bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkyl and Aryl Thiol Addition to [1.1.1]Propellane: Scope and Limitations of a Fast Conjugation Reaction
Authors: Bär Robin M. , Kirschner Stefan , Nieger Martin , Bräse Stefan
Published: October 2017

Herein the addition of different thiols to the strained carbon–carbon bond of [1.1.1]propellane (1) is reported. The reaction pathway was investigated, addition reactions with substituted thiols, hydrogen sulfide and protected cysteine were performed, and further modifications of the products were verified. The clean reaction proceeds by a radical chain process, which was confirmed by different deuterium labelling experiments. It shows high functional‐group tolerance, since halo‐, hydroxy‐, methoxy‐, carboxy‐, amino‐ and nitro‐substituted thiols could be added to 1 with few by‐products in 16–90 % yield. Oxidation of the products allows tuning of the polarity and subsequent reactions of the products. The click‐type reaction proceeds even faster with selenols, as was shown in a proof of concept. Thiol addition to 1 offers a facile tool for surface modification, conjugation and tuning of hydrophilicity in bio‐ and medicinal chemistry.
Synthesis of Spirocyclic Pyrrolidines: Advanced Building Blocks for Drug Discovery
Authors: Chalyk Bohdan A. , Butko Maryna V. , Yanshyna Oksana O. , Gavrilenko Konstantin S. , Druzhenko Tetiana V. , Mykhailiuk Pavel K.
Published: October 2017

Invited for the cover of this issue is the group of Pavel K. Mykhailiuk at the Taras Shevchenko National University of Kyiv and Enamine Ltd. The image depicts spirocyclic pyrrolidine—a novel building block for drug discovery. Read the full text of the article at 10.1002/chem.201702362.
Gold‐Doping of Double‐Crown Pd Nanoclusters
Authors: Chen Jishi , Liu Liren , Liu Xu , Liao Lingwen , Zhuang Shengli , Zhou Shiming , Yang Jinlong , Wu Zhikun
Published: October 2017

Double‐crown Ni, Pd, or Pt nanoclusters have attracted extensive interests due to their aesthetic structure and intriguing properties. However, their doping by other metals remains unknown until now. Herein, Pd4(PET)8 and Pd5(PET)10 (PET: SCH2CH2Ph) were successfully doped with gold and the doped nanoclusters were characterized by using multiple techniques such as mass spectrometry and X‐ray crystallography. It is revealed that in the doping not one but two gold atoms replace one Pd with the other double‐crown structure essentially unchanged, and the gold‐doping results in the blue‐shift of the maximum visible absorption, the increase of optical energy gap and the reduction of anti‐aromaticity of monometal Pd nanoclusters. Importantly, it is found that Au4Pd2(PET)8 nanocluster bears chirality originating from not only the helixed Au4Pd2S8 framework, but also unanimous R or S configuration of sulfur atoms in the enantiomer. For the latter chirality origin, it was not previously reported or proposed. Au4Pd2(PET)8 reported here also represents the smallest chiral bimetal nanocluster so far to the best of our knowledge. This work advances one step toward both the tailoring of group 10 metal nanoclusters by doping and the understanding of chirality origin for metal nanoclusters.
Aerosol‐Synthesis of Porous Catalyst Particles with Tailored Pores and Tunable Metal Particle Size
Authors: Röhrbein Jannis , Arias Aurina Martínez , Weber Alfred P.
Published: October 2017

Die Herstellung von porösen geträgerten Katalysatoren mit fein einstellbaren Struktureigenschaften spielt in der heterogenen Katalyse eine große Rolle in der Erforschung von Reaktionsabläufen und Mechanismen. Das Zusammenspiel von nanoskaligen Poren und Aktivkomponenten bietet dabei die Möglichkeit der Optimierung von Reaktionen im Hinblick auf Ausbeute und Selektivität. Gängige Synthesemethoden sind oftmals in der Variationsbreite limitiert. Im Rahmen dieser Arbeit wird ein einfacher und gut skalierbarer Aerosol‐Syntheseweg für die Herstellung nanoskaliger Katalysatoren für die Fischer‐Tropsch‐Synthese aufgezeigt.
Cover Picture: Rapid Detection of Sildenafil Drugs in Liquid Nutraceuticals Based on Surface‐Enhanced Raman Spectroscopy Technology (Chin. J. Chem. 10/2017)
Authors: Zhao Hang , Hasi Wuliji , Bao Lin , Han Siqingaowa , Sha Xuanyu , Sun Jia , Lou Xiutao , Lin Dianyang , Lv Zhiwei
Published: October 2017

The cover picture shows a rapid detection of sildenafil drugs in liquid nutraceuticals based on surface‐enhanced Raman spectroscopy technology. A detailed attribution analysis by density functional theory (DFT) was used to guide specific experiments. The Raman signals were obtained from a silver colloid (Ag col) substrate, and they increased in the presence of the mineral salt, potassium iodide (KI). These methods detected sildenafil in aqueous solutions as low as 1 µg/mL with high signal uniformity (RSD = 3.77%). Raman technology detected low contents of sildenafil drugs in liquid nutraceuticals, not in solid samples. Therefore, SERS technology has great potential for on‐site and real‐time detection of illegal drugs in water and in liquid nutraceuticals. More details are discussed in the article by Hasi et al. on page 1522–1528.

