bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing Surviving Sepsis guidelines in a district general hospital
Authors: Page I , Hardy G , Fairfield J , Orr D , Nichani R
Published: December 2011

We describe efforts made at Blackpool Victoria Hospital to implement the well-established international Surviving Sepsis guidelines. These included posters, pocket guides and stickers inserted in patient notes. All doctors and nurses in acute areas received specific information and education. Sepsis teams comprising both doctors and nurses were formed to encourage implementation and to audit and disseminate data. Data collection occurred from February to November 2009. Cases were considered prospectively at the time of initial assessment and 198 patients were identified; 169 (85%) had blood cultures taken; 146 (74%) had lactate levels measured; and 145 (74%) received antibiotics within the target time. We believe these results demonstrate relatively effective implementation of guidelines in the challenging environment of a district general hospital. Our results could be replicated easily and provide a good way of reducing patient mortality at minimal financial cost.
Dr Roger McNeill and public health in the Highlands and Islands of Scotland
Authors: Sheets JW
Published: December 2011

Roger McNeill was born in 1853 on Colonsay in the Inner Hebrides, the son of a cattle herder. He graduated with a degree in medicine from Edinburgh University, where he studied with Joseph Lister, among others. After working in London during a smallpox epidemic, he received a gold medal and honours for his M.D. thesis in 1881. McNeill returned to Scotland as the Resident Medical Officer at Gesto Hospital on the Isle of Skye. From there, he launched and published the first statistical research about the health of Highland crofters. His was an illustrious yet understated career in public health: he was the first president of the Caledonian Medical Society (1881–82), he earned a Diploma in Public Health from Cambridge University (1889), he was the first Medical Officer of Health for Argyll (1890–1924), wrote The Prevention of Epidemics and the Construction and Management of Isolation Hospitals (1894), and was the first witness before Parliament’s Dewar Committee in Oban in 1912. McNeill and other members of the Caledonian Medical Society testified about medical services in remote Scotland, encouraging a revolution in healthcare throughout the Highlands and Islands. The committee’s report led to the foundation of the Highlands and Islands Medical Service, a forerunner of the National Health Service established in 1948.
Atmospheric CO2 monitoring with single-cell NDIR-based analyzers
Authors: Stephens B. B. , Miles N. L. , Richardson S. J. , Watt A. S. , Davis K. J.
Published: December 2011

Abstract. We describe CO2 concentration measurement systems based on relatively inexpensive single-cell non-dispersive infrared CO2 sensors. The systems utilize signal averaging to obtain precision (1-σ in 100 s) of 0.1 parts per million dry air mole fraction (ppm), frequent calibrations and sample drying in order to achieve state-of-the-art compatibility, and can run autonomously for months at a time. Laboratory tests indicate compatibility among four to six systems to be ±0.1 ppm (1-σ), and field measurements of known reference-gases yield median errors of 0.01 to 0.17 ppm with 1-σ variance of ±0.1 to 0.2 ppm. From May to August 2007, a system co-located with a NOAA-ESRL dual-cell NDIR system at the WLEF tall tower in Wisconsin measured daytime-only daily averages of CO2 that differ by 0.26 ± 0.15 ppm (median ± 1 σ), and from August 2005 to April 2011 a system co-located with weekly NOAA-ESRL network flask collection at Niwot Ridge, Colorado measured coincident CO2 concentrations that differed by −0.06 ± 0.30 ppm (n = 585). Data from these systems are now supporting a wide range of analyses and this approach may be applicable in future studies where accuracy and initial cost of the sensors are priorities.
Nitrous oxide emissions at the landscape scale: spatial and temporal variability
Authors: Schelde K. , Cellier P. , Bertolini T. , Dalgaard T. , Weidinger T. , Theobald M. R. , Olesen J. E.
Published: December 2011

Abstract. Nitrous oxide (N2O) emissions from agricultural land are variable at the landscape scale due to variability in land use, management, soil type, and topography. A field experiment was carried out in a typical mixed farming landscape in Denmark, to investigate the main drivers of variations in N2O emissions, measured using static chambers. Measurements were done over a period of 20 months, and sampling was intensified during two weeks in spring 2009 when chambers were installed at ten locations or fields to cover different crops and topography and slurry was applied to three of the fields. N2O emissions during the spring 2009 period were relatively low, with maximum values below 20 ng N m−2 s−1. This applied to all land use types including winter grain crops, grassland, meadow, and wetland. Slurry application to wheat fields resulted in short-lived two-fold increases in emissions. The moderate N2O fluxes and their moderate response to slurry application were attributed to dry soil moisture conditions due to the absence of rain during the four previous weeks. Measured cumulated annual emissions from two arable fields that were both fertilized with mineral fertilizer and manure were large (17 kg N2O-N ha−1 yr−1 and 5.5 kg N2O-N ha−1 yr−1, respectively) during the previous year when soil water conditions were favourable for N2O production during the first month following fertilizer application, confirming the importance of the climatic regime on N2O fluxes.
Flavonoid natural sources and their importance in the human diet
Authors: Danihelová Martina , Šturdí­k Ernest
Published: December 2011

