bluuebunny/crossref_metadata_2025 huggingface dataset:
The Synthesis of α‐Azidoesters and Geminal Triazides
Authors: Klahn Philipp , Erhardt Hellmuth , Kotthaus Andreas , Kirsch Stefan F.
Published: June 2014

Three simple methods for the synthesis of geminal triazides are described: Starting from 1) 3‐oxocarboxylic acids, 2) iodomethyl ketones, or 3) terminal olefins, a range of triazidomethyl ketones can be constructed under mild oxidative reaction conditions by the use of IBX‐SO3K, a sulfonylated derivative of 2‐iodoxybenzoic acid (IBX), and NaN3 as an azide source. This is the first report of representatives of this novel class of triazide compounds: Despite their high nitrogen content, the geminal triazides are easy to handle, even when preparative‐scale syntheses are performed. (Caution: These procedures still require protective measures!) The triazides are now broadly available for further studies regarding their properties and reactivity. Furthermore, we show how the method can be used to provide α‐azidoesters, which are potential building blocks for amino acids.
The Molecular Basis of Conjugated Polyyne Biosynthesis in Phytopathogenic Bacteria
Authors: Ross Claudia , Scherlach Kirstin , Kloss Florian , Hertweck Christian
Published: June 2014

Polyynes (polyacetylenes), which are produced by a variety of organisms, play important roles in ecology. Whereas alkyne biosynthesis in plants, fungi, and insects has been studied, the biogenetic origin of highly unstable bacterial polyynes has remained a riddle. Transposon mutagenesis and genome sequencing unveiled the caryoynencin (cay) biosynthesis gene cluster in the plant pathogen B. caryophylli, and homologous gene clusters were found in various other bacteria by comparative genomics. Gene inactivation and phylogenetic analyses revealed that novel desaturase/acetylenase genes mediate bacterial polyyne assembly. A cytochrome P450 monooxygenase is involved in the formation of the allylic alcohol moiety, as evidenced by analysis of a fragile intermediate, which was stabilized by an in situ click reaction. This work not only grants first insight into bacterial polyyne biosynthesis but also demonstrates that the click reaction can be employed to trap fragile polyynes from crude mixtures.
Surface‐Assisted Large‐Scale Ordering of DNA Origami Tiles
Authors: Aghebat Rafat Ali , Pirzer Tobias , Scheible Max B. , Kostina Anna , Simmel Friedrich C.
Published: June 2014

The arrangement of DNA‐based nanostructures into extended higher order assemblies is an important step towards their utilization as functional molecular materials. We herein demonstrate that by electrostatically controlling the adhesion and mobility of DNA origami structures on mica surfaces by the simple addition of monovalent cations, large ordered 2D arrays of origami tiles can be generated. The lattices can be formed either by close‐packing of symmetric, non‐interacting DNA origami structures, or by utilizing blunt‐end stacking interactions between the origami units. The resulting crystalline lattices can be readily utilized as templates for the ordered arrangement of proteins.
Lanthanide‐Based Functional Misfit‐Layered Nanotubes
Authors: Panchakarla Leela S. , Popovitz‐Biro Ronit , Houben Lothar , Dunin‐Borkowski Rafal E. , Tenne Reshef
Published: June 2014

The synthesis of nanotubes from layered compounds has generated substantial scientific interest. “Misfit” layered compounds (MLCs) of the general formula [(MX)1+x]m[TX2]n, where M can include Pb, Sb, rare earths; T=Cr, Nb, and X=S, Se can form layered structures, even though each sub‐system alone is not necessarily a layered or a stable compound. A simple chemical method is used to synthesize these complex nanotubes from lanthanide‐based misfit compounds. Quaternary nanotubular structures formed by partial substitution of the lanthanide atom in nanotubes by other elements are also confirmed. The driving force and mechanism of formation of these nanotubes is investigated by systematic temperature and time‐dependent studies. A stress‐inducement mechanism is proposed to explain the formation of the nanotubes. The resulting materials may find applications in fields that include thermoelectrics, light emitters, and catalysis and address fundamental physical issues in low dimensions.
Evolution of the properties of a poly(l‐lactic acid) scaffold with double porosity during in vitro degradation in a phosphate‐buffered saline solution
Authors: Deplaine Harmony , Acosta‐Santamaría Victor A. , Vidaurre Ana , Gómez Ribelles José Luis , Doblaré Manuel , Ochoa Ignacio , Gallego Ferrer Gloria
Published: June 2014

A poly(l‐lactic acid) scaffold prepared by a combination of freeze‐extraction and porogen‐leaching methods was submitted to static degradation in a phosphate‐buffered saline solution at pH 7.4 and 37°C for up to 12 months. After 6 months of degradation, the scaffold maintained its integrity, although noticeable changes in its permeability and pore size were recorded. After 12 months, scanning electron microscopy pictures showed that most of the trabeculae were broken, and the sample disaggregated under minimum loading. Neither weight loss nor crystallinity changes in the first heating calorimetric scan were observed during the degradation experiment. However, after 12 months, a rise in the crystallinity from 13 to 38% and a drop in the glass‐transition temperature from 58 to 54°C were measured in the second heating scan. The onset of thermal degradation moved from 300 to 210°C after 12 months. Although the elastic modulus suffered only a very slight reduction with degradation time, the aggregate modulus decreased 44% after 6 months. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40956.
Aid Volatility: Is It a Problem inTuvalu?
Authors: Iulai Letasi
Published: June 2014