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Protocol for Computational Enzymatic Reactivity Based on Geometry Optimisation
Authors: Cerqueira N. M. F. S. A. , Fernandes P. A. , Ramos M. J.
Published: October 2017

Enzymes play a biologically essential role in performing and controlling an important share of the chemical processes occurring in life. However, despite their critical role in nature, attaining a clear understanding of the way an enzyme acts is still cumbersome. Computational enzymology is playing an increasingly important role in this field of research. It allows the elucidation of a complete and detailed mechanism of an enzymatic reaction, including the characterization of reaction intermediates and transition states from both structural and energetic points of view, which is something that no other single experiment can produce alone.

In this review, we present a general computational strategy to study enzymatic mechanisms based on adiabatic mapping and free geometry optimization. These methods allow chemical reactions to be studied with high theoretical levels, and allow a more exhaustive exploration of the chemical reactional space than other available methods, albeit being limited to the extent that they explore the enzyme conformational space.

Special attention is given to the choice of the theoretical levels, as well as describing the model systems that are currently used to study enzymatic reactions. With this, we aim to provide a good introduction for non‐specialised users in this field of research. We also provide a selection of hand‐picked examples from our own work that illustrate the power of computational enzymology to study catalytic mechanisms. Some of these studies constitute pioneering work in the field that were later validated by experimental means.
How Chi Sequence Modifies RecBCD Single‐Stranded DNA Translocase Activity
Authors: Cho Chia‐Chuan , Chung Cinya , Li Hung‐Wen
Published: October 2017

E. coli RecBCD initiates homologous repair as well as degrades foreign DNA. Recognition of chi sequence (5′‐GCTGGTGG‐3′) switches RecBCD from a destructive, nucleolytic mode into a repair‐active one that promotes RecA‐mediated recombination. RecBCD includes a 3′‐to‐5′ single‐stranded DNA (ssDNA) translocase in RecB subunit, a 5′‐to‐3′ translocase in RecD, and a secondary translocase activity associated with RecBC. To understand how chi specifically affects each translocase activity, we directly visualized individual RecBCD translocating along DNA substrates containing a ssDNA gap of different polarities, with or without chi. Disappearance of RecBCD from the ssDNA signals the loss of the ssDNA translocase activity. For substrates containing a ssDNA gap that RecBCD encounters in the 3′‐to‐5′ polarity (3′‐to‐5′ ssDNA), wild‐type RecBCD disappears from the DNA substrates with similarly high percentage, either with chi or without. This suggests that (1) the 3′‐to‐5′ translocase in RecB is unaffected by chi and (2) it is low in processivity. With substrates containing a ssDNA gap that RecBCD encounters in the 5′‐to‐3′ polarity (5′‐to‐3′ ssDNA), we found that the leaving percentage increases significantly with chi, implying inactivation of the 5′‐to‐3′ translocase of RecD upon chi recognition. Surprisingly, the RecD defective mutant RecBCDK177Q showed only ≈50 % leaving on 5′‐to‐3′ ssDNA, directly revealing the presence of RecBC secondary translocase and its activity is unaffected by chi. Multiple ssDNA translocases within the RecBCD complex both before and after chi ensures processive unwinding of DNA substrates required for efficient recombination events.
Non‐oxidative Coupling of Methane to Ethylene Using Mo2C/[B]ZSM‐5
Authors: Sheng Huibo , Schreiner Edward P. , Zheng Weiqing , Lobo Raul F.
Published: October 2017

Methane non‐oxidative coupling to ethylene was investigated on Mo2C/[B]ZSM‐5 catalyst at 923 K and atmospheric pressure. In contrast to Mo2C/[Al]ZSM‐5 catalysts for methane aromatization, this material exhibits very high ethylene selectivity (>90 %) and low aromatics (benzene and naphthalene) selectivity. The much weaker Brønsted acidity of [B]ZSM‐5 leads to a slow rate of ethylene oligomerization. The stability of the catalyst is greatly enhanced with 93 % of the initial reaction rate remaining after 18 h of time on stream. In‐situ UV/VIS spectra indicate that prior to carburization, mono/binuclear Mo oxides are initially well dispersed onto the zeolite support. Mo carbides clusters, formed during carburization with methane, appear similar to clusters formed in [Al]ZSM‐5, as indicated by the X‐ray Absorption Spectroscopy (XAS) data.
Fabrication of a Robust Tantalum Nitride Photoanode from a Flame‐Heating‐Derived Compact Oxide Film
Authors: Shao Chenyi , Han Jingfeng , Liu Guiji , Wang Zhiliang , Zhao Yongle , Zong Xu , Li Can
Published: October 2017

