bluuebunny/crossref_metadata_2025 huggingface dataset:
Usability Considerations of Mobile Learning Applications
Authors: Mostakhdemin-Hosseini Ali
Published: July 2009

Abstract- Mobile usability is not one-dimensional property of user interface, it has many components and attributes [1] The most attributes associated with the mobile usability are as following: Satisfaction, Efficiency, Learnability, Lack of Errors, and Memorability

The assessment and importance of the usability attributes varies based on the application and the type of the users. For the expert usersâ?? lack of errors, reliability and efficiency are important and for the novice users beside mentioned factors the adjustability, learnability and memorability are essentials factors. This paper reveals different usability considerations for mobile learning system with approparte guidelines.
A Mobile Learning Model for Universities -Re-blending the Current Learning Environment
Authors: Khaddage Ferial , Lanham Elicia , Zhou Wanlei
Published: July 2009

The use of mobile technologies in education impacts learner motivation, collaboration, information sharing, mobility and interactivity which provide opportunities for learners, teachers and the university. This paper investigates the use of mobile learning technologies in higher education, and proposes a blended mobile learning model, which has the ability to serve the emerging learning process and delivery, and provide a well balanced learning environment that meets the current learnersâ?? needs.
Induction of Antigen-Specific Tolerance by Oral Administration of Lactococcus lactis Delivered Immunodominant DQ8-Restricted Gliadin Peptide in Sensitized Nonobese Diabetic Ab° Dq8 Transgenic Mice
Authors: Huibregtse Inge L. , Marietta Eric V. , Rashtak Shadi , Koning Frits , Rottiers Pieter , David Chella S. , van Deventer Sander J. H. , Murray Joseph A.
Published: July 2009

Active delivery of recombinant autoantigens or allergens at the intestinal mucosa by genetically modified Lactococcus lactis (LL) provides a novel therapeutic approach for the induction of tolerance. Celiac disease is associated with either HLA-DQ2- or HLA-DQ8-restricted responses to specific antigenic epitopes of gliadin, and may be treated by induction of Ag-specific tolerance. We investigated whether oral administration of LL-delivered DQ8-specific gliadin epitope induces Ag-specific tolerance. LL was engineered to secrete a deamidated DQ8 gliadin epitope (LL-eDQ8d) and the induction of Ag-specific tolerance was studied in NOD AB° DQ8 transgenic mice. Tolerance was assessed by delayed-type hypersensitivity reaction, cytokine measurements, eDQ8d-specific proliferation, and regulatory T cell analysis. Oral administration of LL-eDQ8d induced suppression of local and systemic DQ8-restricted T cell responses in NOD AB° DQ8 transgenic mice. Treatment resulted in an Ag-specific decrease of the proliferative capacity of inguinal lymph node (ILN) cells and lamina propria cells. Production of IL-10 and TGF-β and a significant induction of Foxp3+ regulatory T cells were associated with the eDQ8d-specific suppression induced by LL-eDQ8d. These data provide support for the development of effective therapeutic approaches for gluten-sensitive disorders using orally administered Ag-secreting LL. Such treatments may be effective even in the setting of established hypersensitivity.
CD44 Costimulation Promotes FoxP3+ Regulatory T Cell Persistence and Function via Production of IL-2, IL-10, and TGF-β
Authors: Bollyky Paul L. , Falk Ben A. , Long S. Alice , Preisinger Anton , Braun Kathy R. , Wu Rebecca P. , Evanko Stephen P. , Buckner Jane H. , Wight Thomas N. , Nepom Gerald T.
Published: July 2009

Work by our group and others has demonstrated a role for the extracellular matrix receptor CD44 and its ligand hyaluronan in CD4+CD25+ regulatory T cell (Treg) function. Herein, we explore the mechanistic basis for this observation. Using mouse FoxP3/GFP+ Treg, we find that CD44 costimulation promotes expression of FoxP3, in part through production of IL-2. This promotion of IL-2 production was resistant to cyclosporin A treatment, suggesting that CD44 costimulation may promote IL-2 production through bypassing FoxP3-mediated suppression of NFAT. CD44 costimulation increased production of IL-10 in a partially IL-2-dependent manner and also promoted cell surface TGF-β expression. Consistent with these findings, Treg from CD44 knockout mice demonstrated impaired regulatory function ex vivo and depressed production of IL-10 and cell surface TGF-β. These data reveal a novel role for CD44 cross-linking in the production of regulatory cytokines. Similar salutary effects on FoxP3 expression were observed upon costimulation with hyaluronan, the primary natural ligand for CD44. This effect is dependent upon CD44 cross-linking; while both high-molecular-weight hyaluronan (HA) and plate-bound anti-CD44 Ab promoted FoxP3 expression, neither low-molecular weight HA nor soluble anti-CD44 Ab did so. The implication is that intact high-molecular weight HA can cross-link CD44 only in those settings where it predominates over fragmentary LMW-HA, namely, in uninflamed tissue. We propose that intact but not fragmented extracellular is capable of cross-linking CD44 and thereby maintains immunologic tolerance in uninjured or healing tissue.
Smoking-Dependent Reprogramming of Alveolar Macrophage Polarization: Implication for Pathogenesis of Chronic Obstructive Pulmonary Disease
Authors: Shaykhiev Renat , Krause Anja , Salit Jacqueline , Strulovici-Barel Yael , Harvey Ben-Gary , O'Connor Timothy P. , Crystal Ronald G.
Published: July 2009

