for the first time by using a novel plasma reactor with a water electrode. The total selectivity to oxygenates was approximately 50–60 %, with acetic acid being the major component at 40.2 % selectivity, the highest value reported for acetic acid thus far. Interestingly, the direct plasma synthesis of acetic acid from CH4 and CO2 is an ideal reaction with 100 % atom economy, but it is almost impossible by thermal catalysis owing to the significant thermodynamic barrier. The combination of plasma and catalyst in this process shows great potential for manipulating the distribution of liquid chemical products in a given process.
Thiourea modified hyper‐crosslinked polystyrene resin for heavy metal ions removal from aqueous solutions
Authors: Yang Zujin , Huang Xiaonan , Yao Xingdong , Ji Hongbing
Published: August 2017

A hyper‐crosslinked resin chemically modified with thiourea (TM‐HPS) was synthesized, characterized, and evaluated for the removal of heavy metal ions (Pb2+, Cd2+, and Cu2+) from aqueous solutions. The structural characterization results showed that a few thiourea groups were grafted on the surface of the resin with a big BET surface area and a large number of narrow micropores. Various experimental conditions such as pH, contact time, temperature, and initial metal concentration of the three heavy metal ions onto TM‐HPS were investigated systematically. The results indicated that the prepared resin was effective for the removal of the heavy metal ions from aqueous solutions. The isotherm data could be better fitted by Langmuir model, yielding maximum adsorption capacities of 689.65, 432.90, and 290.69 mg/g for Pd2+, Cd2+, and Cu2+, respectively. And the adsorption kinetics of the three metal ions followed the pseudo‐second‐order equation. FTIR and XPS analysis of TM‐HPS before and after adsorption further revealed that the adsorption mechanism could be a synergistic effect between functional groups and metal ions and electrostatic attraction, which may provide a new insight into the design of highly effective adsorbents and their potential technological applications for the removal of heavy metal ions from aqueous solutions. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45568.
Preparation of amidoxime‐modified polyacrylonitrile nanofibrous adsorbents for the extraction of copper(II) and lead(II) ions and dye from aqueous media
Authors: Ren Jing , Yan Chunqiu , Liu Qingwen , Yang Qingbiao , Lu Guanxiu , Song Yan , Li Yaoxian
Published: August 2017

Amidoxime‐modified polyacrylonitrile nanofibrous films (AOPAN NFs) were prepared via an electrospinning technique. The traditional preparation methods for amidoximated polyacrylonitrile (AOPAN) solution were changed and improved. First, the PAN solution was modified by hydroxylamine hydrochloride to produce an AOPAN solution, and then, a small amount of inhibitor was added to the AOPAN solution for electrospinning. We found that the crosslinking of the AOPAN solution was inhibited by the addition of a small amount of inhibitor; at the same time, the storage time of the AOPAN solution was prolonged. In addition, the prepared AOPAN solution was electrospun into nanofibrous films, which could be used as excellent adsorption materials for Cu(II), Pb(II), and methyl orange (MO) after drying. The maximal adsorption capacities for Cu(II), Pb(II), and MO were 143.47, 178.57, and 68.07 mg/g, respectively. The adsorption capacities of the nanofibrous films were more than 50% that of the first adsorption after four recycling runs; this indicated the reusability of the nanofibrous films for water treatment. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45697.
Physiological and Metabolomic Analysis of Issatchenkia orientalis MTY1 With Multiple Tolerance for Cellulosic Bioethanol Production
Authors: Seong Yeong‐Je , Lee Hye‐Jin , Lee Jung‐Eun , Kim Sooah , Lee Do Yup , Kim Kyoung Heon , Park Yong‐Cheol
Published: August 2017

