bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 2‐ and 2,7‐Functionalized Pyrene Derivatives: An Application of Selective CH Borylation
Authors: Crawford Andrew G. , Liu Zhiqiang , Mkhalid Ibraheem A. I. , Thibault Marie‐Hélène , Schwarz Nicolle , Alcaraz Gilles , Steffen Andreas , Collings Jonathan C. , Batsanov Andrei S. , Howard Judith A. K. , Marder Todd B. 
Published: March 2012

AbstractAn efficient synthetic route to 2‐ and 2,7‐substituted pyrenes is described. The regiospecific direct CH borylation of pyrene with an iridium‐based catalyst, prepared in situ by the reaction of [{Ir(μ‐OMe)cod}2] (cod=1,5‐cyclooctadiene) with 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine, gives 2,7‐bis(Bpin)pyrene (1) and 2‐(Bpin)pyrene (2, pin=OCMe2CMe2O). From 1, by simple derivatization strategies, we synthesized 2,7‐bis(R)‐pyrenes with R=BF3K (3), Br (4), OH (5), B(OH)2 (6), and OTf (7). Using these nominally nucleophilic and electrophilic derivatives as coupling partners in Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross‐coupling reactions, we obtained 2,7‐bis(R)‐pyrenes with R=(4‐CO2C8H17)C6H4 (8), Ph (9), C≡CPh (10), C≡C[{4‐B(Mes)2}C6H4] (11), C≡CTMS (12), C≡C[(4‐NMe2)C6H4] (14), C≡CH (15), N(Ph)[(4‐OMe)C6H4] (16), and R=OTf, R′=C≡CTMS (13). Lithiation of 4, followed by reaction with CO2, yielded pyrene‐2,7‐dicarboxylic acid (17), whilst borylation of 2‐tBu‐pyrene gave 2‐tBu‐7‐Bpin‐pyrene (18) selectively. By similar routes (including Negishi cross‐coupling reactions), monosubstituted 2‐R‐pyrenes with R=BF3K (19), Br (20), OH (21), B(OH)2 (22), [4‐B(Mes)2]C6H4 (23), B(Mes)2 (24), OTf (25), C≡CPh (26), C≡CTMS (27), (4‐CO2Me)C6H4 (28), C≡CH (29), C3H6CO2Me (30), OC3H6CO2Me (31), C3H6CO2H (32), OC3H6CO2H (33), and O(CH2)12Br (34) were obtained from 2. These derivatives are of synthetic and photophysical interest because they contain donor, acceptor, and conjugated substituents. The crystal structures of compounds 4, 5, 7, 12, 18, 19, 21, 23, 26, and 28–31 have also been obtained from single‐crystal X‐ray diffraction data, revealing a diversity of packing modes, which are described in the Supporting Information. A detailed discussion of the structures of 1 and 2, their polymorphs, solvates, and co‐crystals is reported separately.
Increasing Profitability by Accelerated Product‐ and Process Development with Modular and Scalable Apparatuses
Authors: Brodhagen Andreas , Grünewald Marcus , Kleiner Matthias , Lier Stefan 
Published: March 2012

AbstractDie zunehmende Fokussierung der chemischen Industrie in Europa auf Spezialitätenprodukte erfordert neue, ganzheitliche Ansätze bei der Produkt‐ und Verfahrensentwicklung. Durch modulare und skalierbare Apparatekonzepte lässt sich eine rasche und kostengünstige Anpassung der Produktionskapazität an Marktentwicklungen erzielen. Am Beispiel einer Fallstudie für ein Spezialitätenprodukt werden die Einflüsse der schnellen Marktanpassung auf die Wirtschaftlichkeit und damit Wettbewerbsfähigkeit dargestellt und bewertet. Die Kapitalwertanalyse zeigt, dass insbesondere die Verkürzung des Zeitbedarfs von der Produktentwicklung bis zur fertigen Produktionsanlage durch smarte Produktionstechnologien zu einer Erhöhung der Wirtschaftlichkeit führt.
Shorter Time‐to‐Market with Micro‐Conti Processes
Authors: Grundemann Laura , Schoenitz Martin , Scholl Stephan 
Published: March 2012