Photoelectrochemical (PEC) water splitting provides an attractive way of converting solar energy into hydrogen energy. To make this approach practical, it is crucial to develop strategies that can be used to fabricate efficient photoelectrodes in a scalable manner. Herein, we report a rapid flame heating method to prepare a Ta2O5 precursor film for a Ta3N5 photoanode. By varying the parameters of flame heating, rational control over the physicochemical nature of the Ta2O5 precursor film can be realized. With the following nitridation treatment, the compact precursor film can be transformed into a tight‐knit Ta3N5‐based nitride film which strongly stuck to the underlying conductive Ta substrate. As a result of the close interfacial connections and reasonable conductivity achieved through the manipulation of the duration of flame heating, an enhanced charge‐separation efficiency was obtained for the as‐prepared Ta3N5 photoanode. Furthermore, with the help of a ferrihydrite layer, the photocurrent density for PEC water oxidation on the optimum Ta3N5 photoanode reached circa 3.53 mA cm−2 at 1.23 V vs. RHE, which is among the best values reported for planar Ta3N5‐based photoanodes. This report highlights the advantages of flame heating over traditional heating methods for preparing precursor films for further processing or functionalization.
Testbed@TWISC: A network security experiment platform
Authors: Tsai Pang‐Wei , Yang Chu‐Sing
Published: October 2017

As the internet continues to grow in width and depth, its very architecture brings many challenges in network research. One significant issue is cybersecurity. Owing to the characteristics of network connectivity, malicious actions may cause losses during information exchanges in communication. Therefore, studying suspicious behaviors and covering potential exploits are necessary to protect networked computers. To determine possible threats, researchers need an experimental environment that enables them to explore and practice. A network emulation testbed provides such a platform to fulfill these purposes. This paper introduces Testbed@TWISC, a large‐scale network emulation testbed on Taiwan's research and education network that supported open research and cybersecurity education for almost 10 years. The paper reviews this testbed's origination, development, and operation experiences. Several findings and open issues of the testbed are also discussed. Readers who plan to build network security testbeds may find useful information in this paper for a case study.
Detection possibilities of pore structures
Authors: Anders Nicole
Published: October 2017

Autoclaved aerated concrete, hereafter referred to as AAC, is characterized as a building material by its very good thermal insulation. This is achieved by a very high porosity of the microstructure. The size of the pores ranges from millimetres to nanometres and depends on the position as well as on the origin of the pore. These can be differentiated into propellant pores, web pores and intercrystalline or interparticle pores. Because of the broad pore size range, it has not been fully explained until now, which pore sizes significantly affect the building material qualities and to what extent. The overall pore size distribution of AAC can only be detected by a combination of different microstructure analysis methods.

For this purpose, nitrogen sorption analysis, mercury intrusion and 3D micro computer tomography were used as an effective combination. Three samples were tested, which show different mineralogical phase compositions because of the differentiation of the formulation. On the basis of these samples and the pore size distribution, which is usually used for the description of the frost and resistance to de‐icing salt of concrete, initial insights into the influence of the respective pore size on the building material properties of AAC could be gained.
Extension of the conditions for application of the simplified calculation methods according to DIN EN 1996‐3/NA for the design of unreinforced masonry walls
Authors: Mazur René , Purkert Benjamin
Published: October 2017

Dedicated to University Prof. Dr.‐Ing. Carl‐Alexander Graubner for his 60th birthday

The simplified calculation methods for unreinforced masonry structures given in DIN EN 1996‐3/NA are an easily applicable design standard for an efficient and fast verification of the resistance of mainly vertically loaded masonry walls. However, the design rules are not based on mechanical models. Instead, they are empirical approaches for a simplified estimation of the load bearing capacity. For this reason, the range of application of DIN EN 1996‐3/NA is limited by several conditions to ensure a sufficient safety of this design procedure.

With regard to extending the conditions for application, extensive comparative calculations were carried out. Thereby, considering clearly defined boundary conditions, the load bearing capacity according to DIN EN 1996‐3/NA was compared to that according to DIN EN 1996‐1‐1/NA. It was the aim of this comparison to identify load bearing reserves of the simplified calculation methods to point out potential for an extension regarding the maximum permissible clear wall height and the slab span. As a result, it can be stated, that an increase of the maximum wall height up to 6.0 m and the maximum slab span of 7.0 m is possible in certain cases.
Useful aspects of diagnosis of imprint cytology in intraoperative consultation of ovarian tumors: comparison between imprint cytology and frozen sections
Authors: Azami Shiho , Aoki Yuuji , Iino Mizuki , Sakaguchi Asumi , Ogura Kanako , Ogishima Daiki , Matsumoto Toshiharu
Published: October 2017

Background

In the intraoperative consultation of ovarian tumors, the histological diagnosis of frozen sections (FS) of large tumors is frequently difficult because of the limited number of tumor samples. The application of imprint cytology (IC), in which samples are obtained from wide areas of the tumors, is useful for intraoperative consultation. However, the useful aspects of IC have not been clearly defined. The present study is a detailed comparison of IC and FS that clearly defines the useful aspects of IC.

Methods

Fifty‐five cases of ovarian tumors that were examined using both IC and FS were evaluated. The histological diagnoses consisted of benign (16), borderline (6), and malignancy (33). All of the malignant tumors consisted of various types of carcinoma.

Results

Benignity and malignancy were accurately diagnosed by both IC and FS. In the borderline group, the diagnostic accuracy of IC was very low (1/6: 16.6%) compared with FS (4/6: 66.6%). The diagnostic accuracy including benign, borderline, and malignant groups was 90.9% (50/55) for IC and 96.3% (53/55) for FS. Concerning the diagnosis of the types of carcinoma, the overall diagnostic accuracy of IC (25/31: 80.6%) was greater than that of FS (21/31: 67.7%), especially for the diagnosis of clear cell carcinoma (IC, 100%; FS, 80%) and mixed carcinoma (IC, 66.6%; FS, 16.6%).