Flavonoids as natural bioactive compounds are present in almost every sort of fruits, vegetables and from them derived products. Flavonols may be found mainly in fruits and vegetables, while flavones are abundant in herbs and spices. Rich natural sources of flavanols are tea, cocoa, grape seeds or apple skin. Flavanones are primarily found in a variety of citrus fruits and anthocyanidins in many coloured berries. Soy is rich in isoflavonoids. Average daily intake of flavonoids is approximately in the range of 150 to 300 mg. It strongly depends on individual, country and culture usages. In west countries main dietary sources of flavonoids consist of tea, wine and fruits, while in east countries there is consumed mainly soy with high isoflavonoid content. Many studies have shown, that intake of fruits and vegetables with high flavonoid content is associated with lowered risk of incidence of some diseases such as cardiovascular or cancer. These findings are attributed to experimentally confirmed biological effects of flavonoids - antioxidant, anti-inflammatory, anti-allergic, anticancer or cardioprotective. The final effect is however depending on their bioavailability, which is in the case of flavonoids not high, because in the nature dominating flavonoid glycosides can poorly penetrate through lipophilic cell membranes. Final effective molecules are flavonoid metabolites, that more or less retain their biological activities.
Natural surfactants and their use in food industry
Authors: Tmáková Lenka , Sekretár Stanislav , Schmidt Štefan , Hlásniková Jarmila , Vrbiková Lenka , Kreps František
Published: December 2011

Microorganisms produce wide range of surfactants, generally called biosurfactants. These compounds are mainly divided according to their molecular weight, physico - chemical properties and mode of action. Saponins, plant surfactants, have properties of  soap and they are high foaming and therefore are used in cosmetic (shampoos, liquid soaps et cetera) and food industry (sweeteners, food additives into the effervescents et cetera). Most of them are spread in plants of agriculture importance and some of them are basic segments in human food. They often occur in plants (in more then 100 species). Saponins can be find in vegetables as a soya, a bean, a lentil, a spinach, a tomato, a potato, a garlic, a onion. Today biosurfactants are mainly used in bioremediation but they can be utilized in many sectors of food industry. We have paid attention to some microbial and plant surfactants and their prospects of exploitation in this industry.
The Role of Particle Geometry and Mechanics in the Biological Domain
Authors: Best James P. , Yan Yan , Caruso Frank
Published: December 2011

Nanostructured particulate materials are expected to revolutionize diagnostics and the delivery of therapeutics for healthcare. To date, chemistry‐derived solutions have been the major focus in the design of materials to control interactions with biological systems. Only recently has control over a new set of physical parameters, including size, shape, and rigidity, been explored to optimize the biological response and the in vivo performance of nanoengineered delivery vectors. This Review highlights the methods used to manipulate the physical properties of particles and the relevance of these physical properties to cellular and circulatory interactions. Finally, the importance of future work to synergistically tailor both physical and chemical properties of particulate materials is discussed, with the aim of improving control over particle interactions in the biological domain.
Occupational hazards of endoscopic surgery
Authors: Little Rachel M. , Deal Allison M. , Zanation Adam M. , McKinney Kibwei , Senior Brent A. , Ebert Charles S.
Published: December 2011

Background:

Minimally invasive surgery has taken its toll on the physical well‐being of surgeons. There have been many physical consequences for surgeons. However, few have been investigated, specifically for otolaryngologists performing endoscopic endonasal surgery (EES). The purpose of this study is to define the prevalence, quality, and severity of physical symptoms that otolaryngologists experience as they relate to the surgeons' use of ergonomically designed endoscopic instruments in endonasal surgery.

Methods:

A 25‐question survey was administered between September 2010 and March 2011 to practicing otolaryngologists. The questions addressed demographics, physical symptoms, ergonomics, and operating room environment. Data were analyzed using Fisher's exact, Wilcoxon rank sum, and Jonckheere‐Terpstra statistics.

Results:

Sixty‐two surgeons responded with a median age of 36 years. Responders performed a median of 150 EESs per year and 37% had completed an endoscopic fellowship. The majority (77%) of responders had experienced physical discomfort or symptoms that they attributed to EES. Thirteen percent (13%) of those who had experienced symptoms felt that their symptoms were persistent. Only 23% of those experiencing symptoms had sought medical care. No significant associations were seen between surgeon age, number of cases, standing, or having adjustable video display with experiencing discomfort (all p > 0.49). Interestingly, fewer surgeons completing an endoscopic fellowship experienced discomfort (70% vs 82%, p = 0.35).

Conclusion:

Our data showed that 77% of physicians who regularly perform EES suffer physical discomfort or symptoms attributable to EES. As expanded endonasal procedures become more prevalent, additional data and ergonomic analysis are necessary to reverse this trend and reduce possible long‐term damage for surgeons. © 2011 ARS‐AAOA, LLC.
Paranasal sinus and skull base fibro‐osseous lesions: when is biopsy indicated for diagnosis?
Authors: Efune Guy , Perez Carlos L. , Tong Liyue , Rihani Jordan , Batra Pete S.
Published: December 2011

Background:

Paranasal sinus fibro‐osseous (FO) lesions represent a heterogeneous group, often sharing overlapping radiographic and pathologic features posing a dilemma in accurate diagnosis. The objective of this study was to correlate preoperative radiologic and postoperative histologic diagnosis to help guide a diagnostic algorithm.

Methods:

Retrospective analysis of 60 FO lesions between 1994 and 2010.