Empirical evidence on aid volatility shows that it adversely impacts recipient countries. This study seeks to find if aid volatility matters inTuvalu—a small aid recipient country in thePacific. The study finds that, with a coefficient of variation of 0.49, aid volatility inTuvalu is significant. It is also found that project aid is more volatile than aid that goes to budget support and routine programs such as scholarships. Aid volatility results in incomplete projects, high transaction costs, ‘Dutch disease’ and fiscal planning problems. To manage the adverse impacts of aid volatility,Tuvalu needs to strengthen itsConsolidatedInvestmentFund to buffer for any disruptions in aid disbursements, provide a sound policy and institutional climate, target aid to budget support and programs instead of specific projects, and implement large infrastructure projects in phases.
From Intervention to Partnership—Prospects for Development Partnership in Solomon Islands after the RAMSI
Authors: Barbara Julien
Published: June 2014

This article considers prospects for effective development partnership in Solomon Islands following the transition of development assistance from the Regional Assistance Mission to Solomon Islands (RAMSI) to bilateral donors in 2013. It focuses on the shifting nature of Australian aid that has transitioned from an interventionary approach under RAMSI to a partnership‐based approach under the bilateral program. Prospects for partnership in Solomon Islands are complicated by issues of state fragility, political instability and aid dependency that undermine local ownership and alignment. While the rhetoric of partnership guided RAMSI transition, Australia's post‐RAMSI aid responds to these challenges through a hybrid approach incorporating partnership and interventionary modalities. This hybrid approach reflects Australia's role in the co‐production of sovereignty in Solomon Islands. Recognition of the hybrid nature of Australian aid, and, by implication, Australia's ‘ownership’ of development problems in Solomon Islands, will be important to the effectiveness of future support.
Efficient Synthesis of Novel 3‐Aryl‐5‐(4‐chloro‐2‐morpholinothiazol‐5‐yl)‐4,5‐dihydro‐1H‐pyrazoles and Their Antifungal Activity Alone and in Combination with Commercial Antifungal Agents
Authors: Ramírez Juan , Rodríguez María Victoria , Quiroga Jairo , Abonia Rodrigo , Sortino Maximiliano , Zacchino Susana A. , Insuasty Braulio
Published: June 2014

The α,β‐unsaturated carbonyl compounds 5a–f were prepared by reaction between 2‐chloro‐4‐morpholinothiazol‐5‐carbaldehyde 3 and substituted acetophenones 4a–f. Treatment of compounds 5a–f with hydrazine hydrate employing mild reaction conditions led to the formation of 4,5‐dihydro‐1H‐pyrazoles 6a–f. Then the treatment with acetic anhydride or formic acid afforded the expected 4,5‐dihydro‐1H‐pyrazoles 7a–f and 8a–f. The antifungal activity of each series of synthesized compounds was determined against the clinically important fungi Candida albicans and Cryptococcus neoformans. In addition, the most active compounds 7e and 7f were tested in combination with the commercial antifungal agents: fluconazole, itraconazole, and amphotericin B. Compound 7e showed a synergistic effect with fluconazole against C. albicans while 7f showed synergistic activities with all tested antifungal drugs against the same yeast.
Informed consent and the prescription of nonsteroidal antiinflammatory drugs
Authors: Katz Jeffrey N. , Daltroy Lawren H. , Brennan Troyen A. , Liang Matthew H.
Published: June 2014

Objective. To examine disclosure of side effects of nonsteroidal antiinflammatory drugs (NSAIDs) and to identify patient‐ and physician‐specific factors associated with greater disclosure.

Methods. Forty‐six encounters between rheumatologists and new adult outpatients who were prescribed an NSAID they had not been taking prior to the visit were audiotaped. Reviewers coded the NSAID prescribed, specific side effects mentioned, demographic features of patients and physicians, and patient clinical characteristics. Neither patients nor physicians were aware that side effect disclosure was being studied.

Results. A mean of 1.7 side effects was mentioned per encounter. Epigastric discomfort was mentioned in 72% of encounters, while other side effects, including hepatic, renal, hematologic, or central nervous system effects, were mentioned in ≤15% of encounters. Three factors were identified as independent predictors of less disclosure of side effects: senior clinician (versus less experienced), patient not taking another NSAID immediately prior to the visit, and patient age <40. Increased disclosure by less experienced clinicians occurred exclusively with patients who were taking another NSAID prior to the visit.

Conclusion. Disclosure of side effects other than epigastric discomfort to patients who are prescribed a new NSAID is limited. Patients not taking NSAIDs previously, who presumably have the most to gain from such discussions, are told the least. These results have implications with regard to doctor—patient decision‐making and malpractice litigation in the outpatient setting.
Psychological well‐being among people with recently diagnosed rheumatoid arthritis: Do self‐perceptions of abilities make a difference?
Authors: Blalock Susan J. , Devellis Brenda M. , Devellis Robert F. , Giorgino Karen B. , Sauter Suzanne van H. , Jordan Joanne M. , Keefe Francis J. , Mutran Elizabeth J.
Published: June 2014

Objective. Satisfaction with abilities and perceived importance of abilities are 2 factors involved in the process of self‐evaluation. We examined the role that these factors play in adjustment to rheumatoid arthritis (RA).