Conclusion

The useful aspects of IC in the intraoperative consultation are the diagnosis of benignity or malignancy and the accuracy of diagnosing clear cell carcinoma and mixed carcinoma.
Weight suppression and bulimic syndrome maintenance: Preliminary findings for the mediating role of leptin
Authors: Keel Pamela K. , Bodell Lindsay P. , Haedt‐Matt Alissa A. , Williams Diana L. , Appelbaum Jonathan
Published: October 2017

Objective

Longitudinal studies support a prospective relationship between weight suppression (WS) and bulimic syndrome (BN‐S) maintenance. Although biobehavioral mechanisms have been proposed to explain this link, such mechanisms have yet to be identified. Given that weight loss would reduce leptin levels which may influence eating, this study examined whether reduced leptin levels mediate the link between greater WS and longer illness duration.

Method

Women (N = 53), ages 18–45 years, were recruited from the community if they met criteria for a BN‐S, including either DSM‐5 bulimia nervosa (BN; n = 33) or purging disorder (PD: n = 20), and fell within a healthy weight range (18.5–26.5 kg/m2). Participants completed clinical assessments and provided blood samples to measure circulating leptin.

Results

Significant associations were found among greater WS, lower leptin concentrations, and longer duration of illness. Mediation analyses using bootstrapping procedures indicated all paths were significant and that leptin mediated the link between WS and illness duration. An alternative model in which longer illness duration contributed to leptin, via greater WS, was not supported.

Discussion

Longitudinal research is needed to support temporal associations and explore behavioral mechanisms linking leptin to illness trajectory.
Geoarchaeological study of abandoned Roman urban and suburban contexts from central Adriatic Italy
Authors: Vermeulen Frank , Pincé Possum , Weekers Lara , De Dapper Morgan
Published: October 2017

Over the past 15 years the Potenza Valley Survey project investigated Iron Age to Medieval settlement dynamics in the Central Adriatic Potenza Valley. Part of this research focuses on the Roman abandoned towns of Potentia and Trea by performing an integrated geoarchaeological study of their townscape. This largely noninvasive research consists of remote sensing analysis, geophysical surveys (magnetometry, electrical resistivity, and ground‐penetrating radar), and geomorphological fieldwork such as microtopographic measurements and hand augering. The chosen techniques depend on the nature of each town and are integrated with more traditionally achieved research data. This paper presents the main interdisciplinary results of work on these two Roman towns and highlights the importance of obtaining complementary data and performing hand augering as a stratigraphic control of the remote sensing and geophysical results. Insights into the character and layout of the cities, the structural influence on the surrounding area, and the human‐environment interactions and dynamics through time of both Roman cities could be achieved. Moreover, the results offer guidelines for conservation strategies of these abandoned towns and their suburbium, which are necessary to protect them from present‐day threats such as agriculture and tourism. In this way the paper offers an insight in the tremendous potential of well‐integrated geoarchaeological investigations of partly or fully abandoned urban contexts in the Mediterranean area and beyond.
One‐pot reactions for the synthesis of 5‐sulfonyl quinolines via domino N‐acylation and remote C‐H sulfonylation
Authors: Du Yi , Wei Li , Liu Yunyun
Published: October 2017

The synthesis of N‐acylated 5‐sulfonyl 8‐aminoquinolines has been performed via the three‐component reactions of 8‐aminoquinolines, acyl chlorides and sodium sulfinates for the first time. This new synthetic approach is highly facile by employing cheap copper salt as promoter and enabling the product formation via domino N‐acylation and selective remote C‐5 sulfonylation.
Efficacy and safety of vinorelbine plus cisplatin chemotherapy for patients with recurrent and/or metastatic salivary gland cancer of the head and neck
Authors: Hong Min Hee , Kim Chang Gon , Koh Yoon Woo , Choi Eun Chang , Kim Jinna , Yoon Sun Och , Kim Hye Ryun , Cho Byoung Chul
Published: October 2017

Background

The purpose of this study was to investigate the efficacy and safety of vinorelbine plus cisplatin chemotherapy in patients with recurrent and/or metastatic salivary gland cancer of the head and neck.

Methods

In this single‐arm phase II study, patients with recurrent and/or metastatic salivary gland cancer were treated with i.v. vinorelbine (25 mg/m2) on days 1 and 8 plus cisplatin (80 mg/m2) on day 1 every 3 weeks for 4 or 6 cycles. The primary endpoint was the objective response rate. Progression‐free survival (PFS), overall survival (OS), and adverse events were also assessed.

Results

Between September 2008 and November 2014, 40 patients with recurrent and/or metastatic salivary gland cancer received vinorelbine plus cisplatin chemotherapy. The objective response rate was 35.0%, including 1 complete response. Median PFS and OS rates were 6.3 months and 16.9 months, respectively. No treatment‐related deaths occurred.

