bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Th1 Cells and Experimental Autoimmune Encephalomyelitis by Glycogen Synthase Kinase-3
Authors: Beurel Eléonore , Kaidanovich-Beilin Oksana , Yeh Wen-I , Song Ling , Palomo Valle , Michalek Suzanne M. , Woodgett James R. , Harrington Laurie E. , Eldar-Finkelman Hagit , Martinez Ana , Jope Richard S.
Published: April 2013

Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), a debilitating autoimmune disease of the CNS, for which only limited therapeutic interventions are available. Because MS is mediated in part by autoreactive T cells, particularly Th17 and Th1 cells, in the current study, we tested whether inhibitors of glycogen synthase kinase-3 (GSK3), previously reported to reduce Th17 cell generation, also alter Th1 cell production or alleviate EAE. GSK3 inhibitors were found to impede the production of Th1 cells by reducing STAT1 activation. Molecularly reducing the expression of either of the two GSK3 isoforms demonstrated that Th17 cell production was sensitive to reduced levels of GSK3β and Th1 cell production was inhibited in GSK3α-deficient cells. Administration of the selective GSK3 inhibitors TDZD-8, VP2.51, VP0.7, or L803-mts significantly reduced the clinical symptoms of myelin oligodendrocyte glycoprotein35–55-induced EAE in mice, nearly eliminating the chronic progressive phase, and reduced the number of Th17 and Th1 cells in the spinal cord. Administration of TDZD-8 or L803-mts after the initial disease episode alleviated clinical symptoms in a relapsing-remitting model of proteolipid protein139–151-induced EAE. Furthermore, deletion of GSK3β specifically in T cells was sufficient to alleviate myelin oligodendrocyte glycoprotein35–55-induced EAE. These results demonstrate the isoform-selective effects of GSK3 on T cell generation and the therapeutic effects of GSK3 inhibitors in EAE, as well as showing that GSK3 inhibition in T cells is sufficient to reduce the severity of EAE, suggesting that GSK3 may be a feasible target for developing new therapeutic interventions for MS.
Development of foreign invested hospitals in China: obstacles and coping strategies
Authors: Liu Yongjun , Xue Yajiong , Liu Gordon , Ma Aixia
Published: April 2013

Since the Chinese government allowed foreign investors to open hospitals in China, the development of foreign invested hospitals has been slow. This paper reviews China’s policies and regulations on foreign invested hospitals. The purpose is to identify obstacles hindering the development of foreign invested hospitals and to propose strategies to overcome these obstacles. A case study was conducted to collect data from four foreign invested hospitals in China. The primary data include interviews, field surveys, and site visits. The secondary data include articles from newspapers and websites, hospital documentations, and media reports. The case study revealed four major obstacles facing foreign invested hospitals: unfavorable tax regulations, high service fees, low power status, and difficulty in physician recruitment. To overcome these obstacles, this paper recommends that foreign invested hospitals should develop external relationships with the government and other China’s public hospitals, reduce misunderstanding from patients and physicians, and select location and size wisely. This paper should be valuable for foreign investors who are interested in opening hospitals in China by helping them understand the regulatory context, avoid pitfalls, and develop suitable strategies.
Impact of a disinfecting technique on microbial contamination of computer keyboards and telephone handsets
Authors: Messina Gabriele , Ceriale Emma , Burgassi Sandra , Russo Carmela , Defranceschi Chiara , Mariani Lorenzo , Taddei Lucilla , Lenzi Daniele , Manzi Pietro
Published: April 2013

Background: Computers and telephones are ubiquitous in the hospital and have been shown to be contaminated with potentially pathogenic microorganism. The aim of the study was to determine microbial contamination on computer keyboards and telephone handsets and the effectiveness of a disinfecting technique (DT). Methods: A matched cross-over study, involving an overall of 50 computer keyboards and 50 telephone handsets, was conducted in three hospitals, located in the Local Health Area of Siena (Italy) before and after the use of an innovative DT consisting of a malleable-elastic compound, containing ethanol, which adheres to surfaces, removes dirt and disinfects. Total bacterial count was evaluated and several types of bacteria and fungi were researched pre- and post- use of the DT. Non parametric tests: Wilcoxon signed rank and Mann Whitney, were used, when appropriate. Results: The DT was effective in disinfecting the objects. In fact, Colony-Forming Units (CFUs) decreased to zero in most comparisons. All the comparisons showed significant differences (p<0.001) after the DT, both for computer keyboards and telephone handsets. The only exception was found for molds in telephones (p=0.062). Keyboards emerged to be dirtier than telephones handsets (p<0.05) for several types of bacteria. Conclusions: The data suggest that microbial contamination of keyboards and telephones is considerable. These objects can be a vehicle for Health Care-Associated Infections HAIs and their disinfection should not be neglected. The DT showed to be appropriate for the disinfecting purpose.
The financial ecosystem available to early-stage biotechnology firms and its misalignment with interests of these firms, of the biotechnology industry and with global disease burden
Authors: Toth Gergely
Published: April 2013