When exposed to a specific microenvironment, macrophages acquire either M1- or M2-polarized phenotypes associated with inflammation and tissue remodeling, respectively. Alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for chronic obstructive pulmonary disease (COPD), a disease characterized by lung inflammation and remodeling. Transcriptional profiling of AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers, and 12 COPD smokers was performed to test the hypothesis whether smoking alters AM polarization, resulting in a disease-relevant activation phenotype. The analysis revealed that AM of healthy smokers exhibited a unique polarization pattern characterized by substantial suppression of M1-related inflammatory/immune genes and induction of genes associated with various M2-polarization programs relevant to tissue remodeling and immunoregulation. Such reciprocal changes progressed with the development of COPD, with M1-related gene expression being most dramatically down-regulated (p < 0.0001 vs healthy nonsmokers, p < 0.002 vs healthy smokers). Results were confirmed with TaqMan real-time PCR and flow cytometry. Among progressively down-regulated M1-related genes were those encoding type I chemokines CXCL9, CXCL10, CXCL11, and CCL5. Progressive activation of M2-related program was characterized by induction of tissue remodeling and immunoregulatory genes such as matrix metalloproteinase (MMP)2, MMP7, and adenosine A3 receptor (ADORA3). Principal component analysis revealed that differential expression of polarization-related genes has substantial contribution to global AM phenotypes associated with smoking and COPD. In summary, the data provide transcriptome-based evidence that AM likely contribute to COPD pathogenesis in a noninflammatory manner due to their smoking-induced reprogramming toward M1-deactivated, partially M2-polarized macrophages.
Neuron-Interacting Satellite Glial Cells in Human Trigeminal Ganglia Have an APC Phenotype
Authors: van Velzen Monique , Laman Jon D. , KleinJan Alex , Poot Angelique , Osterhaus Albert D. M. E. , Verjans Georges M. G. M.
Published: July 2009

Satellite glial cells (SGC) in sensory ganglia tightly envelop the neuronal cell body to form discrete anatomical units. This type of glial cell is considered neuroectoderm-derived and provides physical support to neuron somata. There are scattered hints in the literature suggesting that SGC have an immune-related function within sensory ganglia. In this study, we addressed the hypothesis that SGC are tissue-resident APC. The immune phenotype and function of a large series (n = 40) of human trigeminal ganglia (TG) were assessed by detailed flow cytometry, in situ analyses, and functional in vitro assays. Human TG-resident SGC (TG-SGC) uniformly expressed the common leukocyte marker CD45, albeit at lower levels compared with infiltrating T cells, and the macrophage markers CD14, CD68, and CD11b. In addition, TG-SGC expressed the myeloid dendritic cell (DC) marker CD11c, the T cell costimulatory molecules CD40, CD54, CD80, and CD86 and MHC class II. However, the mature DC marker CD83 was absent on TG-SGC. Functionally, TG-SGC phagocytosed fluorescent bacteria, but were unable to induce an allogeneic MLR. Finally, TG-infiltrating T cells expressed the T cell inhibitory molecules CD94/NKG2A and PD-1, and the interacting TG-SGC expressed the cognate ligands HLA-E and PD-L1, respectively. In conclusion, the data demonstrate that human TG-SGC have a unique leukocyte phenotype, with features of both macrophages and immature myeloid DC, indicating that they have a role as TG-resident APC with potential T cell modulatory properties.
Poly I:C-Induced Activation of NK Cells by CD8α+ Dendritic Cells via the IPS-1 and TRIF-Dependent Pathways
Authors: Miyake Tohru , Kumagai Yutaro , Kato Hiroki , Guo Zijin , Matsushita Kazufumi , Satoh Takashi , Kawagoe Tatsukata , Kumar Himanshu , Jang Myoung Ho , Kawai Taro , Tani Tohru , Takeuchi Osamu , Akira Shizuo
Published: July 2009

NK cells play essential roles in eliminating virally infected cells and tumor cells. Polyinosinic-polycytidylic acid (poly I:C), a double-stranded RNA analog recognized by melanoma-differentiation associated gene 5 (MDA5) and TLR3, activates NK cells in vivo. MDA5 and TLR3 signal through distinct adaptor molecules, IFN-promoter stimulator-1 (IPS-1) and Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF), respectively. However, it remains unclear how NK cells are activated by poly I:C in vivo. In this study, we demonstrate that the IPS-1-dependent and the TRIF-dependent pathways are essential for NK cell activation to poly I:C stimulation in mice, whereas deficiency in either IPS-1 or TRIF only modestly impairs the poly I:C-induced NK cell activation. Furthermore, both IPS-1 and TRIF contributed to suppression of implanted B16 tumor growth in response to poly I:C administration via NK cell activation. Presence of IPS-1 and TRIF in dendritic cells (DCs), but not NK cells, was required for production of IFN-γ to poly I:C in NK cells in vitro. Moreover CD8α+ conventional dendritic cells (cDCs), but not CD8α− cDCs, expressed genes for type I IFNs, IL-6, and IL-12p40 in response to poly I:C stimulation, and were also responsible for inducing IFN-γ production in NK cells. Taken together, poly I:C activates the IPS-1- and TRIF-dependent pathways in CD8α+ cDCs, which in turn leads to NK cell activation.
Earliest history of coal mining and grindstone quarrying at Joggins, Nova Scotia, and its implications for the meaning of the place name “Joggins”
Authors: Falcon-Lang Howard J.
Published: July 2009