Conclusion

Administering vinorelbine plus cisplatin chemotherapy to patients with recurrent and/or metastatic salivary gland cancers is safe and effective.
Management of the lateral neck compartment in patients with sporadic medullary thyroid cancer
Authors: Pena Israel , Clayman Gary L. , Grubbs Elizabeth G. , Bergeron Jeffrey M. , Waguespack Steven G. , Cabanillas Maria E. , Dadu Ramona , Hu Mimi I. , Fellman Bryan M. , Li Yisheng , Gross Neil D. , Lai Stephen Y. , Sturgis Erich M. , Zafereo Mark E.
Published: October 2017

Background

The purpose of this retrospective analysis was to evaluate the benefits of an elective lateral neck dissection (ELND) in patients with medullary thyroid cancer (MTC) without radiographically apparent lateral neck metastases.

Methods

Patients with sporadic MTC without radiographic evidence of lateral neck metastasis who underwent definitive surgery were divided into 2 groups based on surgical approach: no ELND (the observation group) and ipsilateral or bilateral ELND (the ELND group). Primary outcomes were biochemical cure, locoregional recurrence, distant metastasis, and overall survival (OS).

Results

Sixty‐six patients met inclusion criteria: 44 patients (67%) in the observation group and 22 patients (33%) in the ELND group. Two of 44 patients (5%) in the observation group developed subsequent (ipsilateral) lateral neck disease. At last follow‐up, locoregional disease control rates among the observation and ELND groups were 98% and 100% (P > .999), respectively, whereas biochemical cure rates were 82% and 85% (P > .999), respectively, and 5‐year OSs were 84% and 100% (P = .156), respectively.

Conclusion

Patients with MTC without lateral neck metastasis have similar biochemical cure rates with observation or elective dissection of lateral neck compartments.
Local control in sinonasal malignant melanoma: Comparing conventional to hypofractionated radiotherapy
Authors: Lansu Jules , Klop Willem Martin , Heemsbergen Wilma , Navran Arash , Al‐Mamgani Abrahim , Langendijk Johannes A. , Kaanders Johannes H. , Terhaard Chris , Karakullukcu Baris , Hamming‐Vrieze Olga
Published: October 2017

Background

The purpose of this study was to analyze the effect of fractionation schedule on local control in postoperative radiotherapy (RT) for sinonasal malignant melanoma.

Methods

Sixty‐three patients who were treated with surgery and postoperative RT in 4 accredited head and neck cancer centers in the Netherlands between 1998 and 2013 were retrospectively studied. Outcomes with conventional fractionation (2‐2.4 Gy per fraction; n = 27) were compared to hypofractionation (4‐6 Gy per fraction; n = 36). The primary endpoint was local control and the secondary endpoint was toxicity.

Results

Comparable local control rates were found after 2 and 5 years (63% vs 64% and 47% vs 53%; P = .73 for, respectively, conventional fractionation vs hypofractionation). Local recurrences were predominantly present ipsilateral (92%) and within the irradiated volume (88%). Late toxicity grade ≥ 3 was observed in 2 of 63 patients, 1 patient in both groups.

Conclusion

Radiotherapy fractionation schedule did not influence the local control rate or the incidence of late toxicity in patients treated with surgery and RT for sinonasal malignant melanoma in this retrospective analysis. Due to this retrospective nature and the limited number of patients, strong recommendations cannot be made. Expected toxicity, patient convenience, and workload may be taken into account for the choice of fractionation schedule until conclusive evidence becomes available.
Memory encoding‐related anterior hippocampal potentials are modulated by deep brain stimulation of the entorhinal area
Authors: Hansen Niels , Chaieb Leila , Derner Marlene , Hampel Kevin G. , Elger Christian E. , Surges Rainer , Staresina Bernhard , Axmacher Nikolai , Fell Juergen
Published: October 2017

Background

Deep brain stimulation (DBS) of the human entorhinal area using 50 Hz pulses has revealed conflicting results regarding memory performance. Moreover, its impact on memory‐related hippocampal potentials has not yet been investigated.

Methods

We recorded data from seven epilepsy patients implanted with depth electrodes in the entorhinal cortex, hippocampus, amygdala, and parahippocampal cortex. Entorhinal DBS (bipolar, biphasic 50 Hz pulses, on‐ and off‐cycles of 15 s) was applied with low amplitude (0.1 mA) to resemble physiologic conditions. During DBS on‐ and off‐periods, patients learned noun‐color associations that were later tested.

Results

During entorhinal DBS we observed more positive deflections of event‐related potentials (ranging from 700 to 950 ms) in the anterior hippocampus for the on‐ vs. off‐condition. We detected no effects in the amygdala, mid hippocampus and parahippocampal cortex. On the behavioral level, no differences in memory performance (item and source memory) were apparent in the on‐ vs. off‐condition, neither across all trials nor across patients.