The development and commercialization of new therapeutics have had immense impact on the quality and length of human life.Â  Nevertheless, the biotechnology and the pharmaceutical industry have evolved to be driven mostly by a profit oriented market system, in which distinct stakeholders interact with different motivations to make the development and commercialization of therapeutics a reality.Â  This study discusses the funding ecosystem available for early-stage biotechnology companies and its influence on the their strategic business objectives and on the biotechnology industry.Â  On the basis of this, distinct paradoxes in the funding ecosystem are uncovered, which suggest that the present ecosystem is not well aligned with the interests of these biotechnology firms, the biotechnology industry, and it neglects strategic disease burden needs. It is recommended that even partial resolution of these paradoxes will enable further growth in the industry and lead to more innovative therapies for untreatable diseases with large social and economic burdens.Â  In light of this, the study proposes improvements of financing approaches and an increase of available capital in the funding ecosystem of early-state biotechnology companies.
A Patient Centric Commercial Model for Cancer Care
Authors: Rao Sanjay
Published: April 2013

Cancer is one of the most challenging diseases of all - not only in terms of the clinical barriers to offering its sufferers respite from devastating consequences, but also to manufacturers and marketers of treatments that attempt to control its impact. Products developed and manufactured through biotechnology dominate the commercial landscape for treating a variety of cancer types. The recent spate of new biologic launches for treating cancer delivered through injections, infusions and orally will only increase in the next five years. The task of developing a viable commercial model for the effective delivery of cancer treatments to its customers lies at the center of ensuring that advances in cancer care are harnessed for their full potential. Both by definition and due to the reality of the cancer landscape, such a model is best conceptualized with the patient at its center. This article describes elements of a patient centric commercial model for cancer care, after recognizing the challenges and opportunities inherent in its commercialization and marketing. The impact of such a model resides in its ability to offer tangible benefits to patients by improving access to leading edge treatments, energizing communication at the point of care, and adequately harnessing the emerging promise of new technology - rather than an emphasis on share-of-voice based selling. By viewing the patient at the center of a commercial model, manufacturers and marketers of cancer care treatments can offer products that provide ongoing care for the cancer patient from initiation through palliation, thereby building loyalty and realizing the full potential inherent in such treatments.
Bowman v. Monsanto: Revisiting the Exhaustion Doctrine and its Application to Biotechnology and Digital Technologies
Authors: Finston Susan Kling
Published: April 2013

On February 19, 2013, the U.S. Supreme Court heard oral argument in Bowman v. Monsanto â€“ the first case to directly present the question of how the Exhaustion Doctrine should apply to patents relating to biotechnology and digital technology inventions.Â  The Petitioner, Vernon Hugh Bowman, asserts that the Exhaustion Doctrine should be extended to advanced agricultural technologies where the technology itself is contained in genetically modified seeds that may be reproduced through successive generations of seeds without limitation, and that companies like Monsanto can instead rely on remedies found in contract law to protect its commercial interests.Â  The Respondent, Monsanto Corporation, supported by the U.S. Government, (not surprisingly) disagrees, contending that an extension of the Exhaustion Doctrine of this magnitude would undercut effective patent protection for inventions that may reproduce perfectly over generations, undermining R&D in innovative technologies. Â During the Bowman v. Monsanto oral argument on February 19th, the Justices focused on the broad scope of the exception sought by the Petitioner to patent rights for GM seed as an extension of the Exhaustion Doctrine to biotechnology and digital technology inventions, and did not appear persuaded either that the only reasonable use of the soybeans by Bowman was to plant them or that right holders would find effective modes of protection through contract law.Â  The Justices noted that this was the first case to present the intersection of the Exhaustion Doctrine and effective protection for inventions that may be reproduced across generations â€“ that intersection to be the issue of greatest interest to the Court inÂ  Bowman v. Monsanto, where the Court may be unlikely to create a sweeping exception to patent rights for biotechnology or digital technology inventions that has not been contemplated by the Congress.
Capturing Value
Authors: Burrill G. Steven
Published: April 2013

Todayâ€™s pressure on pharmaceutical companies reflects greater pressures throughout the entire healthcare ecosystem as payers, patients, and providers wrestle with escalating costs and drive Â healthcare systems around the world away from being cost-based to becoming value-based. Â For pharmaceutical companies, this means not only a greater emphasis on creating value, but seeking new ways to capture value as well, particularly at a time when drugs will need to demonstrate they provide benefits commensurate with their costs and governments and payers squeeze down prices. Â Â  The challenge for drugmakers, broadly speaking, is to both find new ways to create value and capture value.
The Materiality of Signs: Enchainment and Animacy in Woodland Southeastern North American Pottery
Authors: Wallis Neill J.
Published: April 2013

Archaeological examinations of symbolic meaning often have been hampered by the Saussurean concept of signs as coded messages of preexisting meanings. The arbitrary and imprecise manner by which meaning is represented in material culture according to Saussure tends to stymie archaeological investigations of symbolism. As an alternative, archaeologists recently have drawn on Peirce’s semiotic to investigate how materiality is bound to the creation of meanings through the process of signification. This study examines how the symbolism expressed in pottery of the Middle Woodland period southeastern United States, Swift Creek Complicated Stamped and Weeden Island effigy vessels, might be better explained as icons and indexes that were enlisted to have particular social effects. Examining the semiotic potentials of these objects helps explain their apparent uses and the significance of alternative representations of the same subjects.
Paleoindian Exploitation of Mammals in Eastern Washington State
Authors: Lyman R. Lee
Published: April 2013