Results:

The mean age was 42.3 years with average follow‐up of 12.5 months. The preliminary radiologic diagnosis was osteoma in 22 (36.7%), fibrous dysplasia (FD) in 9 (15%), ossifying fibroma (OF) vs FD in 5 (8.3%), and OF in 3 (5%) cases. The diagnosis was indeterminate in 21 (35%) cases. Management consisted of excision in 29 (48.3%), observation in 17 (28.3%), and biopsy in 14 (23.3%) patients. For patients undergoing resection or biopsy, positive predictive value of preoperative radiology was 100% (10/10) for osteoma, 85.7% (6/7) for FD, and 33.3% (1/3) for OF cases. For the indeterminate lesions, most common pathologic diagnoses for 21 patients included osteoma in 4 (17.4%), arrested pneumatization in 3 (14.3%), OF in 3 (14.3%), and FD in 2 (9.5%). For FD vs OF cases, 3 underwent surgery, revealing osteoma, FD, and OF in 1 patient each.

Conclusion:

In this series, radiologic‐histopathologic correlation was high for osteoma and FD and low for OF and OF vs FD. This data suggests that patients with classic radiologic characteristics of osteoma and FD may be observed, unless resection is warranted based on clinical symptomatology. Preoperative diagnosis of OF, OF vs FD, or indeterminate lesions may warrant a biopsy to establish firm diagnosis to guide definitive management, especially if preoperative computed tomography (CT) imaging is concerning for an aggressive FO neoplasm. © 2011 ARS‐AAOA, LLC.
Targeted endoscopic salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma
Authors: Ho Allen S. , Kaplan Michael J. , Fee Willard E. , Yao Mike , Sunwoo John B. , Hwang Peter H.
Published: December 2011

Background:

Despite modern radiotherapy and open surgical techniques, treatment of recurrent nasopharyngeal carcinoma (NPC) remains challenging, with substantial morbidity involved. Targeted endoscopic nasopharyngectomy was evaluated as a viable oncologic alternative to open nasopharyngectomy or radiation for recurrent NPC.

Methods:

Thirteen patients who underwent endoscopic nasopharyngectomy for recurrent NPC between August 2005 and August 2010 were retrospectively reviewed. Average age at surgery was 55.7 years, with mean follow‐up period 24.2 months. Two‐year disease‐free survival, 2‐year overall survival, margin status, and complication rate were measured.

Results:

Including resections for subsequent recurrences, 19 endoscopic procedures were performed with curative intent. Mean operating room (OR) time was 278 minutes, mean estimated blood loss was 197 mL, and mean length of hospitalization was 1.0 days. Negative margins were obtained in 78.9% of procedures: positive margins involved the parapharyngeal space, oropharynx, fossa of Rosenmuller, and infratemporal fossa. Stereotactic radiation was given postoperatively for localized positive margins. Four patients required repeat endoscopic nasopharyngectomy for re‐recurrence, despite having their margins cleared or controlled with adjuvant treatment. Two‐year local disease‐free and overall survival rates were 69.2% and 100.0%, respectively. The overall minor complication rate was 52.6%, with no major complications.

Conclusion:

Targeted endoscopic nasopharyngectomy is beneficial in locally recurrent NPC, with favorable morbidity and complication rates. Endoscopic surveillance and serial imaging together facilitate the early identification of re‐recurrences, which often may be treated with additional directed resection. Postoperative stereotactic radiation may serve as an appropriate adjunct modality for disease control at positive margins. © 2011 ARS‐AAOA, LLC.
Chiral separation of D,L‐tyrosine through nitrocellulose membrane
Authors: Jiang Yun‐Dong , Zhang Jun‐Hui , Xie Sheng‐Ming , Lv Yin‐Chun , Zhang Mei , Ma Chao , Yuan Li‐Ming
Published: December 2011

Enantioselective membrane was prepared using nitrocellulose as membrane material. The flux and permselective properties of membrane using water solution of D,L‐tyrosine as feed solution were studied. The top surface and cross‐section morphology of the resulting membrane were examined by scanning electron microscopy. The optical resolution of over 85% enantiomeric excess was achieved when the enantioselective membrane was prepared with 25 wt % nitrocellulose and 15 wt % N,N‐dimethylformamide in the casting solution of methanol, 10°C temperature of water bath for the gelation of the membrane, and the operating pressure and the feed concentration of the D,L‐tyrosine were 6 kgf/cm2 and 0.25 mg/mL, respectively. Since the nitrocellulose contains a large amount of chirality active carbons on the backbone structure and is possible to form helical structure, it is considered to be the reason for the enantioselectivity of the membrane. This is the first report that nitrocellulose can be used as a membrane material. This work indicates that the large‐scale purification of chiral molecules from racemic mixtures will be realized by the enantioselective membrane technique in the near future and that the enantioselective nitrocellulose membrane could soon become very attractive for industrial uses. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Modification and characterization of poly (ethylene terephthalate)‐grafted‐acrylic acid/acryl amide fiber for removal of lead from human plasma and environmental samples
Authors: Ahmad Panahi Homayon , Abdouss Majid , Ghiabi Frozan , Moniri Elham , Mousavi Shoushtari Ahmad
Published: December 2011