Discussion

Our findings indicate that entorhinal DBS with low amplitude has an impact on memory encoding‐related potentials within the anterior hippocampus, but not on memory performance per se.
A multilevel examination of the relationship between role overload and employee subjective health: The buffering effect of support climates
Authors: Alfes Kerstin , Shantz Amanda D. , Ritz Adrian
Published: October 2017

Although the belief that support alleviates the detrimental effect of job demands on employee health is intuitive, past research has produced an equivocal picture, requiring a renewed evaluation of this relationship. In the present study, we examine three sources of support (from the organization, leader, and team) that employees may draw from to reduce the negative effect of a specific job demand, that is, role overload. Unlike most prior research, we focus on these sources of support at the group level of analysis to determine the relative effectiveness of organizational support climate, leadership climate, and team climate as moderators of the role overload–subjective health relationship. Hierarchical linear modeling of data from 2,288 employees nested in 132 workgroups in a state administration of Switzerland revealed that, after controlling for individual perceptions of support, team climate weakened the negative relationship between role overload and health. We did not find support for the buffering effect of organizational support or leadership climates. The article provides a nuanced test of the support‐buffering hypothesis by simultaneously exploring individual and group‐level sources of support and by demonstrating that some sources of support matter more than others in ameliorating the negative outcomes of role overload.
The assessment of the United States quantitative easing policy: Evidence from global stock markets
Authors: Su Jung‐Bin , Hung Ken
Published: October 2017

This study assesses the performance of the quantitative easing policy implemented by the United States (US) on the stock markets with a framework of structure break. The empirical results show that the business cycle or the value of gross domestic production has a negative impact on the stock markets for most of the countries even if both gross domestic production and many stock prices are procyclical. Moreover, the purchases of US Treasury securities and mortgage‐backed securities respectively affect the stock markets synchronously and laggardly. Notably, they both have a positive impact on the stock markets during the study period. Finally, during the after structure break period, the volatility can be easily affected by bad news, and the investors have the lower profit or even the greater loss and bear the greater risk and variation of risk owing to the global financial crisis caused by the US. On the basis of the above findings, some policy implications are offered in this study.
miR‐200c regulates endothelin‐1 induced PASMCs abnormal proliferation and apoptosis
Authors: Yuan Chao , Xu Min , Rong Rong , Mei Yong , Cai Wenyan , Li Lin , Xue Yao , Zhu Baoli , Sun Kai , Han Lei
Published: October 2017

miR‐200c is an antioncogene in multiple tumors. However, its function in the pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly investigated nor understood. In this study, we discovered that miR‐200c was able to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs) treated with endothelin‐1 (ET‐1). miR‐200c also induced cell proliferation and suppressed cell apoptosis in PASMCs in vitro. However, miR‐200c had no effect on G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR‐200c as a new regulator of the microtubule associated protein 2 (MAP‐2) and zinc finger E‐box binding homeobox1 (ZEB‐1) in PASMCs. miR‐200c inhibited MAP‐2 and ZEB‐1 expression by directly binding to their 3′‐untranslated regions(3′UTR) according to luciferase assay results. Our findings provide novel insights into the mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH diagnosis and treatment. © 2017 IUBMB Life, 69(11):877–886, 2017
Protective effects of curcumin against aflatoxicosis: A comprehensive review
Authors: Mohajeri Mohammad , Behnam Behzad , Cicero Arrigo F. G. , Sahebkar Amirhossein
Published: October 2017

Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non‐enzymatic antioxidants are manifestations of aflatoxicosis. Curcuma longa L. (turmeric) is a medicinal plant widely utilized all over the world for culinary and phytomedical purposes. Considering the antioxidant characteristic of curcumin, the main active component of turmeric, this review is intended to critically summarize the available evidence supporting possible effectiveness of curcumin against aflatoxicosis. Curcumin can serve as a promising candidate for attenuation of the adverse consequences of aflatoxicosis, acting mainly through intrinsic antioxidant effects aroused from its structure, modulation of the immune system as reflected by interleukin‐1β and transforming growth factor‐β, and interfering with AF's biotransformation by cytochrome P450 isoenzymes CYP1A, CYP3A, CYP2A, CYP2B, and CYP2C.
Discovery and characterization of novel trans‐spliced products of human polyoma JC virus late transcripts from PML patients
Authors: Saribas A. Sami , DeVoto Julia , Golla Akhil , Wollebo Hassen S. , White Martyn K. , Safak Mahmut
Published: October 2017

Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a rare fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (∼5 kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis‐splicing. Here, we report the discovery and characterization of two novel open reading frames (ORF1 and ORF2) associated with JCV late transcripts, generated by an unusual splicing process called trans‐splicing. These ORFs result from (i) the trans‐splicing of two different lengths of the 5′‐short coding region of VP1 between the coding regions of agnoprotein and VP2 after replacing the intron located between these two coding regions and (ii) frame‐shifts occurring within the VP2 coding sequences terminated by a stop codon. ORF1 and ORF2 are capable of encoding 58 and 72 aa long proteins respectively and are expressed in infected cells and PML patients. Each ORF protein shares a common coding region with VP1 and has a unique coding sequence of their own. When the expression of the unique coding regions of ORFs is blocked by a stop codon insertion in the viral background, the mutant virus replicates less efficiently when compared to wild‐type, suggesting that the newly discovered ORFs play critical roles in the JCV life cycle.
Comprehensive transcriptome analysis of fluid shear stress altered gene expression in renal epithelial cells
Authors: Kunnen Steven J. , Malas Tareq B. , Semeins Cornelis M. , Bakker Astrid D. , Peters Dorien J. M.
Published: October 2017