Yeast with multiple tolerance onto harsh conditions has a number of advantages for bioethanol production. In this study, an alcohol yeast of Issatchenkia orientalis MTY1 is isolated in a Korean winery and its multiple tolerance against high temperature and acidic conditions is characterized in microaerobic batch cultures and by metabolomic analysis. In a series of batch cultures using 100 g L−1 glucose, I. orientalis MTY1 possesses wider growth ranges at pH 2–8 and 30–45 °C than a conventional yeast of Saccharomyces cerevisiae D452‐2. Moreover, I. orientalis MTY1 showes higher cell growth and ethanol productivity in the presence of acetic acid or furfural than S. cerevisiae D452‐2. I. orientalis MTY1 produces 41.4 g L−1 ethanol with 1.5 g L−1 h−1 productivity at 42 °C and pH 4.2 in the presence of 4 g L−1 acetic acid, whereas a thermo‐tolerant yeast of Kluyvermyces marxianus ATCC36907 does not grow. By metabolomics by GC‐TOF MS and statistical analysis of 125 metabolite peaks, it is revealed that the thermo‐tolerance of I. orientalis MTY1 might be ascribed to higher contents of unsaturated fatty acids, purines and pyrimidines than S. cerevisiae D452‐2. Conclusively, I. orientalis MTY1 could be a potent workhorse with multiple tolerance against harsh conditions considered in cellulosic bioethanol production.
Prospects for Bio‐Industrial Application of an Extremely Alkaline Mannanase FromBacillus subtilissubsp.inaquosorumCSB31
Authors: Regmi Sudip , Yoo Hah Y. , Choi Yun H. , Choi Yoon S. , Yoo Jin C. , Kim Seung W.
Published: August 2017

Mannan‐degrading enzymes have been growing interest in bio‐industrial applications, such as the pulp and paper, food, and pharmaceutical industries. In this study, an extremely alkaline mannanase (MnB31) is produced byBacillus subtilissubsp.inaquosorumCSB31. MnB31 is purified to 17.92‐fold with a 21.51% yield and specific activity of 1,796.13 U mg−1by anion‐exchange and gel filtration column chromatography. The biochemical characterization of MnB31 is performed, and the results are as follows: molecular weight of ≈47 kDa with an optimum temperature of 60 °C and pH of 12.5. The enzyme is strongly activated by Co2+, Mn2+, Na+, and K+, and inhibited by Zn2+, Ni2+, and Mg2+. Halo‐tolerance (10% NaCl), urea stability (3 M), and protease resistance are also observed. The kinetic parameters of MnB31 are found to beKmof 0.043 mg ml−1, andVmaxof 1,046 ± 3.605 U mg−1, respectively. In addition, the thermodynamical parameters are investigated; the activation energy (Ea) is found to be 31.36 kJ mol−1with aKcatvalue of 156.9 × 104 s−1, ΔH (28.59 kJ mol−1), ΔG (42.38 kJ mol−1), ΔS (−41.39 J mol−1 K−1),Q10(1.40), ΔGE–S(−8.697 kJ mol−1), and ΔGE‐T(−48.22 kJ mol−1). These results suggest that MnB31 has potential bio‐industrial application, due to its greater hydrolytic efficiency and feasibility of enzymatic reaction.
Escherichia coli “TatExpress” strains super‐secrete human growth hormone into the bacterial periplasm by the Tat pathway
Authors: Browning Douglas F. , Richards Kirsty L. , Peswani Amber R. , Roobol Jo , Busby Stephen J.W. , Robinson Colin
Published: August 2017

Numerous high‐value proteins are secreted into the Escherichia coli periplasm by the General Secretory (Sec) pathway, but Sec‐based production chassis cannot handle many potential target proteins. The Tat pathway offers a promising alternative because it transports fully folded proteins; however, yields have been too low for commercial use. To facilitate Tat export, we have engineered the TatExpress series of super‐secreting strains by introducing the strong inducible bacterial promoter, ptac, upstream of the chromosomal tatABCD operon, to drive its expression in E. coli strains commonly used by industry (e.g., W3110 and BL21). This modification significantly improves the Tat‐dependent secretion of human growth hormone (hGH) into the bacterial periplasm, to the extent that secreted hGH is the dominant periplasmic protein after only 1 hr induction. TatExpress strains accumulate in excess of 30 mg L−1 periplasmic recombinant hGH, even in shake flask cultures. A second target protein, an scFv, is also shown to be exported at much higher rates in TatExpress strains.
Recombinant RNA Polymerase from Geobacillus sp. GHH01 as tool for rapid generation of metagenomic RNAs using in vitro technologies
Authors: Kinfu Birhanu M. , Jahnke Maike , Janus Mareike , Besirlioglu Volkan , Roggenbuck Michael , Meurer Richard , Vojcic Ljubica , Borchert Martin , Schwaneberg Ulrich , Chow Jennifer , Streit Wolfgang R.
Published: August 2017

