bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional effects of mutations in the tropomyosin‐binding sites of tropomodulin1 and tropomodulin3
Authors: Lewis Raymond A. , Yamashiro Sawako , Gokhin David S. , Fowler Velia M.
Published: June 2014

Tropomodulins (Tmods) interact with tropomyosins (TMs) via two TM‐binding sites and cap the pointed ends of TM‐coated actin filaments. To study the functional interplay between TM binding and TM‐actin filament capping by Tmods, we introduced disabling mutations into the first, second, or both TM‐binding sites of full‐length Tmod1 (Tmod1‐L27G, Tmod1‐I131D, and Tmod1‐L27G/I131D, respectively) and full‐length Tmod3 (Tmod3‐L29G, Tmod3‐L134D, and Tmod3‐L29G/L134D, respectively). Tmod1 and Tmod3 showed somewhat different TM‐binding site utilization, but nearly all TM binding was abolished in Tmod1‐L27G/I131D and Tmod3‐L29G/L134D. Disruption of Tmod‐TM binding had a modest effect on Tmod1's ability and no effect on Tmod3's ability to stabilize TM‐actin pointed ends against latrunculin A‐induced depolymerization. However, disruption of Tmod‐TM binding did significantly impair the ability of Tmod3 to reduce elongation rates at pointed ends with α/βTM, albeit less so with TM5NM1, and not at all with TM5b. For Tmod1, disruption of Tmod‐TM binding only slightly impaired its ability to reduce elongation rates with α/βTM and TM5NM1, but not at all with TM5b. Thus, Tmod‐TM binding has a greater influence on Tmods' ability to inhibit subunit association as compared to dissociation from TM‐actin pointed ends, particularly for α/βTM, with Tmod3's activity being more dependent on TM binding than Tmod1's activity. Nevertheless, disruption of Tmod1‐TM binding precluded Tmod1 targeting to thin filament pointed ends in cardiac myocytes, suggesting that the functional effects of Tmod‐TM binding on TM‐coated actin filament capping can be significantly modulated by the in vivo conformation of the pointed end or other factors in the intracellular environment. © 2014 Wiley Periodicals, Inc.
Breast cancer screening: Time for rational discourse
Authors: Brawley Otis W. , O'Regan Ruth M.
Published: June 2014

Breast cancer screening has limitations, but most of the evidence demonstrates that it saves lives. Women still should be encouraged to have screening mammograms but also should be made aware of their limitations.
Failure of researchers, reviewers, editors, and the media to understand flaws in cancer screening studies: Application to an article in Cancer
Authors: Berry Donald A.
Published: June 2014

Observational studies present inferential challenges. These challenges are acute in cancer screening studies, in which lead‐time and length biases are ever present. These biases can make any study worthless. Moreover, a flawed study's impact on the public can be deleterious when its conclusions are publicized by a naïve media. Flawed studies can also make the public learn to be wary of any article or reports of articles claiming to be scientific. Here, the author addresses these and related issues in the context of a study published in Cancer. Cancer 2014;120:2784–2791. © 2014 American Cancer Society.
Postoperative serum methylation levels of TAC1 and SEPT9 are independent predictors of recurrence and survival of patients with colorectal cancer
Authors: Tham CheeKian , Chew MinHoe , Soong Richie , Lim JitFong , Ang MeiKim , Tang ChoongLeong , Zhao Yi , Ong Simon Y. K. , Liu Yanqun
Published: June 2014

BACKGROUND

Serum carcinoembryonic antigen (CEA) is the only marker recommended for surveillance of colorectal cancer (CRC) recurrence; its sensitivity and specificity, however, are suboptimal. This study sought to evaluate the values of postoperative serum methylation levels of 7 genes for prognostication and especially for recurrence detection after curative resection.

METHODS

This prospective cohort study included 150 patients with stage I‐III CRC from whom 3 consecutive blood sampling was taken 1 week before, and 6 months and 1 year after operation. Methylation levels of 7 genes were evaluated via quantitative methylation‐specific polymerase chain reaction. Serum CEA was measured in parallel. Univariate and multivariate survival analyses were followed by construction of receiver operating characteristic curves for recurrence detection.

RESULTS

After a median follow‐up of 59 months, 43 patients (28.7%) developed recurrent lesions. High serum methylation levels of TAC1 in serum at 6‐month follow‐up (6M‐FU), and SEPT9 at 1‐year follow‐up (1Y‐FU) were independent predictors for tumor recurrence and unfavorable cancer‐specific survival (CSS) (P < .05 in all tests). Serum NELL1 methylation levels were significant alone for CSS at both 6M‐FU and 1Y‐FU, but not for disease‐free survival. Dynamic changes of TAC1 and SEPT9 with methylation increment were also independently predictive for recurrence (P < .05 in all tests). More importantly, TAC1 at 6M‐FU and SEPT9 at 1Y‐FU exhibited earlier detection of potential recurrences compared with concurrent serum CEA.