Methods. Data were collected, via telephone interview and mailed questionnaire, from 234 individuals with recently diagnosed RA. Disease severity information was obtained from participants' physicians.

Results. Consistent with study hypotheses, satisfaction was associated with psychological well‐being only among those who viewed as very important the abilities being evaluated.

Conclusion. These findings increase understanding of the conditions under which low levels of satisfaction are likely to be associated with psychological distress.
Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis
Authors: Chikanza Ian C. , Petrou Petros , Kingsley Gabrielle , Chrousos George , Panayi Gabriel S.
Published: June 2014

Objective. To determine the integrity of the hypothalamic‐pituitary‐adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA).

Methods. Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls.

Results. Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin‐1β (IL‐1β) and IL‐6. The corticotropin‐releasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function.

Conclusion. These findings suggest that RA patients have an abnormality of the HPA axis response to immune/inflammatory stimuli which may reside in the hypothalamus. This hypothalamic abnormality may be an additional, and hitherto unrecognized, factor in the pathogenesis of RA.
The spectrum of pericardial tamponade in systemic lupus erythematosus: Report of ten patients
Authors: Kahl Leslie E.
Published: June 2014

Objective. To describe the range of clinical manifestations and the outcome of pericardial tamponade in patients with systemic lupus erythematosus (SLE).

Methods. Patients with pericarditis and with pericardial tamponade were identified from our computerized database of 395 SLE patients. Medical records were reviewed to establish activity of SLE at the time of tamponade, as well as clinical and laboratory features, treatment, and outcome of the tamponade.

Results. Pericarditis occurred in 75 patients (19%), with 11 episodes of tamponade in 10 of them (13%; 2.5% of entire series). Tamponade was the initial manifestation of SLE in 4 patients. Seven episodes occurred during active lupus, with nephritis present in 6. Signs of venous congestion, including ascites and facial or peripheral edema, were the most common manifestation of tamponade. Pericardial fluid was exudative, and pericardial tissue demonstrated a range of findings including fibrinous and fibrotic changes, acute and chronic inflammatory infiltrates, and vascular proliferation. Tamponade was fatal in 1 patient, and 2 patients each had recurrent effusions and pericardial thickening.

Conclusion. Pericardial tamponade may occur at any point in the course of SLE, and should be considered in patients with unexplained signs of venous congestion. The differential diagnosis includes active SLE, uremia, and infection. Treatment with high‐dose steroids and either pericardiocentesis or placement of a pericardial window is indicated, but recurrent effusions or pericardial thickening may develop.
The effect of cyclosporin a on early and late stages of experimental lupus
Authors: Blank M. , Ben‐Bassat M. , Shoenfeld Y.
Published: June 2014

Objective. To investigate the effect of cyclosporin A (CSA) on the development of lupus in an experimental model.

Methods. Lupus was induced in naive mice following injection of a human anti—double‐stranded DNA (anti‐dsDNA) monoclonal antibody carrying the 16/6 idiotype (Id). CSA was injected into the mice at an early stage of the disease (2 months after immunization) and at a late stage (4 months after immunization).

Results. CSA was found to have a suppressive effect on autoantibody production, as well as on the appearance of other disease manifestations, in the mice with lupus. The effects of the drug were more prominent when the mice were treated at an early stage. This was reflected by a dramatic decrease, to normal levels, in autoantibodies to dsDNA, histones, cardiolipin, Sm, RNP, SS‐A/Ro, SS‐B/La, and anti—DNA 16/6 Id. Similar effects on the erythrocyte sedimentation rate, white blood cell count, and urinary protein levels were noted. These data were supported by electron microscopy analysis showing a lack of immunoglobulin deposition in the kidneys of mice in which treatment was started early.

Conclusion. This study demonstrates that, similar to findings in other autoimmune conditions (e.g., insulin‐dependent diabetes mellitus), administration of CSA at an early stage in systemic lupus erythematosus may be more beneficial than if the drug is given at a later stage.
Cardiac involvement in systemic sclerosis
Authors: Anvari Anahit , Graninger Winfried , Schneider Barbara , Sochor Heinz , Weber Heinz , Schmidinger Herwig
Published: June 2014

Objective. To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms.

Methods. Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients.

Results. These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress‐induced reversible myocardial perfusion abnormalities in 6.

Conclusion. These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms.
Restricted junctional usage of T cell receptor Vβ2 and Vβ13 genes, which are overrepresented on infiltrating T cells in the lips of patients with sjögren's syndrome
Authors: Yonaha Fumiko , Sumida Takayuki , Maeda Toshiro , Tomioka Hisao , Koike Takao , Yoshida Sho
Published: June 2014

Objective. To analyze the clonality of T cell receptor (TCR) Vβ2—and Vβ13—positive T cells, which are predominantly expressed in the lips of patients with Sjögren's syndrome (SS).