The exciting promises of functional metagenomics for the efficient discovery of novel biomolecules from nature are often hindered by factors associated with expression hosts. Aiming to shift functional metagenomics to a host independent innovative system, we here report on the cloning, heterologous expression, and reconstitution of an RNA polymerase (RNAP) from the thermophilic Geobacillus sp. GHH01 and in vitro transcription thereafter. The five genes coding for RNAP subunits, a house keeping sigma factor and two transcription elongation factors were cloned and over expressed as His6‐tagged and/ or tag‐free proteins. Purified subunits were reconstituted into a functional polymerase through either the classical method of denaturation and subsequent renaturation or through a new resource and time efficient thermo‐reconstitution method which takes advantage of the subunits’ temperature stability. Additionally, all subunits were cloned into a single vector system for a co‐expression and in vivo reconstitution to the RNAP core enzyme. Both the core and holoenzyme form of the RNAP exhibited a robust transcription activity and were stable up to a temperature of 55°C close to their fullest activity. The Geobacillus RNAP showed a remarkable in vitro transcription profile recognizing DNA template sequences of diverse bacteria and archaea as well as metagenomic samples. Coupled with a subsequent in vitro translation step, this recombinant transcription system could allow a new, clone‐free, and functional metagenomic screening approach.
Cascading effect in bioprocessing—The impact of mild hypothermia on CHO cell behavior and host cell protein composition
Authors: Goey Cher H. , Tsang Joshua M.H. , Bell David , Kontoravdi Cleo
Published: August 2017

A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture conditions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, that is antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behavior. Mild hypothermic conditions introduced on day 5 of fed‐batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra 5 days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.
Cell‐free production of a therapeutic protein: Expression, purification, and characterization of recombinant streptokinase using a CHO lysate
Authors: Tran Kevin , Gurramkonda Chandrasekhar , Cooper Merideth A. , Pilli Manohar , Taris Joseph E. , Selock Nicholas , Han Tzu‐Chiang , Tolosa Michael , Zuber Adil , Peñalber‐Johnstone Chariz , Dinkins Christina , Pezeshk Niloufar , Kostov Yordan , Frey Douglas D. , Tolosa Leah , Wood David W. , Rao Govind
Published: August 2017

The use of cell‐free systems to produce recombinant proteins has grown rapidly over the past decade. In particular, cell‐free protein synthesis (CFPS) systems based on mammalian cells provide alternative methods for the production of many proteins, including those that contain disulfide bonds, glycosylation, and complex structures such as monoclonal antibodies. In the present study, we show robust production of turbo green fluorescent protein (tGFP) and streptokinase in a cell‐free system using instrumented mini‐bioreactors for highly reproducible protein production. We achieved recombinant protein production (∼600 μg/ml of tGFP and 500 μg/ml streptokinase) in 2.5 hr of expression time, comparable to previously reported yields for cell‐free protein expression. Also, we demonstrate the use of two different affinity tags for product capture and compare those to a tag‐free self‐cleaving intein capture technology. The intein purification method provided a product recovery of 86%, compared with 52% for conventionally tagged proteins, while resulting in a 30% increase in total units of activity of purified recombinant streptokinase compared with conventionally tagged proteins. These promising beneficial features combined with the intein technology makes feasible the development of dose‐level production of therapeutic proteins at the point‐of‐care.
Deletion of Fmr1 results in sex‐specific changes in behavior
Authors: Nolan Suzanne O. , Reynolds Conner D. , Smith Gregory D. , Holley Andrew J. , Escobar Brianna , Chandler Matthew A. , Volquardsen Megan , Jefferson Taylor , Pandian Ashvini , Smith Tileena , Huebschman Jessica , Lugo Joaquin N.
Published: August 2017

Objective

In this study, we used a systemic Fmr1 knockout in order to investigate both genotype‐ and sex‐specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear‐related learning and memory.

Background

Fragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes.

Methods

Using wild‐type and systemic homozygous Fmr1 knockout mice, we assessed a variety of behavioral paradigms in adult animals, including the open field test, elevated plus maze, nose‐poke assay, accelerating rotarod, social partition task, three‐chambered social task, and two different fear conditioning paradigms. Tests were ordered such that the most invasive tests were performed last in the sequence, and testing paradigms for similar behaviors were performed in separate cohorts to minimize testing effects.

Results

Our results indicate several sex‐specific changes in Fmr1 knockout mice, including male‐specific increases in activity levels, and female‐specific increases in repetitive behaviors on both the nose‐poke assay and motor coordination on the accelerating rotarod task. The results also indicated that Fmr1 deletion results in deficits in fear learning and memory across both sexes, and no changes in social behavior across two tasks.

