bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of a Donor–Acceptor Diblock Copolymer via Two Mechanistically Distinct, Sequential Polymerizations Using a Single Catalyst
Authors: Ono Robert J. , Todd Alexander D. , Hu Zhongjian , Vanden Bout David A. , Bielawski Christopher W.
Published: July 2013

Treatment of a Ni‐terminated poly(3‐hexylthiophene) (P3HT), generated in situ from 5‐chloromagnesio‐2‐bromo‐3‐hexylthiophene and Ni(1,3‐bis(diphenylphosphino)propane)Cl2, with a perylene diimide‐functionalized arylisocyanide monomer effects a chain‐extension polymerization to afford a donor–acceptor diblock copolymer using a single catalyst and in a single reaction vessel. The two mechanistically distinct polymerizations proceed in a controlled, chain growth fashion, allowing the molecular weight of both the P3HT and poly(isocyanide) blocks to be tuned by adjusting the initial monomer‐to‐catalyst ratios. The resulting materials are found to self‐assemble into crystalline, lamellar stacks of donor and acceptor components in the solid state, and also exhibit fluorescence quenching in thin films, properties which poise these materials for use in organic photovoltaic applications.

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Acyclic Diene Metathesis Polymerization and Heck Polymer–Polymer Conjugation for the Synthesis of Star‐shaped Block Copolymers
Authors: de Espinosa Lucas Montero , Winkler Matthias , Meier Michael A. R.
Published: July 2013

Three‐ and four‐arm star shaped polymers, as well as diblock copolymers, are synthesized via acyclic diene metathesis (ADMET) polymerization. This is accomplished by using an asymmetric α,ω‐diene containing a terminal double bond and an acrylate, which is polymerized in the presence of multifunctional acrylates as selective and irreversible chain transfer agents using Hoveyda‐Grubbs second generation catalyst. High cross‐metathesis selectivities are achieved at low temperatures enabling good control over molecular weights. Furthermore, additional polyethyleneglycol (PEG) blocks are attached to these polymers via Heck coupling of the acrylate end‐groups of these polymers with aryl iodide functionalized PEG, obtaining three‐ and four‐arm star shaped di‐ and triblock copolymers with molecular weights up to 31 kDa.

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15N NMR spectra and reactivity of 2,4,6‐triazidopyridines, 2,4,6‐triazidopyrimidine and 2,4,6‐triazido‐s‐triazine
Authors: Chapyshev Sergei V. , Ushakov Evgeny N. , Chernyak Alexander V.
Published: July 2013

2,4,6‐Triazido‐s‐triazine, 2,4,6‐triazidopyrimidine and six different 2,4,6‐triazidopyridines were studied by 15N NMR spectroscopy. The assignment of signals in the spectra was performed using the gauge‐independent atomic orbital (GIAO)–Tao‐Perdew‐Staroverov‐Scuseria exchange‐correlation functional (TPSS)h/6‐311+G(d,p) calculations on the M06‐2X/6‐311+G(d,p) optimized molecular geometries. The Truhlar and coworkers' continuum solvation model called SMD was applied to treat solvent effects. With this approach, the root mean square error in estimations of the 15N chemical shifts for the azido groups was just 1.9 ppm. It was shown that the different reactivity of the α‐ and γ‐azido groups in pyridines correlates well with the chemical shifts of the Nα signals of these groups. Of two nonequivalent azido groups of azines, the azido group with the most shielded Nα signal is the most electron‐deficient and reactive toward electron‐rich reagents. By contrast, the azido group of azines with the most deshielded Nα signal is the most reactive toward electron‐poor reagents. Copyright © 2013 John Wiley & Sons, Ltd.
Anti‐Müllerian hormone (AMH), inhibin‐α, growth differentiation factor 9 (GDF9), and bone morphogenic protein‐15 (BMP15) mRNA and protein are influenced by photoperiod‐induced ovarian regression and recrudescence in Siberian hamster ovaries
Authors: Shahed Asha , Young Kelly A.
Published: July 2013

Exposure of Siberian hamsters to short photoperiod (SD) inhibits ovarian function, including folliculogenesis, whereas function is restored with their transfer to long photoperiods (LD). To investigate the mechanism of photo‐stimulated recrudescence, we assessed key folliculogenic factors–anti‐Müllerian hormone (AMH), inhibin‐α, growth differentiation factor‐9 (GDF9), and bone morphogenic protein‐15 (BMP15)–across the estrus cycle and in photo‐regressed and recrudescing ovaries. Adult hamsters were exposed to either LD or SD for 14 weeks, which respectively represent functional and regressed ovaries. Select regressed hamsters were transferred back to LD for 2 (post‐transfer week 2; PTw2) or 8 weeks (PTw8). Ovaries were collected and fixed in formalin for immunohistochemistry or frozen in liquid nitrogen for real‐time PCR. AMH, inhibin‐α, GDF9, and BMP15 mRNA and protein were detected in all stages of the estrus cycle. Fourteen weeks of SD exposure increased (P < 0.05) ovarian AMH, GDF9, and BMP15, but not inhibin‐α mRNA levels as compared to LD. Transfer of regressed hamsters to stimulatory long photoperiod for 8 weeks returned AMH and GDF9 mRNA levels to LD‐treated levels, and further increased mRNA levels for inhibin‐α and BMP15. Immunostaining for AMH, inhibin‐α, GDF9, and BMP15 proteins was most intense in preantral/antral follicles and oocytes. The overall immunostaining extent for AMH and inhibin‐α generally mirrored the mRNA data, though no changes were observed for GDF9 or BMP15 immunostaining. Shifts in mRNA and protein levels across photoperiod conditions suggest possible syncretic roles for these folliculogenic factors in photo‐stimulated recrudescence via potential regulation of follicle recruitment, preservation, and development. Mol. Reprod. Dev. 80: 895–907, 2013. © 2013 Wiley Periodicals, Inc.
Expression dynamics of pluripotency genes in chicken primordial germ cells before and after colonization of the genital ridges
Authors: Naeemipour Mohsen , Dehghani Hesam , Bassami Mohammadreza , Bahrami Ahmadreza
Published: July 2013