Methods. The junctional sequences of complementary DNA clones encoding TCR Vβ2 and Vβ13 genes were determined by the polymerase chain reaction. Forty‐one Vβ2 and 45 Vβ13 clones established from the lips of 3 SS patients were sequenced.

Results. The Vβ2/Jβ2.3 pair was enriched in 2 of the 3 patients (44% and 46% of the clones, respectively), and the Vβ13/Jβ2.1 sequence was dominant in 2 of the 3 (23% and 45%). These pairs were not used preferentially in peripheral blood lymphocytes from the same patients.

Conclusion. Infiltrating Vβ2‐ and Vβ13‐positive T cells from the lips of all 3 patients with SS were polyclonal, but the junctional usage of cells from 2 lip samples was restricted, compared with cells from peripheral blood. This suggests that not all expanded cells from the lips of SS patients are stimulated by superantigens.
Antineutrophil cytoplasmic autoantibody—associated vasculitis presenting as sjögren's syndrome
Authors: Böttinger Erwin P. , Niles John L. , Collins A. Bernard , McCluskey Robert T. , Arnaout M. Amin
Published: June 2014

A 63‐year‐old woman, in whom a diagnosis of Sjögren's syndrome was initially made, proved to have systemic vasculitis with salivary gland involvement and necrotizing and crescentic glomerulonephritis. Antineutrophil cytoplasmic autoantibodies (ANCA) against myeloperoxidase were positive. ANCA‐associated vasculitis should be considered in the differential diagnosis of Sjögren's syndrome. A positive finding on immunoassay for ANCA against myeloperoxidase or proteinase 3 may help establish the diagnosis.
Heavy and light chain composition of serum IgA and IgA rheumatoid factor in henoch‐schönlein purpura
Authors: Saulsbury Frank T.
Published: June 2014

Objective. To characterize the heavy and light chain composition of serum IgA and IgA rheumatoid factor (RF) in 34 children with Henoch‐Schönlein purpura (HSP).

Methods. Serum IgA and IgA subclass concentrations were measured by radial immunodiffusion. IgA‐RF and the light chain composition of serum IgA and IgA‐RF were determined by enzyme immunoassay.

Results. Serum IgA and IgAl concentrations were higher in HSP patients than controls (P = 0.0001), but there was no difference in IgA2 concentrations between the two groups. IgA‐RF was present in 19 of 34 HSP patients; it was composed predominantly of IgAl. The κ: λ ratio of serum IgA was virtually identical in patients and controls, but the κ: λ ratio of IgA‐RF was significantly higher than that of the serum IgA from the 19 IgA‐RF seropositive patients (P = 0.0003).

Conclusion. Serum IgAl is preferentially increased in children with HSP, but the light chain composition of IgA is not different from that in controls. IgA‐RF is common in HSP; it is composed predominantly of IgA1 and it is enriched in κ light chains.
Suppression of renal disease and arthritis, and prolongation of survival in MRL‐lpr mice treated with an extract of tripterygium wilfordii hook F
Authors: Gu Wen‐Zhen , Banerjee Subhashis , Rauch Joyce , Brandwein Sydney R.
Published: June 2014

Objective. Treatment of MRL‐lpr/lpr mice with Tripterygium wilfordii Hook f (TWHf) to evaluate its effects on mortality, renal disease, and arthritis.

Methods. Mice were fed water (group A, control), TWHf (group B), or first water and then TWHf (group C) from age 7 weeks until age 21 weeks.

Results. Arthritis and glomerulonephritis were decreased in groups B and C mice, and survival was increased in group B mice.

Conclusion. TWHf decreases the mortality rate, and severity of glomerulonephritis and arthritis in MRL‐Ipr/lpr mice.
Premature death with bladder outlet obstruction and hyperprolactinemia in new zealand black × new zealand white mice treated with ethinyl estradiol and 17 beta—estradiol
Authors: Walker Sara E. , McMurray Robert W. , Besch‐Williford Cynthia L. , Keisler Duane H.
Published: June 2014

Objective. To determine causes of death, estrogen toxicity, and hyperprolactinemia in a murine model of systemic lupus erythematosus (SLE).

Methods. Female New Zealand Black × New Zealand White (NZB × NZW) mice were implanted with ethinyl estradiol, 17 beta—estradiol, or empty capsules (controls).

Results. Estrogen‐treated mice developed striking hyperprolactinemia and died prematurely with genitourinary complications.

Conclusion. Implanted estrogens, including 17 beta—estradiol in a dose reported previously to stimulate SLE, contribute to premature death in NZB × NZW mice, through toxic effects. Estrogen therapy increases the level of prolactin, an immunostimulatory hormone.
Phase Transition Originating from Order–Disorder Transformations of Carboxy Oxygen Atoms Coupled with Dynamic Proton Motions in [PhCH2NH(CH3)2]2C2O4⋅H2C2O4
Authors: Tang Yuanyuan , Ji Chengmin , Sun Zhihua , Zhang Shuquan , Chen Tianliang , Luo Junhua
Published: June 2014