Conclusion

These findings highlight the importance of including female subjects in preclinical studies, as simply studying the impact of genetic mutations in males does not yield a complete picture of the phenotype. Further research should explore these marked phenotypic differences among the sexes. Moreover, given that treatment strategies are typically equivalent between the sexes, the results highlight a potential need for sex‐specific therapeutics.
Concomitant coronary artery disease and its management in patients referred to transcatheter aortic valve implantation: Insights from the POL‐TAVI Registry
Authors: Huczek Zenon , Zbroński Karol , Grodecki Kajetan , Scisło Piotr , Rymuza Bartosz , Kochman Janusz , Dąbrowski Maciej , Witkowski Adam , Wojakowski Wojciech , Parma Radosław , Ochała Andrzej , Grygier Marek , Olasińska‐Wiśniewska Anna , Araszkiewicz Aleksander , Jagielak Dariusz , Ciećwierz Dariusz , Puchta Dominika , Paczwa Katarzyna , Filipiak Krzysztof J. , Wilimski Radosław , Zembala Marian , Opolski Grzegorz
Published: August 2017

Background

Coronary artery disease (CAD) and degenerative aortic stenosis often coexist. However, the impact of CAD and its management on the prognosis after transcatheter aortic valve implantation (TAVI) remains uncertain. We sought to evaluate the impact of obstructive CAD, SYNTAX score (Ss), and percutaneous coronary intervention (PCI) prior to TAVI on short‐term outcome.

Methods

Overall, 896 patients who underwent TAVI after heart team decision was included. Pre‐procedural angiograms were analysed to calculate baseline Ss (bSs) and residual Ss (rSs). Baseline, procedural and follow‐up data up to 30 days was acquired from the national POL‐TAVI registry.

Results

Patients with obstructive CAD at baseline (n = 462, 52%) had higher mortality as compared with the remaining (8.7 vs. 5.1%, log‐rank P = 0.039). Also, after correction for confounding factors obstructive CAD was identified as independent predictor of mortality (hazard ratio [HR] 1.74, 95% confidence intervals [CIs] 1.03–2.94, P = 0.037). In obstructive CAD, neither bSs (AUC 0.47, CI 0.38–0.56, P = 0.47) nor rSs (AUC 0.47, CI 0.30–0.64, P = 0.72 for those undergoing PCI and AUC 0.48, CI 0.37–0.59, P = 0.75 for the remaining) was predictive of mortality. When revascularization status was considered, patients with PCI prior to TAVI had similar outcome as those without obstructive CAD at baseline (7.7 vs. 5.1%, log‐rank P = 0.23) with no negative impact on mortality (HR 1.13, CI 0.62–2.09, P = 0.69).

Conclusions

In conclusion, obstructive CAD at baseline evaluation for TAVI has independent negative impact on short‐term prognosis. However, neither baseline nor residual Ss values have prognostic ability in patients undergoing TAVI. Revascularization prior to TAVI seems to improve survival to levels comparable with patients without obstructive CAD at baseline.
Hemodynamic analysis of a novel bioresorbable scaffold in porcine coronary artery model
Authors: Tenekecioglu Erhan , Torii Ryo , Bourantas Christos V. , Cavalcante Rafael , Sotomi Yohei , Zeng Yaping , Collet Carlos , Crake Tom , Abizaid Alexandre , Onuma Yoshinobu , Su Solomon , Santoso Teguh , Serruys Patrick W.
Published: August 2017

Background

The shear stress distribution assessment can provide useful insights for the hemodynamic performance of the implanted stent/scaffold. Our aim was to investigate the effect of a novel bioresorbable scaffold, Mirage on local hemodynamics in animal models.

Method

The main epicardial coronary arteries of 7 healthy mini‐pigs were implanted with 11 Mirage Microfiber sirolimus‐eluting Bioresorbable Scaffolds (MMSES). Optical coherence tomography (OCT) was performed post scaffold implantation and the obtained images were fused with angiographic data to reconstruct the coronary artery anatomy. Blood flow simulation was performed and Endothelial Shear Stress(ESS) distribution was estimated for each of the 11 scaffolds. ESS data were extracted in each circumferential 5‐degree subunit of each cross‐section in the scaffolded segment. The generalized linear mixed‐effect analysis was implemented for the comparison of ESS in two scaffold groups; 150‐µm strut thickness MMSES and 125‐µm strut thickness MMSES.

Results

ESS was significantly higher in MMSES (150 µm) [0.85(0.49–1.40) Pa], compared to MMSES (125 µm) [0.68(0.35–1.18) Pa]. Both MMSES (150 µm) and MMSES (125 µm) revealed low recirculation zone percentages per luminal surface area [3.17% ± 1.97% in MMSES (150 µm), 2.71% ± 1.32% in MMSES (125 µm)].