CONCLUSIONS

Levels of TAC1 and SEPT9 methylation detected in postoperative sera of patients with CRC appear to be novel promising prognostic markers and may probably be considered for monitoring of CRC recurrence. Cancer 2014;120:3131–3141. © 2014 American Cancer Society.
The effects of the nonselective benzodiazepine lorazepam and the α2/α3 subunit‐selective GABAA receptor modulators AZD7325 and AZD6280 on plasma prolactin levels
Authors: te Beek Erik T. , Chen Xia , Jacobs Gabriël E. , Nahon Kimberly J. , de Kam Marieke L. , Lappalainen Jaakko , Cross Alan J. , van Gerven Joop M. A. , Hay Justin L.
Published: June 2014

Compounds with selectivity for GABAA receptor subtypes may differ significantly from nonselective benzodiazepines in their dopaminergic effects in vivo. To explore the exact role of the GABAA receptor subtypes in the regulation of prolactin secretion and the differential effects of selective and nonselective GABA receptor modulators, the effects of the nonselective benzodiazepine lorazepam, as well as two novel α2/α3 subunit‐selective GABAA receptor modulators AZD7325 and AZD6280, on prolactin levels were measured in healthy male volunteers. Following administration of lorazepam at 2 mg doses and AZD6280 at 10 mg and 40 mg doses, prolactin levels increased significantly compared with placebo (difference 42.0%, 19.8%, and 32.8%, respectively), suggesting that the α2 and/or α3 receptor subtypes are involved in GABAergic modulation of prolactin secretion, although possible roles of the α1 and α5 receptor subtypes are not excluded. The increases in prolactin levels after administration of AZD7325 at 2 mg and 10 mg doses (difference 7.6% and 10.5%, respectively) did not reach statistical significance, suggesting that doses of AZD7325 or intrinsic efficacy at the α2 and α3 receptor subtypes may have been too low.
Effect of CYP2C19 polymorphism on the pharmacokinetics of rosuvastatin in healthy Taiwanese subjects
Authors: Finkelman Richard D. , Wang Tzung‐Dau , Wang Yi , Azumaya Connie T. , Birmingham Bruce K. , Wissmar Jenny , Mosqueda‐Garcia Rogelio
Published: June 2014

CYP2C19 contributes to N‐desmethyl rosuvastatin formation in “in vitro” models. Approximately 80% of Taiwanese are CYP2C19 extensive metabolizers (EMs, CYP2C19*1/*1, *1/*2, or *1/*3). We studied the potential effect of CYP2C19 genotypes on rosuvastatin pharmacokinetics in healthy Taiwanese subjects following single and multiple daily oral doses of rosuvastatin calcium (20 mg). Geometric mean ratios for poor metabolizers (PMs): EMs for rosuvastatin were 0.974 and 0.872 for area under the curve and maximum plasma concentration on day 1 (1.01 and 0.965 on day 17) and for N‐desmethyl rosuvastatin, 1.21 and 1.07 on day 1 (1.14 and 1.09 on day 17), respectively. Changes of lipid profiles from baseline to day 18 for PMs and EMs were −52.4% and −53.3% (low‐density lipoprotein cholesterol), and −34.2% and −30.0% (total cholesterol), respectively. Rosuvastatin was generally well‐tolerated by both PMs and EMs. These results suggest that CYP2C19 polymorphism does not affect rosuvastatin pharmacokinetics in healthy Taiwanese in a clinically meaningful way.
Band‐Gap Manipulations of Monolayer Graphene by Phenyl Radical Adsorptions: A Density Functional Theory Study
Authors: Huang Lin , Sk Mahasin Alam , Chen Peng , Lim Kok Hwa
Published: June 2014

Phenyl radical (Ph.) adsorption on monolayer graphene sheets is used to investigate the band‐gap manipulation of graphene through density functional theory. Adsorption of a single Ph. on graphene breaks the aromatic π‐bond and generates an unpaired electron, which is delocalized to the ortho or para position. Adsorption of a second radical at the ortho or para position saturates the radical by electron pairing and results in semiconducting graphene. Adsorption of a second radical at the ortho position (ortho–ortho pairing) is found to be more favorable than adsorption at the para position (ortho–para pairing), and the ortho–ortho pairing has stronger effects on band‐gap opening compared with ortho–para pairing. Adsorption of even numbers of Ph. on graphene by ortho–ortho and ortho–para pairings, in general, increases the band gap. Our study shows promise of band‐gap manipulation in monolayer graphene by Ph. adsorption, leading to potential wider applications of graphene.
Photocatalytic Hydrogen Evolution by Oleic Acid‐Capped CdS, CdSe, and CdS0.75Se0.25 Alloy Nanocrystals
Authors: Aslan Emre , Birinci Okan , Aljabour Abdalaziz , Özel Faruk , Akın Ilker , Hatay Patir Imren , Kus Mahmut , Ersoz Mustafa
Published: June 2014

Photocatalytic generation of hydrogen by using oleic acid‐capped CdS, CdSe, and CdS0.75Se0.25 alloy nanocrystals (quantum dots) has been investigated under visible‐light irradiation by employing Na2S and Na2SO3 as hole scavengers. Highly photostable CdS0.75Se0.25 alloy nanocrystals gave the highest hydrogen evolution rate (1466 μmol h−1 g−1), which was about three times higher than that of CdS and seven times higher than that of CdSe.
Tunable and Selective Conversion of 5‐HMF to 2,5‐Furandimethanol and 2,5‐Dimethylfuran over Copper‐Doped Porous Metal Oxides
Authors: Kumalaputri Angela J. , Bottari Giovanni , Erne Petra M. , Heeres Hero J. , Barta Katalin
Published: June 2014