A new molecular phase transition material, [PhCH2NH(CH3)2]2C2O4⋅H2C2O4, which undergoes a reversible phase transition at 151.6 K, has been successfully synthesized. Differential scanning calorimetry (DSC), specific heat capacity, and dielectric measurements confirm its reversible phase transition with a large thermal hysteresis of 15.1 K, demonstrating that the phase transition is typical first order. Variable‐temperature single‐crystal X‐ray diffraction analyses reveal that the order–disorder transformations of carboxy oxygen atoms induce the structural phase transition. A slight reorientation of the oxalic acid unit is discovered to accompany the ordering of carboxy oxygen atoms at low temperature. The DSC measurement result of the deuterated analog is different to that of 1, indicating that proton dynamic motions in hydrogen bonds also contribute to the phase transition.
Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells
Authors: Mahler Gretchen J. , Frendl Christopher M. , Cao Qingfeng , Butcher Jonathan T.
Published: June 2014

Understanding the role of mechanical forces on cell behavior is critical for tissue engineering, regenerative medicine, and disease initiation studies. Current hemodynamic bioreactors are largely limited to 2D substrates or the application of general flow conditions at a tissue level, which eliminates the investigation of some essential physiological and pathological responses. One example is the mesenchymal transformation of endothelial cells in response to shear stress. Endothelial to mesenchymal transformation (EndMT) is a valve morphogenic mechanism associated with aortic valve disease initiation. The aortic valve experiences oscillatory shear on the disease‐susceptible fibrosa, and the role of hemodynamics on adult EndMT is unknown. The goal of this work was to develop and characterize a microfluidic bioreactor that applies physiologically relevant laminar or oscillatory shear stresses to endothelial cells and permits the quantitative analysis of 3D cell–extracellular matrix (ECM) interactions. In this study, porcine aortic valve endothelial cells were seeded onto 3D collagen I gels and exposed to different magnitudes of steady or oscillatory shear stress for 48 h. Cells elongated and aligned perpendicular to laminar, but not oscillatory shear. Low steady shear stress (2 dyne/cm2) and oscillatory shear stress upregulated EndMT (ACTA2, Snail, TGFB1) and inflammation (ICAM1, NFKB1) related gene expression, EndMT‐related (αSMA) protein expression, and matrix invasion when compared with static controls or cells exposed to high steady shear (10 and 20 dyne/cm2). Our system enables direct testing of the role of shear stress on endothelial cell mesenchymal transformation in a dynamic, 3D environment and shows that hemodynamics regulate EndMT in adult valve endothelial cells. Biotechnol. Bioeng. 2014;111: 2326–2337. © 2014 Wiley Periodicals, Inc.
Industrial Product Design: Materials for the Machinery
Authors: Rähse Wilfried
Published: June 2014

The materials for production plants must be chemically resistant under operating conditions for a long period of time. Typical materials are metals, especially stainless steel, superalloys, and nonmetals such as graphite, borosilicate glass, and ceramics, as well as plastics. The product manufacturers prefer highly alloyed stainless steel with ∼17–18 % Cr and 12 % Ni (AISI 304 and 316 grades). The danger of pitting and stress corrosion decreases with increasing amounts of molybdenum. The pharmaceutical and food industries utilize machinery in stainless steel with surfaces in mirror finish to avoid infection with microorganisms in the entire plant. The surface smoothing is performed by mechanical methods or by electropolishing. Besides stainless steel, the chemical industry takes advantage of nonferrous metals, alloys, metallic oxides, and carbides as well as plastics for processing and storage of aggressive substances. These materials are mainly used for linings and coatings. In many cases, they are applied by thermal spraying (sputtering).
Neutral Nickel Ethylene Oligo‐ and Polymerization Catalysts: Towards Computational Catalyst Prediction and Design
Authors: Heyndrickx Wouter , Occhipinti Giovanni , Jensen Vidar R.
Published: June 2014

DFT calculations have been used to elucidate the chain termination mechanisms for neutral nickel ethylene oligo‐ and polymerization catalysts and to rationalize the kind of oligomers and polymers produced by each catalyst. The catalysts studied are the (κ2‐O,O)‐coordinated (1,1,1,5,5,5‐hexafluoro‐2,4‐acetylacetonato)nickel catalyst I, the (κ2‐P,O)‐coordinated SHOP‐type nickel catalyst II, the (κ2‐N,O)‐coordinated anilinotropone and salicylaldiminato nickel catalysts III and IV, respectively, and the (κ2‐P,N)‐coordinated phosphinosulfonamide nickel catalyst V. Numerous termination pathways involving β‐H elimination and β‐H transfer steps have been investigated, and the most probable routes identified. Despite the complexity and multitude of the possible termination pathways, the information most critical to chain termination is contained in only few transition states. In addition, by consideration of the propagation pathway, we have been able to estimate chain lengths and discriminate between oligo‐ and polymerization catalysts. In agreement with experiment, we found the Gibbs free energy difference between the overall barrier for the most facile propagation and termination pathways to be close to 0 kcal mol−1 for the ethylene oligomerization catalysts I and V, whereas values of at least 7 kcal mol−1 in favor of propagation were determined for the polymerization catalysts III and IV. Because of the shared intermediates between the termination and branching pathways, we have been able to identify the preferred cis/trans regiochemistry of β‐H elimination and show that a pronounced difference in σ donation of the two bridgehead atoms of the bidentate ligand can suppress hydride formation and thus branching. The degree of rationalization obtained here from a handful of key intermediates and transition states is promising for the use of computational methods in the screening and prediction of new catalysts of the title class.
Multi‐Stimuli‐Responsive Organometallic Gels Based on Ferrocene‐Linked Poly(Aryl Ether) Dendrons: Reversible Redox Switching and Pb2+‐Ion Sensing
Authors: Lakshmi Neelakandan Vidhya , Mandal Dipendu , Ghosh Sundargopal , Prasad Edamana
Published: June 2014