The rich history of coal mining and grindstone quarrying at Joggins, Nova Scotia, prior to Lyell’s visit in 1842 is less well known than its subsequent history. Franquelin first observed coal there in 1686, and within little more than a decade Acadian coal mines had sprung up at the Coal Cliffs. Following the British acquisition of Nova Scotia in 1713, the coal mines attracted Captain Belcher and other New England traders, who loaded their ships with coal for sale in Boston. In 1731, eager to impose duty on this unregulated trade, the Nova Scotia Council sponsored a British coal mine at Joggins operated by Major Cope. Unable to safely load ships at the Coal Cliffs, Cope constructed a wharf and coal depot at Gran’choggin (present-day Downing Cove), seven miles to the north of the mine. It was by association with this depot that the Coal Cliffs later became known as Joggins. Cope’s coal mine survived less than eighteen months before the Mi’kmaq, aided and abetted by Acadians, destroyed the site in 1732. Following this episode, Acadians worked the Joggins coal mines until they fell under the control of British forces engaged in the Seven Years War in 1756. Subsequently, the Lords of Trade suppressed coal mining at Joggins, fearing it would harm British imports, and full-scale operations did not recommence until 1847. During this lull, the grindstone industry boomed. Beginning sometime before 1764, the principal stone quarries operated at Lower Cove, where the famous Blue-Grit was cut. Grindstone quarries were also worked on the Maringouin Peninsula and the two opposing sides of Chignecto Bay became known as the North and South Joggins.
A Macroneuropteris scheuchzeri tree preserved in growth position in the Middle Pennsylvanian Sydney Mines Formation, Nova Scotia, Canada
Authors: Falcon-Lang Howard J.
Published: July 2009

Fossil plants preserved in growth position provide important insights into the architecture and ecology of ancient plants. Here I describe an upright tree of Macroneuropteris scheuchzeri rooted above the Point Aconi Coal in the Middle Pennsylvanian Sydney Mines Formation of Nova Scotia – the first example of an autochthonous pteridosperm described in the literature. The fossil tree has a sharply tapering trunk surrounded in its lower part by a large number of downward-recurved senescent petioles, which form a skirt. Petioles borne in an upright or horizontal position, interpreted as fronds that were still photosynthetically active when buried, are confined to the uppermost preserved part of the tree. Adapted to growth in rapidly aggrading coastal wetlands, the skirt of Macroneuropteris scheuchzeri probably acted to prop up the trunk while additionally trapping large mounds of mud around the base of the tree and stabilizing coastal wetlands. The tree had a sprawling habit and a maximum height of about 2 m. Similar, but smaller, trees found in adjacent beds probably represent juvenile specimens of the same species.

RÉSUMÉ

Les végétaux fossiles conservés dans leur position de croissance fournissent des renseignements précieux sur l’architecture et l’écologie des plantes anciennes. Je décris dans le présent document un Macroneuropteris scheuchzeri droit enraciné au‑dessus de charbon de Point Aconi dans la Formation du Pennsylvanien moyen de Sydney Mines, en Nouvelle‑Écosse – premier exemple de ptéridosperme autochtone décrit dans les ouvrages. L’arbre fossile possède un tronc nettement effilé entouré dans sa partie inférieure d’un grand nombre de pétioles sénescents recourbés vers le bas, qui forment une jupe. Des pétioles en position verticale ou horizontale, interprétés comme des frondes qui étaient encore actives sur le plan photosynthétique au moment de l’enfouissement, sont confinés à la partie la plus élevée de l’arbre conservée. Adaptée à la croissance dans les milieux humides côtiers d’alluvionnement rapide, la jupe du Macroneuropteris scheuchzeri servait probablement à maintenir le tronc et permettait en même temps d’emprisonner de gros monticules de boue autour de la base de l’arbre et de stabiliser les milieux humides côtiers. L’arbre, qui avait tendance à s’étendre, atteignait une hauteur maximale d’environ deux mètres. Des arbres semblables mais plus petits découverts dans des couches adjacentes représentent probablement de jeunes spécimens de la même espèce. [Traduit par la redaction]
Defect‐Mediated Polarization Switching in Ferroelectrics and Related Materials: From Mesoscopic Mechanisms to Atomistic Control
Authors: Kalinin Sergei V. , Rodriguez Brian J. , Borisevich Albina Y. , Baddorf Arthur P. , Balke Nina , Chang Hye Jung , Chen Long‐Qing , Choudhury Samrat , Jesse Stephen , Maksymovych Peter , Nikiforov Maxim P. , Pennycook Stephen J.
Published: July 2009