Renal epithelial cells are exposed to mechanical forces due to flow‐induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction, and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano‐sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid‐shear regulated genes and pathways in renal epithelial cells. Functional enrichment‐analysis revealed TGF‐β, MAPK, and Wnt signaling as core signaling pathways up‐regulated by shear. Inhibitors of TGF‐β and MAPK/ERK signaling modulate a wide range of mechanosensitive genes, identifying these pathways as master regulators of shear‐induced gene expression. However, the main down‐regulated pathway, that is, JAK/STAT, is independent of TGF‐β and MAPK/ERK. Other up‐regulated cytokine pathways include FGF, HB‐EGF, PDGF, and CXC. Cellular responses to shear are modified at several levels, indicated by altered expression of genes involved in cell‐matrix, cytoskeleton, and glycocalyx remodeling, as well as glycolysis and cholesterol metabolism. Cilia ablation abolished shear induced expression of a subset of genes, but genes involved in TGF‐β, MAPK, and Wnt signaling were hardly affected, suggesting that other mechano‐sensors play a prominent role in the shear stress response of renal epithelial cells. Modulations in signaling due to variations in fluid shear stress are relevant for renal physiology and pathology, as suggested by elevated gene expression at pathological levels of shear stress compared to physiological shear.
Effect of mono‐(2‐ethylhexyl) phthalate (MEHP) on proliferation of and steroid hormone synthesis in rat ovarian granulosa cells in vitro
Authors: Li Na , Liu Te , Guo Kun , Zhu Jian , Yu Guangyan , Wang Shuyue , Ye Lin
Published: October 2017

This study aimed to examine the proliferation of and secretion by rat ovarian granulosa cells (GCs) treated with mono‐(2‐ethylhexyl) phthalate (MEHP). Ovarian GCs were incubated with MEHP at concentration of 0, 25, 50, 100, and 200 µM for 24 hr. Cell viability was determined using the MTT Cell Proliferation Assay. Progesterone and estradiol production was evaluated by radioimmunoassay (RIA) and the expression of FSHR, PR, and ER was measured by immunocytochemistry. StAR, P450scc, 3β‐HSD, 17β‐HSD, and P450arom mRNA levels were determined by RT‐PCR. MEHP markedly attenuated proliferation of GCs, increased expression of sex hormone receptors and key enzymes in progesterone production, and stimulated steroid hormone secretion. The result of these analyses demonstrates that MEHP exposure of GCs may have effects on rat ovarian functions.
Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography
Authors: Mkrtschjan Michael A. , Gaikwad Snehal B. , Kappenman Kevin J. , Solís Christopher , Dommaraju Sagar , Le Long V. , Desai Tejal A. , Russell Brenda
Published: October 2017

Cell migration is regulated by several mechanotransduction pathways, which consist of sensing and converting mechanical microenvironmental cues to internal biochemical cellular signals, such as protein phosphorylation and lipid signaling. While there has been significant progress in understanding protein changes in the context of mechanotransduction, lipid signaling is more difficult to investigate. In this study, physical cues of stiffness (10, 100, 400 kPa, and glass), and microrod or micropost topography were manipulated in order to reprogram primary fibroblasts and assess the effects of lipid signaling on the actin cytoskeleton. In an in vitro wound closure assay, primary cardiac fibroblast migration velocity was significantly higher on soft polymeric substrata. Modulation of PIP2 availability through neomycin treatment nearly doubled migration velocity on 10 kPa substrata, with significant increases on all stiffnesses. The distance between focal adhesions and the lamellar membrane (using wortmannin treatment to increase PIP2 via PI3K inhibition) was significantly shortest compared to untreated fibroblasts grown on the same surface. PIP2 localized to the leading edge of migrating fibroblasts more prominently in neomycin‐treated cells. The membrane‐bound protein, lamellipodin, did not vary under any condition. Additionally, fifteen micron‐high micropost topography, which blocks migration, concentrates PIP2 near to the post. Actin dynamics within stress fibers, measured by fluorescence recovery after photobleaching, was not significantly different with stiffness, microtopography, nor with drug treatment. PIP2‐modulating drugs delivered from microrod structures also affected migration velocity. Thus, manipulation of the microenvironment and lipid signaling regulatory drugs might be beneficial in improving therapeutics geared toward wound healing.
Development and application of a real‐time polymerase chain reaction assay for detection of a novel gut bacteriophage (crAssphage)
Authors: Liang Yuying , Jin Xin , Huang Yuan , Chen Shuiping
Published: October 2017

crAssphage is a novel and by far the most abundant bacteriophage in human gut. This bacteriophage might modulate gut microbiota balance so as to be involved in some diseases like obesity, diabetes, metabolic disorders, hypertension, and cancer. Therefore, a rapid and reliable detection and quantification method for crAssphage is essential for studying its molecular epidemiology and pathogenicity in human diseases. The primers‐probes set for the quantitative real‐time PCR assay was designed based on the DNA polymerase gene (ORF00018) of crAssphage. The sensitivity and specificity, as well as comparison testing with the conventional PCR and sequencing were evaluated. The assay could specifically detect crAssphage, and no cross‐reactions with other gut microbes were observed. The detection limit was 15.6 copies/μL of clinical samples (46.8 copies/reaction). When using clinical samples, the assay showed higher ability to detect samples with low viral DNA copies and had an agreement of 93.33% when compared with the conventional PCR amplification and sequencing. The established real‐time PCR assay is a sensitive, specific, and repeatable method for quantitatively detecting crAssphage, and thus is a very useful tool for investigating the molecular epidemiology, dynamics, and pathogenicity of crAssphage in human diseases.
Changes in extreme precipitation in the Yangtze River basin and its association with global mean temperature and ENSO
Authors: Lü Mingquan , Wu Sheng‐Jun , Chen Jilong , Chen Chundi , Wen Zhaofei , Huang Yuanyang
Published: October 2017