Eleven mammalian archaeofaunas associated with the Western Stemmed Point Tradition (WSPT) in the Columbia Basin of intermontane northwestern North America and recovered from eastern Washington State suggest that local Paleoindians were variable in subsistence pursuits. The 11 faunas are strongly if imperfectly nested taxonomically, suggesting that they all derived from the same metacommunity. Taxonomic abundances evidenced by several faunas indicate a focus on large mammals (>25 kg body weight), others indicate a focus on small mammals (<5 kg body weight), and still others indicate generalized exploitation of a diverse array of mammalian body sizes. Early WSPT assemblages point to a broad diet, whereas late WSPT assemblages show a focus on artiodactyls. Middle and late Holocene mammalian faunas from the same and nearby areas indicate that Archaic-stage subsistence was more focused on large mammals than local early Paleoindian adaptations. The traditional model that specialized big-game-hunting Paleoindians were followed chronologically by more generalized or broad-spectrum adaptations of the Archaic is not supported in the Columbia Basin.
Clovis Paleoecology and Lithic Technology in the Central Rio Grande Rift Region, New Mexico
Authors: Hamilton Marcus J. , Buchanan Briggs , Huckell Bruce B. , Holliday Vance T. , Shackley M. Steven , Hill Matthew E.
Published: April 2013

Clovis sites occur throughout the southwestern United States and northwestern Mexico, but are poorly documented in the central Rio Grande rift region. Here, we present data from two relatively unknown Clovis projectile point assemblages from this region: the first is from the Mockingbird Gap Clovis site and the second is from a survey of the surrounding region. Our goals are to reconstruct general features of the paleoecological adaptation of Clovis populations in the region using raw material sourcing and then to compare the point technology in the region to other Clovis assemblages in the Southwest and across the continent. Our results show that both assemblages were manufactured from similar suites of raw materials that come almost exclusively from the central Rio Grande rift region and the adjacent mountains of New Mexico. Additionally, we show that Clovis projectile points in the study region are significantly smaller than the continental average. Our results suggest that Clovis populations in this region operated within a large, well-known, and relatively high-elevation territory encompassing much of northern and western New Mexico.
Rethinking the Study of Landscape Management Practices Among Hunter-Gatherers in North America
Authors: Lightfoot Kent G. , Cuthrell Rob Q. , Striplen Chuck J. , Hylkema Mark G.
Published: April 2013

There has been little movement to systematically incorporate the study of indigenous landscape management practices into the method and theory of hunter-gatherer research in North American archaeology, despite a growing interest in this topic. The purposes of this article are twofold. One is to address why, until quite recently, archaeologists have been reluctant to engage in the current debate about the scale and ecological impact of these practices, particularly anthropogenic burning. We argue that this stems from a long tradition of viewing hunter-gatherers as passive, immediate-return foragers, as well as from the daunting methodological challenges of identifying landscape management activities using archaeological data. Our second purpose is to explore how archaeologists can make significant contributions to our understanding of past resource management practices through the creation of new kinds of collaborative, interdisciplinary eco-archaeological programs. Based on the current work of scholars in archaeological and environmental disciplines, as well as on our own implementation of such an approach in central California, we discuss the importance of maintaining mutual relationships with local tribes, the challenges of coordinating multiple data sets, and the process of rethinking our analytical methods and temporal scales for undertaking hunter-gatherer studies.
Polyvalent Metaphors in South-Central California Missionary Processes
Authors: Robinson David
Published: April 2013

The Spanish missionary entrada (A.D. 1769 to 1833) along the California coast created a series of complex encounters between multiple cultural discourses. The Franciscan mission system directly brought colonial and indigenous cultural metaphorical understandings into play. Missionary and indigenous discourse interacted largely via the media of material culture, animals, embellished architecture, and landscape—media interpreted through preexisting cultural metaphors and understandings. Investigating how metaphors played a role in constituting colonial entanglements is important in understanding cultural interactions and change. Metaphors structured colonial interactions, simultaneously hindering and enabling missionary–indigenous relationships. These relationships created parameters for unforeseen transitory configurations: a process best theorized under the term polyvalence. By adopting polyvalence, the processes of colonialism can be approached without usage of ethnic or racialized terms such as creolization, hybridity, or amalgamation. In the case of indigenous south-central California, it is suggested here that widely different forms of evidence can be better appreciated without recourse to terms laden with racial or ethnic connotations. The evidence suggests that while missions may have failed to create entirely new ethnic groups, missionary endeavors did result in unanticipated outcomes, presenting problems and creative opportunities for indigenous groups living within immediate coastal and extended interior populations.
Moments, Movements, and Metaphors: Paul Sidney Martin, Pedagogy, and Professionalization in Field Schools, 1926–1974
Authors: Chazin Hannah , Nash Stephen E.
Published: April 2013

Paul Sidney Martin identified two “watershed” moments in his career: (1) his adoption of the tenets of the New Archaeology and (2) the changes he made in his approach to pedagogy at the Vernon field school. We explore the relationship between these two watershed moments using Martin’s archival record. We find that, rather than being watershed moments, these changes have deeper roots in the trajectory of Martin’s work and career and moreover are clearly linked to broader historical occurrences, such as World War II, the G.I. Bill, the Civil Rights Act of 1964, and the establishment of the National Science Foundation. Furthermore, we find that the New Archaeology’s emphasis on egalitarian science—the metaphor of “archaeology as commune”—serves as a link among its theoretical innovations, methodology, and pedagogy.
An Integrated Geoarchaeology of a Late Woodland Sand Mound
Authors: Sherwood Sarah C. , Blitz John H. , Downs Lauren E.
Published: April 2013