Conclusion

Thinner strut Mirage scaffolds induced lower shear stress due to the small size vessels treated as compared to the thick strut version of the Mirage which was implanted in relatively bigger size vessels. Vessel size should be taken into account in planning BRS implantation. Small vessels may not get benefit from BRS implantation even with a streamlined strut profile. This pilot study warrants comparative assessment with commercially available bioresorbable scaffolds.
Estimation of liquid‐liquid equilibrium of type 2 systems (water + valeric acid + monobasic ester or dibasic ester or alcohol) using SERLAS, SERLAS‐modified, and SERLAS‐integrated
Authors: Senol Aynur , Baslioglu Burcu , Bilgin Mehmet
Published: August 2017

This paper studies liquid‐liquid equilibrium (LLE) of the type 2 systems (water + valeric acid + dibasic ester or monobasic ester or alcohol) at T = (298.2 ± 0.1) K and p = (101.3 ± 0.7) kPa. Equilibrium distribution of valeric acid onto (water + solvent) two‐phase system is better for more structured diethyl sebacate and ethyl caprylate as compared to less structured diethyl succinate, diethyl malonate, ethyl valerate, and isoamyl alcohol. The two‐phase envelope size and the tie line slope on the phase diagrams are varying as follows: ethyl caprylate > diethyl sebacate > ethyl valerate > diethyl succinate ≈ diethyl malonate > isoamyl alcohol. The SERLAS‐integrated (solvation energy relation for liquid associated systems‐integrated) molecular model with nine physical descriptors, originated from LSER (linear solvation energy relation) principles in conjunction with group‐contribution method, is proposed and applied to the prediction of type 2 LLE properties. By combining SERLAS with UNIFAC‐Dortmund, we are able to get along with a simultaneous impact of both methods for satisfactorily simulating type 2 phase behaviour so long as solvent effects are concerned. SERLAS, SERLAS‐modified, SERLAS‐integrated, and UNIFAC‐original models have been stringently tested for consistency in reproducing phase equilibrium properties with average deviations inferior to 28.8 %, 44.3 %, 21.3 %, and 30.4 %, respectively.
Utilization of sol‐gel CuO‐ZnO‐Al2O3 catalysts in the methanol steam reforming for hydrogen production
Authors: Fornari Arielle Cristina , Menechini Neto Raphael , Lenzi Giane Gonçalves , dos Santos Onélia Aparecida Andreo , de Matos Jorge Luiz Mario
Published: August 2017

In this work five CuO‐ZnO‐Al2O3 catalysts were synthesized using the sol‐gel method, with different Cu percentages, for use in the methanol steam reforming reaction, at 300 °C, aiming to generate hydrogen for PEM (Polymer Electrolyte Membrane) fuel cells. The specific area and total pore volume of the materials decreased with increasing Cu content and consequently reduced the alumina content. Also, the area decreased with increasing the calcination temperature, due to the sintering and coalescence of Cu crystals. The metal dispersion decreased (from 32 to 4 %) with increasing the Cu amount (from 8.9 to 48.4 %). For this reaction, the catalyst with the second highest Cu concentration (40.6 %) was the most active and had the higher Cu area (34.8 m2Cu/gcat). Meanwhile, the catalyst with the lowest Cu content (8.9 %) had its active sites better used, presenting the highest turnover frequency, specific area, and metal dispersion. The experimental results indicated that there was an optimum composition for the catalyst, which would provide the best area and dispersion for the reaction, with a view to industrial application. This composition was statistically calculated to be 33 % (g/g) of Cu.
Distribution of corticotropin‐releasing factor (CRF) receptor binding in the mouse brain using a new, high‐affinity radioligand, [125I]‐PD‐Sauvagine
Authors: Tan Laura A. , Vaughan Joan M. , Perrin Marilyn H. , Rivier Jean E. , Sawchenko Paul E.
Published: August 2017