Mammalian species utilize an inductive mechanism of germ cell specification, diverting the fate of some of somatic cells toward pluripotency and germ‐cell totipotency. It is not known if avian species utilize a similar mechanism nor if, analogous to mammalian primordial germ cells (PGCs), pluripotency genes are continuously upregulated in migrating and genital ridge‐colonizing avian PGCs. Thus, this study was conducted to quantify and to analyze the expression profile of pluripotency genes at different stages of chicken PGCs development at Hamburger and Hamilton (HH) stage 14, when the majority of PGCs have entered into the bloodstream; at HH stage 18, when PGCs have resided for 8–12 hr in the bloodstream; and at HH stage 28, when the majority of PGCs are found in the genital ridge. The transcription for Oct4, Sox2, and Nanog continuously decreased from HH stage 14 to HH stage 28. In addition, equal amounts of total RNA could be isolated from chicken PGCs at each stage of development, indicating that the observed drop of transcription of pluripotency genes is not a consequence of transcriptional repression in general. Decreased expression for all three proteins was also observed at HH stage 28. Furthermore, in comparison to blood PGCs, those residing in the gonad have lost their full capacity for colony formation. Our results indicate that, in contrast to mammalian PGCs, chicken PGCs continuously downregulate the expression of pluripotency genes and show a progressive loss of pluripotency‐associated features during different stages of germ‐line migration. Mol. Reprod. Dev. 80: 849–861, 2013. © 2013 Wiley Periodicals, Inc.
Open‐cage fullerenes as tailor‐made container for a single water molecule
Authors: Shi Lijun , Gan Liangbing
Published: July 2013

Water is the most important liquid on earth. Clusters of water have been investigated extensively in an effort to understand the bulk property of water. But the behavior of single water molecule without H‐bond has been rarely studied. Open‐cage [60]fullerenes have been shown to trap a single water molecule selectively over molecules with comparable size and act as the smallest “water bottle”. Copyright © 2013 John Wiley & Sons, Ltd.
In situ irregularity identification and scintillation estimation using wavelets and CINDI on C/NOFS
Authors: Stoneback R. A. , Heelis R. A. , Caton R. G. , Su Y.‐J. , Groves K. M.
Published: July 2013

Wavelets are a time‐domain method that is able to extract both time and frequency information from a signal. The Morlet wavelet is used here to characterize the magnitude of ionospheric irregularities using measurements of the total ion density from the Coupled Ion Neutral Dynamics Investigation package onboard the Communications/Navigation Outage Forecasting System spacecraft. The power in ionospheric irregularities at scale sizes less than 128 km is used to generate an irregularity amplitude index. This index is used with a phase screen analysis to form an estimate of scintillation at the satellite location. The temporal information retained in a wavelet analysis also allows for an accurate power spectrum calculation even when used on short segments of data which is useful for real‐time processing of irregularity detection onboard a satellite or for analyzing the long data sets produced by a satellite. To validate the process, a comparison of the in situ scintillation estimate and Scintillation Network and Decision Aid measurements of the S4 index is presented.
Synchronization in heterogeneous networks of discrete‐time introspective right‐invertible agents
Authors: Wang Xu , Saberi Ali , Yang Tao
Published: July 2013

This paper studies output synchronization problem, formation problem, and regulated synchronization problem for a heterogenous network of discrete‐time introspective right‐invertible agents. We first propose a decentralized control scheme to solve the output synchronization problem for a set of communication topologies. Moreover, if the synchronization trajectories are assumed to be bounded, a universal controller can be constructed for all communication topologies, which contain a directed spanning tree. The design can be applied to solve the formation problem with arbitrary formation vectors. In the regulated synchronization problem, we assume only the root receives information from exosystem. We then design a decentralized controller to solve the problem for a set of communication topologies. Copyright © 2013 John Wiley & Sons, Ltd.
Comparative Evaluation of Intestinal Nitric Oxide in Embryonic Zebrafish Exposed to Metal Oxide Nanoparticles
Authors: Özel Rıfat Emrah , Alkasir Ramiz S. J. , Ray Kayla , Wallace Kenneth N. , Andreescu Silvana
Published: July 2013

Nanoparticle (NP) exposure may induce oxidative stress through generation of reactive oxygen and nitrogen species, which can lead to cellular and tissue damage. The digestive system is one of the initial organs affected by NP exposure. Here, it is demonstrated that exposure to metal oxide NPs induces differential changes in zebrafish intestinal NO concentrations. Intestinal NO concentrations are quantified electrochemically with a carbon fiber microelectrode inserted in the intestine of live embryos. Specificity of the electrochemical signals is demonstrated by NO‐specific pharmacological manipulations and the results are correlated with the 4,5‐diaminofluorescein‐diacetate (DAF‐FM‐DA). NPs are demonstrated to either induce or reduce physiological NO levels depending on their redox reactivity, type and dose. NO level is altered following exposure of zebrafish embryos to CuO and CeO2 NPs at various stages and concentrations. CuO NPs increase NO concentration, suggesting an intestinal oxidative damage. In contrast, low CeO2 NP concentration exposure significantly reduces NO levels, suggesting NO scavenging activity. However, high concentration exposure results in increased NO. Alterations in NO concentration suggest changes in intestinal physiology and oxidative stress, which will ultimately correspond to NPs toxicity. This work also demonstrates the use of electrochemistry to monitor in vivo changes of NO within zebrafish organs.
Antibody Conjugated PLGA Nanoparticles for Targeted Delivery of Paclitaxel Palmitate: Efficacy and Biofate in a Lung Cancer Mouse Model
Authors: Karra Nour , Nassar Taher , Ripin Alina Nemirovski , Schwob Ouri , Borlak Jürgen , Benita Simon
Published: July 2013