We describe the design, synthesis, and “stimuli‐responsive” study of ferrocene‐linked Fréchet‐type [poly(aryl ether)]‐dendron‐based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low‐molecular‐weight gelators (LMWGs) form robust gels in both polar and non‐polar solvent/solvent mixtures. The organometallic gels undergo stimuli‐responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb2+ ions (detection limit ≈10−8 M). The metal ion‐sensing results in a gel–sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal–ligand binding nature has been analyzed by using 1H NMR spectroscopy, mass spectrometry, and DFT calculations.
Organocatalytic Enantio‐ and Diastereoselective Conjugate Addition to Nitroolefins: When β‐Ketoamides Surpass β‐Ketoesters
Authors: Du Haiying , Rodriguez Jean , Bugaut Xavier , Constantieux Thierry
Published: June 2014

Our findings on the bifunctional squaramide‐catalyzed enantioselective conjugate addition of β‐ketoamides to nitroolefins are disclosed. It appears that simple acyclic methylene β‐ketoamides, unlike the extensively studied β‐ketoesters, afford the products in excellent diastereoselectivities, and maintain high yields and enantioselectivities. Moreover, competition and kinetic studies were conducted to rationalize the observed reactivity and selectivity. The high level of diastereocontrol, along with the amenability of the amide group to postfunctionalization, dramatically increase the synthetic usefulness of the transformation.
Design of Leaving Groups in Radical CC Fragmentations: Through‐Bond 2c–3e Interactions in Self‐Terminating Radical Cascades
Authors: Mondal Sayantan , Gold Brian , Mohamed Rana K. , Alabugin Igor V.
Published: June 2014

Radical cascades terminated by β‐scission of exocyclic CC bonds allow for the formation of aromatic products. Whereas β‐scission is common for weaker bonds, achieving this reactivity for carbon–carbon bonds requires careful design of radical leaving groups. It has now been found that the energetic penalty for breaking a strong σ‐bond can be compensated by the gain of aromaticity in the product and by the stabilizing two‐center, three‐electron “half‐bond” present in the radical fragment. Furthermore, through‐bond communication of a radical and a lone pair accelerates the fragmentation by selectively stabilizing the transition state. The stereoelectronic design of radical leaving groups leads to a new, convenient route to Sn‐functionalized aromatics.
Design of a Combinational Magnesium Catalyst for the Stereocontrolled Cross Reaction of Enones
Authors: Yang Dongxu , Wang Linqing , Han Fengxia , Zhao Depeng , Wang Rui
Published: June 2014

The first stereocontrolled cross reaction of enones has been realized. A novel combinational magnesium catalyst was designed to address the enantioselectivity problem between reaction partners with an intermolecular symmetric structure and bearing identical functional groups. This new catalytic strategy was proven to be effective to introduce high levels of enantioselectivity in the cross reaction of enones.
Mechanistic Insight into the Electronic Influences Imposed by Substituent Variation in Polyazine‐Bridged Ruthenium(II)/Rhodium(III) Supramolecules
Authors: White Travis A. , Mallalieu Hannah E. , Wang Jing , Brewer Karen J.
Published: June 2014

Invited for the cover of this issue are researchers from the Department of Chemistry at Virginia Tech featuring work on electrochemical properties of photochemical molecular devices for solar hydrogen production. The image highlights the complexity of the redox chemistry of the studied supramolecules, detailing speciation following reduction. Mr. Skye King assisted in the development of the molecular models for the cover. Read the full text of the article at 10.1002/chem.201402564.
Silavinylidene Stabilized by an N‐Heterocyclic Carbene: A Theoretically Predicted Stable Molecule
Authors: Xu Jing , Ding Yi‐Hong , Andrada Diego M. , Frenking Gernot
Published: June 2014

Quantum chemical calculations show that the N‐heterocyclic carbene (NHC)‐stabilized silavinylidene, NHCtBu→CSiR2 is a strongly bonded complex, which has a linear arrangement of the donor and acceptor moieties. The molecule is the energetically lowest lying isomer of the NHC‐stabilized R2CSi isomers and it is stable towards dimerization when R is a bulky substituent. The silavinylidene complex is the only species of the silylidene homologues NHCtBu→EE′R2 (E, E′=C–Pb) which possesses a linear arrangement. The unusual bonding situation is explained in terms of donor–acceptor interactions between NHCtBu as σ donor and CSiR2 in the doubly excited singlet state 3a1⇒2b2 which leads to a significantly shorter CSiR2 bond compared with free CSiR2.
Intrinsic Chirality and Prochirality at Air/R‐(+)‐ and S‐(–)‐Limonene Interfaces: Spectral Signatures With Interference Chiral Sum‐Frequency Generation Vibrational Spectroscopy
Authors: Fu Li , Zhang Yun , Wei Zhe‐Hao , Wang Hong‐Fei
Published: June 2014