The Graveline Mound (22JA503) is a sand platform mound in Jackson County, Mississippi, built on a low, late Pleistocene terrace on the Mississippi Sound. The Late Woodland mound (A.D. 590–780) is composed of local soils, and its presence today is a testament to the ancient builders’ knowledge of earthen construction materials and methods. Central to the study of the mound is an integrated geoarchaeological approach that uses stratigraphy and micromorphology to decipher material source and selection, construction techniques, and periodicity, in combination with more traditional artifacts, revealing the activities that created this ultimately monumental space. The mound was built in three rapid stages beginning with a low earthwork demarcating a ritual precinct used during late spring/early summer. Stage II quickly followed with a series of alternating zoned fills, sealing the space that was then subsequently covered by Stage III, a massive hard red surface that marked the location with a platform mound.
Chronometric Hygiene of Radiocarbon Databases for Early Durable Cooking Vessel Technologies in Northeastern North America
Authors: Taché Karine , Hart John P.
Published: April 2013

The earliest widespread pottery in northeastern North America is known as Vinette 1, a designation made by Ritchie and MacNeish (1949) over 60 years ago. While variation exists within this type (Taché 2005), external and internal cordmarked surfaces, thick walls, and large crushed-rock temper generally characterize this pottery. The history of this pottery, including its inception, geographical spread, temporal overlap with steatite vessels, and eventual replacement by other pottery technologies, is far from clear. In this article, we examine the existing database of radiocarbon assays associated with Vinette 1 pottery and steatite vessels, perform a chronometrie hygiene of those age estimates, and introduce 21 new AMS assays on charred cooking residues adhering to Vinette 1 sherd interiors. The results suggest a much more temporally restricted history for Vinette 1 pottery technology and a long period of coexistence with steatite vessels. However, the small number of reliable age estimates available for both technologies prevents a detailed assessment of their respective histories.
White House Budget Proposal Supports Science Agencies and Programs
Authors: Showstack Randy
Published: April 2013

The proposed federal budget for fiscal year (FY) 2014, which the Obama administration sent to Congress on 10 April, would provide overall strong support for federal science agencies in a tight budget environment. The proposal calls for $142.8 billion for federal research and development (R&D), an increase of almost $1.9 billion, or 1.3%, above the 2012 enacted level in current dollars. However, the proposed budget is a slight decrease when factoring in an expected 4% inflation between 2012 and 2014.
Bright Blue Solution Processed Triple‐Layer Polymer Light‐Emitting Diodes Realized by Thermal Layer Stabilization and Orthogonal Solvents
Authors: Trattnig Roman , Pevzner Leonid , Jäger Monika , Schlesinger Raphael , Nardi Marco Vittorio , Ligorio Giovanni , Christodoulou Christos , Koch Norbert , Baumgarten Martin , Müllen Klaus , List Emil J. W.
Published: April 2013

The realization of fully solution processed multilayer polymer light‐emitting diodes (PLEDs) constitutes the pivotal point to push PLED technology to its full potential. Herein, a fully solution processed triple‐layer PLED realized by combining two different deposition strategies is presented. The approach allows a successive deposition of more than two polymeric layers without extensively redissolving already present layers. For that purpose, a poly(9,9‐dioctyl‐fluorene‐co‐N‐(4‐butylphenyl)‐diphenylamine) (TFB) layer is stabilized by a hard‐bake process as hole transport layer on top of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). As emitting layer, a deep blue emitting pyrene‐triphenylamine copolymer is deposited from toluene solution. To complete the device assembly 9,9‐bis(3‐(5′,6′‐bis(4‐(polyethylene glycol)phenyl)‐[1,1′:4′,1″‐terphenyl]‐2′‐yl)propyl)‐9′,9′‐dioctyl‐2,7‐polyfluorene (PEGPF), a novel polyfluorene‐type polymer with polar sidechains, which acts as the electron transport layer, is deposited from methanol in an orthogonal solvent approach. Atomic force microscopy verifies that all deposited layers stay perfectly intact with respect to morphology and layer thickness upon multiple solvent treatments. Photoelectron spectroscopy reveals that the offsets of the respective frontier energy levels at the individual polymer interfaces lead to a charge carrier confinement in the emitting layer, thus enhancing the exciton formation probability in the device stack. The solution processed PLED‐stack exhibits bright blue light emission with a maximum luminance of 16 540 cd m−2 and a maximum device efficiency of 1.42 cd A−1, which denotes a five‐fold increase compared to corresponding single‐layer devices and demonstrates the potential of the presented concept.
Catalytic Methods for Imine Synthesis
Authors: Patil Rajendra D. , Adimurthy Subbarayappa
Published: April 2013

This Focus Review describes different methods that have been reported for the synthesis of imines. It is organized according to the methods used for imine synthesis starting with metal catalysis, including Ru, Au, V, Cu, Mn, Co and Pd catalysis. Other methods, such as photocatalysis, electrocatalysis, organocatalysis, and so on, are also emphasized. Ample information on the condensation of carbonyl compounds/alcohols with amines and direct oxidation of amines to give imines is discussed. Furthermore, among various metal‐catalyzed reactions, specific attention has been paid to copper‐catalyzed imine synthesis, as copper is less toxic than other heavy metals, comparatively inexpensive, and is easily accessible.
Direct CH Arylation of Heteroarenes Catalyzed by Palladium/ Nitrogen‐Based Ligand Complexes
Authors: Shibahara Fumitoshi , Murai Toshiaki
Published: April 2013