Tunable and selective hydrogenation of the platform chemical 5‐hydroxymethylfurfural into valuable C6 building blocks and liquid fuel additives is achieved with copper‐doped porous metal oxides in ethanol. A new catalyst composition with improved hydrogenation/hydrogenolysis activity is obtained by introducing small amounts of ruthenium dopant into the previously reported Cu0.59Mg2.34Al1.00 structure. At a mild reaction temperature (100 °C), 2,5‐furandimethanol is obtained with excellent selectivity up to >99 %. Higher reaction temperatures (220 °C) favor selective deoxygenation to 2,5‐dimethylfuran and minor product 2,5‐dimethyltetrahydrofuran with a combined yield as high as 81 %. Notably, these high product yields are maintained at a substrate concentration up to 10 wt % and a low catalyst loading. The influence of different alcohol solvents on product selectivity is explored. Furthermore, reaction intermediates formed at different reaction temperatures are identified. The composition of these product mixtures provides mechanistic insight into the nature of the reduction pathways that influence product selectivity. The catalysts are characterized by elemental analysis, TEM, and BET techniques before and after the reaction. Catalyst recycling experiments are conducted in batch and in a continuous‐flow setup.
Lithium‐Ion Transport through a Tailored Disordered Phase on the LiNi0.5Mn1.5O4 Surface for High‐Power Cathode Materials
Authors: Jo Mi Ru , Kim Yong‐Il , Kim Yunok , Chae Ji Su , Roh Kwang Chul , Yoon Won‐Sub , Kang Yong‐Mook
Published: June 2014

The phase control of spinel LiNi0.5Mn1.5O4 was achieved through surface treatment that led to an enhancement of its electrochemical properties. Li+ diffusion inside spinel LiNi0.5Mn1.5O4 could be promoted by modifying the surface structure of LiNi0.5Mn1.5O4 through phosphidation into a disordered phase (Fd3m) that allows facile Li+ transport. Phosphidated LiNi0.5Mn1.5O4 showed a significantly enhanced electrochemical performance, even at high rates exceeding 10 C, demonstrating that the improved kinetics (related to the amount of Mn3+) can render LiNi0.5Mn1.5O4 competitive as a high‐power cathode material for electric vehicles and hybrid electric vehicles.
Refining the Neuberger model: Uracil processing by activated B cells
Authors: Maul Robert W. , Gearhart Patricia J.
Published: June 2014

During the immune response, B cells undergo a programed mutagenic cascade to promote increased affinity and expanded antibody function. The two processes, somatic hypermutation (SHM) and class switch recombination (CSR), are initiated by the protein activation‐induced deaminase (AID), which converts cytosine to uracil in the immunoglobulin loci. The presence of uracil in DNA promotes DNA mutagenesis though a subset of DNA repair proteins. Two distinct mechanisms have been proposed to control uracil processing. The first is through base removal by uracil DNA glycosylase (UNG), and the second is through detection by the mismatch repair (MMR) complex MSH2/6. In a study published in this issue of European Journal of Immunology, Dingler et al. [Eur. J. Immunol. 2014. 44: 1925‐1935] examine uracil processing in B cells in the absence of UNG and SMUG1 glycosylases. Similar to UNG, SMUG1 is an uracil glycosylase which can remove the uracil base. While Smug1−/− mice show no clear deficiency in SHM or CSR, Ung−/−Smug1−/− mice display exacerbated phenotypes, suggesting a back‐up role for SMUG1 in antibody diversity. This new information expands the model of uracil processing in B cells and raises several interesting questions about the dynamic relationship between base excision repair and MMR.
Decoration of Carbon Nanostructures with Metal Sulfides by Sonolysis of Single‐Molecule Precursors
Authors: Estrada Ana C. , Mendoza Ernest , Trindade Tito
Published: June 2014

Carbon nanostructures have emerged in recent decades as uniquely convenient materials for a number of technologies. Some of their envisaged applications require hybrid nanostructures that result from the coupling of semiconducting phases to the carbon materials. Here, we describe a new sonochemical method to decorate carbon‐based materials (multiwalled carbon nanotubes, graphene oxide, and graphite flakes) with metal sulfide nanophases. In this research, we have used a CdII alkyldithiocarbamate complex as a single source to produce CdS nanophases that nucleate and grow over the carbon substrates. However, other metal sulfides can be produced by a similar methodology, which paves the way to a scalable method for the preparation of hybrid metal sulfide/carbon nanomaterials.
Stable N‐Phosphanyl Acyclic Diaminocarbenes
Authors: Marchenko Anatoliy , Koidan Georgyi , Hurieva Anastasiya , Kurpiieva Olena , Vlasenko Yurii , Rozhenko Alexander B. , Kostyuk Aleksandr
Published: June 2014

The deprotonation of N‐di‐tert‐butylphosphanyl‐N‐aryl‐N′‐diisopropylformamidinium salts led to a new type of stable acyclic N‐phosphanyl‐diaminocarbene (PADC). Carbenes 8a–8d were separated as single compounds. The molecular structure of 8c was determined by X‐ray diffraction analysis. The PADC 8 possess an optimal substitution pattern at the nitrogen atoms, and the N–Ccarbene–N bond angle is 120.7°. Structural changes near the carbenic carbon atom, such as substitution of phenyl with mesityl, phosphanyl with selenophosphoryl, or the diisopropylamino group with 2,2,6,6‐tetramethylpiperidino, rendered them unstable. The PADCs underwent N,C‐phosphorus shifts to afford new C‐phosphanylformamidines.
Preparation and physical properties of calcium pectinate films modified with sunflower wax
Authors: Baümler Erica R. , Carelli Amalia A. , Martini Silvana
Published: June 2014