AbstractTraditional process development consists of four main phases resulting in time‐consuming and cost‐intensive launches for new products and processes. By employing microprocess technology, transferring batch to continuous processes or setting up a continuous process for low to medium production capacities from scratch becomes technically feasible. Since volumetric flow rates on lab‐scale are often similar to production rates, the scale‐up factor is low. Thus, individual development phases can be omitted reducing the time‐to‐market for new products and/or processes. Based on two case studies, the development phase of micro‐conti processes is described and conclusions are drawn regarding the 50 % idea as laid down in the Tutzing theses.
Ionic Liquid Modified Resin for the Adsorptive Removal of Dibutyl Phthalate: Equilibrium, Kinetic, and Thermodynamic Studies
Authors: Qureshi Umair A. , Solangi Amber R. , Memon Saima Q. , Taqvi Syed I. H. , Memon Najma 
Published: March 2012

AbstractThis study evaluated the adsorptive properties of dibutyl phthalate (DBP) on room temperature ionic liquid (RTIL) modified XAD‐4 resin. The modified RTIL‐XAD 4 sorbent was characterized by FTIR. Effect of varying experimental conditions such as pH, contact time, temperature, shaking speed, concentrations, and interfering species were investigated by batch adsorption experiments. Adsorption was found to be most favorable at pH 6 within 30 min. Experimental data were evaluated in terms of kinetic, equilibrium, and thermodynamic modeling. Kinetics of the sorption was found to follow pseudo second order rate equation whereas Freundlich and D–R isotherms were the most suitable models to explain sorption phenomenon. Thermodynamically sorption was endothermic, irreversible, and spontaneous in nature.
Exploring the Anticancer Activity of Functionalized Isoindigos: Synthesis, Drug‐like Potential, Mode of Action and Effect on Tumor‐Induced Xenografts
Authors: Wee Xi Kai , Yang Tianming , Go Mei Lin 
Published: March 2012

AbstractMeisoindigo has been used as an indirubin substitute for the treatment of chronic myeloid leukemia (CML) for several years. In view of its poor solubility and erratic absorption, several investigations have focused on developing analogues with more desirable physicochemical profiles. Here, we investigated the structure–activity relationship (SAR) of meisoindigo with respect to its antiproliferative activity on leukemic K562 cells and found that appending a phenalkyl side chain onto the lactam NH resulted in analogues that retained good activity. Furthermore, analogues in which the phenyl ring was substituted with a basic heterocycle were significantly more soluble than meisoindigo while retaining acceptable antiproliferative profiles. The most promising analogue (E)‐1‐(2‐(4‐methylpiperazin‐1‐yl)ethyl)‐[3,3′‐biindolinylidene]‐2,2′‐dione (5‐4) is more potent than meisoindigo across a panel of malignant cells, with at least 40 times greater solubility than meisoindigo, little or no tendency to aggregate in solution and capable of significantly extending the lifespans of animals with K562 induced xenografts. Mechanistically, it induced apoptotic cell death and disrupted the progression of K562 cells from the G1 to G2 phase. Taken together, our findings highlighted the feasibility of addressing the physicochemical deficits of the isoindigo scaffold by systematic modifications which was achieved without overt loss of growth inhibitory activity.
Further data supporting that paclitaxel‐associated acute pain syndrome is associated with development of peripheral neuropathy
Authors: Reeves Brandi N. , Dakhil Shaker R. , Sloan Jeff A. , Wolf Sherry L. , Burger Kelli N. , Kamal Arif , Le‐Lindqwister Nguyet A. , Soori Gamini S. , Jaslowski Anthony J. , Kelaghan Joseph , Novotny Paul J. , Lachance Daniel H. , Loprinzi Charles L. 
Published: March 2012

AbstractBACKGROUND:Paclitaxel causes an acute pain syndrome (P‐APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P‐APS and eventual peripheral neuropathy symptoms.METHODS:Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy‐Induced Peripheral Neuropathy 20‐item instruments were completed weekly.RESULTS:The P‐APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P‐APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P‐APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain.CONCLUSIONS:Patients with worse P‐APS severities appear to have more eventual chemotherapy‐induced peripheral neuropathy. This provides support for the concept that P‐APS is a form of nerve pathology. Cancer 2012. © 2012 American Cancer Society.
A note from history: Landmarks in history of cancer, part 4
Authors: Hajdu Steven I. 
Published: March 2012