Significant progress has been made in transition‐metal‐catalyzed direct functionalization of heteroarenes since the beginning of the 21st century. Particularly, palladium‐catalyzed direct CH arylations of heteroarenes have been extensively studied. Although a variety of catalytic systems have been applied in these reactions, phosphine‐based ligands have mainly been used, and low reactivity at some positions, such as at the C4 position of azoles and the C3 position of heteroles, has remained a problem. Recently, the application of nitrogen‐based ligands in palladium‐catalyzed direct CH arylations has attracted significant attention because the resulting catalytic systems are uniquely reactive. This Focus Review discusses recent advances in the use of palladium/nitrogen‐based ligand systems for direct CH arylation of heteroarenes.
Chemische Bildgebung auf der Nanometerskala mittels spitzenverstärkter Raman‐Spektroskopie
Authors: Schmid Thomas , Opilik Lothar , Blum Carolin , Zenobi Renato
Published: April 2013

Chemische Analysemethoden auf der Nanometerskala sind von zentraler Bedeutung für die Charakterisierung von Nanostrukturen moderner Materialien und biologischer Systeme. Spitzenverstärkte Raman‐Spektroskopie (tip‐enhanced Raman spectroscopy, TERS) kombiniert die chemische Information, welche durch Raman‐Spektroskopie erhalten werden kann, mit der von der oberflächenverstärkten Raman‐Streuung (SERS) bekannten Signalverstärkung und der hohen räumlichen Auflösung der Rasterkraftmikroskopie (AFM) bzw. der Rastertunnelmikroskopie (STM). Dabei wird eine metallische oder metallisierte Spitze in den Fokus eines Lasers gebracht, wodurch ein stark verstärktes elektromagnetisches Feld am Spitzenende resultiert, welches als sehr kleine Lichtquelle für Raman‐spektroskopische Messungen auf der Nanometerskala dient. Dieser Aufsatz beschäftigt sich hauptsächlich mit den Voraussetzungen für eine effiziente Kopplung des Laserlichts an die Spitze sowie den verbliebenen Herausforderungen und Tücken der spitzenverstärkten Raman‐Spektroskopie, welche für die chemische Bildgebung mittels TERS berücksichtigt werden müssen. Beispiele aus aktuellen Publikationen demonstrieren das Potential von TERS für die chemische Bildgebung mit einer räumlichen Auflösung von ca. 10 nm und einer Sensitivität, welche den Nachweis weniger Moleküle ermöglicht in Anwendungen, die von den Materialwissenschaften bis hin zu den Biowissenschaften reichen.
Neue Strategien zur Totalsynthese von anorganischen Nanostrukturen
Authors: Buck Matthew R. , Schaak Raymond E.
Published: April 2013

Die rege Nachfrage nach komplexen Nanomaterialien mit präzise kontrollierten Architekturen und Grenzflächen hat zu einer enormen Entwicklung bei innovativen Syntheseverfahren geführt. Dieser Aufsatz beleuchtet Schlüsselstrategien für die chemische Umwandlung und schrittweise Synthese von anorganischen Mehrkomponenten‐Nanostrukturen, wobei existierende Umwandlungsreaktionen im Nanobereich in Klassen eingeordnet werden, die den bei der Synthese von organischen Molekülen verwendeten entsprechen. Ein Schwerpunkt liegt auf der Übertragung von Konzepten aus der Molekülsynthese auf nanoskalige Systeme: Dazu gehören unter anderem Ortsselektivität, Regio‐ und Chemoselektivität, orthogonale Reaktivität, Kupplungsreaktionen, Strategien zum Schützen und Entschützen sowie Verfahren zur Trennung und Aufreinigung. Das so geschaffene Regelwerk stellt ein neues Modell für die “Totalsynthese” von komplexen anorganischen Nanostrukturen dar, dem die Prinzipien von mehrstufigen Totalsynthesen komplexer organischer Molekülverbindungen und Naturstoffe zugrundeliegen.
Emerging Strategies for the Total Synthesis of Inorganic Nanostructures
Authors: Buck Matthew R. , Schaak Raymond E.
Published: April 2013

New synthetic innovations are rapidly being developed to address the demand for complex, next‐generation nanomaterials with rigorously controlled architectures and interfaces. This Review highlights key strategies for the chemical transformation and stepwise synthesis of multicomponent inorganic nanostructures, with the existing nanoscale transformations categorized into classes of reactions that are related to those used in the synthesis of organic molecules. The application of concepts used in molecular synthesis—including site‐selectivity, regio‐ and chemoselectivity, orthogonal reactivity, coupling reactions, protection/deprotection strategies, and procedures for separation and purification—to nanoscale systems is emphasized. Collectively, the resulting synthetic concept represents an emerging model for the synthesis of complex inorganic nanostructures on the basis of the guiding principles that underpin the multistep total synthesis of complex organic molecules and natural products.
Selective hydroformylation of various olefins using diphosphinite ligands
Authors: Khan Shoeb R. , Bhanage Bhalchandra M.
Published: April 2013