The corticotropin‐releasing factor (CRF) family of peptides includes CRF and three urocortins, which signal through two distinct G‐protein coupled receptors, CRF1 and CRF2. Although the cellular distribution of CRF receptor expression has been well characterized at the mRNA level, the localization of receptor protein, and, by inference, of functional receptors, has been limited by a lack of reliable immunohistochemical evidence. Recently, a CRF‐related peptide, termed PD‐sauvagine, was isolated from the skin of the frog, Pachymedusa dacnicolor, and validated as a high‐affinity ligand for CRF receptor studies. A radiolabeled analog, [125I]‐PD‐sauvagine, with high signal‐to‐noise ratio, was used in autoradiographic studies to map the distribution of CRF receptor binding sites in the mouse brain. Through the use of receptor‐deficient mice and subtype‐specific antagonists, CRF1 and CRF2 binding sites were isolated, and found to be readily reconcilable with regional patterns of mRNA expression. Binding site distributions within a given structure sometimes differed from mRNA patterns, however, particularly in laminated structures of the isocortex, hippocampus, and cerebellum, presumably reflecting the trafficking of receptors to their operational homes on neuronal (mostly dendritic) processes. Binding patterns of [125I]‐PD‐sauvagine provided independent assessments of controversial receptor localizations, failing to provide support for CRF1 expression in central autonomic components of the limbic forebrain, the locus coeruleus and cerebellar Purkinje cells, or for CRF2 in any aspect of the cerebellar cortex. Though lacking in ideal resolution, in vitro binding of the PD‐sauvagine radioligand currently provides the most sensitive and accurate available tool for localizing CRF receptors in rodent brain.
A map of sensilla and neurons in the taste system of drosophila larvae
Authors: Rist Anna , Thum Andreas S.
Published: August 2017

In Drosophila melanogaster larvae, the prime site of external taste reception is the terminal organ (TO). Though investigation on the TO's implications in taste perception has been expanding rapidly, the sensilla of the TO have been essentially unexplored. In this study, we performed a systematic anatomical and molecular analysis of the TO. We precisely define morphological types of TO sensilla taking advantage of volume electron microscopy and 3D image analysis. We corroborate the presence of five external types of sensilla: papilla, pit, spot, knob, and modified papilla. Detailed 3D analysis of their structural organization allowed a finer discrimination into subtypes. We classify three subtypes of papilla and pit sensilla, respectively, and two subtypes of knob sensilla. Further, we determine the repertoire of receptor genes for each sensillum by analyzing GAL4 driver lines of Ir, Gr, Ppk, and Trp receptor genes. We construct a map of the TO, in which the receptor genes are mapped to neurons of individual sensilla. While modified papillum and spot sensilla are not labeled by any GAL4 driver, neurons of the pit, papilla, and knob type are labeled by partially overlapping but different subsets of GAL4 driver lines of the Ir, Gr, and Ppk gene family. The results suggest that pit, papilla and knob sensilla act in contact chemosensation. However, they likely do these employing different stimulus transduction mechanisms to sense the diverse chemicals of their environment.
Global Infinite Energy Solutions for the 2D Gravity Water Waves System
Authors: Wang Xuecheng
Published: August 2017

We prove global existence and a modified scattering property for the solutions of the 2D gravity water waves system in the infinite depth setting for a class of initial data, which is only required to be small above the level . No assumption is made below this level. Therefore, the nonlinear solution can have infinite energy. As a direct consequence, the momentum condition assumed on the physical velocity in all previous small energy results by Ionescu‐Pusateri, Alazard‐Delort, and Ifrim‐Tataru is removed.© 2017 Wiley Periodicals, Inc.
TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment
Authors: Faustman Denise L.
Published: August 2017

In the past decade, interest in the century‐old tuberculosis vaccine, bacillus Calmette‐Guerin (BCG), has been revived for potential new therapeutic uses in type 1 diabetes and other forms of autoimmunity. Diverse clinical trials are now proving the value of BCG in prevention and treatment of type 1 diabetes, in the treatment of new onset multiple sclerosis and other immune conditions. BCG contains the avirulent tuberculosis strain Mycobacterium bovis, a vaccine originally developed for tuberculosis prevention. BCG induces a host response that is driven in part by tumour necrosis factor (TNF). Induction of TNF through BCG vaccination or through selective agonism of TNF receptor 2 (TNFR2) has 2 desired cellular immune effects: (1) selective death of autoreactive T cells and (2) expansion of beneficial regulatory T cells (Tregs). In human clinical trials in both type 1 diabetes and multiple sclerosis, administration of the BCG vaccine to diseased adults has shown great promise. In a Phase I trial in advanced type 1 diabetes (mean duration of diabetes 15 years), 2 BCG vaccinations spaced 4 weeks apart selectively eliminated autoreactive T cells, induced beneficial Tregs, and allowed for a transient and small restoration of insulin production. The advancing global clinical trials using BCG combined with mechanistic data on BCGs induction of Tregs suggest value in this generic agent and possible immune reversal of the type 1 diabetic autoimmune process.
To mdivi‐1 or not to mdivi‐1: Is that the question?
Authors: Smith George , Gallo Gianluca
Published: August 2017