A new fibrous adsorbent was prepared by grafting acrylic acid/acryl amide (AA/AAm) comonomers onto poly (ethylene terephthalate) (PET) fibers. The resulting sorbent has been characterized by Fourier transform infrared (FT‐IR), elemental analysis, thermogravimetric analysis (TGA), FT‐Raman, and scanning electron microscopy (SEM) and studied for the preconcentration and determination of trace Pb (II) ion from human biological fluid and environmental water samples. The optimum pH value for sorption of the metal ion was 8. The sorption capacity of functionalized resin is 44.1 mg g−1. The chelating sorbent can be reused for 20 cycles of sorption–desorption without any significant change in sorption capacity. A recovery of 100.2% was obtained for the metal ion with 0.5M nitric acid as eluting agent. Effect of grafting yield, shaking time, shape of sorbent, and pH of the medium on adsorption of the metal ion were investigated. Scatchard analysis revealed that the homogeneous binding sites were formed in the polymers. The equilibrium adsorption data of Pb (II) on modified fiber were analyzed by Langmuir, Freundlich, Temkin, and Redlich‐Peterson models. Based on equilibrium adsorption data, the Langmuir, Freundlich, and Temkin constants were determined as 0.236, 10.544, and 9.497 at pH 8 and 20°C, respectively. The method was applied for lead ions determination from human plasma and sea water sample. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Increased recycling of polyamines is associated with global DNA hypomethylation in rheumatoid arthritis synovial fibroblasts
Authors: Karouzakis Emmanuel , Gay Renate E. , Gay Steffen , Neidhart Michel
Published: December 2011

Objective

Global DNA hypomethylation in rheumatoid arthritis synovial fibroblasts (RASFs) contributes to their intrinsic activation. The aim of this study was to investigate whether increased polyamine metabolism is associated with a decreased level of S‐adenosyl methionine (SAM), causing global DNA hypomethylation.

Methods

Synovial fibroblasts were isolated from synovial tissue obtained from 12 patients with RA and from 6 patients with osteoarthritis (OA). The cells were stained for S‐adenosyl methionine decarboxylase (AMD), spermidine/spermine N1‐acetyltransferase (SSAT1), polyamine‐modulated factor 1–binding protein 1 (PMFBP1), solute carrier family 3 member 2 (SLC3A2), DNA methyltransferase 1 (DNMT‐1), α9 integrin, and β1 integrin and analyzed by flow cytometry. Nuclear 5‐methylcytosine (5‐MeC) was measured by flow cytometry, the expression of diacetylspermine (DASp) in cell culture supernatants and cell extracts was determined by enzyme‐linked immunosorbent assay, and SAM expression in cell extracts was measured by fluorometry.

Results

The expression of SSAT1, AMD, and PMFBP1 was significantly increased in RASFs compared with OASFs. The expression of DASp in cell culture supernatants and the expression of SLC3A2 were significantly elevated in RASFs. The levels of SAM in cell culture extracts, as well as the levels of DNMT‐1 protein and 5‐MeC, were significantly reduced in RASFs. Parameters of polyamine metabolism were negatively correlated with the expression of SAM, DNMT‐1, and 5‐MeC.

Conclusion

These data clearly show that intrinsic elevations of PMFBP1 and SSAT1 enhance the catabolism and recycling of polyamines in RASFs and suggest that high consumption of SAM via this pathway is an important factor contributing to global DNA hypomethylation in these cells.
Interactions of surfactants with a water treatment protein from Moringa oleifera seeds in solution studied by zeta‐potential and light scattering measurements
Authors: Kwaambwa Habauka M. , Rennie Adrian R.
Published: December 2011

Protein extracted from Moringa oleifera (MO) seeds has been advocated as a cheap and environmental friendly alternative to ionic flocculants for water purification. However, the nature and mechanism of its interaction with particles in water, as well as with dissolved surface‐active molecules, are not well understood. In this article, we report studies of the protein and its interaction with four surfactants using dynamic light scattering (DLS), zeta‐potential and turbidity measurements. Zeta‐potential measurements identified points of charge reversal and the turbidity and DLS measurements were used to characterize the microstructure and size of protein‐surfactant complexes. From the points of charge reversal, it was estimated that 7 anions are required to neutralize the positive charges of each protein molecule at pH 7. For protein mixtures with sodium dodecyl sulfate and dodecyl di‐acid sodium salt, the peak in turbidity corresponds to concentrations with a large change in zeta‐potential. No turbidity was observed for protein mixtures with either the nonionic surfactant Triton X‐100 or the zwitterionic surfactant N‐dodecyl‐N,N‐dimethyl‐3‐ammonio‐1‐propanesulfonate. Changes of pH in the range 4–10 have little effect on the zeta‐potential, turbidity, and the hydrodynamic radius reflecting the high isoelectric point of the protein. Addition of small amounts of salt has little effect on the size of protein in solution. These results are discussed in the context of the use of the MO protein in water treatment. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 209–218, 2012.
Novel structures of self‐associating stapled peptides
Authors: Bhattacharya Shibani , Zhang Hongtao , Cowburn David , Debnath Asim K.
Published: December 2011