AbstractIn the second half of the 19th century, most cancer patients were cared for by surgeons who exerted ascesis and limited their operations to 1 or 2 specific areas. To assist surgeons and other physicians in caring for their patients, pathologists described newly discovered entities, refined the microscopic classification of tumors, and introduced the grading of cancers. The discoveries of Rontgen and the Curies revolutionized the diagnosis and treatment of cancers. The search for the cause of cancers extended to infectious organisms, chemicals, and radioactive materials. The 50 years covered in this review formed the groundwork for the coordinated, specialized care of cancer patients at institutions dedicated to render the most promising treatment. Cancer 2012. © 2012 American Cancer Society.
p38 mitogen‐activated protein kinase signaling, ERCC1 expression, and viability of lung cancer cells from never or light smoker patients
Authors: Planchard David , Camara‐Clayette Valérie , Dorvault Nicolas , Soria Jean‐Charles , Fouret Pierre 
Published: March 2012

AbstractBACKGROUND:Expression of DNA‐repair proteins and activated mitogen‐activated protein kinases (MAPKs) may differ according to smoking status. The authors investigated whether p38 MAPK activity contributed to the viability of cisplatin in lung cancer cell lines from never or light smokers and to ERCC1 mRNA expression.METHODS:Activated p38 MAPK was tested as a predictor for ERCC1 levels in 117 lung adenocarcinomas. Cell viabilities of NCI‐H1975, NCI‐H1793, NCI‐H1650, and NCI‐H1651 cell lines, derived from never or light smokers, were measured after treatment with the p38 MAPK inhibitor SB202190 and cisplatin. The role of p38α (MAPK14) and p38β (MAPK11) isoforms and ERCC1 was evaluated using RNA interference.RESULTS:ERCC1 protein‐level expression was predicted by activated p38 MAPK in lung adenocarcinoma tissues. The p38‐specific inhibitor SB202190 strongly decreased cell viability (43%‐63%). SB202190 plus cisplatin significantly decreased cell viability in every cell line, including cisplatin‐resistant NCI‐H1793. Genetic inhibition, targeting both MAPK11 and MAPK14, reduced the viability of the different cell lines: down‐regulation of p38β accounted for most of this effect. Cisplatin's effect was greater after MAPK11 down‐regulation for NCI‐H1651, and MAPK14 down‐regulation for NCI‐H1650. In addition, both SB202190 and MAPK11 inhibition reduced excision repair cross‐complementing 1 mRNA levels.CONCLUSIONS:Lung cancer cells from never or light smokers rely on p38 MAPK signaling for survival. MAPK11 is involved in that pathway and might contribute to ERCC1 expression. Sensitization to cisplatin can be achieved by pharmacological inhibition of p38 MAPK signaling. Cancer 2012. © 2012 American Cancer Society.
Ethical aspects of participation in the Database of Genotypes and Phenotypes of the National Center for Biotechnology Information
Authors: Peppercorn Jeffrey , Shapira Iuliana , Deshields Teressa , Kroetz Deanna , Friedman Paula , Spears Patricia , Collyar Deborah E. , Shulman Lawrence N. , Dressler Lynn , Bertagnolli Monica M. 
Published: March 2012

AbstractBACKGROUND:The rapid pace of genetics research, coupled with evolving standards for informed consent, can create ethical challenges regarding future use of tissue or information from completed clinical trials. The Cancer and Leukemia Group B (CALGB) Oncology Cooperative Group was faced with an ethical dilemma regarding sharing genetic data from a completed genome‐wide association study (GWAS) that was conducted as part of a large, multicenter breast cancer clinical trial with a national database: the Database of Genotypes and Phenotypes National Center for Biotechnology Information (dbGaP).METHODS:The CALGB Ethics Committee conducted a series of multidisciplinary meetings and teleconferences involving patient advocates, bioethicists, clinical researchers, and clinical oncologists to evaluate the ethical issues raised by this case and to identify lessons for improving informed consent to future genetics research in oncology trials.RESULTS:The Ethics Committee recommended that GWAS data be provided to dbGaP consistent with documented consent for future use of tissue among trial participants. Ethical issues, including adequacy of informed consent to future research, limitations of privacy in modern genetics research, the potential impact of population‐based genetics research on health disparities, and recontact of research participants for clinical care or further research, were identified as major ethical considerations in this area.CONCLUSIONS:Although modern standards for informed consent should not prohibit research or sharing of data consistent with participant's intent and the public interest, there is an urgent need for national consensus on the appropriate use of archived tissue and standardized informed consent for future research among cancer clinical trial participants. Cancer 2012. © 2012 American Cancer Society.
Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection
Authors: Malouf Gabriel G. , Brugières Laurence , Le Deley Marie‐Cécile , Faivre Sandrine , Fabre Monique , Paradis Valérie , Aerts Isabelle , Le Tourneau Christophe , Dreyer Chantal , Branchereau Sophie , Belghiti Jacques , Raymond Eric 
Published: March 2012