The fission/division and fusion of mitochondria are fundamental aspects of mitochondrial biology. The balance of fission and fusion sets the length of mitochondria in cells to serve their physiological requirements. The fission of mitochondria is markedly induced in many disease states and in response to cellular injury, resulting in the fragmentation of mitochondria into dysfunctional units. The mechanism that drives fission is dependent on the dynamin related protein 1 (Drp1) GTPase. mdivi‐1 is a quinazolinone originally described as a selective inhibitor of Drp1, over other dynamin family members, and reported to inhibit mitochondrial fission. A recent study has challenged the activity of mdivi‐1 as an inhibitor of Drp1. This study raises serious issues regarding the interpretation of data addressing the effects of mdivi‐1 as reflective of the inhibition of Drp1 and thus fission. This commentary considers the evidence for and against mdivi‐1 as an inhibitor of Drp1 and presents the following considerations; (1) the activity of mdivi‐1 toward Drp1 GTPase activity requires further biochemical investigation, (2) as there is a large body of literature using mdivi‐1 in vitro with effects as predicted for inhibition of Drp1 and mitochondrial fission, reviewed herein, the evidence is in favor of mdivi‐1's originally described bioactivity, and (3) until the issue is resolved, experimental interpretations for the effects of mdivi‐1 on inhibition of fission in cell and tissue experiments warrants stringent positive controls directly addressing the effects of mdivi‐1 on fission. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1260–1268, 2017
Steroid profile and IRMS analysis of musk administration for doping control
Authors: Wang Jingzhu , He Yi , Liu Xin , Yang Zhiyong , Yang Wenning
Published: August 2017

Musk, the dried secretion of the musk pod (sac) of adult male musk deer, has been used as traditional Chinese Medicine (TCM) in China and south‐east Asian countries for thousands of years. Due to the anabolic steroid component in this TCM, musk preparations have been included in the list of medical products containing prohibited substances employed for doping by the State Food and Drug Administration of China. The application of musk pod formulation was claimed to be responsible for some adverse analytical findings (AAFs) in the 2011 FIFA Women's World Cup. Our preliminary study has suggested that musk ingestion did not lead to AAFs of doping control with the single dosage of 100 mg. However, the influences of musk administration in large and multi dosage are still unclear. The aim of this study is to further investigate the influences of musk administration for doping control. Wild and domestic deer musk samples were collected. The concentrations and δ13C‐values of steroids in musk were analyzed. In an excretion study, 200 and 100 mg of wild and domestic deer musk samples were administrated by 29 subjects, respectively. Fluctuations in steroid profile could be observed, and the ratio of 5α‐androstane‐3α,17β‐diol to 5β‐androstane‐3α,17β‐diol was more sensitive than other parameters. In the IRMS test, the ∆Δδ13C‐value between endogenous reference compound and etiocholanolone was a sensitive parameter, and AAFs were obtained. It is the first time to confirm with excretion study that musk administration could lead to positive result of doping control. Copyright © 2017 John Wiley & Sons, Ltd.
Sudden gains in the outpatient treatment of anorexia nervosa: A process‐outcome study
Authors: Cartwright Anna , Cheng Yat Ping , Schmidt Ulrike , Landau Sabine
Published: August 2017

Objective

Sudden gains (SGs), broadly defined as sudden symptom reductions occurring between two consecutive treatment sessions, have been associated with improved treatment outcomes in anxiety and depression. The present study is the first to formally define SGs in anorexia nervosa and explore the characteristics, demographic and baseline clinical predictors, and clinical impact of SGs in anorexia nervosa.

Method

This is a secondary analysis of data from 89 outpatients with broadly defined anorexia nervosa who received one of two psychotherapeutic interventions as part of the MOSAIC trial (Schmidt et al., 2015). SGs were defined using session‐by‐session body mass index (BMI) measures. This study investigated whether SGs were associated with changes in BMI, eating disorder symptomology, general psychopathology, and psychosocial impairment between baseline and 6, 12, and 24 months follow‐up.