Aberrant signaling of the epidermal growth factor receptor (EGFR) is common to a variety of human cancers and is also found to be over‐expressed in most cases of non‐small cell lung cancer. For the development of a molecularly targeted therapy, cetuximab‐conjugated nanoparticles (immunonanoparticles, INPs) are designed and loaded with the lipophilic paclitaxel palmitate (pcpl) prodrug. Oleyl cysteineamide (OCA) is synthesized whereby its amphiphilic nature enables interfacial anchoring and thiol surface functionalization of PLGA NPs, facilitating bioconjugation to cetuximab by thioether bonds. It is demonstrated that the in vitro targeting efficiency and improved cellular internalization and cytotoxicity of this targeted delivery system in lung cancer cells over‐expressing EGFR. A quantitative measure of the high binding affinity of INPs to EGFR is demonstrated using surface plasmon resonance. In vivo tolerability and enhanced efficacy of cetuximab pcpl INPs in a metastatic lung cancer model are reported. Its therapeutic efficacy in A549‐luc‐C8 lung tumors is shown using non‐invasive bioluminescent imaging. Intravenous administration of cetuximab pcpl INPs to mice results in significantly higher inhibition of tumor growth and increased survival rates as compared to the non‐targeted drug solution, drug‐loaded nanoparticles or blank INPs. Pharmacokinetics and organ biodistribution of the prodrug and parent drug are evaluated by LC‐MS/MS in lung tumor bearing mice. No enhanced total accumulation of nanoparticles or INPs is found at the tumor tissue. However, persistent pcpl levels with sustained conversion and release of paclitaxel are observed for the encapsulated prodrug possibly suggesting the formation of a drug reservoir. The overall results indicate the potential of this promising targeted platform for the improved treatment of lung cancer and other EGFR positive tumors.
The predator pendulum revisited: Social conflict over wolves and their management in the western United States
Authors: Bruskotter Jeremy T.
Published: July 2013

The reintroduction, recovery, and management of gray wolves (Canis lupus) in the western United States has long been a source of controversy and acrimonious public debate. I discuss 3 factors that perpetuate confusion and conflict over wolves and their management: 1) the role of science and politics in wildlife management, 2) rhetoric and political actions of elected officials and political appointees, and 3) justification of wolf harvest and specific practices employed during hunting and trapping seasons. Wildlife professionals could reduce the controversy surrounding wolves by 1) clearly delineating policy decisions from the scientific input used to inform these decisions; 2) clearly articulating scientific concepts when they are used in agency communications; 3) employing collaborative public‐involvement processes designed to reduce conflicts (e.g., collaborative learning, alternative dispute resolution); and 4) setting hunting and trapping regulations with public input concerning the timing of seasons, and methods and locations of take. Longitudinal studies designed to assess how human attitudes and behaviors change in response to changing policies would be particularly valuable for understanding and potentially reducing conflicts over wolves (and other wildlife) in the future. Such data could be collected through collaborations between social scientists, who possess expertise in relevant research methods and theoretical knowledge, and state Cooperative Fish and Wildlife Research units, who possess experience working with state agencies. © 2013 The Wildlife Society.
Exotic grass invasion and wildlife abundance and diversity, South‐Central United States
Authors: Fulbright Timothy E. , Hickman Karen R. , Hewitt David G.
Published: July 2013

Exotic grasses dominate rangelands in parts of the South‐central United States. We reviewed the literature on the effects of exotic grasses on wildlife functional groups and species, and examined the state of the art of managing exotic vegetation in the South‐central United States. In cases where researchers reported that exotic grasses reduced wildlife species abundance or diversity, the exotics were dominants in the grassland community. In a few cases, plant communities dominated by exotic grasses appeared to provide desirable habitat for a wildlife species. Giant reed (Arundo donax), for example, provided habitat for white‐collared seedeaters (Sporophila torqueola) along the lower Rio Grande. Old World bluestems change soil microbial populations in a manner that inhibits colonization by native grasses. A threshold level of relative exotic grass abundance may exist below which presence of exotic grasses does not affect wildlife. The majority of peer‐reviewed literature from the South‐central United States on exotic grasses and wildlife is descriptive. Managers should base strategies to manage exotic grasses for wildlife on an understanding of the underlying reasons that certain wildlife species are benefited or negatively impacted by these grasses. © 2013 The Wildlife Society.
Psychosocial Burden of Sickle Cell Disease on Parents with an Affected Child in Cameroon
Authors: Wonkam Ambroise , Mba Caryl Zameyo , Mbanya Dora , Ngogang Jeanne , Ramesar Raj , Angwafo Fru F.
Published: July 2013

The chronicity of Sickle Cell Disease (SCD) could impair the quality of life of caregivers. We performed a quantitative study to assess various indices of psychosocial burden on Cameroonian parents (N = 130) with at least one living SCD‐affected child. Demographic and medical information were obtained from the participants and the review of the patients’ medical records. The survey instrument included a 38‐item stress factors scale using Likert‐type statements, evaluating general perceptions of stress and five main specific stressors: disease factors (clinical severity), hospital factors, financial factors, family factors (life/dynamic) and SCD‐child factors (perceived quality of life). The items pertaining to burden involved four response options with increasing severity: 0, 1, 2 or 3. Descriptive statistics and non‐parametric tests were used for analysis. Participants were typically aged 38 years, urban dwellers (89 %), female (80 %), married (60.2 %), employed (61.7 %) and had secondary/tertiary education (82 %). Median age of SCD‐affected children was 9 years. The median age at diagnosis of SCD was 6 months; 47.8 % had more than 3 painful crises per year. The majority of participants (88.3 %) experienced moderate to severe difficulty coping with SCD. On a 0–3 scale, median score of SCD clinical severity was the major factor to undermine the coping ability of parents (2.2); vaso‐occlusive painful events (>3 per year) was the disease‐related stressor that most impacted their coping ability. The family life dynamic was the least stressful (0.7). Unemployment affected all the stressors’ categories. Stressors scores also increased with female, single, low education level, age of SCD‐affected children or more than 3 children in the family. In Cameroon, there is an urgent need to implement practices that ensure affordable access to health‐care and activities that would reduce SCD morbidity.
Newborn Screening: Education, Consent, and the Residual Blood Spot. The Position of the National Society of Genetic Counselors
Authors: Blout Carrie , Walsh Vockley Cate , Gaviglio Amy , Fox Michelle , Croke Brook , Williamson Dean Lori ,   The Newborn Screening Task Force on behalf of the NSGC Public Policy Committee
Published: July 2013

Newborn screening (NBS) is a minimally invasive lifesaving test. There is currently no federal mandate for NBS, thus states determine their own screening panel based on the recommendations of the Secretary's Advisory Committee on Heritable Disorders in Newborn and Children (SACHDNC), which was recently re‐chartered as the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children (DACHDNC). After NBS is completed, a couple of residual blood spots remain. While some states allow these spots to be used for public health and scientific research purposes, parents are not always informed about these additional uses. This paper addresses the National Society of Genetic Counselors’ (NSGC's) position about NBS and blood spot storage/use and the rationale for these positions. The National Society of Genetic Counselors strongly supports newborn screening for the uniform screening panel of conditions recommended by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. NSGC also supports storage and use of blood spot samples by newborn screening laboratories and transparent policies that govern these activities.
Effects of pH, Temperature and Ionic Strength on Aggregation Behavior of Dodecyldiethoxylamine Oxide
Authors: Wang Ruitao , Li Yunling , Song Yongbo , Zhi Lifei
Published: July 2013

The isoelectric point of dodecyldiethoxylamine oxide (DDEAO) containing hydroxyethyl groups was determined with the method of acid–base titration. The isoelectric point value of DDEAO is 7.8. The effects of pH, temperature and ionic strength on the aggregation behavior of DDEAO were investigated by surface tension measurements. The results show a good surface activity over a large pH range, especially under weakly acidic conditions. The surface activity of DDEAO increases trend increasing temperature. The thermodynamic parameters were also evaluated and the results show that the micelle formation is entropy‐driven within the temperature range investigated. CMC values decrease with increases in ionic strength. The packing parameters (P) were evaluated and ensure the formation of vesicles for DDEAO at various pH values, which is expected to have potential applications in some fields, such as in nanomaterials synthesis and the application in drug delivery.
Enhancing of Corrosion Inhibition and the Biocidal Effect of Phosphonium Surfactant Compounds for Oil Field Equipment
Authors: Aiad Ismail A. , Tawfik Salah M. , Shaban Samy M. , Abd‐Elaal Ali A. , El‐Shafie Mohamed
Published: July 2013

It is well known that tetra hydroxymethyl phosphonium sulfate (THPS) is commonly used in oil fields as a biocide for sulfate‐reducing bacteria (SRB), but it has low corrosion inhibition. In this study, four phosphonium surfactant compounds were synthesized via a coupling reaction between THPS and different fatty acids namely: decanoic, dodecanoic, palmitic and stearic acids to produce the corresponding surfactants. The chemical structure of the synthesized surfactants was confirmed using FTIR and 1H‐NMR spectroscopy. The surface activity of the prepared compounds was determined by surface tension measurements. The critical micelle concentration (CMC) of each surfactant compound was determined. The corrosion inhibition of the synthesized compounds on carbon steel in 0.5 M HCl was studied by weight loss measurements, potentiodynamic and electrochemical impedance spectroscopy. The effect of the inhibitor concentration and hydrophobic chain length on the their efficiency was also studied. It was found that the CMC of each compound depends on its chemical structure. It was also found that the corrosion inhibition efficiency depends on both of concentration and molecular structure of the inhibitors. Polarization curves revealed that the inhibitors used represent mixed‐type inhibitors, which hinder the cathodic and anodic parts of the corrosion reaction in acidic media. Adsorption of used inhibitors leads to a reduction in the double layer capacitance and an increase in the charge transfer resistance. Also the biocidal effect of these compounds was enhanced.
Two‐year predictors of runaway and homeless episodes following shelter services among substance abusing adolescents
Authors: Slesnick Natasha , Guo Xiamei , Brakenhoff Brittany , Feng Xin
Published: July 2013

Given high levels of health and psychological costs associated with the family disruption of homelessness, identifying predictors of runaway and homeless episodes is an important goal. The current study followed 179 substance abusing, shelter‐recruited adolescents who participated in a randomized clinical trial. Predictors of runaway and homeless episodes were examined over a two year period. Results from the hierarchical linear modeling analysis showed that family cohesion and substance use, but not family conflict or depressive symptoms, delinquency, or school enrollment predicted future runaway and homeless episodes. Findings suggest that increasing family support, care and connection and reducing substance use are important targets of intervention efforts in preventing future runaway and homeless episodes amongst a high risk sample of adolescents.
Firms’ Strategic Response to Service Uncertainty: An Empirical Signaling Study
Authors: Mishra Debi P.
Published: July 2013

Managing uncertainty is critical for the survival, growth, and profitability of service firms. Despite its importance, the extant literature largely ignores how firms respond to service uncertainty. To address this gap, this study develops and tests a conceptual model of uncertainty by integrating the literature on signaling and organization theories. The conceptual model identifies two salient sources of uncertainty in the firm-customer interface, i.e., (i) performance ambiguity, and (ii) input uncertainty. Given performance ambiguity, customers face an adverse selection problem because they cannot judge service quality ex-ante. Signaling theory suggests that firms may deploy signals such as certification and customer bonds to mitigate adverse selection. Managers also need to minimize the negative effects of input uncertainty engendered by the variable nature of customer demand. Based on the organization theory literature, formalized procedures and routines represent the general solution to input uncertainty. I empirically investigate whether managers’ responses are congruent with the hypothesized model by analyzing data collected from 287 managers in automotive service organizations via a mail survey procedure. Overall, results of empirical tests conducted via the Latent Variable Structural Equations (LVSE) method provide unequivocal support for the hypothesized consequences of customer uncertainty. I discuss the implications of this study for services research and outline future research directions.
IRF3 and ERK MAP‐kinases control nitric oxide production from macrophages in response to poly‐I:C
Authors: Moore Tyler C. , Petro Thomas M.
Published: July 2013

Understanding nitric oxide (NO) in innate anti‐viral immunity and immune‐mediated pathology is hampered by incomplete details of its transcriptional and signaling factors. We found in macrophages that IRF3, ERK MAP‐kinases, and PKR are essential to NO production in response to RNA‐virus mimic, poly I:C, a TLR3 agonist. ERK's role in NO induction may be through phosphorylation of serine‐171 of IRF3 and expression of NO‐inducing cytokines, IL‐6 and IFN‐β. However, these cytokines induced less NO in IRF3 knockout or knockdown macrophages. These findings show that ERK and IRF3 coordinate induction of NO by macrophages in response to stimulation of TLR3.
A note on the kinetics of enzyme action: A decomposition that highlights thermodynamic effects
Authors: Noor Elad , Flamholz Avi , Liebermeister Wolfram , Bar-Even Arren , Milo Ron
Published: July 2013

Michaelis and Menten's mechanism for enzymatic catalysis is remarkable both in its simplicity and its wide applicability. The extension for reversible processes, as done by Haldane, makes it even more relevant as most enzymes catalyze reactions that are reversible in nature and carry in vivo flux in both directions. Here, we decompose the reversible Michaelis–Menten equation into three terms, each with a clear physical meaning: catalytic capacity, substrate saturation and thermodynamic driving force. This decomposition facilitates a better understanding of enzyme kinetics and highlights the relationship between thermodynamics and kinetics, a relationship which is often neglected. We further demonstrate how our separable rate law can be understood from different points of view, shedding light on factors shaping enzyme catalysis.
Additivity‐based design of the strongest possible turkey ovomucoid third domain inhibitors for porcine pancreatic elastase (PPE) andStreptomyces griseusprotease B (SGPB)
Authors: Qasim Mohammad A. , Wang Lixia , Qasim Sabiha , Lu Stephen , Lu Wuyuan , Wynn Richard , Yi Zheng-Ping , Laskowski Michael
Published: July 2013

We describe here successful designs of strong inhibitors for porcine pancreatic elastase (PPE) andStreptomyces griseusprotease B (SGPB). For each enzyme two inhibitor variants were designed. In one, the reactive site residue (position 18) was retained and the best residues were substituted at contact positions 13, 14, and 15. In the other variant the best residues were substituted at all contact positions except the reactive site where a Gly was substituted. The four designed variants were: for PPE, T13E14Y15‐OMTKY3 and T13E14Y15G18M21P32V36‐OMTKY3, and for SGPB, S13D14Y15‐OMTKY3 and S13D14Y15G18I19K21‐OMTKY3. The free energies of association (ΔG0) of expressed variants have been measured with the proteases for which they were designed as well as with five other serine proteases and the results are discussed.
Oscillatory enzyme reactions and Michaelis–Menten kinetics
Authors: Goldbeter Albert
Published: July 2013

Oscillations occur in a number of enzymatic systems as a result of feedback regulation. How Michaelis–Menten kinetics influences oscillatory behavior in enzyme systems is investigated in models for oscillations in the activity of phosphofructokinase (PFK) in glycolysis and of cyclin‐dependent kinases in the cell cycle. The model for the PFK reaction is based on a product‐activated allosteric enzyme reaction coupled to enzymatic degradation of the reaction product. The Michaelian nature of the product decay term markedly influences the period, amplitude and waveform of the oscillations. Likewise, a model for oscillations of Cdc2 kinase in embryonic cell cycles based on Michaelis–Menten phosphorylation–dephosphorylation kinetics shows that the occurrence and amplitude of the oscillations strongly depend on the ultrasensitivity of the enzymatic cascade that controls the activity of the cyclin‐dependent kinase.
The average enzyme principle
Authors: Reznik Ed , Chaudhary Osman , Segrè Daniel
Published: July 2013

The Michaelis–Menten equation for an irreversible enzymatic reaction depends linearly on the enzyme concentration. Even if the enzyme concentration changes in time, this linearity implies that the amount of substrate depleted during a given time interval depends only on the average enzyme concentration. Here, we use a time re‐scaling approach to generalize this result to a broad category of multi‐reaction systems, whose constituent enzymes have the same dependence on time, e.g. they belong to the same regulon. This “average enzyme principle” provides a natural methodology for jointly studying metabolism and its regulation.
Prediction of lethal pulmonary hypoplasia among high‐risk fetuses via 2D and 3D ultrasonography
Authors: de Castro Rezende Guilherme , Pereira Alamanda Kfoury , Araujo Júnior Edward , Reis Zilma Silveira Nogueira , Vieira Cabral Antonio Carlos
Published: July 2013

Objective

To compare accuracy between 3D and 2D ultrasonography for predicting lethal pulmonary hypoplasia (LPH) among high‐risk fetuses.

Methods

In a cross‐sectional prospective study at a fetal medicine referral center in Brazil, bilateral fetal lung scans were evaluated for 54 fetuses with suspected LPH between May 2008 and June 2011. Measurements for predicting LPH were ultrasonographic fetal lung volume/estimated fetal weight ratio (US‐FLW), observed/expected thoracic circumference (o/e‐TC), observed/expected thoracic circumference/abdominal circumference (o/e‐TC/AC), observed/expected thoracic area/heart area (o/e‐TA/HA), observed/expected amniotic fluid index (o/e‐AFI), and observed/expected total fetal lung volume (o/e‐Tot‐FLV). To evaluate accuracy in predicting LPH, receiver operating characteristic (ROC) curves were calculated, and areas under the curves (AUCs) were compared. The intraclass correlation coefficient (ICC) was used to assess 3D lung volume reproducibility.

Results

Data were compared for 47 newborns, of whom 34 had LPH (perinatal mortality 74.5%). The AUCs for predicting LPH were 0.93, 0.69, 0.55, 0.46, 0.71, and 0.86 for US‐FLW, o/e‐TC, o/e‐TC/AC, o/e‐TA/HA, o/e–AFI, and o/e‐Tot–FLV, respectively. No significant intraobserver difference was observed in measurements of the right (ICC, 0.973; P < 0.0001) or left (ICC, 0.950; P < 0.0001) lung volumes.

Conclusion

Among high‐risk fetuses, US‐FLW by 2D/3D and o/e‐Tot‐FLV by 3D ultrasonography were more accurate than 2D parameters for predicting LPH.
Late Neanderthals at Jarama VI (central Iberia)?
Authors: Kehl Martin , Burow Christoph , Hilgers Alexandra , Navazo Marta , Pastoors Andreas , Weniger Gerd-Christian , Wood Rachel , Jordá Pardo Jesús F.
Published: July 2013

Previous geochronological and archaeological studies on the rock shelter Jarama VI suggested a late survival of Neanderthals in central Iberia and the presence of lithic assemblages of Early Upper Paleolithic affinity. New data on granulometry, mineralogical composition, geochemical fingerprints and micromorphology of the sequence corroborate the previous notion that the archaeological units JVI.2.1 to JVI.2.3 are slackwater deposits of superfloods, which did not experience significant post-depositional changes, whereas the artifact-rich units JVI.3 and JVI.1 mainly received sediment inputs by sheetwash and cave spall. New AMS radiocarbon measurements on three samples of cut-marked bone using the ultrafiltration technique yielded ages close to, or beyond, the limit of radiocarbon dating at ca. 50 14C ka BP, and hence suggest much higher antiquity than assumed previously. Furthermore, elevated temperature post-IR IRSL luminescence measurements on K feldspars yielded burial ages for subunits JVI.2.2 and JVI.2.3 between 50 and 60 ka. Finally, our reappraisal of the stone industry strongly suggests that the whole sequence is of Mousterian affinity. In conclusion, Jarama VI most probably does not document a late survival of Neanderthals nor an Early Upper Paleolithic occupation in central Iberia, but rather indicates an occupation breakdown after the Middle Paleolithic.
Breaking the Ice: The establishment of overland winter postal routes in the late Qing China
Authors: TSAI WEIPIN
Published: July 2013

This paper looks at the establishment of experimental winter overland postal routes in the late 1870s and 1880s, which eventually led to the creation of the Great Qing Imperial Post Office in 1896. The history of this experiment sheds much light on important issues in the establishment of what was to become the country's most crucial information-bearing network, in particular those related to collaboration and negotiation between foreign and Chinese officials, and those between local interests and the central authorities. It also explores how foreign processes and management had to be adapted in order to function in a Chinese context.

In March 1878, Robert Hart, inspector general of the Chinese Maritime Customs Service, instructed Gustav Detring, commissioner of Tianjin Port, to investigate the possibility of introducing overland public postal routes in China, beginning with Beijing to Tianijn, Niuzhuang, Yantai, and then to Zhenjiang, a treaty port on the lower Yangtze River.

The three main challenges involved were: to establish a reliable workforce, to design appropriate routes, and to win the cooperation of local governing officials. Although the winter service was initiated on time, problems repeatedly arose from each one of these challenges.
Präanalytik in der Hämatologie – Fallen und Tücken
Authors: Méndez Adriana , Bargetzi Mario , Huber Andreas , Cantoni Nathan
Published: July 2013

Um präanalytische Fehler zu vermeiden, sind bereits vor der Blutentnahme einige Punkte zu beachten. Eine korrekte Identifikation des Patienten, bereitstellen der für die gewünschte Analyse richtigen Entnahmeröhrchen, die dann korrekt beschriftet und in der richtigen Reihenfolge abgenommen werden, sowie das Einhalten der entsprechenden Entnahme- und Transporttemperaturen sind Grundvoraussetzung für die nachfolgenden Untersuchungen im Labor. Ebenfalls, insbesondere bei Spezialanalysen, ist die Weitergabe von Zusatzinformationen über den Patienten für die Interpretation der erhobenen Resultate entscheidend. Das Labor wiederum sollte bei unklaren Laborbefunden den Kontakt mit dem Kliniker suchen, um eine Erklärung der unerwarteten Resultate anzustreben.
Stolpersteine bei der Beurteilung der arteriellen Blutgase
Authors: Thurnheer Robert
Published: July 2013

Die arterielle Blutgasanalyse ist eine sehr wertvolle Untersuchung im klinischen Alltag. Sie liefert Informationen über die Oxigenierung, Ventilation und den Säure-Basen-Status eines Patienten. Für die Präanalytik sind eine problemlose Entnahme, rasche Verarbeitung sowie Angabe der Körpertemperatur wichtig. Bei der Beurteilung der Oxigenierung muss das FIO2 angegeben und das PaO2 mit der Sauerstoff-Sättigung in einem plausiblen Verhältnis stehen. Bei vermuteten Intoxikationen sollte die Sättigung mit CO-Oximetrie bestimmt werden. Die Effizienz der Ventilation, gemessen am PaCO2, soll im Zusammenhang mit dem PaO2 beurteilt werden. Ein „normales“ oder erhöhtes PaCO2 bei Hypoxämie ist pathologisch. Ein „normales“ pH schließt alleine eine Säure-Basen-Störung nicht aus, das PaCO2 und Bicarbonat sind stets mit einzubeziehen. Bei Verteilungsstörungen soll nach Anpassung des FiO2 bis 30 min. mit Entnahme einer ABGA gewartet werden, um steady-state – Bedingungen vorzufinden. Eine ABGA sollte nie ohne den klinischen Kontext beurteilt werden. Stark von der klinischen Hypothese abweichende Resultate sollen hinterfragt, durch Wiederholung der Untersuchung bestätigt werden oder zur Erweiterung der Differentialdiagnose veranlassen. Bei Hypoxämie soll rasch Sauerstoff eingesetzt werden, bei Hyperkapnie soll die Ventilation gesteigert werden, bei metabolischen Störungen des Säure-Basen-Haushaltes ist meist die Behandlung der Grunderkrankung zielführend.
Endokrinologische Laboruntersuchungen – wo liegen die Probleme?
Authors: Henzen Christoph , Kraenzlin Marius , Meier Christian
Published: July 2013

Endokrinologische Erkrankungen sind in der allgemein-internistischen Praxis häufig. Neben Anamnese und Klinik sind in der Diagnostik verschiedener Krankheitsbilder Laborabklärung notwendig. Diese haben zum Ziel, eine klinische Verdachtsdiagnose zu bestätigen, die Indikation zu einer Behandlung zu prüfen und werden zur Verlaufskontrolle, insbesondere zur Überprüfung der Therapiewirksamkeit einer Behandlung herangezogen. In diesem Artikel soll auf häufig durchgeführte endokrinologische Laborabklärungen bei Diabetes mellitus, Hypo- bzw. Hyperthyreose, beim Hypogonadismus des Mannes und der Nebenniereninsuffizienz eingegangen werden. Insbesondere werden präanalytische und analytische Aspekte der verschiedenen Laborparameter beleuchtet und der Einfluss deren Bestimmung für den klinischen Alltag diskutiert.
Wie Eltern erwachsener Menschen mit Epilepsie das Beste aus ihrer Situation machen – eine qualitative Studie
Authors: Müller Margrit , Jaggi Sabina , Spirig Rebecca , Mahrer-Imhof Romy
Published: July 2013

Epilepsie ist eine häufige chronische Krankheit und sie betrifft Menschen in allen Altersgruppen. Die präventive Einnahme von Medikamenten beugt epileptischen Anfällen vor, dennoch hat die Erkrankung Auswirkungen auf den Alltag von Patient(inn)en und ihren Familien. Aus der Forschung mit Familienmitgliedern von Menschen mit Epilepsie ist bekannt, dass diese vermehrt unter Sorgen und Depressionen leiden und sich in ihrer Alltagsgestaltung eingeschränkt fühlen. Die vorliegende Studie untersuchte, wie Eltern mit dem Kranksein ihrer zwischenzeitlich erwachsenen Kinder umzugehen lernten und heute im Alltag umgehen. Narrative Interviews mit 14 Eltern wurden nach den Grundsätzen der interpretierenden Phänomenologie auf das Erleben der Eltern analysiert. Alle Befragten betonten, dass sie gelernt haben, das Beste aus ihrer Situation zu machen. Ihre Erfahrungen können beschrieben werden als: «gemeinsam auf dem Weg sein», «auf einem Grat wandern» sowie «kämpfen und sich sorgen». Die Beschreibungen von Paradigmafällen berücksichtigen die Lebenswelt und Erfahrungen von Eltern in ihrem Kontext und erfassen Phänomene, welche über die bisher in der Literatur beschriebenen Belastungen und Sorgen hinausgehen. Da die Eltern vielfach auch für erwachsene Menschen mit Epilepsie wichtige Bezugspersonen bleiben, sind sie in deren Beratung und Behandlungsplanung einzubeziehen.
Wie schätzen Pflegende die Suizidalität von Patient(inn)en ein? Erhebung in psychiatrischen Institutionen der deutschen Schweiz
Authors: Rabenschlag Franziska , Hoffmann Sven , Kozel Bernd , Sprenger Rosmarie
Published: July 2013

Pflegende in der Psychiatrie leisten im interdisziplinären Behandlungsprozess einen zentralen Beitrag zur Wahrnehmung und Einschätzung der Suizidalität. Um dieser Verantwortung gerecht zu werden, empfiehlt sich der Einsatz von Instrumenten zur Einschätzung der Suizidalität. Dafür gibt es eine Vielzahl von Fragebögen und anderen Methoden, die Pflegende in der Praxis jedoch nicht einheitlich verwenden. Diese punktuelle Querschnitterhebung ging den Fragen nach: Wie schätzen Pflegende in deutschschweizerischen psychiatrischen Kliniken die Suizidalität von Patient(inn)en ein? Welche Instrumente verwenden sie dabei? Die Umfrage richtete sich an die Stationsleitenden aller deutschsprachigen psychiatrischen Kliniken der Schweiz (n = 32). Dabei gab die Hälfte der angefragten Stationsleitenden an (n = 119; 50,63 %), dass Pflegende auf der Station Instrumente zur Einschätzung der Suizidalität verwenden. Bei 13 % der verwendeten Instrumente handelte es sich um erforschte, validierte Instrumente. Pflegende schätzen die Suizidalität am häufigsten bei einer (vermuteten) Gefährdung, seltener beim Eintritt und am wenigsten häufig beim Austritt ein. Suizidhandlungen treten jedoch gehäuft kurz vor und nach dem Austritt aus einer stationären psychiatrischen Behandlung auf. Deshalb empfiehlt es sich, die Suizidalität auch vor dem Austritt einzuschätzen.
Pflegeethik und die Sorge um den Zugang zu Pflege
Authors: Monteverde Settimio
Published: July 2013

Die gegenwärtige Verdichtung ethischer Fragen im Pflegealltag zeigt die Verwobenheit von Pflegeethik und Pflegepraxis. Doch was für eine Rolle spielen dabei ethische Theorien? Der vorliegende Beitrag untersucht diese Frage anhand der Care-Ethik. Ihre Rezeption in der Pflege hat dazu geführt, die Bedeutung von Beziehungen und Gender sowie Asymmetrien an Macht, Wissen und Erfahrung in professionellen Beziehungen zu thematisieren. Der Beitrag beschreibt verschiedene Aspekte dieser Rezeption sowie die Kritik, die diese ausgelöst hat. Danach hebt er die Aktualität der Care-Ethik anhand einer neueren Leseart hervor. Diese nimmt zunächst die historische Wahrnehmung Pflegender als randständige Akteurinnen und Akteure im Gesundheitswesen auf. Doch die heutige Realität des Mangels an Pflege rückt diese mittelfristig nicht an den Rand, sondern ins Zentrum der gesundheitspolitischen Aufmerksamkeit. Die Randthematik aber bleibt. Sie betrifft jedoch immer weniger die Pflegenden selber und immer mehr diejenigen, die Pflege empfangen. Darunter zählen Bevölkerungsgruppen, die aufgrund von Merkmalen wie Hochaltrigkeit, Multimorbidität oder fehlender Gesundheitskompetenz an den Rand definierter Versorgungsketten gedrängt werden. Der Beitrag plädiert für ein umfassenderes Verständnis der Care-Ethik in der Pflege: Die «klassische» individualethische Lesart und ihr Fokus auf die Beziehung zwischen Pflegende(r) und Patient(in) werden erweitert um eine sozialethische Leseart, die Care als Sorge um den Zugang zu Pflege versteht.
The carbonylation and covalent dimerization of human superoxide dismutase 1 caused by its bicarbonate-dependent peroxidase activity is inhibited by the radical scavenger tempol
Authors: Queiroz Raphael F. , Paviani Verônica , Coelho Fernando R. , Marques Emerson F. , Di Mascio Paolo , Augusto Ohara
Published: July 2013

Tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) reduces tissue injury in animal models of various diseases via mechanisms that are not completely understood. Recently, we reported that high doses of tempol moderately increased survival in a rat model of ALS (amyotrophic lateral sclerosis) while decreasing the levels of oxidized hSOD1 (human Cu,Zn-superoxide dismutase) in spinal cord tissues. To better understand such a protective effect in vivo, we studied the effects of tempol on hSOD1 oxidation in vitro. The chosen oxidizing system was the bicarbonate-dependent peroxidase activity of hSOD1 that consumes H2O2 to produce carbonate radical, which oxidizes the enzyme. Most of the experiments were performed with 30 μM hSOD1, 25 mM bicarbonate, 1 mM H2O2, 0.1 mM DTPA (diethylenetriaminepenta-acetic acid) and 50 mM phosphate buffer at a final pH of 7.4. The results showed that tempol (5–75 μM) does not inhibit hSOD1 turnover, but decreases its resulting oxidation to carbonylated and covalently dimerized forms. Tempol acted by scavenging the carbonate radical produced and by recombining with hSOD1-derived radicals. As a result, tempol was consumed nearly stoichiometrically with hSOD1 monomers. MS analyses of turned-over hSOD1 and of a related peptide oxidized by the carbonate radical indicated the formation of a relatively unstable adduct between tempol and hSOD1-Trp32•. Tempol consumption by the bicarbonate-dependent peroxidase activity of hSOD1 may be one of the reasons why high doses of tempol were required to afford protection in an ALS rat model. Overall, the results of the present study confirm that tempol can protect against protein oxidation and the ensuing consequences.
Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates recruitment to transcription initiation sites
Authors: Aregger Michael , Cowling Victoria H.
Published: July 2013

Gene expression in eukaryotes is dependent on the mRNA methyl cap which mediates mRNA processing and translation initiation. Synthesis of the methyl cap initiates with the addition of 7-methylguanosine to the initiating nucleotide of RNA pol II (polymerase II) transcripts, which occurs predominantly during transcription and in mammals is catalysed by RNGTT (RNA guanylyltransferase and 5′ phosphatase) and RNMT (RNA guanine-7 methyltransferase). RNMT has a methyltransferase domain and an N-terminal domain whose function is unclear; it is conserved in mammals, but not required for cap methyltransferase activity. In the present study we report that the N-terminal domain is necessary and sufficient for RNMT recruitment to transcription initiation sites and that recruitment occurs in a DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidazole)-dependent manner. The RNMT-activating subunit, RAM (RNMT-activating miniprotein), is also recruited to transcription initiation sites via an interaction with RNMT. The RNMT N-terminal domain is required for transcript expression, translation and cell proliferation.