In this study, the preparation of films made from calcium pectinate (CP) and sunflower waxes (SFW) by casting is described. The optical properties, water resistance, thermal behavior, and rheological properties of SFW/CP films were examined. At higher SFW content irregular surfaces were obtained. Films made from a 2% aqueous pectin solution (PA) showed the best inclusion of the lipid material. Compared to SFW‐free films, SFW/CP films were less transparent, being the SFW concentration the responsible for the loss of transparency. The swelling index was affected by SFW inclusion and PA concentration. In general, water adsorption was not affected by SFW concentration, but it was affected by the environmental conditions. The inclusion of SFW did not improve the moisture barrier efficiency of the films. The thermal behavior of SFW/CP films revealed a melting peak in the range of 70–80°C attributed to the melting of SFW. The rheological analysis showed G′ values between 2.98 × 105 and 71.9 × 105 Pa for films stored at lower water activities, and they ranged from 3.07 × 105 to 38.4 × 105 Pa at higher environmental humidity. In both cases, G′ values were affected by SFW inclusion. A linear viscoelastic region (LVR) was observed for all the samples.

Practical applications: A flexible and adequate film for handling and wrapping was obtained in this study. The addition of SFW to the CP films network was possible, and the films were easily prepared. This could be a potential application for waxes obtained from sunflower oil refining processes.

Preparation of films made from calcium pectinate (CP) and sunflower waxes (SFW) by casting is described. The optical properties, water resistance, thermal behavior and rheological properties of SFW/CP films were also examined.
Convergent Synthesis and Conformational Analysis of the Hexasaccharide Repeating Unit of the O‐Antigen of Shigella flexneri Serotype 1d
Authors: Dhara Debashis , Kar Rajiv Kumar , Bhunia Anirban , Misra Anup Kumar
Published: June 2014

A hexasaccharide repeating unit of the O‐antigen of the cell wall of Shigella flexneri type 1d has been synthesized using a stereoselective [3+3] block glycosylation approach. Recently developed glycosylation conditions were used in the synthesis. A thioglycoside was used as an orthogonal glycosyl donor during the synthesis. The synthesized hexasaccharide was subjected to detailed NMR spectroscopic and molecular modeling studies to determine its conformational behavior in water. The NOE‐based two‐dimensional NOSEY experiment and all‐atom explicit molecular dynamics (MD) simulation studies suggest that the oligosaccharide is not very flexible, that it remains rigid with respect to the glycosidic linkages between the sugar moieties.
Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality
Authors: Russom Christine L. , LaLone Carlie A. , Villeneuve Daniel L. , Ankley Gerald T.
Published: June 2014

Adverse outcome pathways (AOPs) are designed to describe linkages of key events within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event. Risk assessors have traditionally relied on data from apical endpoints (e.g., mortality, growth, reproduction) to derive benchmark values for use in determining the potential adverse impacts of chemicals. One goal in building reliable and well-characterized AOPs is to identify relevant in vitro assays and/or in vivo biomarkers that could be used in screening the potential hazard of substances, thereby reducing costs and increasing the number of chemicals that can be evaluated in a timely fashion. The purpose of this review article is to build an AOP for substances with a molecular initiating event of acetylcholinesterase inhibition leading to acute mortality following guidance developed by the Organisation for Economic Cooperation and Development. In contrast to most other AOPs developed to date, in which coverage is for a relatively limited taxonomic group or life stage, this AOP is applicable to a wide range of species at multiple life stages. Furthermore, while development of most AOPs has relied on data for a few model chemicals, the AOP described in the present review captures information from a large number of studies with a diversity of organophosphate and carbamate insecticides. Environ Toxicol Chem 2014;33:2157–2169. Published 2014 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study
Authors: Mukaetova‐Ladinska Elizabeta B. , Abdel‐All Zeinab , Andrade Joana , Alves da Silva Joaquim , O'Brien John T. , Kalaria Raj N.
Published: June 2014

Background

Clusterin protein in plasma has been found to differentiate between people with and without cognitive changes. However, these findings are not conclusive, despite the clusterin gene variations repeatedly being linked to increased risk for dementia, in particular Alzheimer's disease (AD).

Method

We analysed the level of clusterin in platelet and plasma in 25 subjects with a clinical diagnosis of AD and 26 subjects with no cognitive impairment.

Results

In the current study, we report that the levels of both plasma and platelet clusterin are similar between AD and cognitively intact individuals. Clusterin plasma and platelet levels, as well as the plasma/platelet clusterin ratio, were not affected by age, gender, cognitive impairment and/or overt behavioural symptomatology, including presence of hallucinations and delusions, as well as depression. However, the plasma/platelet clusterin ratio was positively associated in with the Neuropsychiatric Inventory measures of agitation, apathy, irritability and motor aberrant behaviour in AD subjects.