Results

SGs, experienced by 61.8% of patients, mostly occurred during the early and middle phases of treatment. A larger proportion of SGs predicted larger increases in BMI between baseline and 6, 12, and 24 months follow‐up. Amongst those experiencing at least one SG, fewer days between baseline and a patient's first SG predicted a larger increase in BMI between baseline and both 6 and 12 months follow‐up. The proportion and timing of SGs did not predict changes in other outcome measures.

Discussion

SGs in BMI during the outpatient treatment of anorexia nervosa are clinically useful predictors of longer‐term weight outcomes.
Classification of Monovarietal Sardinian Extra Virgin Olive Oils by 1H NMR Metabolomic
Authors: Culeddu Nicola , Chessa Matilde , Bandino Giovanni , Sedda Piergiorgio , Zurru Roberto , Anedda Roberto , Motroni Andrea , Molinu Maria Giovanna , Dettori Sandro , Santona Mario
Published: August 2017

The chemical composition affects the sensory properties and quality of Extra Virgin Olive Oil (EVOO). In addition, its knowledge can supply valuable information about the cultivar and its geographical origin. The goal of this study is to obtain a protocol in order to be able to recognize the composition of various Sardinian oils and to consequently correlate them with their production areas. High‐resolution 1H NMR spectroscopy was used to analyze 100 (82 training + 18 test sets) samples of EVOO from the Bosana cultivar, collected from different growing areas in Sardinia (Italy). Growth areas were classified on the basis of FAO‐UNEP aridity index. NMR data were processed with multivariate statistical analysis. NMR profiling presents a connection between environmental factors of Sardinian cultivation areas and the chemical composition of EVOO. An NMR‐based metabolomic approach that uses six “one‐to‐one” OPLS‐DA models allowed us to discriminate the different influence of evapotranspiration, solar exposure, and altitude on the chemical composition of Bosana EVOO. Practical Applications: Detailed knowledge of NMR spectra pattern variations could have a potential impact on olive oil market. The application of the 1H NMR metabolomic, based on chemometric models, can be a useful tool in order to certificate the geographical origin of EVOO.

An NMR‐based metabolomic approach,using “one‐to‐one” OPLS‐DA models, allows to identify biomarkers of different production zones in “Bosana” Sardinian EVOO.
Development of high‐throughput and high sensitivity capillary gel electrophoresis platform method for Western, Eastern, and Venezuelan equine encephalitis (WEVEE) virus like particles (VLPs) purity determination and characterization
Authors: Gollapudi Deepika , Wycuff Diane L , Schwartz Richard M , Cooper Jonathan W , Cheng KC
Published: August 2017

In this paper, we describe development of a high‐throughput, highly sensitive method based on Lab Chip CGE‐SDS platform for purity determination and characterization of virus‐like particle (VLP) vaccines. A capillary gel electrophoresis approach requiring about 41 s per sample for analysis and demonstrating sensitivity to protein initial concentrations as low as 20 μg/mL, this method has been used previously to evaluate monoclonal antibodies, but this application for lot release assay of VLPs using this platform is unique. The method was qualified and shown to be accurate for the quantitation of VLP purity. Assay repeatability was confirmed to be less than 2% relative standard deviation of the mean (% RSD) with interday precision less than 2% RSD. The assay can evaluate purified VLPs in a concentration range of 20–249 μg/mL for VEE and 20–250 μg/mL for EEE and WEE VLPs.
Ultrasensitive SPR detection of miRNA‐93 using antibody‐enhanced and enzymatic signal amplification
Authors: Schmieder Stefan , Weißpflog Janek , Danz Norbert , Hübner Max , Kreth Simone , Klotzbach Udo , Sonntag Frank
Published: August 2017

MiRNAs are endogenous noncoding RNA molecules. They play important gene‐regulatory roles by binding to the mRNA of target genes thereby leading to either transcript degradation or translational repression. In virtually all diseases, distinct alterations of miRNA expression profiles have been found thus suggesting miRNAs as interesting biomarkers. Here, we present an SPR biosensor that utilizes disposable, injection‐molded sensor chip/microfluidic hybrids combined with a lateral imaging optical system for parallel analysis of three one‐dimensional spot arrays to detect miRNA‐93. To increase the sensitivity of the biosensor we used two different amplification strategies. By adding an RNA‐DNA‐hybrid antibody for primary signal amplification, a limit of detection of 10 pmol/L was achieved. Based on that method we demonstrate the detection of miRNA‐93 in total RNA lysate from HEK‐293 cells. Utilizing an enzymatic signal amplification with Poly(A) polymerase, the sensitivity could be increased even further leading to a limit of detection of 1 fmol/L.