Extreme precipitation events may lead to secondary disasters such as floods, landslides and erosion. The Yangtze River basin (YRB), which is home to a large population, is susceptible to flooding associated with heavy rainfall. Many dams have been constructed or planned for in the YRB. Understanding the changing behaviour of extreme precipitation and its relationship with other climatic factors will increase planners' ability to plan for, manage and respond to related flood events. This study investigated the trends in annual and seasonal maximum daily precipitation (Mx1day) using the iterative Mann–Kendall test. The non‐stationary Mx1day values were modelled to detect whether such changes were associated with rising local temperature (LTEM), global surface temperature (GTEM) or the El Niño–Southern Oscillation (ENSO). Location and scale parameters were considered individually in the non‐stationary generalized extreme value model during this study. Rising trends in annual Mx1day were identified at 73% of the stations studied. The June–July–August seasonal Mx1day exhibited the most pronounced increase among the four seasons. When location and scale were considered, 78 stations and 31 stations exhibited non‐stationary Mx1day, respectively. The impacts of both LTEM and ENSO on observed annual Mx1day in the YRB did not have field significance, while the impacts of GTEM did. At the YRB scale, the median sensitivity of the annual Mx1day to GTEM was 7.05% °C−1, while the median sensitivity of the annual Mx1day to LTEM was only 0.8% °C−1. The relationship between annual Mx1day and GTEM was more suitable for the Clausius–Clapeyron equation. The relationships between ENSO and observed seasonal Mx1day in March–April–May, June–July–August (JJA) and September–October–November (SON) were not field significant. However, a significant negative correlation between December–January–February Mx1day and ENSO was identified. The opposite effects of ENSO on extreme precipitation in JJA and SON may weaken the influence of ENSO on annual Mx1day.
Provider views on the management of Ewing sarcoma of the spine and pelvis
Authors: Zhu Chong , Olson Kristofor A. , Roth Michael , Geller David S. , Gorlick Richard G. , Gill Jonathan , Laack Nadia N. , Randall RL
Published: October 2017

Background

Curative therapy for ES requires both chemotherapy and local control of primary tumor. There is no universally accepted standard approach to local control modalities. This survey was conducted to determine practice patterns and factors influencing the choice to offer various local control modalities to patients with ES of the spine and pelvis.

Methods

The survey consisted of four scenarios involving a 15‐year‐old girl who presented with Ewing sarcoma of thoracic vertebra, sacrum, iliac wing, and acetabulum with or without neurologic compromise. The questionnaire was sent to oncologists, orthopedic surgeons, and radiation oncologists, asking their recommendations for local control modality.

Results

Among 94 respondents, radiotherapy was most frequently chosen for sacral tumors (68.1%) and T10 vertebral tumors (46.2%) whereas surgery was preferred for iliac wing pelvic tumors (45.7%) and acetabular tumors (43.6%). Orthopedic surgeons were significantly more likely to offer surgery than radiation oncologists (OR 3.07, 95%CI 1.37‐6.88, P = 0.007). Providers outside North America were more likely to offer combined surgery plus radiotherapy (OR 10.58, 95%CI 5.41‐20.70, P < 0.001).

Conclusion

Considerable heterogeneity exists in local control modalities for Ewing sarcoma of the spine and pelvis. Specialty and location of practice may influence treatment recommendations.
Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery
Authors: Matsuo Koji , Johnson Marian S. , Im Dwight D. , Ross Malcolm S. , Bush Stephen H. , Yunokawa Mayu , Blake Erin A. , Takano Tadao , Klobocista Merieme M. , Hasegawa Kosei , Ueda Yutaka , Shida Masako , Baba Tsukasa , Satoh Shinya , Yokoyama Takuhei , Machida Hiroko , Ikeda Yuji , Adachi Sosuke , Miyake Takahito M. , Iwasaki Keita , Yanai Shiori , Takeuchi Satoshi , Nishimura Masato , Nagano Tadayoshi , Takekuma Munetaka , Shahzad Mian M. K. , Pejovic Tanja , Omatsu Kohei , Kelley Joseph L. , Ueland Frederick R. , Roman Lynda D.
Published: October 2017

Background and Objectives

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy.

Methods

This is a nested case‐control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based‐surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy‐based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression‐free survival (PFS) and cause‐specific survival (CSS) were examined.

Results

The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted‐hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75‐1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted‐HR 1.13, 95%CI 0.68‐1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted‐HR 0.38, 95%CI 0.15‐0.93, P = 0.027; and CSS, unadjusted‐HR 0.21, 95%CI 0.07‐0.61, P = 0.002.

Conclusion

Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.