Hydrocarbon stapling of peptides is a powerful technique to transform linear peptides into cell‐permeable helical structures that can bind to specific biological targets. In this study, we have used high resolution solution NMR techniques complemented by dynamic light scattering to characterize extensively a family of hydrocarbon stapled peptides with known inhibitory activity against HIV‐1 capsid assembly to evaluate the various factors that modulate activity. The helical peptides share a common binding motif but differ in charge, the length, and position of the staple. An important outcome of the study was to show the peptides, share a propensity to self‐associate into organized polymeric structures mediated predominantly by hydrophobic interactions between the olefinic chain and the aromatic side‐chains from the peptide. We have also investigated in detail the structural significance of the length and position of the staple, and of olefinic bond isomerization in stabilizing the helical conformation of the peptides as potential factors driving polymerization. This study presents the numerous challenges of designing biologically active stapled peptides and the conclusions have broad implications for optimizing a promising new class of compounds in drug discovery. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 253–264, 2012.
Transgene delivery using poly(amino ether)‐gold nanorod assemblies
Authors: Ramos James , Rege Kaushal
Published: December 2011

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment, and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)‐functionalized gold nanorods (PAE‐GNRs) using a layer‐by‐layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE‐GNR assemblies. PAE‐GNR assemblies demonstrate long‐term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub‐toxic concentrations of PAE‐GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE‐GNRs generated using 1,4C‐1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k‐GNRs), a current standard for polymer‐mediated gene delivery. The roles of polyelectrolyte chemistry and zeta‐potential in determining transgene expression efficacies of PAE‐GNR assemblies were investigated. Our results indicate that stable and effective PAE‐GNR assemblies are a promising engineered platform for transgene delivery. PAE‐GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform. Biotechnol. Bioeng. 2012; 109:1336–1346. © 2011 Wiley Periodicals, Inc.
Target concentration dependence of DNA melting temperature on oligonucleotide microarrays
Authors: Ozel Ayse Bilge , Srivannavit Onnop , Rouillard Jean‐Marie , Gulari Erdogan
Published: December 2011

The design of microarrays is currently based on studies focusing on DNA hybridization reaction in bulk solution. However, the presence of a surface to which the probe strand is attached can make the solution‐based approximations invalid, resulting in sub‐optimum hybridization conditions. To determine the effect of surfaces on DNA duplex formation, the authors studied the dependence of DNA melting temperature (Tm) on target concentration. An automated system was developed to capture the melting profiles of a 25‐mer perfect‐match probe–target pair initially hybridized at 23°C. Target concentrations ranged from 0.0165 to 15 nM with different probe amounts (0.03–0.82 pmol on a surface area of 1018 Å2), a constant probe density (5 × 1012 molecules/cm2) and spacer length (15 dT). The authors found that Tm for duplexes anchored to a surface is lower than in‐solution, and this difference increases with increasing target concentration. In a representative set, a target concentration increase from 0.5 to 15 nM with 0.82 pmol of probe on the surface resulted in a Tm decrease of 6°C when compared with a 4°C increase in solution. At very low target concentrations, a multi‐melting process was observed in low temperature domains of the curves. This was attributed to the presence of truncated or mismatch probes. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
Rapid Synthesis of New DNMT Inhibitors Derivatives of Procainamide
Authors: Halby Ludovic , Champion Christine , Sénamaud‐Beaufort Catherine , Ajjan Sophie , Drujon Thierry , Rajavelu Arumugam , Ceccaldi Alexandre , Jurkowska Renata , Lequin Olivier , Nelson William G. , Guy Alain , Jeltsch Albert , Guianvarc'h Dominique , Ferroud Clotilde , Arimondo Paola B.
Published: December 2011

DNA methyltransferases (DNMTs) are responsible for DNA methylation, an epigenetic modification involved in gene regulation. Families of conjugates of procainamide, an inhibitor of DNMT1, were conceived and produced by rapid synthetic pathways. Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on two tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory potency. The inhibition potency of procainamide conjugated to phthalimide through alkyl linkers depended on the length of the linker; the dodecane linker was the best.
Luminescent Organoplatinum(II) Complexes with Functionalized Cyclometalated C^N^C Ligands: Structures, Photophysical Properties, and Material Applications
Authors: Kui Steven C. F. , Hung Faan‐Fung , Lai Shiu‐Lun , Yuen Mai‐Yan , Kwok Chi‐Chung , Low Kam‐Hung , Chui Stephen Sin‐Yin , Che Chi‐Ming
Published: December 2011