AbstractBACKGROUND:The purpose of the current study was to describe pure and mixed fibrolamellar hepatocellular carcinoma (FL‐HCC).METHODS:Consecutive patients with pure and mixed FL‐HCC were identified from a central pathological review using Edmondson's criteria. Clinical, pathological, and epigenetic characteristics of patients who underwent curative surgery were evaluated. Overall and disease‐free survival as well as patterns of disease recurrence were examined. Methylation levels of L1 retrotransposon (LINE‐1) repetitive elements and Ras association domain family 1A gene (RASSF1) promoter were also assessed using pyrosequencing.RESULTS:Forty of 53 patients with a median age of 22 years (range, 9 years‐;65 years) met the criteria for analysis. Central pathological review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL‐HCC. Pure FL‐HCC typically occurred in patients aged < 30 years. These patients often presented with lymph node metastasis at the time of diagnosis and frequently experienced extrahepatic recurrences (n = 16). Conversely, mixed FL‐HCC appeared to resemble to classic HCC, occurring in patients aged > 40 years and frequently involving the liver as the primary site of disease recurrence. With a median follow‐up of 7.8 years, the median overall survival from the time of diagnosis in all patients was 6.4 years (range, 3.2 years‐12 years). Multivariate analysis found that the risk of death was increased in patients with higher American Joint Committee on Cancer disease stages (P = .003) and those with mixed FL‐HCC (P = .03). Methylation analysis of LINE‐1 repetitive elements and RASSF1 promoter revealed different methylation levels between pure and mixed FL‐HCC, suggesting a different epigenetic background.CONCLUSIONS:Pure and mixed FL‐HCC display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities. Cancer 2012. © 2012 American Cancer Society.
Novel Fe3+‐Based 1H MRI β‐Galactosidase Reporter Molecules
Authors: Yu Jian‐Xin , Gulaka Praveen K. , Liu Li , Kodibagkar Vikram D. , Mason Ralph P. 
Published: March 2012

AbstractThere is increasing interest in the development of reporter agents to reveal enzyme activity in vivo using imaging in small animals. We have previously demonstrated the feasibility of detecting lacZ gene activity using the commercially available 3,4‐cyclohexenoesculetin‐β‐D‐galactopyranoside (S‐Gal) as a 1H MRI reporter. Specifically, β‐galactosidase (β‐gal) releases the aglycone, which forms a magnetic resonance contrast‐inducing paramagnetic precipitate in the presence of Fe3+. Contrast was primarily T2‐weighted signal loss, but T1 effects were also observed. Since T1‐contrast generally provides signal enhancement as opposed to loss, it appeared attractive to explore whether analogues could be generated with enhanced characteristics. We now report the design and synthesis of novel analogues together with characterization of 1H MRI contrast based on both T1 and T2 response to β‐gal activity in vitro for the lead agent.
Self‐Limited Reaction‐Diffusion in Nanostructured Substrates: Surface Coverage Dynamics and Analytic Approximations to ALD Saturation Times
Authors: Yanguas‐Gil Angel , Elam Jeffrey W. 
Published: March 2012

AbstractWe present a general model based on a time‐dependent, reaction–diffusion equation to determine the dosing times and coverage profiles in structured substrates during atomic layer deposition (ALD). We first derive expressions comprising a non‐linear diffusion–reaction equation coupled to a surface kinetic equation. In their non‐dimensional forms, these equations show that coverage dynamics during ALD in nanostructured substrates depend only on two non‐dimensional parameters, the Damkoler and precursor excess (number of molecules per surface site in the nanostructure) numbers. Using the assumptions of molecular flow in a circular pore, we derive a general, analytic equation to predict saturation exposure times. To demonstrate the utility of our model, we derive additional expressions incorporating a precursor loss term relevant to predicting exposure times during ozone‐based ALD. Because our model makes no assumptions about the diffusion coefficient or sample geometry, it can easily be adapted to describe a broad range of ALD systems such as trenches and vias, anodized alumina, or aerogels under almost any conditions including molecular, viscous, and transition flow regimes
Using knowledge of development to promote recovery of function after brain damage
Authors: Michel George F. 
Published: March 2012