Conclusion

Previous inconsistencies in reported blood clusterin levels may be a result of underlying non‐cognitive symptoms in people with AD. Our findings need now to be replicated in larger group of dementia subjects. Copyright © 2014 John Wiley & Sons, Ltd.
Unqualified Directors in Insolvency: A Comparative Study on the Desirability of Civil Law Directors' Disqualification in the Netherlands
Authors: Reker Tom
Published: June 2014

The current global economic, and therefore political, climate has given rise to legislative responses within insolvency law, aiming to increase the legal arsenal against fraudulent behaviour. A recent proposal of the Dutch government to introduce a civil law disqualification instrument is a quintessential example of this tendency. In this article, the usefulness of this proposal is questioned. The usefulness of the civil law instrument is tested by comparing it with its Dutch criminal law equivalent. Furthermore, several proposals for alteration, based on foreign counterparts, will be formulated in order to increase the effectiveness of the aforementioned arsenal as a whole. Comparisons are made with similar instruments in Australia, England, Germany and the USA. Throughout the article, it will be asserted that, in order for the proposal to optimally reflect the principles of effectiveness and its civil law nature, a reallocation of certain elements of the proposal to its criminal law equivalent is required. Copyright © 2014 INSOL International and John Wiley & Sons, Ltd
Antifouling coating with controllable and sustained silver release for long‐term inhibition of infection and encrustation in urinary catheters
Authors: Wang Rong , Neoh Koon Gee , Kang En‐Tang , Tambyah Paul Anantharajah , Chiong Edmund
Published: June 2014

Urinary tract infections constitute a large proportion of nosocomial infections, and the urinary catheter is the most important predisposing factor. Encrustation induced by urease‐producing uropathogens like Proteus mirabilis causes further complications. In the present work, a strategy for controllable and sustained release of silver over several weeks has been developed for combating bacterial infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were first immobilized on polydopamine (PDA) pre‐treated silicone catheter surface and this was followed by another PDA coating. The number of AgNP‐PDA bilayers could be manipulated to control the amount of silver loaded and its subsequent release. Poly(sulfobetaine methacrylate‐co‐acrylamide) was then grafted to provide an antifouling outer layer, and to ensure free diffusion of Ag from the surface. The micron‐scale combination of an antifouling coating with AgNP‐PDA bilayers reduced colonization of the urinary catheter by uropathogens by approximately two orders of magnitude. With one and two AgNP‐PDA bilayers, the coated catheter could resist encrustation for 12 and 45 days, respectively, compared with approximately 6 days with the Dover™ silver‐coated catheter. Such anti‐infective and anti‐encrustation catheters can potentially have a large impact on reducing patient morbidity and healthcare expenditure. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 519–528, 2015.
Efficient and Easy One‐Pot Synthesis of New 3,5‐Dioxo‐thiazolo[2,3‐a] pyrimidine‐6‐carbonitrile and 4,6‐Dioxo‐pyrimido[2,1‐b][1,3]thiazine‐7‐carbonitrile Derivatives
Authors: Serrar H. , Boukhris S. , Hassikou A. , Souizi A.
Published: June 2014

An easy, fast, and cheap way for the synthesis of the new 3,5‐dioxo‐thiazolo[2,3‐a] pyrimidine‐6‐carbonitriles and 4,6‐dioxo‐pyrimido[2,1‐b][1,3]thiazine‐7‐carbonitriles using epoxides α‐functionalized.
An Efficient, Multicomponent, One‐pot Synthesis of Tetra Substituted Pyrans in Water
Authors: Pagadala R. , Maddila S. , Jonnalagadda S. B.
Published: June 2014

A new and environmentally benign multi‐component synthesis of tetra substituted 4H‐pyran derivatives is developed via the one‐pot reaction of an aromatic aldehyde, malononitrile, and 1,3‐diketone in the presence of NaOH with water as the solvent at RT. The reaction is efficient and affords excellent yields of the products.
Benign Approaches for the Microwave‐assisted Synthesis of Five‐membered 1,2‐N,N‐heterocycles
Authors: Kaur Navjeet
Published: June 2014

The development of new strategies for the synthesis of small‐sized heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in the synthesis of two nitrogen atoms containing five‐membered heterocyclic compounds is presented, focusing on the developments in the last 5–10 years. This contribution covers the literature concerning the total synthesis of five‐membered 1,2‐N,N‐heterocycles.
Thermal diffusivity enhancement in nanofluids based on pyrolytic titania nanopowders: importance of aggregate morphology
Authors: Rondino F. , D'Amato R. , Terranova G. , Borsella E. , Falconieri M.
Published: June 2014

Nanoparticle suspensions (nanofluids) have been subject of several investigations in the last few years for their potential applications, one of them being the improvement of heat transfer characteristics of thermal fluids. However, notwithstanding the numerous studies on thermal properties of nanofluids containing various kinds of nanoparticles, in many cases, the results are conflicting, and the models proposed to explain the experiments are controversial. In this paper, the thermal conductivity enhancement in dispersions, based on titania nanoparticles produced by laser‐assisted pyrolysis, is investigated using an optical technique known as forced Rayleigh light scattering. Measurements on these systems exhibited a linear relation between the thermal conductivity enhancement and the nanoparticle volume fractions with a maximum increase of 6% with respect to the base fluid ethanol at 0.6% titania content. Comparison of the experimental data with the aggregation model developed by Prasher et al. highlighted the crucial role of the morphology of pyrolytic nanoparticle aggregates on determining the thermal conductivity enhancement. Copyright © 2014 John Wiley & Sons, Ltd.
Iron in Restless Legs Syndrome
Authors: Schulte Eva C. , Kaffe Maria , Schormair Barbara , Winkelmann Juliane
Published: June 2014