We report in this work detailed measurements of the chiral and achiral sum‐frequency vibrational spectra in the C‐H stretching vibration region (2800–3050 cm‐1) of the air/liquid interfaces of R‐(+)‐limonene and S‐(−)‐limonene, using the recently developed high‐resolution broadband sum‐frequency generation vibrational spectroscopy (HR‐BB‐SFG‐VS). The achiral SFG spectra of R‐limonene and S‐limonene, as well as the RS racemic mixture (50/50 equal amount mixture), show that the corresponding molecular groups of the R and S enantiomers are with the same interfacial orientations. The interference chiral SFG spectra of the limonene enantiomers exhibit a spectral signature from the chiral response of the Cα‐H stretching mode, and a spectral signature from the prochiral response of the CH2 asymmetric stretching mode, respectively. The chiral spectral feature of the Cα‐H stretching mode changes sign from R‐(+)‐limonene to S‐(–)‐limonene surfaces, and disappears for the RS racemic mixture surface. While the prochiral spectral feature of the CH2 asymmetric stretching mode is the same for R‐(+)‐limonene and S‐(–)‐limonene surfaces, and also surprisingly remains the same for the RS racemic mixture surface. Therefore, the structures of the R‐(+)‐limonene and the S‐(–)‐limonene at the liquid interfaces are nevertheless not mirror images to each other, even though the corresponding groups have the same tilt angle from the interfacial normal, i.e., the R‐(+)‐limonene and the S‐(–)‐limonene at the surface are diastereomeric instead of enantiomeric. These results provide detailed information in understanding the structure and chirality of molecular interfaces and demonstrate the sensitivity and potential of SFG‐VS as a unique spectroscopic tool for chirality characterization and chiral recognition at the molecular interface. Chirality 26:509–520, 2014. © 2014 Wiley Periodicals, Inc.
Determination of Characteristic Geometrical Parameters for the Design of Pillow‐Plate Heat Exchangers
Authors: Piper Mark , Olenberg Alexander , Tran Julian M. , Goedecke Robert , Scholl Stephan , Kenig Eugeny
Published: June 2014

Thermoblech‐Wärmeübertrager sind eine vielversprechende Alternative zu konventionellen Apparaten. Zur Erstellung ihrer Dimensionierungsgrundlagen werden Daten zu charakteristischen Geometrieparametern benötigt, für die es in der Literatur bisher keine festgelegte Bestimmungsweise gibt. In dieser Arbeit wird die Geometrie der Thermobleche durch Verformungssimulationen exakt nachgebildet. Anschließend werden Näherungsgleichungen zur Geometriebestimmung hergeleitet und validiert. Darauf basierend werden Vorschläge zur orientierenden Ermittlung der charakteristischen Geometrieparameter abgeleitet.
Hypoglycemia From a Cardiologist's Perspective
Authors: Sanon Vani P. , Sanon Saurabh , Kanakia Rushit , Yu Hu , Araj Faris , Oliveros Rene , Chilton Robert
Published: June 2014

Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers activation of the sympathoadrenal system, leading to an increase in counter‐regulatory hormones and, consequently, increased myocardial workload and oxygen demand. Additionally, hypoglycemia triggers proinflammatory and hematologic changes that provide the substrate for possible myocardial ischemia in the already‐diseased diabetic cardiovascular system. Hypoglycemia creates electrophysiologic alterations causing P‐R–interval shortening, ST‐segment depression, T‐wave flattening, reduction of T‐wave area, and QTc‐interval prolongation. Patients who experience hypoglycemia are at an increased risk of silent ischemia as well as QTc prolongation and consequent arrhythmias. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an increase in all‐cause mortality with intensive glycemic control, whereas the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study and Veteran's Affairs Diabetes Trial (VADT) showed no benefit with aggressive glycemic control. Women, elderly patients, and those with renal insufficiency are more vulnerable to hypoglycemic events. In fact, hypoglycemia is the most common metabolic complication experienced by older patients with DM in the United States. The concurrent use of medications like β‐blockers warrants caution in DM because they can mask warning signs of hypoglycemia. Here we aim to elucidate the pathophysiology, review the electrocardiographic changes, analyze the current clinical literature, and consider the safety considerations of hypoglycemia as it relates to the cardiovascular system. In conclusion, in the current era of DM and its vascular ramifications, hypoglycemia from a cardiologist's perspective deserves due attention.
Optimization of the Antiviral Potency and Lipophilicity of Halogenated 2,6‐Diarylpyridinamines as a Novel Class of HIV‐1 NNRTIS
Authors: Wu Zhi‐Yuan , Liu Na , Qin Bingjie , Huang Li , Yu Fei , Qian Keduo , Morris‐Natschke Susan L. , Jiang Shibo , Chen Chin Ho , Lee Kuo‐Hsiung , Xie Lan
Published: June 2014