The plethora of lattice and electronic behaviors in ferroelectric and multiferroic materials and heterostructures opens vistas into novel physical phenomena including magnetoelectric coupling and ferroelectric tunneling. The development of new classes of electronic, energy‐storage, and information‐technology devices depends critically on understanding and controlling field‐induced polarization switching. Polarization reversal is controlled by defects that determine activation energy, critical switching bias, and the selection between thermodynamically equivalent polarization states in multiaxial ferroelectrics. Understanding and controlling defect functionality in ferroelectric materials is as critical to the future of oxide electronics and solid‐state electrochemistry as defects in semiconductors are for semiconductor electronics. Here, recent advances in understanding the defect‐mediated switching mechanisms, enabled by recent advances in electron and scanning probe microscopy, are discussed. The synergy between local probes and structural methods offers a pathway to decipher deterministic polarization switching mechanisms on the level of a single atomically defined defect.
Carbon Nanotubes and Nanofluidic Transport
Authors: Holt Jason Knowles
Published: July 2009

Recent strides have been made in both the modeling and measurement of fluid flow on the nanoscale. Carbon nanotubes, with their atomic dimensions and atomic smoothness, are ideal materials for studying such flows. This Progress Report describes recent modeling and experimental advances concerning fluid transport in carbon nanotubes. The varied flow characteristics predicted by molecular dynamics are described, as are the roles of defects and chirality on transport. Analytical models are increasingly being used to describe nanofluidic transport by relaxing many of the assumptions commonly used to describe bulk water. Recent experimental studies examine the size dependence of flow enhancements through carbon nanotubes and use varied spectroscopies to probe water structure and dynamics in these systems. Carbon nanotubes are finding increasing applications in biology, from protein filters to platforms for cell interrogation.
Highly Selective Oxidation of Alkylphenols to Benzoquinones with Hydrogen Peroxide over Silica‐Supported Titanium Catalysts: Titanium Cluster Site versus Titanium Single Site
Authors: Kholdeeva Oxana A. , Ivanchikova Irina D. , Guidotti Matteo , Pirovano Claudio , Ravasio Nicoletta , Barmatova Marina V. , Chesalov Yurii A.
Published: July 2009

Titanium‐silica catalysts have been prepared by supporting titanium(IV) precursors with different nuclearity {mononuclear titanocene dichloride Ti(Cp)2Cl2, dinuclear titanium diethyl tartrate and the tetranuclear titanium peroxo complex (NH4)8[Ti4(C6H4O7)4(O2)4]⋅8 H2O} onto the surface of silica materials with different textural characteristics. The supported catalysts have been explored as highly active and reusable catalysts for the oxidation of 2,3,6‐trimethylphenol (TMP) and 2,6‐dimethylphenol (DMP) to 2,3,5‐trimethyl‐1,4‐benzoquinone (TMBQ, vitamin E key intermediate) and 2,6‐dimethyl‐1,4‐benzoquinone (DMBQ), respectively, using aqueous hydrogen peroxide as green oxidant. Catalysts prepared by grafting mononuclear Ti(Cp)2Cl2 revealed a strong dependence of the product selectivity on the surface concentration of titanium active centers. Mesoporous materials with titanium surface concentration in the range of 0.6–1.0 Ti/nm2 were identified as optimal catalysts for the transformation of alkylphenols to benzoquinones. Catalysts having <0.6 Ti/nm2 produced a mixture of benzoquinones and dimeric by‐products. Conversely, when di‐/tetranuclear titanium precursors were employed for the catalyst preparation, a diminution of the titanium surface concentration had no impact on the benzoquinone selectivity, which was typically as high as 96–99%. DR‐UV spectroscopic studies revealed that the catalysts capable of producing alkylbenzoquinones with nearly quantitative yields possess titanium dimers and/or subnanometer‐size clusters homogeneously distributed on a silica surface. On the contrary, catalysts with isolated titanium sites give a considerable amount of dimeric by‐products. This is the first example which clearly demonstrates the advantages of titanium cluster‐site catalysts over titanium single‐site catalysts in hydrogen peroxide‐based selective oxidation reaction.
Prevention of Manganese Precipitation during the Continuous Selective Partial Oxidation of Methyl Aromatics with Molecular Oxygen in Supercritical Water
Authors: Fraga‐Dubreuil Joan , Garcia‐Verdugo Eduardo , Hamley Paul A. , Perez Eduardo , Pearson Ian , Thomas W. Barry , Housley Duncan , Partenheimer Walt , Poliakoff Martyn
Published: July 2009

Presented here is an investigation of the activity and recovery of the homogeneous manganese/bromide catalyst during the continuous flow oxidation of o‐xylene, as model substrate, with molecular oxygen (O2) in supercritical water (scH2O). Two strategies are discussed for preventing catalyst precipitation, mainly in the form of oxides such as manganese(IV) oxide, The first strategy involves varying the manganese:bromide ratio using either manganese(II) acetate or manganese(II) bromide in the presence of hydrobromic and other acids. The results show that the effect of acidity and bromide concentration plays an important role in preventing the manganese/bromide catalyst from precipitating. The second strategy uses aromatic carboxylic acids in combination with the manganese/bromide catalyst, particularly benzoic acid, which improves the catalyst recovery dramatically over a certain range of acid concentrations. Our studies show how the presence of an organic acid and/or its precursors is important in stabilising the catalyst. Our results are rationalised on the basis of a tentative reaction mechanism.
Promiscuous Substrate Binding Explains the Enzymatic Stereo‐ and Regiocontrolled Synthesis of Enantiopure Hydroxy Ketones and Diols
Authors: Kurina‐Sanz Marcela , Bisogno Fabricio R. , Lavandera Iván , Orden Alejandro A. , Gotor Vicente
Published: July 2009

Regio‐ and stereoselective reductions of several diketones to afford enantiopure hydroxy ketones or diols were accomplished using isolated alcohol dehydrogenases (ADHs). Results could be rationalised taking into account different (promiscuous) substrate‐binding modes in the active site of the enzyme. Furthermore, interesting natural cyclic diketones were also reduced with high regio‐ and stereoselectivity. Some of the 1,2‐ and 1,3‐diketones used in this study were reduced by employing a low excess of the hydrogen donor (2‐propanol) due to the quasi‐irreversibility of these ADH‐catalysed processes. Thus, using lower quantities of co‐substrate, scale‐up could be easily achieved.
Copper‐Catalyzed One‐Pot Synthesis of 2‐Alkylidene‐1,2,3,4‐ tetrahydropyrimidines
Authors: Lu Wei , Song Wangze , Hong Deng , Lu Ping , Wang Yanguang
Published: July 2009

A one‐pot synthesis of N‐sulfonyl‐2‐alkylidene‐1,2,3,4‐tetrahydropyrimidines via a highly selective and copper‐catalyzed multicomponent reaction of sulfonyl azides, terminal alkynes and α,β‐unsaturated imines has been developed. The α,β‐unsaturated imine substrates could be generated from amines and α,β‐unsaturated aldehydes in a one‐pot process. The procedure is concise, general and efficient.
Enantio‐ and Diastereoselective Mannich‐Type Reactions of α‐Cyano Ketones with N‐Boc Aldimines Catalyzed by Chiral Bifunctional Urea
Authors: Lee Ju Hee , Kim Dae Young
Published: July 2009

The catalytic enantioselective electrophilic Mannich‐type reaction promoted by chiral bifunctional organocatalysts is described. The treatment of α‐cyano ketones with N‐Boc‐aldimines under mild reaction conditions afforded the corresponding β‐amino‐α‐cyano ketones with excellent diastereoselectivities (up to syn/anti=100/0), and excellent enantioselectivities (up to 99% ee).
Ruthenium(II) Acetate Catalyst for Direct Functionalisation of sp2‐CH Bonds with Aryl Chlorides and Access to Tris‐ Heterocyclic Molecules
Authors: Požgan Franc , Dixneuf Pierre H.
Published: July 2009

The in situ generated (p‐cymene)ruthenium diacetate [Ru(OAc)2(p‐cymene)] catalyst 2, prepared from the (p‐cymene)ruthenium dichloride dimer {[RuCl2(p‐cymene)]2, 1} and potassium acetate (KOAc), acts as an excellent catalyst for ortho CH bond functionalisation of 2‐pyridylbenzene with unactivated aryl chlorides in the presence of potassium carbonate (K2CO3). Quantitative diarylation can be reached in 1 h at 120 °C. The diarylation of 2‐pyridylbenzene with 2‐halopyridines and 2‐ and 3‐halothiophenes was performed with 1 in the presence of KOAc or K2CO3 under more drastic conditions to generate the potential tridentate ligands, tris[1,2,3‐(2‐pyridyl)]benzenes and bis(2,6‐thiophenyl)2‐pyridylbenzenes.
Kalte Moleküle: Herstellung, Anwendungen und Herausforderungen
Authors: Schnell Melanie , Meijer Gerard
Published: July 2009

Die Forschung an kalten Molekülen hat sich in den letzten Jahren rasant entwickelt. Es gibt mittlerweile eine Reihe etablierter Methoden, um Moleküle in der Gasphase auf Temperaturen im Millikelvin‐Bereich zu kühlen. Dennoch konzentriert sich ein Schwerpunkt der aktuellen Forschung darauf, neue Wege zu finden, um die Temperaturen der Moleküle dem absoluten Nullpunkt noch näher zu bringen. Proben kalter Moleküle bieten nicht nur wichtige Anwendungen für die hochauflösende Spektroskopie, die von den verlängerten Wechselwirkungszeiten der langsamen Moleküle mit der elektromagnetischen Strahlung profitiert. Sie versprechen auch einen Zugang zu einem exotischen Regime der chemischen Reaktivität, in dem Phänomene wie Quantentunneln und ‒resonanzen vorherrschen. Dieser Aufsatz beginnt mit einer Einführung in die Methoden, mit denen kalte Moleküle hergestellt werden können, mit besonderem Schwerpunkt auf der Stark‐Abbremsung und auf Molekülfallen. Ein wichtiger Teil des Aufsatzes ist neben den teilweise bereits realisierten auch den zukünftig möglichen Anwendungen kalter Moleküle gewidmet, die beide mithilfe ausgewählter Beispiele näher beleuchtet werden.
Synthesis and In‐Vitro Anti‐Hepatitis‐B Virus Activity of 6H‐[1]Benzothiopyrano[4,3‐b] quinolin‐10‐ols
Authors: Jia Wei , Zhao Yanfang , Li Rongdong , Wu Yanjiao , Li Zebiao , Gong Ping
Published: July 2009

A series of 9‐methoxy‐6H‐[1]benzothiopyrano[4,3‐b]quinolin‐10‐ols with a Mannich side chain were synthesized and evaluated for their anti‐Hepatitis B virus (HBV) activity in HepG2.2.15 cells. Some compounds showed significant anti‐HBV activity with IC50 values less than 41 μM. Among them, compound 9b was the most effective anti‐HBV agent (IC50 = 1.7 μM, SI = 60.3).
GPR, ERT and magnetic investigations inside the Martyrium of St Philip, Hierapolis, Turkey
Authors: Nuzzo Luigia , Leucci Giovanni , Negri Sergio
Published: July 2009

Hierapolis, Denizli, Turkey, was one of the most important Hellenistic‐Roman cities in Asia Minor. Located about 250 km east of Izmir, the area is a UNESCO World Heritage Site because of its magnificent archaeological remains and the white travertine pool formations created by its peculiar geothermal setting. The Italian Archaeological Mission in more than 50 years of activity in Hierapolis has brought to light and restored important vestiges of the ancient city, helping to understand the urban layout in the various epochs of its development. In 2001–2003 geophysical surveys were performed by the University of Lecce in several areas inside the archaeological site of Hierapolis to support the archaeological excavations. This paper reports the results of the integrated geophysical surveys performed in 2003 inside the Martyrium of Saint Philip, a mausoleum built on the place where it is believed that the Apostle was martyred. Ground‐penetrating radar (GPR), electrical resistivity tomography (ERT) and magnetic gradient investigations were carried out in the central octagonal room, whereas the accessible lateral rooms were surveyed with GPR and occasionally ERT. The acquisition was performed along a series of closely spaced lines and the processed data were visualized as two‐dimensional vertical sections (GPR), map view (magnetic gradiometry), depth slices or three‐dimensional volumes (GPR and ERT) to allow an integrated interpretation of the geophysical results. The analysis of the geophysical datasets revealed a series of anomalies in both the central and lateral rooms that could be ascribed to the building foundations and to other possible archaeological structures, probably related to earlier stages of the sacred building and to tombs, as well as other anomalies (voids, fractures) of presumable natural origin. Copyright © 2009 John Wiley & Sons, Ltd.
Genetic skeletal disorders of the fetus and infant: Pathologic and molecular findings in a series of 41 cases
Authors: Konstantinidou Anastasia E. , Agrogiannis Georgios , Sifakis Stavros , Karantanas Apostolos , Harakoglou Vassileios , Kaminopetros Petros , Hatzaki Angeliki , Petersen Michael B. , Karadimas Charalampos , Velissariou Voula , Velonis Stylianos , Papantoniou Nikolaos , Antsaklis Aristeidis , Patsouris Efstratios
Published: July 2009

BACKGROUND: Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy. METHODS: In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10‐year period. RESULTS: Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12–37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases. CONCLUSIONS: The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Women's perspectives on counseling about risks for medication‐induced birth defects
Authors: Santucci Aimee K. , Gold Melanie A. , Akers Aletha Y. , Borrero Sonya , Schwarz Eleanor Bimla
Published: July 2009

PURPOSE: This qualitative study explored women's experiences with counseling about medication‐induced birth defects, as well as how and when they would like to receive information on medication‐induced birth defects from their health care providers (HCPs). METHODS: We conducted four focus groups with 36 women of reproductive age (18–45 years old) in Pittsburgh, Pennsylvania. Twenty‐one women were using medications to treat a chronic health condition, and two were pregnant. Content analysis was performed by three independent coders using a grounded theory approach. Discrepancies were resolved by consensus. RESULTS: Women reported depending on their HCPs for information about the risks of teratogenic effects of medications on a pregnancy, but felt the information they had been provided was not always comprehensive. Women want HCPs to initiate discussions about potentially teratogenic medications at the time the medications are prescribed, regardless of whether the woman is sexually active or planning a pregnancy. Women want clear information about all potential outcomes for a fetus. Factors women reported as being critical to effective teratogenic risk counseling included privacy, sufficient time to discuss the topic, and a trusting relationship with their HCP. CONCLUSIONS: Women of reproductive age think that providing information about the possible teratogenic effects of medications could be improved by routine discussions of teratogenic risks at the time medications are prescribed. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.
Vom Samentier zur Samenzelle: Die Neudeutung der Zeugung im 19. Jahrhundert
Authors: Vienne Florence
Published: July 2009

From Spermatic Animalcules to Sperm Cells: The Reconceptualization of Generation in the 19th Century. At the end of the 18th and still at the beginning of the 19th century most naturalists considered spermatic animalcules to be parasites of the seminal fluid that played no role in procreation. This view was progressively questioned by 19th century physiologists. They gradually redefined the spermatic animals as (cellular) products of the male organism, as agents of fertilization and bearers of the male heredity material. This article discusses this change from two different perspectives: on a microhistorical level, it analyzes the experimental research of the naturalist Lazzaro Spallanzani (1729–1799) and of the physiologist Albert Kölliker (1817–1905) in order to show how spermatozoa were turned into a new epistemic object of biology – the sperm cell. Further, it asks how the role of the reconceptualization of spermatic animalcules affected the long‐term transformations that gave rise of our modern understanding of heredity, generation and the sexed body. By combining these two perspectives, the article aims to connect historiographies that are often kept separate: the macrohistorical narratives about gender and the body in the modern age and the microhistorical studies of biomedical practices and objects.
Zitation, Legitimation, Affirmation. Schreibweisen des medizinischen Menschenexperiments 1750–1840
Authors: Sabisch Katja
Published: July 2009

Citation, Legitimation, Affirmation. Notations of Medical Experiments on Human Subjects 1750–1840. This paper deals with the problem of representing human subjects in experimental records and focuses the early experimentation on human beings between 1750 and 1840. Unlike the scientific fragmentation of the body since 1840, which coincides with a specific technique of writing down experiments on human subjects by making them disappear behind numbers and charts, a close reading of different experimental records before the ‘vivisectional turn’ shows the status of the experimental subject as a witness or even as an agreer. Based on the assumption that the individual played a crucial role in representing experimental practices until the middle of the nineteenth century, the paper wants to point out how this was linked to the discursive practice of citation, legitimation, and affirmation.
An elaborate education of basic genetic programming using C++
Authors: Sahoo Nirod C. , Chin Jeremy G. W.
Published: July 2009

Evolutionary search is a global search method based on natural selection. In engineering curriculum, these techniques are taught in courses like Evolutionary Computation, Engineering Optimization, etc. Genetic algorithm (GA) is popular among these algorithms. Genetic programming (GP), developed by John Koza, is a powerful extension of GA where a chromosome/computer program (CP) is coded as a rooted point‐labeled tree with ordered branches. The search space is the space of all possible CPs (trees) consisting of functions and terminals appropriate to the problem domain. GP uses, like GA, crossover and mutation for evolution. Due to tree‐structured coding of individuals, the initial population generation, genetic operators' use, and tree decoding for fitness evaluations demand careful computer programming. This article describes the programming steps of GP implementation (using C++ language) for students' easy understanding with pseudocodes for each step. Two application examples are also illustrated. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 434–448, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20165
Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption
Authors: Lin Wan‐Teng , Huang Chi‐Chang , Lin Tien‐Jen , Chen Jiun‐Rong , Shieh Ming‐Jer , Peng Hsiang‐Chi , Yang Suh‐Ching , Huang Chih‐Yang
Published: July 2009

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.
Targeting Mitochondria with Organelle‐Specific Compounds: Strategies and Applications
Authors: Yousif Lema F. , Stewart Kelly M. , Kelley Shana O.
Published: July 2009

Mitochondria are the energy factories of the cell and also serve as a checkpoint regulating programmed cell death. Not surprisingly, dysfunctional mitochondria are implicated in a variety of diseases ranging from metabolic disorders to cancer. Treatment of these diseases through the delivery of targeted drugs, however, is impeded by the difficulty of penetrating the membranes that define this organelle. The properties of this barrier serve as a major obstacle to drug delivery and a lack of effective transporters has hindered the advancement of mitochondrial medicine. Recently, however, synthetic transporters that show promise for the mito‐specific delivery of bioactive cargos have begun to emerge. This review summarizes the most exciting of these developments and discusses their applications.
Phosphodiester Substrates for Incorporation of Nucleotides in DNA Using HIV‐1 Reverse Transcriptase
Authors: Giraut Anne , Dyubankova Natalia , Song Xiao‐ping , Herdewijn Piet
Published: July 2009

In previous research we demonstrated that some amino acid derivatives of deoxyadenosine 5′‐O‐monophosphate act as substrates for incorporation into DNA by HIV‐1 reverse transcriptase while retaining the canonical base‐pair selectivity for all natural bases. Thus, some amino acids mimic the pyrophosphate group in the polymerization process with this enzyme. Herein we extended this study to the evaluation of a range of potential new leaving groups with aromatic and aliphatic structures carrying one or two carboxylic acid functions. Out of this series, the isophthalic acid derivative of deoxyadenosine 5′‐O‐monophosphate gave single‐nucleotide incorporation results similar to those obtained with the L‐aspartic acid phosphoramidate of deoxyadenosine monophosphate. The glycolic acid analogue is a better substrate than the glycine congener, supporting the good leaving group properties of a phosphodiester linkage. These investigations provide new insight into the structural requirements for leaving groups that can mimic the pyrophosphate moiety of nucleoside triphosphates.
Numerical Simulation of Mold Filling Processes with Polyurethane Foams
Authors: Geier S. , Winkler C. , Piesche M.
Published: July 2009

Design and dimensioning of manufacturing processes based on filling molds with polyurethane foams still require the use of highly empirical approaches. This includes numerous experimental runs with expensive prototypes. Therefore, a method has to be found to analyze the molding process at an early stage of product development to shorten time‐to‐market cycles and cut costs by using fewer prototypes. With the computational power available today and growing computational power in the future, the tool of choice is the numerical simulation of mold filling processes with computational fluid dynamics software.
A Heat‐Integrated Reverse‐Flow Reactor Concept for Endothermic High‐Temperature Syntheses. Part II: Development of a Reformer Prototype for Hydrogen Production
Authors: Tellaeche C. , Glöckler B. , Kolios G. , Nieken U.
Published: July 2009

In the first part of the contribution, the asymmetric operation of a reverse‐flow reactor for endothermic high‐temperature syntheses has been introduced and front phenomena have been discussed. The current part presents the implementation of the concept to the production of hydrogen by methane steam reforming. A key element of the developed reformer is the integration of combustion chambers for in situ heat generation during reheating of the bed. To avoid local temperature peaks, the concept of flameless combustion is used. The concept was adapted to the requirements of the unsteady operation. A proper design of the combustion chamber was developed using computational fluid dynamics calculations, tracer experiments and tests in a single combustion chamber. The concept was further tested under periodic operation in a laboratory setup. The formation of the desired, axially extended high‐temperature plateau in the center of the reactor could be shown experimentally. The results prove the adequacy of the reverse‐flow reformer to attain a stable periodic operation without excess temperatures.
A Heat‐Integrated Reverse‐Flow Reactor Concept for Endothermic High‐Temperature Syntheses. Part I: Fundamentals – Short‐Cut Theory and Experimental Verification of a Traveling Endothermic Reaction Zone
Authors: Glöckler B. , Kolios G. , Tellaeche C. , Nieken U.
Published: July 2009

Coupling endothermic and exothermic reactions in multifunctional reactors poses a challenge concerning the reactor temperature control. A reactor concept particularly suitable to combine high productivity and efficient thermal integration with moderate temperatures is presented. This is accomplished by operating an adiabatic fixed‐bed reactor in an asymmetric reverse‐flow mode with alternating production and regeneration cycles. The key feature of this reactor concept is a distributed heat supply during the regeneration cycle, enabling a rigid temperature control and efficient utilization of the heat capacity of the fixed bed. This issue is divided into two parts. The first part (this article) presents a short‐cut method for analysis and for optimal reactor design as well as the experimental evidence of the existence of traveling endothermic reaction zones. The second part describes the experimental implementation of the concept in the prototype of a methane steam reformer for hydrogen production using controlled heat release by flameless combustion.
Conceptual Design of Integrated Chromatographic Processes for the Production of Single (Stereo‐)Isomers
Authors: García Palacios J. , Kaspereit M. , Kienle A.
Published: July 2009

A fundamental investigation is performed for integrated processes that combine continuous chromatography and isomerization reactions to produce a single (stereo‐)isomer. The focus is on the conceptual design of different process concepts and their theoretical analysis. The investigated process variants include reactor‐separator‐recycle systems, schemes with side reactors, and chromatographic reactors. As a new option, continuous chromatographic reactors with internally distributed functionalities are suggested. Using parameters of a model system, the performance of the processes is compared based on optimizations of corresponding models. The results reveal the potential and the limits of the different approaches under various conditions. It is found that the suggested new options can allow for significantly enhanced process performance.
Lewis Acid Controlled Regioselectivity in Styrene Hydrocyanation
Authors: Bini Laura , Pidko Evgeny A. , Müller Christian , van Santen Rutger A. , Vogt Dieter
Published: July 2009

According to present knowledge, the Ni‐catalyzed hydrocyanation of styrene leads predominantly to the branched product 2‐phenylpropionitrile (98 %). We observed a dramatic inversion of the regioselectivity upon addition of a Lewis acid. Up to 83 % of the linear product 3‐phenylpropionitrile was obtained by applying phosphite ligands in the presence of AlCl3. The mechanism of the Ni‐catalyzed reaction and the influence of additional Lewis acids have been investigated by means of deuterium labeling experiments, NMR studies, and DFT calculations. Furthermore, the behavior of different Lewis acids, such as CuCN, could be rationalized and predicted by DFT calculations.
Conformational Flexibility and Dynamics of Two (1→6)‐Linked Disaccharides Related to an Oligosaccharide Epitope Expressed on Malignant Tumour Cells
Authors: Olsson Ulrika , Säwén Elin , Stenutz Roland , Widmalm Göran
Published: July 2009

The conformational flexibility and dynamics of two (1→6)‐linked disaccharides that are related to the action of the glycosyl transferase GnT‐V have been investigated. NMR NOE and T‐ROE spectroscopy experiments, conformation‐dependent coupling constants and molecular dynamics (MD) simulations were used in the analyses. To facilitate these studies, the compounds were synthesised as α‐d‐[6‐13C]‐Manp‐OMe derivatives, which reduced the 1H NMR spectral overlap and facilitated the determination of two‐ and three‐bond 1H,1H, 1H,13C and 13C,13C‐coupling constants. The population distribution for the glycosidic ω torsion angle in α‐d‐Manp‐(1→6)‐α‐d‐Manp‐OMe for gt/gg/tg was equal to 45:50:5, whereas in α‐d‐Manp‐OMe it was determined to be 56:36:8. The dynamic model that was generated for β‐d‐GlcpNAc‐(1→6)‐α‐d‐Manp‐OMe by MD simulations employing the PARM22/SU01 CHARMM‐based force field was in very good agreement with experimental observations. β‐d‐GlcpNAc‐(1→6)‐α‐d‐Manp‐OMe is described by an equilibrium of populated states in which the ϕ torsion angle has the exo‐anomeric conformation, the ψ torsion angle an extended antiperiplanar conformation and the ω torsion angle a distribution of populations predominantly between the gauche–trans and the gauche–gauche conformational states (i.e., gt/gg/tg) is equal to 60:35:5, respectively. The use of site‐specific 13C labelling in these disaccharides leads to increased spectral dispersion, thereby making NMR spectroscopy based conformational analysis possible that otherwise might be difficult to attain.