A series of [(R′‐C^N^C‐R′′)Pt(L)] complexes with doubly deprotonated cyclometalated R′‐C^N^C‐R′′ ligands (R′‐C^N^C‐R′′=2,6‐diphenylpyridine derivatives) functionalized with carbazole, fluorene, or thiophene unit(s) have been synthesized and their photophysical properties studied. The X‐ray crystal structures reveal extensive intermolecular π⋅⋅⋅π and CH⋅⋅⋅π interactions between the cyclometalated C^N^C ligands. Compared to previously reported cyclometalated platinum(II) complexes [(C^N^C)Pt(L)], which are non‐emissive in solution at room temperature, the carbazole‐, fluorene‐ and thiophene‐functionalized [(R′‐C^N^C‐R′′)Pt(L)] (L=DMSO 1–9, CNAr, 1 a–9 a) complexes are emissive in solution at room temperature with λmax at 564–619 nm and Φ=0.02–0.26. The emissions of the [(R′‐C^N^C‐R′′)Pt(L)] complexes are attributed to electronic excited states with mixed 3MLCT and 3IL character. The carbazole/fluorene/thiophene unit(s) allow the tuning of the electronic properties of the [(R′‐C^N^C‐R′′)Pt] moiety, with the emission maxima in a range of 564–619 nm. These are the first examples of organoplatinum(II) complexes bearing doubly deprotonated cyclometalated C^N^C ligands that are emissive in solution at room temperature. In non‐degassed DMSO, the emission intensities of 6 a–9 a are enhanced upon exposure to ambient light. This phenomenon is caused by reacting photogenerated 1O2 with a DMSO molecule to form dimethyl sulfone, leading to the removal of dissolved oxygen in solution. Self‐assembled nanowires and nanorods are obtained from precipitation of 3 a in THF/H2O and 8 a in DMSO/Et2O, respectively. The [(R′‐C^N^C‐R′′)Pt(L)] complexes are soluble in common organic solvents with a high thermal stability (>300 °C), rendering them as phosphorescent dopants for organic light‐emitting diode (OLEDs) applications. Red OLEDs with CIE coordinates of (0.65±0.01, 0.35±0.01) were fabricated from 7 a or 8 a. A maximum external efficiency (ηExt) of 12.6 % was obtained for the device using 8 a as emitter.
Activation of Diboron Reagents with Brønsted Bases and Alcohols: An Experimental and Theoretical Perspective of the Organocatalytic Boron Conjugate Addition Reaction
Authors: Pubill‐Ulldemolins Cristina , Bonet Amadeu , Bo Carles , Gulyás Henrik , Fernández Elena
Published: December 2011

Bases play an important role in organocatalytic boron conjugate addition reactions. The sole use of MeOH and a base can efficiently transform acyclic and cyclic activated olefins into the corresponding β‐borated products in the presence of diboron reagents. Inorganic and organic bases deprotonate MeOH in the presence of diboron reagents. It is concluded, on the basis of theoretical calculations, NMR spectroscopic data, and ESI‐MS experiments, that the methoxide anion forms a Lewis acid–base adduct with the diboron reagent. The sp2 B atom of the methoxide–diboron adduct gains a strongly nucleophilic character, and attacks the electron‐deficient olefin. The methanol protonates the intermediate, generating the product and another methoxide anion. This appears to be the simplest method to activate diboron reagents and make them suitable for incorporation into target organic molecules.
Computational and Experimental Evidence of Through‐Space NMR Spectroscopic J Coupling of Hydrogen Atoms
Authors: Dračínský Martin , Jansa Petr , Bouř Petr
Published: December 2011

J coupling in NMR spectroscopy is conventionally associated with covalent bonds. A noncovalent contribution often called through‐space coupling (TSC) has been observed for heavy atoms. In this study, the TSC was detected and analyzed for the more common 1H1H coupling as well. In synthesized model molecules the hydrogen positions could be well controlled. For several coupling constants the through‐space mechanism was even found to be the predominant factor. The nature and magnitude of the phenomenon were also analyzed by density functional computations. Calculated carbon‐ and hydrogen‐coupling maps and perturbed electronic densities suggest that the aromatic system strongly participates in the noncovalent contribution. Unlike covalent coupling, which is usually governed by the Fermi contact, TSC is dominated by the diamagnetic term comprising interactions of nuclei with the electron orbital angular momentum. The computations further revealed a strong distance and conformational dependence of TSC. This suggests that the through‐space coupling can be explored in molecular structural studies in the same way as the covalent one.
4‐Nitramino‐3,5‐dinitropyrazole‐Based Energetic Salts
Authors: Zhang Yanqiang , Parrish Damon A. , Shreeve Jean'ne M.
Published: December 2011

4‐Nitramino‐3,5‐dinitropyrazole was prepared and stabilized through the formation of its ammonium salt. With selected cations, 14 nitrogen‐rich energetic salts were synthesized in high yield by metathesis reactions. These salts were fully characterized by 1H, 13C NMR, and IR spectroscopy and elemental analysis. Additionally, the structures of the ammonium, 3,4,5‐triaminotriazolium, and biguanidinium salts were confirmed by single‐crystal X‐ray diffraction. Based on experimental and calculated values, the 4‐nitramino‐3,5‐dinitropyrazolate salts show properties, such as decomposition temperatures (115–229 °C), detonation pressures (23.27–37.42 GPa) and velocities (7713–9013 ms−1), and impact sensitivities (5–40 J) that place them with energetics such as RDX and TATB.
Hydrodynamics of a rectangular liquid JET in an immiscible liquid–liquid system
Authors: Bhatelia Tejas J. , Parmar Harisinh B. , Phan Chi , Pareek Vishnu K. , Tadé Moses O. , Evans Geoffrey M.
Published: December 2011

Volume of fluid and continuum surface force methodologies were applied to two‐ and three‐dimensionally model the motion of a liquid jet injected vertically downward from a rectangular nozzle into another immiscible liquid. Grid independent solutions were obtained for a 10 mm2 nozzle with aspect ratios in the range 1–10. It was found that unlike the 3D simulation, the 2D CFD model was not able to predict the necking and breakup features observed in the experimental system. The 3D model showed that upon exiting the rectangular nozzle the liquid jet underwent a transition before becoming circular in cross‐section and eventually reaching an equilibrium diameter prior to breakup into droplets. For a given nozzle geometry it was found that equilibrium jet diameter increased with increasing liquid volumetric flowrate, with good agreement between CFD simulations and experimental observations. The 3D model was applied to rectangular nozzles with different aspect ratios and it was found that for a given liquid flowrate there was an optimum aspect ratio for generating minimum‐sized droplets, which was approximately 30% less than for a circular nozzle with the same cross‐sectional area. © 2011 Canadian Society for Chemical Engineering
CO2 exchange along a hydrologic gradient in the Kenai Lowlands, AK: feedback implications of wetland drying and vegetation succession
Authors: Ives Susan L. , Sullivan Patrick F. , Dial Roman , Berg Edward E. , Welker Jeffrey M.
Published: December 2011

Boreal wetlands hold vast stocks of soil carbon (C), which may be vulnerable to changes in climate. In southcentral Alaska, wetlands of the Kenai Lowlands have experienced a warming and drying trend that has led to woody vegetation encroachment into herbaceous wetlands. We examined whether predicted higher rates of gross ecosystem photosynthesis (GEP) would be offset by higher rates of ecosystem respiration (ER) in woody wetland communities. We measured net ecosystem exchange (NEE) in four communities along a hydrologic and vegetation gradient during (1) a warm and dry growing season, (2) a more typical cool and wet growing season and (3) the intervening winter. We fit simple GEP and ER models to our data and estimated annual NEE for each community using hourly measurements of photosynthetically active radiation and air temperature. We found that woody communities exhibited greater GEP than herbaceous communities under cool and moist conditions, but more similar GEP under warm and dry conditions. Woody communities also showed greater ER than herbaceous communities during all seasons, outpacing GEP during the warm and dry growing season. On an annual basis, we estimated that herbaceous communities were either net sinks or approximately CO2 neutral, ranging from −132·8 to 4·7 g CO2–C m−2 y−1. In contrast, woody communities were sources of CO2 to the atmosphere, ranging from 78·8 to 181·7 g CO2–C m−2 y−1. Our results suggest that the initial encroachment of woody vegetation into herbaceous wetlands will lead to a substantial loss of C, particularly if conditions continue to become warmer and drier. Copyright © 2011 John Wiley & Sons, Ltd.
Direct visualization of electrophoretic mobility shift assays using nanoparticle–aptamer conjugates
Authors: Wang Min S. , Reed Scott M.
Published: December 2011

Here, we demonstrate that aptamers tethered to gold nanoparticles enable direct visualization of protein–oligonucleotide interactions during gel electrophoresis. This technique is used to confirm that an aptamer previously identified as binding to C‐reactive protein (CRP) only binds to the monomeric form of CRP. While native, pentameric CRP (pCRP) is used in clinical assays to predict cardiovascular disease (CVD) risk, it is the monomeric isoform that is more strongly associated with pro‐inflammatory and pro‐atherogenic effects. To visualize this selectivity, the CRP–aptamer was conjugated to streptavidin‐coated gold nanoparticles and the mobility of the free oligonucleotide–nanoparticle conjugate (ON‐NP) and the protein/ON‐NP complex bands were visualized and recorded during electrophoresis using a simple digital camera. At a concentration of 6 μg/mL, monomeric CRP showed a significant decrease in the observed ON‐NP mobility, whereas no change in mobility was observed with pCRP up to 18 μg/mL. Advantages of this nanoparticle‐based electrophoretic mobility shift assay (NP‐EMSA) over the traditional EMSA include real‐time detection of protein–oligonucleotide interactions, the avoidance of harmful radioisotopes, and elimination of the need for expensive gel imagers. The availability of both the NP‐EMSA technique and an mCRP‐specific probe will allow for improved clinical diagnostic to more accurately predict future CVD risk.
Internal evaluation, historically speaking
Authors: Mathison Sandra
Published: December 2011

The author analyzes the growth and nature of internal evaluation from the 1960s to the present and suggests that internal evaluation has been on the increase because of its perceived importance. Although the 1960s were characterized by a rich intellectual development of evaluation theory and practice, the fiscal conservatism of the 1980s ushered in evaluation practice focused more specifically on cost effectiveness. During that time, internal evaluation began to increase. In the 1990s this trend continued and was intensified by the reinvention of government known as the New Public Management. The author argues that in this results‐oriented neoliberal context, evaluation is maintained as an internal function, but focuses primarily on descriptive accounts of performance. The chapter concludes with some speculation about the nature of future internal evaluation. © Wiley Periodicals, Inc., and the American Evaluation Association.
Evaluation survivor: How to outwit, outplay, and outlast as an internal government evaluator
Authors: Kniker Ted
Published: December 2011

This chapter describes the author's experience and insights as the chief of evaluation for public diplomacy at the U.S. Department of State, and as a consultant assisting federal agencies in a multitude of evaluation activities relating what helps and hinders internal evaluation functions. The article discusses the challenges faced by the internal evaluators, how they overcame these challenges, and how they compare to trends observed by the author in other federal evaluation offices. Ideas are provided for how to better incorporate evaluation functions into organizational management. © Wiley Periodicals, Inc., and the American Evaluation Association.
Internal evaluation in American public school districts: The importance of externally driven accountability mandates
Authors: King Jean A. , Rohmer‐Hirt Johnna A.
Published: December 2011

From the 1980s to the present, educational accountability in the United States has grown dramatically. Such accountability in U.S. school districts, although driven primarily by external demands, has internal manifestations as well. The chapter traces the historical development of internal evaluation in American school districts, then highlights four current forms of internal evaluation (standardized testing programs, evaluations of externally funded programs, support for school improvement planning, and evaluation capacity building), along with a brief description of the decade‐long development of internal evaluation in one school district. The unique features of internal evaluation in educational settings are highlighted, and the chapter concludes with implications of current practice for the continuing development of internal educational evaluation. © Wiley Periodicals, Inc., and the American Evaluation Association.
Issues in internal evaluation: Implications for practice, training, and research
Authors: Volkov Boris B. , Baron Michelle E.
Published: December 2011

This chapter highlights themes running throughout the preceding chapters and illustrates important issues in improving the design, implementation, and use of internal evaluation. The authors contemplate where internal evaluation might go in the future by suggesting new directions for how internal evaluation is conceptualized and practiced to realize its potential for enhancing the organizational and program growth and competitive advantage. © Wiley Periodicals, Inc., and the American Evaluation Association.
The Omo‐Turkana Basin Fossil Hominins and Their Contribution to Our Understanding of Human Evolution in Africa
Authors: Wood Bernard , Leakey Meave
Published: December 2011

The Omo‐Turkana Basin, including the hominin fossil sites around Lake Turkana and the sites along the lower reaches of the Omo River, has made and continues to make an important contribution to improving our murky understanding of human evolution. This review highlights the various ways the Omo‐Turkana Basin fossil record has contributed to, and continues to challenge, interpretations of human evolution. Despite many diagrams that look suspiciously like comprehensive hypotheses about human evolutionary history, any sensible paleoanthropologist knows that the early hominin fossil record is too meager to do anything other than offer very provisional statements about hominin taxonomy and phylogeny. If history tells us anything, it is that we still have much to learn about the hominin clade. Thus, we summarize the current state of knowledge of the hominin species represented at the Omo‐Turkana Basin sites. We then focus on three specific topics for which the fossil evidence is especially relevant: the origin and nature of Paranthropus; the origin and nature of early Homo; and the ongoing debate about whether the pattern of human evolution is more consistent with speciation by cladogenesis, with greater taxonomic diversity or with speciation by anagenetic transformation, resulting in less taxonomic diversity and a more linear interpretation of human evolutionary history. © Wiley Periodicals, Inc.
Aberrantly methylated PKP1 in the progression of Barrett's esophagus to esophageal adenocarcinoma
Authors: Kaz Andrew M. , Luo Yanxin , Dzieciatkowski Slavomir , Chak Amitabh , Willis Joseph E. , Upton Melissa P. , Leidner Rom S. , Grady William M.
Published: December 2011

The aberrant DNA methylation of tumor suppressor genes occurs frequently in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) and likely affects the initiation and progression of BE to EAC. In the present study, we discovered PKP1 as a novel methylated gene in EAC and then investigated the role of loss of PKP1, a constituent of the desmosome complex found in stratified epithelial layers, on the behavior of Barrett's esophagus and esophageal adenocarcinoma cells. By using primary esophageal tissue samples we determined that PKP1 was rarely methylated in normal squamous esophagus (5/55; 9.1%) and BE (5/39; 12.8%) and more frequently methylated in Barrett's esophagus with high‐grade dysplasia (HGD) or EAC (20/60; 33.3%; P < 0.05). Furthermore, PKP1 levels were decreased in BE and HGD/EAC cases compared to normal squamous esophagus cases. Knockdown of PKP1 in the BE cell lines CP‐A and CP‐D (both normally express PKP1) resulted in increased cell motility. Thus, PKP1 loss secondary to promoter methylation, as well as other mechanisms, may promote the progression of BE to EAC in a subset of patients via decreased desmosome assembly and increased cell motility. © 2011 Wiley Periodicals, Inc.
Direct evaluation of individual hydrogen bond energy in situ in intra‐ and intermolecular multiple hydrogen bonds system
Authors: Liu Cui , Zhao Dong‐Xia , Yang Zhong‐Zhi
Published: December 2011

The results of evaluating the individual hydrogen bond (H‐bond) strength are expected to be helpful for the rational design of new strategies for molecular recognition or supramolecular assemblies. Unfortunately, there is few obvious and unambiguous means of evaluating the energy of a single H‐bond within a multiple H‐bonds system. We present a local analytic model, ABEEMσπ H‐bond energy (HBE) model based on ab initio calculations (MP2) as benchmark, to directly and rapidly evaluate the individual HBE in situ in inter‐ and intramolecular multiple H‐bonds system. This model describes the HBE as the sum of electrostatic and van der Waals (vdW) interactions which all depend upon the geometry and environment, and the ambient environment of H‐bond in the model is accounted fairly. Thus, it can fairly consider the cooperative effect and secondary effect. The application range of ABEEMσπ HBE model is rather wide. This work has discussed the individual H‐bond in DNA base pair and protein peptide dimers. The results indicate that the interactions among donor H atom, acceptor atom as well as those atoms connected to them with 1,2 or 1,3 relationships are all important for evaluating the HBE, although the interaction between the donor H atom and the acceptor atom is large. Furthermore, our model quantitatively indicates the polarization ability of N, O, and S in a new style, and gives the percentage of the polarization effect in HBE, which can not be given by fixed partial charge force field. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012