Novel diphosphinite ligands are synthesized by the reaction of various derivatives of 1,3‐diols with chlorodiphenylphosphine. The synthesized ligands exhibited considerable impact on hydroformylation of various olefins with excellent regioselectivity toward branched aldehyde. The effect of solvent, temperature, pressure and catalyst loading on the hydroformylation reaction is also described. The synthesized diphosphinite ligands with rhodium precursor works under milder reaction conditions as compared to traditional phosphine and phosphite‐based ligands. Copyright © 2013 John Wiley & Sons, Ltd.
Poly(vinylidene fluoride)–acrylic rubber partially miscible blends: Phase behavior and its effects on the mechanical properties
Authors: Abolhasani Mohammad Mahdi , Guo Qipeng , Jalali‐Arani Azam , Nazockdast Hossein
Published: April 2013

A phase diagram of poly(vinylidene fluoride) (PVDF) and acrylic rubber (ACM) was plotted, and the effects of the extent of miscibility on the mechanical properties of the polymer blends were examined. A compressible, regular solution model was used to forecast the phase diagram of this blend. The model prediction, the lower critical solution temperature (LCST) over the upper critical solution temperature (UCST), was done qualitatively according to the experimentally determined phase diagram by differential scanning calorimetry (DSC), optical microscopy, and rheological analysis. These experimental methods showed that this system was miscible in ACM‐rich blends (>50% ACM) and partially miscible in PVDF‐rich blends. A wide‐angle X‐ray diffraction study revealed that PVDF/ACM blends such as neat PVDF had a characteristic α‐crystalline peak. The partially miscible blends displayed up to 350% elongation at break; this was a significant increment of this parameter compared to that of neat PVDF(20%). However, the miscible blends showed elongation of up to 1000% [again, a remarkable increase compared to chemically crosslinked ACM (220%)] and displayed excellent mechanical properties and tensile strength and a large elongation at break. For the miscible and partially miscible blends, two different mechanisms were responsible for this improvement in the mechanical properties. It was suggested that in the partially miscible blends, the rubbery depletion layer between the spherulite and the conventional rubber cavitations mechanism were responsible for the increase in the elongation at break, whereas for the miscible blends, the PVDF spherulite acted as a crosslinking junction. The stretched part of the tensile samples in the partially miscible blends showed characteristic β‐crystalline peaks in the Fourier transform infrared spectra, whereas that in the miscible blends showed α‐crystalline peaks. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1247‐1258, 2013
Strictosidine‐related enzymes involved in the alkaloid biosynthesis of Uncaria tomentosa root cultures grown under oxidative stress
Authors: Vera‐Reyes Ileana , Huerta‐Heredia Ariana A. , Ponce‐Noyola Teresa , Flores‐Sanchez Isvett Josefina , Esparza‐García Fernando , Cerda‐García‐Rojas Carlos M. , Trejo‐Tapia Gabriela , Ramos‐Valdivia Ana C.
Published: April 2013

The activity and gene expression of strictosidine‐related enzymes in Uncaria tomentosa root cultures exposed to oxidative stress were studied. Elicitation with 0.2 mM hydrogen peroxide (H2O2) or a combination of 0.8 mM buthionine sulfoximine and 0.2 mM jasmonic acid (BSO‐JA) increased peroxidase activities by twofold at Day 8 and glutathione reductase by 1.4‐fold at Day 5 in H2O2 elicited cultures respect to the control. Production of monoterpenoid oxindole alkaloids (MOA), 3α‐dihydrocadambine, and dolichantoside was stimulated after H2O2 elicitation, reaching levels of 886.4 ± 23.6, 847.7 ± 25.4, and 87.5 ± 7.2 µg/g DW, at Day 8 which were 1.7‐, 2.1‐, and 2.3‐fold higher relative to control. BSO‐JA elicited cultures produced about twice alkaloids than H2O2‐treated cultures, following a biphasic pattern with maxima at 0.5 and 8 days. Alkaloid production was preceded by increase in strictosidine synthase (STR) and strictosidine glucosidase (SGD) activities. After elicitation with H2O2 or BSO‐JA, the STR activity (pKat/mg protein) increased by 1.9‐fold (93.8 ± 17.8 at 24 h) or 2.5‐fold (102.4 ± 2.2 at 6 h) and the SGD activity (pKat/mg protein) by 2.8‐fold (245.2 ± 14.4 at 6 h) or 4.2‐fold (421.2 ± 1.8 at 18 h) relative to control. STR and SGD transcripts were upregulated after elicitation. H2O2‐treated roots showed higher levels of STR at 48–192 h and SGD at 24–48 h, while BSO‐JA treatments showed STR increased at 12 h and SGD at 24 h. Also, LC/ESI‐MS confirmed the biosynthesis of dolichantoside from N‐ω‐methyltryptamine and secologanin by U. tomentosa protein extracts. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:621–630, 2013
Purification and biochemical characterization of feruloyl esterases fromAspergillus terreusMTCC 11096
Authors: Kumar C. Ganesh , Kamle Avijeet , Kamal Ahmed
Published: April 2013