Nineteen new halogenated diarylpyridinamine (DAPA) analogues modified at the phenoxy C‐ring were synthesized and evaluated for anti‐HIV activity and certain drug‐like properties. Ten compounds showed high anti‐HIV activity (EC50<10 nM). In particular, (E)‐6‐(2′′‐bromo‐4′′‐cyanovinyl‐6′′‐methoxy)phenoxy‐N2‐(4′‐cyanophenyl)pyridin‐2,3‐diamine (8 c) displayed low‐nanomolar antiviral potency (3–7 nM) against wild‐type and drug‐resistant viral strains bearing the E138K or K101E mutations, which are associated with resistance to rilvipirine (1 b). Compound 8 c exhibited much lower resistance fold changes (RFC: 1.1–2.1) than 1 b (RFC: 11.8–13.0). Compound 8 c also exhibited better metabolic stability (in vitro half‐life) than 1 b in human liver microsomes, possessed low lipophilicity (clog D: 3.29; measured log P: 3.31), and had desirable lipophilic efficiency indices (LE>0.3, LLE>5, LELP<10). With balanced potency and drug‐like properties, 8 c merits further development as an anti‐HIV drug candidate.
Cancer patients' perceptions regarding the value of the physical examination: A survey study
Authors: Kadakia Kunal C. , Hui David , Chisholm Gary B. , Frisbee‐Hume Susan E. , Williams Janet L. , Bruera Eduardo
Published: June 2014

BACKGROUND

Despite its clinical utility, progressive reliance on technology can lead to devaluing the physical examination in patients with advanced cancer. The primary objective of this study was to determine whether these patients have a positive or negative perception of the physical examination. A secondary objective was to determine whether these perceptions are related to interpersonal/relational values (symbolic) or diagnostic/objective values (pragmatic).

METHODS

One hundred fifty patients with cancer who were receiving concurrent oncology and palliative care were administered a 26‐item survey regarding their overall perception of the physical examination. The primary outcome—patient responses to “In the last 3 months, I believe my experience while being examined has been overall: very negative (a score of −5) to very positive (a score of +5),”—was analyzed using the Sign test. Other items were predefined as either symbolic or pragmatic statements, and patient responses from strongly disagree (a score of 1) to strongly agree (a score of 5) were further analyzed. Multivariable logistic regression was used to test for associations between baseline characteristics and the primary outcome.

RESULTS

Most patients (83%) indicated that the overall experience of being examined was highly positive (median score, 4; interquartile range [IQR], 2‐5; P ≤ .0001). Patients valued both the pragmatic aspects (median score, 5; IQR, 4‐5) and symbolic aspects (median score, 4; IQR, 4‐5) of the physical examination. Increasing age was independently associated with a more positive perception of the physical examination (odds ratio, 1.07 per year; 95% confidence interval, 1.02‐1.12 per year; P = .01).

CONCLUSIONS

Patients with advanced cancer indicate that the physical examination is a highly positive aspect of their care. These benefits are perceived as having both symbolic and pragmatic value. The physical examination should remain a cornerstone of clinical encounters. Cancer 2014;120:2215–2221. © 2014 American Cancer Society.
Young and uninsured: Insurance patterns of recently diagnosed adolescent and young adult cancer survivors in the AYA HOPE study
Authors: Parsons Helen M. , Schmidt Susanne , Harlan Linda C. , Kent Erin E. , Lynch Charles F. , Smith Ashley W. , Keegan Theresa H. M.
Published: June 2014

BACKGROUND

Young adults have historically been the least likely to have health insurance in the United States. Previous studies of survivors of childhood cancer found lower rates of insurance and less access to medical care compared with siblings; however, to the authors' knowledge, no studies to date have examined continuity of insurance after a cancer diagnosis in adolescents and young adults (AYAs).

METHODS

Using the AYA Health Outcomes and Patient Experience study, a cohort of 465 individuals aged 15 to 39 years from participating Surveillance, Epidemiology, and End Results registries, we evaluated changes in and sponsors of health insurance coverage after diagnosis, coverage of physician‐recommended tests, and factors associated with lack of insurance after a cancer diagnosis using chi‐square tests and multivariable logistic regression.

RESULTS

Greater than 25% of AYA survivors of cancer (118 survivors) experienced some period without insurance up to 35 months after diagnosis. Insurance rates were high in the initial year after diagnosis (6 months‐14 months; 93.3%) but decreased substantially at follow‐up (15 months‐35 months; 85.2%). The most common sponsor of health insurance was employer/school coverage (43.7%). Multivariable analysis indicated that older survivors (those aged 25‐39 years vs 15‐19 years; odds ratio, 3.35 [P < .01]) and those with less education (high school or less vs college graduate; odds ratio, 2.80 [P < .01]) were more likely to experience a period without insurance after diagnosis. Furthermore, > 20% of survivors indicated there were physician‐recommended tests/treatments that were not covered by insurance, but > 80% received them regardless of coverage.

CONCLUSIONS

Insurance rates appear to decrease with time since diagnosis in AYA survivors of cancer. Future studies should examine how new policies under the Patient Protection and Affordable Care Act extend access and insurance coverage beyond initial treatment. Cancer 2014;120:2352–2360. © 2014 American Cancer Society.
The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: A comprehensive and evidence‐based comparison and review
Authors: Fong Zhi Ven , Tanabe Kenneth K.
Published: June 2014

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver‐European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines. Cancer 2014;120:2824–2838. © 2014 American Cancer Society.