AbstractKnowledge of normal development of brain–behavior relations plays an important role in understanding how the plasticity of the nervous system can be used to promote recovery of function following brain damage. Aspects of the other articles in this issue are used in justification of the value of such developmental knowledge. Also, the development of amblyopia and its remediation in adulthood is discussed as a model for developing other techniques for ensuring recovery of function after stroke. Although the articles in this issue establish an excellent context for improving actual recovery of function (rather than compensation for deficits), much still needs to be discovered about how we can use developmental knowledge, along with knowledge of the plasticity of the nervous system, to improve remediation techniques. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 54:350‐356, 2012.
Ecohydrological ‘indicators of alteration’ – a robust measure of change in dune slacks
Authors: Robins N S , Jones M L M 
Published: March 2012

ABSTRACTCoastal dunes support a biodiverse wetland habitat, dune slacks, which depend on a seasonally fluctuating, but near‐surface, groundwater level. Any long‐term change in the hydrological regime will impact the ecology. Analysis of long‐term water level hydrographs, using a methodology prescribed for surface water flow gauging data, provides a set of ecohydrological ‘indicators of alteration’. These indicators collectively form a robust quantified measure of change that provides a basis for assessing the ecological impact that may result from a changed hydrological regime. This method was tested using monthly frequency water level data from three west coast UK coastal dunes, over periods of up to 37 years. Mean hydrological variables derived from the hydrographs were compared pre‐impact and post‐impact for a variety of perturbations: medium‐term climate variation and pre‐shoreline and post‐shoreline erosion. The method provided a valid quantification of hydrological change. The low frequency of water‐level data measurements compared with continuous flow‐gauge data precluded analysis of change in inter‐annual variability or perturbation (coefficients of variability) because of the likelihood of missed extreme flood and drought. Principal components analysis was used to identify associations between hydrological indicators and highlighted redundancy among some indicators such as measures of frequency and duration but orthogonality, i.e. independence, of others such as mean water levels and duration of drought. The hydrological effects of climatic variation over a 37‐year period, of management interventions and erosion events that occurred at the three coastal dunes were small compared with the likely impact from projected climate change predictions. Copyright © 2012 John Wiley & Sons, Ltd.
Diaryl‐Substituted Perylene Bis(imides): Synthesis, Separation, Characterization and Comparison of Electrochemical and Optical Properties of 1,7‐ and 1,6‐Regioisomer
Authors: Dey Somnath , Efimov Alexander , Lemmetyinen Helge 
Published: March 2012

AbstractA series of diaryl‐substituted perylene bis(imides) (PBIs) containing electron‐donating and ‐withdrawing aryl groups in the bay region (1‐, 6‐, 7‐ and/or 12‐positions of the perylene core) were synthesized by Suzuki coupling reaction. The corresponding regioisomers, namely, 1,7‐ and 1,6‐regioisomer, were separated from the mixture by conventional column chromatography without any need of recrystallization. All the individual regioisomers were fully characterized by 1H NMR and HRMS spectroscopy. The compounds were studied by optical spectroscopy and electrochemical techniques. The optical and electrochemical properties of 1,7‐regioisomer are slightly different from the 1,6‐regioisomer of the respective diaryl‐PBI. Significant redshift and broadening of the absorption and emission maxima were observed in all synthesized PBIs depending upon the electronic nature of the attached aryl group. This is very first time such large series of 1,6‐diarylperylenetetracarboxydiimides with their corresponding 1,7‐regioisomers were synthesized, separated, characterized and studied in detail.
Pyridine‐Substituted BODIPY as Fluorescent Probe for Hg2+
Authors: Wagner Sally , Brödner Kerstin , Coombs Benjamin A. , Bunz Uwe H. F. 
Published: March 2012

AbstractDialkynylated BODIPYs bearing pyridine or dibutylaniline substituents have been synthesized, and their photophyisical properties in the presence of different metal ions have been studied. 4‐Pyridyl substitution gives a highly selective fluorescence probe for HgII ions.