Aspergillus terreusMTCC 11096 isolated from the soils of agricultural fields cultivating sweet sorghum was previously identified to produce feruloyl esterases (FAEs). The enzymes responsible for feruloyl esterase activity were purified to homogeneity and named as AtFAE‐1, AtFAE‐2, and AtFAE‐3. The enzymes were monomeric having molecular masses of 74, 23 and 36 kDa, respectively. Active protein bands were identified by a developed pH‐dependent zymogram on native PAGE. The three enzymes exhibited variation in pH tolerance ranging between pH 5–8 and thermostability of up to 55°C. Inhibition studies revealed that the serine residue was essential for feruloyl esterase activity; moreover aspartyl and glutamyl residues are not totally involved at the active site. Metal ions such as Ca2+, K+, and Mg2+stabilized the enzyme activity for all three FAEs. Kinetic data indicated that all three enzymes showed catalytic efficiencies (kcat/Km) against different synthesized alkyl and aryl esters indicating their broad substrate specificity. The peptide mass fingerprinting by MALDI/TOF‐MS analysis and enzyme affinity toward methoxy and hydroxy substituents on the benzene ring revealed that the AtFAE‐1 belonged to type A while AtFAE‐2 and AtFAE‐3 were type C FAE. The FAEs could release 65 to 90% of ferulic acid from agrowaste substrates in the presence of xylanase. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:924–932, 2013
Fluorescent Amino Acids: Modular Building Blocks for the Assembly of New Tools for Chemical Biology
Authors: Krueger Andrew T. , Imperiali Barbara
Published: April 2013

Fluorescence spectroscopy is a powerful tool for probing complex biological processes. The ubiquity of peptide–protein and protein–protein interactions in these processes has made them important targets for fluorescence labeling, and to allow sensitive readout of information concerning location, interactions with other biomolecules, and macromolecular dynamics. This review describes recent advances in design, properties and applications in the area of fluorescent amino acids (FlAAs). The ability to site‐selectively incorporate fluorescent amino acid building blocks into a protein or peptide of interest provides the advantage of closely retaining native function and appearance. The development of an array of fluorescent amino acids with a variety of properties, such as environment sensitivity, chelation‐enhanced fluorescence, and profluorescence, has allowed researchers to gain insights into biological processes, including protein conformational changes, binding events, enzyme activities, and protein trafficking and localization.
A semantic‐aware data generator for ETL workflows
Authors: Du Naiqiao , Ye Xiaojun , Wang Jianmin
Published: April 2013

Extract, transform, and load (ETL) processes organized as workflows play an important role in the future data integration for cloud services. ETL designers/administrators need testing data set that is aware of semantics of ETL workflow workloads to evaluate their developed ETL systems. Populating testing ETL systems with meaningful workload data is a difficult task. In this paper, we propose a semantic‐aware data generator for ETL workflows. With given ETL workflow models and workload characterizations, the generator is able to generate synthetic data that capture the semantics of ETL activities. This is carried out by a three‐staged approach. First, we derive expected cardinalities of all the source, intermediate, and target data sets involved in the ETL workflow model with some user‐specified cardinality requirements. Then, with the concept of symbolic test, symbolic data instead of concrete data involved in ETL activities are generated, and semantics of the ETL workflow models are transformed to various constraints over these symbols. At last, concrete data are derived on the basis of resolving constraints. Our generator may facilitate ETL workload test case generation for ETL toolkit performance and function evaluations as well as ETL workflow solution benchmarking. Copyright © 2013 John Wiley & Sons, Ltd.
FrIIDoM: An intelligent driver for automatic configuration in modular display systems
Authors: Bauwens Pieter , Doutreloigne Jan
Published: April 2013

FrIIDoM provides an intelligent solution for automatic configuration in modular display systems. Modular displays are displays that consist of small, identical modules. There are a number of ways they can be used: removing the limitation in multiplexability in passive matrix (PM) displays, increasing brightness in PMOLED displays, reducing power consumption in bistable displays, creating large‐scale displays or displays with variable size and shape. For the modules to work together as one display, some initial configuration is required. FrIIdoM consists of four different drivers, with rising levels of complexity, each with their own way of automating the configuration. The simplest systems just make sure that every module is capable of receiving specific image data, irrespective of the shape of the display. The more complex systems are capable of detecting the presence and location of each module, thus detecting the shape of the display. In the created GUI, the user sees a real‐time view of the display configuration, even when modules are added or removed while the display is running. While FrIIDoM is equipped with the drivers to drive a PM LED display, they can be easily changed to incorporate other types of display technologies. Several test modules were created, and we were able to build and successfully drive random display creations. Copyright © 2013 John Wiley & Sons, Ltd.
Effects of clonality on the genetic variability of rare, insular species: the case of Ruta microcarpa from the Canary Islands
Authors: Meloni M. , Reid A. , Caujapé‐Castells J. , Marrero Á. , Fernández‐Palacios J. M. , Mesa‐Coelo R. A. , Conti E.
Published: April 2013