A link between restless legs syndrome (RLS) and iron has been recognized for several decades. Yet, the precise role that iron or other components of iron metabolism play in bringing aboutRLSis still a matter of debate. During the last few years, many new pieces of evidence from genetics, pathology, imaging, and clinical studies have surfaced. However, the way this evidence fits into the larger picture ofRLSas a disease is not always easily understood. To provide a better understanding of the complex interplay between iron metabolism andRLSand highlight areas that need further elucidation, we systematically and critically review the current literature on the role of iron inRLSpathophysiology and treatment with a special emphasis on genetics, neuropathology, cell and animal models, imaging studies, and therapy.
Treatment Options in Degenerative Cerebellar Ataxia: A Systematic Review
Authors: Sarva Harini , Shanker Vicki Lynn
Published: June 2014

The etiology of cerebellar ataxia (CA) is heterogeneous and includes easily identified and often reversible causes (i.e., drug toxicity and vitamin B12 deficiency) as well as irreversible degenerative conditions. It is the latter that poses a significant therapeutic challenge for practitioners treating this population of patients. To date, there are no U.S. Food and Drug Administration–approved medications for the treatment of CA. The literature, consisting mostly of case reports, case series, and small clinical trials, is sparse and scattered. These studies are difficult to translate clinically because they often describe diverse study populations with various identified and unidentified genetic etiologies. In addition, the reported treatment duration is often brief, and it is uncertain whether any of these options provide substantially lasting benefits. In this article, we review published reports and studies to aid the practitioner counseling patients with degenerative ataxias.
What's special about task in dystonia? A voxel‐based morphometry and diffusion weighted imaging study
Authors: Ramdhani Ritesh A. , Kumar Veena , Velickovic Miodrag , Frucht Steven J. , Tagliati Michele , Simonyan Kristina
Published: June 2014

Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex, and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well‐described phenomenon of task specificity in dystonia remained limited. We used high‐resolution magnetic resonance imaging (MRI) with voxel‐based morphometry and diffusion weighted imaging with tract‐based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task‐specific dystonia forms, writer's cramp and laryngeal dystonia, and two non–task‐specific dystonia forms, cervical dystonia and blepharospasm. A direct comparison between both dystonia forms indicated that characteristic gray matter volumetric changes in task‐specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, and occipital cortex as well as the striatum and cerebellum (lobules VI‐VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in the non–task‐specific group were limited to the left cerebellum (lobule VIIa) only, whereas white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule, and middle cingulate gyrus. Distinct microstructural patterns in task‐specific and non–task‐specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers. © 2014 International Parkinson and Movement Disorder Society
Hyperpolarized gas diffusion MRI for the study of atelectasis and acute respiratory distress syndrome
Authors: Cereda Maurizio , Xin Yi , Kadlecek Stephen , Hamedani Hooman , Rajaei Jennia , Clapp Justin , Rizi Rahim R.
Published: June 2014

Considerable uncertainty remains about the best ventilator strategies for the mitigation of atelectasis and associated airspace stretch in patients with acute respiratory distress syndrome (ARDS). In addition to several immediate physiological effects, atelectasis increases the risk of ventilator‐associated lung injury, which has been shown to significantly worsen ARDS outcomes. A number of lung imaging techniques have made substantial headway in clarifying the mechanisms of atelectasis. This paper reviews the contributions of computed tomography, positron emission tomography, and conventional MRI to understanding this phenomenon. In doing so, it also reveals several important shortcomings inherent to each of these approaches. Once these shortcomings have been made apparent, we describe how hyperpolarized (HP) gas MRI – a technique that is uniquely able to assess responses to mechanical ventilation and lung injury in peripheral airspaces – is poised to fill several of these knowledge gaps. The HP‐MRI‐derived apparent diffusion coefficient (ADC) quantifies the restriction of 3He diffusion by peripheral airspaces, thereby obtaining pulmonary structural information at an extremely small scale. Lastly, this paper reports the results of a series of experiments that measured ADC in mechanically ventilated rats in order to investigate (i) the effect of atelectasis on ventilated airspaces, (ii) the relationship between positive end‐expiratory pressure (PEEP), hysteresis, and the dimensions of peripheral airspaces, and (iii) the ability of PEEP and surfactant to reduce airspace dimensions after lung injury. An increase in ADC was found to be a marker of atelectasis‐induced overdistension. With recruitment, higher airway pressures were shown to reduce stretch rather than worsen it. Moving forward, HP MRI has significant potential to shed further light on the atelectatic processes that occur during mechanical ventilation. Copyright © 2014 John Wiley & Sons, Ltd.
Probing lung microstructure with hyperpolarized 3He gradient echo MRI
Authors: Sukstanskii Alexander L. , Quirk James D. , Yablonskiy Dmitriy A.
Published: June 2014

In this paper we demonstrate that gradient echo MRI with hyperpolarized 3He gas can be used for simultaneously extracting in vivo information about lung ventilation properties, alveolar geometrical parameters, and blood vessel network structure. This new approach is based on multi‐gradient‐echo experimental measurements of hyperpolarized 3He gas MRI signal from human lungs and a proposed theoretical model of this signal. Based on computer simulations of 3He atoms diffusing in the acinar airway tree in the presence of an inhomogeneous magnetic field induced by the susceptibility differences between lung tissue (alveolar septa, blood vessels) and lung airspaces, we derive analytical expressions relating the time‐dependent MR signal to the geometrical parameters of acinar airways and the blood vessel network. Data obtained on eight healthy volunteers are in good agreement with literature values. This information is complementary to the information obtained by means of the in vivo lung morphometry technique with hyperpolarized 3He diffusion MRI previously developed by our group, and opens new opportunities to study lung microstructure in health and disease. Copyright © 2014 John Wiley & Sons, Ltd.
Prescriber response to unsolicited prescription drug monitoring program reports in Massachusetts
Authors: Thomas Cindy Parks , Kim Meelee , Nikitin Ruslan V. , Kreiner Peter , Clark Thomas W. , Carrow Grant M.
Published: June 2014

Purpose

To describe prescriber response to unsolicited patient reports from the Massachusetts prescription drug monitoring program (PDMP).

Methods

Prescribers were surveyed upon receipt of unsolicited reports of their patients' prescription history and three months later. We assessed prescribers' awareness of other prescribers listed in the report, their clinical assessment of medical necessity of all prescribed medications, actions taken by prescribers after receiving the report, and usefulness of the report.

Results

Of the 333 respondents to the initial survey, only 28 (8.4%) were aware of most, all, or nearly all other prescribers. A total of 146 (43.8%) reported having sufficient knowledge to determine whether the prescriptions were medically necessary, of whom 102 (69.6%) felt the prescriptions were unwarranted. Of the 163 respondents to the follow‐up survey, 31.3% added the report to the patient's file, 22.7% discussed the report with other prescribers on the report, 21.5% took no action, and 6% discussed the report with the patient (representing two‐thirds of respondents who saw the patient after receiving the report). Most respondents felt that the report was useful for their practice and easy to understand.

Conclusions

Unsolicited reporting of PDMP data has the potential to improve clinical practice by alerting providers about patients with multiple prescribers and potentially medically unnecessary prescriptions. Copyright © 2014 John Wiley & Sons, Ltd.
Probing phosphorylation‐dependent protein interactions within functional domains of histone deacetylase 5 (HDAC5)
Authors: Guise Amanda J. , Mathias Rommel A. , Rowland Elizabeth A. , Yu Fang , Cristea Ileana M.
Published: June 2014

Class IIa histone deacetylases (HDACs) are critical transcriptional regulators, shuttling between nuclear and cytoplasmic cellular compartments. Within the nucleus, these HDACs repress transcription as components of multiprotein complexes, such as the nuclear corepressor and beclin‐6 corepressor (BCoR) complexes. Cytoplasmic relocalization relieves this transcriptional repressive function. Class IIa HDAC shuttling is controlled, in part, by phosphorylations flanking the nuclear localization signal (NLS). Furthermore, we have reported that phosphorylation within the NLS by the kinase Aurora B modulates the localization and function of the class IIa HDAC5 during mitosis. While we identified numerous additional HDAC5 phosphorylations, their regulatory functions remain unknown. Here, we studied phosphorylation sites within functional HDAC5 domains, including the deacetylation domain (DAC, Ser755), nuclear export signal (NES, Ser1108), and an acidic domain (AD, Ser611). We have generated phosphomutant cell lines to investigate how absence of phosphorylation at these sites impacts HDAC5 localization, enzymatic activity, and protein interactions. Combining molecular biology and quantitative MS, we have defined the interactions and HDAC5‐containing complexes mediated by site‐specific phosphorylation and quantified selected changes using parallel reaction monitoring. These results expand the current understanding of HDAC regulation, and the functions of this critical family of proteins within human cells.
Effect of biopolymer blends on physical and Acoustical properties of biocomposite foams
Authors: Ghaffari Mosanenzadeh Shahrzad , Naguib Hani E. , Park Chul B. , Atalla Noureddine
Published: June 2014

Bio‐based foams are the solution to environmental concerns raised by petrochemical‐based open cell foams used in various industries for sound absorption. While conventional petrochemical‐based polymers take centuries to degrade or may not degrade at all, bio‐based polymers decompose to biomass, water, and carbon dioxide in a matter of months when exposed to proper environment. To increase the potential of replacing current petrochemical foams, mechanical as well as acoustic characteristics of bio‐based foams need to be improved. This article studies the effect of blending two bio‐based polymers and physics of the blends on acoustic and mechanical properties of resulting polymer composite foams. Different blends of polylactide with three grades of polyhydroxyalkanoates were foamed and characterized based on acoustic and mechanical performance. Rheological properties of pure polymers as well as their blends were studied and effect of polymer blends on acoustic absorption of the resulting foams was investigated. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1002–1013
Enzymatically triggered peptide hydrogels for 3D cell encapsulation and culture
Authors: Szkolar Laura , Guilbaud Jean‐Baptiste , Miller Aline F. , Gough Julie E. , Saiani Alberto
Published: June 2014

We have investigated the possibility of using enzymatically triggered peptide hydrogels for the encapsulation and culture of cells. Based on recent work done on the enzymatically triggered gelation of FEFK (F, phenylalanine; E, glutamic acid; K, lysine) using thermolysin, a protease enzyme from Bacillus Thermoproteolyticus Rokko, we have investigated the possibility of using this gelation triggering mechanism to encapsulate cells within a 3D hydrogel matrix. First, the properties of enzymatically triggered hydrogels prepared in phosphate buffer solution were investigated and compared with the properties of hydrogels prepared in HPLC grade water from our previous work. We showed that the use of phosphate buffer solution allowed the production of hydrogels with very high shear moduli (>1 MPa). The gelation kinetics was also investigated, and the mechanical properties of the system were shown to closely follow the synthesis of the octapeptide by the enzyme through reverse hydrolysis. In a second phase, we developed, on the basis of information acquired, a facile protocol for the encapsulation of cells and plating of the hydrogel. Human dermal fibroblasts were then used to exemplify the use of these materials. FEFEFKFK octapeptide hydrogels prepared under the same conditions and with the same mechanical properties were used as a control. We showed that no significant differences were observed between the two systems and that after a decrease in cell number on day 1, cells start to proliferate. After 5 days of culture, the cells can be seen to start to adopt a stretched morphology typical of fibroblasts. The results clearly show that the protocol developed minimises the potential detrimental effect that thermolysin can have on the cells and that these enzymatically triggered hydrogels can be used for the 3D encapsulation and culture of cells. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Anxiolytic‐Like Effect of Illicium verum Fruit Oil, trans‐Anethole and Related Compounds in Mice
Authors: Miyagawa Michiyo , Satou Tadaaki , Yukimune Chihiro , Ishibashi Ayumi , Seimiya Haruna , Yamada Hideo , Hasegawa Toshio , Koike Kazuo
Published: June 2014

The fruit of Illicium verum Hook. f. (star anise) is used by many as a spice. The fragrance of I. verum fruit is characteristically anise‐like. In this study, hexane‐extracted I. verum fruit oil (IVO), trans‐anethole as the main component, and related compounds (propiophenone, 4′‐methoxy‐propiophenone, trans‐β‐methylstyrene) were analyzed in order to clarify the emotional effect of inhaling the fragrance of I. verum fruit. As a result, although 4 μL/L air IVO did not exhibit an anxiolytic‐like effect, 1 μL/L air trans‐anethole exhibited a significant effect (p < 0.05). Moreover, the anxiolytic‐like effect of 1 μL/L air trans‐anethole was significantly greater than 1 μL/L air propiophenone and 1 μL/L air 4′‐methoxy‐propiophenone (p < 0.05). Thus, the anxiolytic‐like effect of trans‐anethole was confirmed, and it is proposed that the methoxyl group and 1‐propenyl group in the para position of the benzene ring are necessary for the effect. Copyright © 2014 John Wiley & Sons, Ltd.
Factor groups, semidirect product and quantum chemistry
Authors: Trindade Marco A. S.
Published: June 2014

In this article, we prove some general theorems about representations of finite groups arising from the inner semidirect product of groups. We show how these results can be used for standard applications of group theory in quantum chemistry through the orthogonality relations for the characters of irreducible representations. In this context, conditions for transitions between energy levels, projection operators, and basis functions were determined. This approach applies to composite systems and it is illustrated by the dihedral group related to glycolate oxidase enzyme. © 2014 Wiley Periodicals, Inc.
A Model Scholar and Preeminent Contributor to Our Understanding of Strategic Entrepreneurship: Arnold C. Cooper (1933–2012)
Authors: Folta Timothy B.
Published: June 2014

This paper discusses the scholarly work of Arnold C. Cooper. He was an influential pioneer in the study of entrepreneurship, strategic management, and technology management, and his work provided an important foundation for subsequent development in those fields. Many of his contributions are a result of methodological approaches to gathering data, enabling him to draw insights from systematic empiricism of phenomena. Many of his most influential works are discussed and linked to subsequent work, including work emanating from this journal. Future research opportunities tied to his work are also elaborated. Copyright © 2014 Strategic Management Society.
Li‐vapor induction growth of single‐crystalline Li4Ti5O12 specimen for transmission electron microscopy
Authors: Kitta Mitsunori , Akita Tomoki , Maeda Yasushi , Tanaka Shingo , Kohyama Masanori
Published: June 2014

Spinel lithium titanate (LTO; Li4Ti5O12) is widely used as an electrode material in lithium‐ion batteries. We have successfully prepared a well‐defined LTO specimen with atomically flat thin edges suitable for transmission electron microscopy (TEM) study. A thin wafer of rutile‐TiO2 was prepared by the traditional thinning procedure for TEM specimens, while it had a damaged amorphous surface layer. By heating with LiOH·H2O, thin edge regions of the TiO2 specimen were transformed into an LTO single crystal. The direction of the LTO growth depends on the orientation of the TiO2 specimen, and the amorphous surface layer of the TiO2 specimen plays an important role in the single‐crystalline growth. Copyright © 2014 John Wiley & Sons, Ltd.
Quantification of phosphorus diffusion and incorporation in silicon nanocrystals embedded in silicon oxide
Authors: Mastromatteo M. , Arduca E. , Napolitani E. , Nicotra G. , De Salvador D. , Bacci L. , Frascaroli J. , Seguini G. , Scuderi M. , Impellizzeri G. , Spinella C. , Perego M. , Carnera A.
Published: June 2014

The interest toward the doping of semiconductor nanostructures has been increasing steadily, but a clear understanding must still be reached, due to challenging characterization issues. In this work, we focused on Si nanocrystals (NCs) embedded in SiO2, which represent the most scalable and one of the most interesting and studied systems, but where an accurate quantification of the evolution of dopant profiles is still lacking. High depth resolution time‐of‐flight SIMS with charge compensation has been used to extract secondary ion depth profiles relative to P and Si elements. The relative sensitivity factors of P in SiO2 and of P in a layer containing Si NCs approximately 4.2 nm in diameter, as well as non‐linearity of P intensity at high P concentrations, were determined by comparison with P dose data extracted by Rutherford backscattering spectrometry analysis. Transmission electron microscopy analyses were performed to characterize the NC size distribution and stability upon thermal annealing. As a final result, we obtained a measurement protocol able to extract with high accuracy fully calibrated P concentration profiles in the SiO2 matrix with embedded Si NCs. Copyright © 2014 John Wiley & Sons, Ltd.