Many plant species combine sexual and clonal reproduction. Clonal propagation has ecological costs mainly related to inbreeding depression and pollen discounting; at the same time, species able to reproduce clonally have ecological and evolutionary advantages being able to persist when conditions are not favorable for sexual reproduction. The presence of clonality has profound consequences on the genetic structure of populations, especially when it represents the predominant reproductive strategy in a population. Theoretical studies suggest that high rate of clonal propagation should increase the effective number of alleles and heterozygosity in a population, while an opposite effect is expected on genetic differentiation among populations and on genotypic diversity. In this study, we ask how clonal propagation affects the genetic diversity of rare insular species, which are often characterized by low levels of genetic diversity, hence at risk of extinction. We used eight polymorphic microsatellite markers to study the genetic structure of the critically endangered insular endemic Ruta microcarpa. We found that clonality appears to positively affect the genetic diversity of R. microcarpa by increasing allelic diversity, polymorphism, and heterozygosity. Moreover, clonal propagation seems to be a more successful reproductive strategy in small, isolated population subjected to environmental stress. Our results suggest that clonal propagation may benefit rare species. However, the advantage of clonal growth may be only short‐lived for prolonged clonal growth could ultimately lead to monoclonal populations. Some degree of sexual reproduction may be needed in a predominantly clonal species to ensure long‐term viability.
Investigations on the Phase Transition between CdV2O6 and Cd2V2O7 and Their Photocatalytic Performances
Authors: Li Di , Bai Xiaojuan , Pan Chengsi , Zhu Yongfa
Published: April 2013

CdV2O6 and Cd2V2O7 were successfully synthesized by a simple hydrothermal process. The effects of the hydrothermal temperature and pH on the phase transition between CdV2O6 and Cd2V2O7 were investigated in detail. That the Cd2V2O7 phase could transform into CdV2O6 was attributed to polymerization of vanadate in an acidic environment as the V/O ratio increased as the pH decreased. V2O74– was stable in a neutral or alkaline environment at an identical hydrothermal temperature, therefore, the Cd2V2O7 phase was obtained after hydrothermal treatment for 24 h. Because the degree of hydrolysis of NH4Cl increased with increasing temperature in the solution, the increased temperature accelerated the speed of the pH decrease. Therefore, the hydrothermal temperature played an important part in the phase transition between CdV2O6 and Cd2V2O7. CdV2O6 and Cd2V2O7 showed high photocatalytic activity for the degradation of methylene blue under visible‐light irradiation.
A 2D → 3D Polycatenated Metal–Organic Framework: Synthesis, Structure, Magnetic and Catalytic Study
Authors: Sen Rupam , Saha Debraj , Mal Dasarath , Brandão Paula , Rogez Guillaume , Lin Zhi
Published: April 2013

A mixed‐ligand 3D metal–organic framework, [Ni(1,2‐cpd)(bpe)(H2O)]n (1) [1,2‐cpd = cis‐cyclopentane‐1,2‐dicarboxylate, bpe = 1,2‐di(4‐pyridyl)ethylene], has been constructed. Topological analysis revealed that the structure is a 3‐c uninodal 2D + 2D → 3D polycatenated net with the Schläfli symbol 63. The compound is catalytically active towards the epoxidation reaction in heterogeneous media. It catalyses almost all types of olefinic substrates with equal efficiency. After reaction it can be recovered quite easily and can be used for further reaction without any loss of activity for several cycles. Variable‐temperature magnetic susceptibility measurement reveals the presence of a weak antiferromagnetic interaction in compound 1.
Electrochemical Detection of Gunshot Residue for Forensic Analysis: A Review
Authors: O'Mahony Aoife M. , Wang Joseph
Published: April 2013

Current demands for detection of Gunshot Residue (GSR) require a reliable and rapid decentralized detection system with high sensitivity and specificity. This article reviews the use of electrochemical devices for GSR detection over the last 35 years and highlights recent advances associated with the demands of GSR field detection such as portability, speed, cost and power. Anodic stripping voltammetry (ASV) has been widely implemented for the detection of the metallic components of GSR at a variety of working electrodes. Efforts toward the detection of the organic components of GSR have also been reported using cyclic‐ and square‐wave voltammetry. The simultaneous detection of both organic and inorganic GSR constituents has recently been examined to increase the overall information content in a single voltammetric scan. As well as this, exploitation of screen‐printing fabrication allows replacement of conventional electrochemical cells with easy‐to‐use sensor strips Sampling methods for electrochemical GSR analysis are also advancing from acid washes or swabs to simpler abrasive methods which integrate sampling and analysis obviating the need for intermediate processing steps. The latest direction of electrochemical detection of GSR involves chemometric treatment to evaluate data allowing for more objective conclusions and increasing the automation of the system. These advances indicate great promise for investigating firearm‐related crimes, and bring significant changes to the detection of GSR making electroanalysis a powerful tool for decentralized forensic analysis.
Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer
Authors: Sonego Maura , Schiappacassi Monica , Lovisa Sara , Dall'Acqua Alessandra , Bagnoli Marina , Lovat Francesca , Libra Massimo , D'Andrea Sara , Canzonieri Vincenzo , Militello Loredana , Napoli Marco , Giorda Giorgio , Pivetta Barbara , Mezzanzanica Delia , Barbareschi Mattia , Valeri Barbara , Canevari Silvana , Colombatti Alfonso , Belletti Barbara , Del Sal Giannino , Baldassarre Gustavo
Published: April 2013

Stathmin is a p53‐target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG‐EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG‐EOC cells carrying a p53 mutant (p53MUT) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53MUT by DNA‐PKCS, eventually modulating p53MUT stability and transcriptional activity. Inhibition of stathmin or DNA‐PKCS impaired p53MUT–dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA‐PKCS, p53MUT overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells.