bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration
Authors: Fathallah Anas M. , Turner Michael R. , Mager Donald E. , Balu‐Iyer Sathy V.
Published: November 2014

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O‐phospho‐L‐serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.
Roles of interstitial fraction and load conditions on the dynamic binding capacity of proteins on capillary‐channeled polymer fiber columns
Authors: Wang Zhengxin , Marcus R. Kenneth
Published: November 2014

Capillary‐channeled polymer (C‐CP) fibers are used as a stationary phase for ion‐exchange chromatography of proteins. Collinear packing of the fibers permits operation at high linear velocities (Uo > 100 mm s−1) and low backpressure (<2,000 psi) on analytical‐scale columns. Rapid solvent transport is matched with very efficient solute mass transfer as fibers are virtually non‐porous with respect to the size of the target protein molecules. Lack of porosity of course limits the equilibrium binding capacity of stationary phases. Breakthrough curves and frontal analysis are used to better understand trade‐offs between the kinetic and thermodynamic properties as C‐CP fibers are applied in preparative situations. Fiber columns packed to different interstitial fraction values affect both the total fiber surface area (e.g., equilibrium binding capacity [EBC]) and the permittivity to flow and mass transport characteristics (e.g., dynamic binding capacity [DBC]). The EBC of the nylon 6 C‐CP fibers was found to be 1.30 mg g−1, with isotherms that were best matched by a Moreau model, showing linearity up to solute concentrations of ∼0.4 mg mL−1. Isotherms generated under flow conditions were equally well approximated using Langmuir, Freundlich, and Moreau isotherm models. Fairly linear responses were seen up to the maximum load concentration of 1.2 mg mL−1. Counterintuitively, dynamic studies revealed that conditions of high column porosity yielded a DBC that is ∼70% higher than the EBC. These findings point to potential advantages in terms downstream processing applications, where protein throughput and yield are critical metrics. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:97–109, 2015
Effect of wine inhibitors on the proteolytic activity of papain from Carica papaya L. latex
Authors: Benucci Ilaria , Esti Marco , Liburdi Katia
Published: November 2014

The influence of potential inhibitors naturally present in wine on the proteolytic activity of papain from Carica papaya latex was investigated to evaluate its applicability in white wine protein haze stabilization. Enzymatic activity was tested against a synthetic tripeptide chromogenic substrate in wine‐like acidic medium that consisted of tartaric buffer (pH 3.2) supplemented with ethanol, free sulfur dioxide (SO2), grape skin and seed tannins within the average ranges of concentrations that are typical in wine. The diagnosis of inhibition type, performed with the graphical method, demonstrated that all of tested wine constituents were reversible inhibitors of papain. The strongest inhibition was exerted by free SO2, which acted as a mixed‐type inhibitor, similar to grape skin and seed tannins. Finally, when tested in table white wines, the catalytic activity of papain, even when if it was ascribable to the hyperbolic behavior of Michaelis‐Menten equation, was determined to be strongly affected by free SO2 and total phenol level. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:48–54, 2015
Genitofemoral neuralgia: A review
Authors: Cesmebasi Alper , Yadav Abhishek , Gielecki Jerzy , Tubbs R. Shane , Loukas Marios
Published: November 2014

Genitofemoral neuralgia is a cause of neuropathic pain that is often debilitating in nature. It is characterized by chronic neuropathic groin pain that is localized along the distribution of the genitofemoral nerve. The symptoms include groin pain, paresthesias, and burning sensation spreading from the lower abdomen to the medial aspect of the thigh. It may present with scrotal pain in male, while females experience symptoms radiating to the labia majora and mons pubis. Genitofemoral neuropathy has been attributed to iatrogenic nerve injury occurring during inguinal and femoral herniorrhaphy, with cases developing after both open and laparoscopic techniques. Diagnosis of genitofemoral neuralgia can be challenging, due to the overlap in sensory distribution the nerve shares with the ilioinguinal and iliohypogastric nerve. Differential nerve blocks are recommended in effort to differentiate the nerves when patients present with lower abdominal and groin pain. Once a diagnosis has been made, there exist several treatment options for genitofemoral neuralgia ranging from medical management, non‐invasive injections, and surgery. Literature has also brought light to radiofrequency ablation and cryoablation performed under ultrasound guidance as emerging treatments. The aim of the current article is to review the anatomy, diagnostic techniques, and treatment options for patients with genitofemoral neuralgia. Clin. Anat. 28:128–135, 2015. © 2014 Wiley Periodicals, Inc.
Clinical structural anatomy of the inferior pyramidal space reconstructed from the living heart: Three‐dimensional visualization using multidetector‐row computed tomography
Authors: Mori Shumpei , Nishii Tatsuya , Takaya Tomofumi , Kashio Kazuhiro , Kasamatsu Akira , Takamine Sachiko , Ito Tatsuro , Fujiwara Sei , Kono Atsushi K. , Hirata Ken‐Ichi
Published: November 2014

The inferior pyramidal space (IPS) comprises the epicardial visceral adipose tissue wedged between the bottoms of the four cardiac chambers from the postero‐inferior epicardial surface of the heart. Understanding the complex anatomy around the IPS is important for clinical cardiologists. Although leading anatomists and radiologists have clarified the anatomy of the IPS in detail, few studies have demonstrated this anatomy in three dimensions. The aim of this study was to visualize the three‐dimensional anatomy of the IPS reconstructed from the living heart using multidetector‐row computed tomography. We also developed an original paper model of the IPS to enhance understanding of its intricate structure. Clin. Anat. 28:878–887, 2015. © 2014 Wiley Periodicals, Inc.
Application of Room‐Temperature Aprotic and Protic Ionic Liquids for Oxidative Folding of Cysteine‐Rich Peptides
Authors: Heimer Pascal , Tietze Alesia A. , Böhm Miriam , Giernoth Ralf , Kuchenbuch Andrea , Stark Annegret , Leipold Enrico , Heinemann Stefan H. , Kandt Christian , Imhof Diana
Published: November 2014

The oxidation of the conotoxin μ‐SIIIA in different ionic liquids was investigated, and the results were compared with those obtained in [C2mim][OAc]. Conversion of the reduced precursor into the oxidized product was observed in the protic ILs methyl‐ and ethylammonium formate (MAF and EAf, respectively), whereas choline dihydrogenphosphate and Ammoeng 110 failed to yield folded peptide. However, the quality and yield of the peptide obtained in MAF and EAF were lower than in the case of the product from [C2mim][OAc]. Reaction conditions (temperature, water content) also had an impact on peptide conversion. A closer look at the activities of μ‐SIIIA versions derived from an up‐scaled synthesis in [C2mim][OAc] revealed a significant loss of the effect on ion channel NaV1.4 relative to the buffer‐oxidized peptide, whereas digestion of either μ‐SIIIA product by trypsin was unaffected. This was attributed to adherence of ions from the IL to the peptide, because the disulfide connectivity is basically the same for the differentially oxidized μ‐SIIIA versions.
Mathematical Modeling and Genetic Algorithm Optimization of Reactive Absorption of H2S
Authors: Bashipour Fatemeh , Khorasani Saied Nouri , Rahimi Amir
Published: November 2014

A rate‐based mathematical model was developed for the reactive absorption of H2S in NaOH, with NaOCl or H2O2 as the chemical oxidant solutions in a packed column. A modified mass transfer coefficient in the gas phase was obtained by genetic algorithm and implemented in the model to correct the assumption of instantaneous reactions. The effects of different operating variables including the inlet H2S concentration, inlet gas mass flux, initial NaOH, concentrations of the chemical oxidants in the scrubbing solutions, and liquid‐to‐gas ratio on the H2S removal efficiency were studied. A genetic algorithm was employed to optimize the operating variables in order to obtain maximum removal efficiency of H2S. The model results were in good agreement with the experimental data.
Multiple Analysis in a Reactive Distillation Column for the Synthesis of tert‐Amyl Methyl Ether
Authors: Ramkissoon Ashley , Moonisar Roshan , Maraj Divya , Riverol Carmen
Published: November 2014

tert‐Amyl methyl ether (TAME) is produced via reactive distillation. A simulation is set up and controlled on Aspen HYSYS v 8.0 for generating the highest purity of TAME. This simulation includes a plug‐flow reactor and a reactive distillation column. Emphasis was put on finding the optimal operating conditions of the reactive distillation column in order to get the maximum purity of TAME. The operational parameters were reflux ratio, number of reactive stages in the distillation column, and condenser pressure. The results indicated the optimal reflux ratio and condenser pressure which could be adapted to industrial scale.
X‐ray Absorption Spectroscopy Investigation of Lithium‐Rich, Cobalt‐Poor Layered‐Oxide Cathode Material with High Capacity
Authors: Buchholz Daniel , Li Jie , Passerini Stefano , Aquilanti Giuliana , Wang Diandian , Giorgetti Marco
Published: November 2014

We present an ex situ X‐ray absorption spectroscopy investigation into lithiation–delithiation of the lithium‐rich, but cobalt‐poor cathode material Li[Li0.2Ni0.16Mn0.56Co0.08]O2. The main focus of this work is to address the role of manganese and oxygen in the electrochemical redox process and, especially, to identify the phenomena occurring during the initial activation, that is, during the first delithiation–lithiation cycle. Although manganese is not taking part in the initial electrochemical oxidation process, the results indicate that complete Ni2+/Ni4+ and partial Co3+/Co4+ redox processes occur. The electrochemical performance of the material, considering the full and partial redox inactivity of Mn and Co, reveals the participation of oxygen in the overall electrochemical redox process. Finally, it is found, surprisingly, that a partial reduction of Co and Ni takes place at the end of the initial activation.
Di‐ and Trinuclear Gold Complexes of Diphenylphosphinoethyl‐Functionalised Imidazolium Salts and their N‐Heterocyclic Carbenes: Synthesis and Photophysical Properties
Authors: Bestgen Sebastian , Gamer Michael T. , Lebedkin Sergei , Kappes Manfred M. , Roesky Peter W.
Published: November 2014

Diphenylphosphinoethyl‐functionalised imidazolium salts and their silver–carbene complexes were used to synthesise a series of di‐ and trinuclear gold complexes through ligand exchange and transmetallation, respectively. Besides a few positively charged macrocyclic compounds with different anions (both with and without activation of the carbene function), we were able to obtain neutral polynuclear complexes by varying the gold precursor. The synthesised gold complexes show a variety of photophysical properties, including bright white photoluminescence at ambient temperature.
Incorporation of Microreactor Measurements into a Pilot‐Scale Phthalic Anhydride Reactor
Authors: Fischer Nico , Hubach Patrick , Woll Christian
Published: November 2014

A major obstacle in the development of industrial catalysts is the scalability of both catalyst performance and synthesis. While utilizing pilot‐scale test reactors allows for a direct transfer from the development stage to the application, it comes at the cost of flexibility. The amount of catalyst required in a pilot‐scale test reactor often surpasses the yields of novel synthesis procedures, requiring extensive scale‐up efforts. Here, pilot‐scale reactors are combined with small lab‐scale reactors, using the example of oxidation of o‐xylene to phthalic anhydride.
Chemie erneuerbarer kohlenstoffbasierter Rohstoffe zur Produktion von Chemikalien und Kraftstoffen
Authors: Vogel G. Herbert
Published: November 2014

Nachhaltigkeit ist ein Begriff, der eine inflationäre Entwicklung genommen hat. Hier wird die Frage erörtert, wie in der Zukunft die Versorgung mit kohlenstoffbasierten Rohstoffen gesichert werden kann, ohne die Natur zusätzlich zu belasten. Es wird gezeigt, dass ein nachhaltiger Brückenbau sinnvollerweise auf den beiden Pfeilern Sonnenenergie und CO2 beruhen sollte. Die natürliche Fotosynthese liefert Biomasse, aus der höherwertige Chemikalien hergestellt werden können, während die künstliche Fotosynthese Kohlenwasserstoffe und/oder Oxigenate zur Herstellung von Kraftstoffe und Grundchemikalien liefert.
Heavy Metal Partitioning in Sediments from Rivers Flowing Through Coal Fields in Mpumalanga, South Africa
Authors: Moyo Stanley , McCrindle Rob , Mokgalaka Ntebogeng , Myburgh Jan
Published: November 2014

The association of elements Cd, Co, Cr, Fe, Mn, Pb, Ti, and V with various geochemical phases in the sediments from the Olifants, Klein Olifants, Wilge rivers and a tributary of the Olifants River was studied using a four‐step sequential extraction scheme. By employing enrichment factors, these elements were found to be contaminating the sediments. Sequential extraction enabled partitioning of the metals into exchangeable, reducible, oxidizable, and residual fractions. Most of the elements were found to exist in the residual fraction, characterized by stable compounds. Application of risk assessment code to the exchangeable fraction revealed that most of the elements posed a medium risk to aquatic life, with the exception of Co, Pb, and Mn, which were classified into the high‐risk category. Non‐residual/more bioavailable fractions were examined using statistics. Correlation analysis was employed to understand the interaction between the more bioavailable fractions of metals with the reducible phase consisting of oxides of Fe and Mn. These oxides contribute to the adsorption of trace metals onto sediments. Co, V, Pb, Cr, and Cd in the reducible fraction were found to be associated with Fe‐oxides, while V, Cr, and Ti were associated with Mn‐oxides, as indicated by significantly high correlation coefficients. Through cluster and factor analysis three anthropogenic activities associated with mining and use of coal and iron and steel manufacturing were found to be contributing metals to the sediments.
Iminosugar‐Based Galactoside Mimics as Inhibitors of Galactocerebrosidase: SAR Studies and Comparison with Other Lysosomal Galactosidases
Authors: Biela‐Banaś Anna , Oulaïdi Farah , Front Sophie , Gallienne Estelle , Ikeda‐Obatake Kyoko , Asano Naoki , Wenger David A. , Martin Olivier R.
Published: November 2014

Several families of iminosugar‐based galactoside mimics were designed, synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were also tested as inhibitors of lysosomal β‐ and α‐galactosidases in order to find new potent and selective pharmacological chaperones for treatment of the lysosomal storage disorder, Krabbe disease. Whereas 1‐C‐alkyl imino‐L‐arabinitols are totally inactive toward the three enzymes, 1‐C‐alkyl imino‐D‐galactitols were found to be active only toward α‐galactosidase A. Finally, 1‐N‐iminosugars provided the best results, as 4‐epi‐isofagomine was found to be a good inhibitor of both lysosomal β‐galactosidase and GALC. Further elaboration of this structure is required to achieve selectivity between these two galactosidases.
Germline PTEN, SDHB‐D, and KLLN alterations in endometrial cancer patients with Cowden and Cowden‐like syndromes: An international, multicenter, prospective study
Authors: Mahdi Haider , Mester Jessica L. , Nizialek Emily A. , Ngeow Joanne , Michener Chad , Eng Charis
Published: November 2014

BACKGROUND

Endometrial cancer has been recognized only recently as a major component of Cowden syndrome (CS). Germline alterations in phosphatase and tensin homolog (PTEN; PTEN_mut+), succinate dehydrogenase B/C/D (SDHB‐D; SDHx_var+), and killin (KLLN_Me+) cause CS and Cowden syndrome–like (CSL) phenotypes. This study was aimed at identifying the prevalence and clinicopathologic predictors of germline PTEN_mut+, SDHx_var+, and KLLN_Me+ in CS/CSL patients presenting with endometrial cancer.

METHODS

PTEN and SDHB‐D mutation and KLLN promoter methylation analyses were performed for 371 prospectively enrolled patients (2005‐2011). PTEN protein was analyzed from patient‐derived lymphoblast lines. The PTEN Cleveland Clinic (CC) score is a weighted, regression‐based risk calculator giving the a priori risk for PTEN_mut+. Demographic and clinicopathologic features were correlated with the specific gene.

RESULTS

Germline PTEN_mut+, SDHx_var+, and KLLN_Me+ were found in 7%, 9.8%, and 10.5% of informative samples, respectively. Predictors of PTEN_mut+ included an age ≤ 50 years (odds ratio [OR] for an age < 30 years, 6.1 [P = .015]; OR for an age of 30‐50 years, 4.4 [P = .001]), macrocephaly (OR, 14.4; P < .001), a higher CC score (OR for a 1‐U increment, 1.35; P < .001), a PTEN protein level within the lowest quartile (OR, 5.1; P = .039), and coexisting renal cancer (OR, 5.7; P = .002). KLLN_Me+ patients were on average 8 years younger than KLLN_Me– patients (44 vs 52 years, P = .018). Predictors of KLLN_Me+ were a younger age and a higher CC score. On the other hand, no clinical predictors of SDH_var+ were found.

CONCLUSIONS

Clinical predictors of PTEN and KLLN alterations, but not SDHx_var+, were identified. These predictors should alert the treating physician to potential heritable risk and the need for referral to genetic professionals. High‐risk cancer surveillance and prophylactic surgery of the uterus may be considered for KLLN_Me+ patients similarly to PTEN_mut+ patients. Cancer 2015;121:688–696. © 2014 American Cancer Society.
A thorough QT/QTc study of the effect of fasiglifam, a GPR40 agonist, on cardiac repolarization in healthy adults
Authors: Lee Ronald D. , Nudurupati Sai , Marcinak John , Viswanathan Prabhakar
Published: November 2014

This double‐blind, randomized, placebo‐ and active‐controlled, parallel group trial evaluated the potential for multiple‐dose fasiglifam to prolong the QT/QTc interval in healthy adults. A total of 280 men and women aged 18–50 years were randomized to receive 14 days of fasiglifam 50 mg (n = 69), fasiglifam 400 mg (n = 70), or placebo (n = 70), or 13 days of placebo followed by single‐dose moxifloxacin 400 mg (positive control; n = 71). The primary endpoint was the least square mean difference between fasiglifam and placebo in time‐matched change from baseline to last dosing day in QT interval corrected using the Fridericia method (QTcF, calculated as QT/RR0.333). For both fasiglifam doses, differences from placebo in QTcF were between −4.9 and 3.0 milliseconds at all postdose time points; maximum upper bounds of the one‐sided 95% confidence interval for the difference were 5.7 milliseconds for fasiglifam 50 mg and 2.3 milliseconds for fasiglifam 400 mg, meeting predefined criteria for absence of prolongation. Alternate correction methods (Bazett and Individual) showed similar results. Fasiglifam was well tolerated; no subject withdrew due to an adverse event after receiving fasiglifam. In summary, multiple‐dose fasiglifam did not affect cardiac repolarization at therapeutic and supratherapeutic doses and was well tolerated in healthy subjects.
Levels of N‐terminal pro brain natriuretic peptide are enhanced in people with the uncomplicated metabolic syndrome: a case‐cohort analysis of the population‐based Casale Monferrato study
Authors: Bruno Graziella , Barutta Federica , Landi Andrea , Pinach Silvia , Caropreso Paola , Mengozzi Giulio , Baldassarre Stefano , Fragapani Salvatore , Civera Stefania , Cavallo Perin Paolo , Gruden Gabriella
Published: November 2014

Background

Both metabolic syndrome (MetS) and N‐amino terminal fragment of the prohormone B‐type natriuretic peptide (NT‐proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT‐proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared with subjects who met none of the defining criteria of the MetS.

Methods

A case‐cohort study from the non‐diabetic population‐based Casale Monferrato study was performed, after exclusion of all subjects with established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2], and CRP values ≥3 mg/L. Cases (n = 161) with MetS were compared with all subjects within the cohort (n = 124) who were completely free of any component of the MetS. Serum NT‐proBNP was centrally measured by immunoenzymatic assay.

Results

NT‐proBNP levels were significantly higher in cases than in control subjects [35.4 (15.5–98.2) vs 24.4 (11.7–49.6) pg/mL, p = 0.014]. In logistic regression analysis, compared with NT‐proBNP values in the lower quartiles (≤49.64 pg/mL), higher values conferred odds ratio 4.17 (1.30–13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP, eGFR, and central obesity. This association was evident even after the exclusion of hypertensive subjects. Further adjustment for log‐HOMA and diastolic blood pressure did not modify the strength of the association, while central obesity was a negative confounder.

Conclusions

Compared with people without any component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor diabetes, had increased NT‐proBNP values, even if they were normotensive and although absolute values were still in the low range. The insulin resistance state did not mediate this association, while central obesity was a negative confounder. Copyright © 2014 John Wiley & Sons, Ltd.
Vascular patterning sets the stage for macro and micro hepatic architecture
Authors: Cast Ashley E. , Walter Teagan J. , Huppert Stacey S.
Published: November 2014

Background The liver is a complex organ with a variety of tissue components that require a precise architecture for optimal function of metabolic and detoxification processes. As a result of the delicate orchestration required between the various hepatic tissues, it is not surprising that impairment of hepatic function can be caused by a variety of factors leading to chronic liver disease. Results Despite the growing rate of chronic liver disease, there are currently few effective treatment options besides orthotopic liver transplantation. Better therapeutic options reside in the potential for genetic and cellular therapies that promote progenitor cell activation aiding de novo epithelial and vascular regeneration, cell replacement, or population of bioartificial hepatic devices. In order to explore this area of new therapeutic potential, it is crucial to understand the factors that promote hepatic function through regulating cell identities and tissue architecture. Conclusions In this commentary, we review the signals regulating liver cell fates during development and regeneration and highlight the importance of patterning the hepatic vascular systems to set the groundwork for the macro and micro hepatic architecture of the epithelium. Developmental Dynamics 244:497–506, 2015. © 2014 Wiley Periodicals, Inc.
Risk for ventricular fibrillation in peripartum cardiomyopathy with severely reduced left ventricular function—value of the wearable cardioverter/defibrillator
Authors: Duncker David , Haghikia Arash , König Thorben , Hohmann Stephan , Gutleben Klaus‐Jürgen , Westenfeld Ralf , Oswald Hanno , Klein Helmut , Bauersachs Johann , Hilfiker‐Kleiner Denise , Veltmann Christian
Published: November 2014

Aims

The true incidence of life‐threatening ventricular tachyarrhythmic events and the risk of sudden cardiac death in the early stage of peripartum cardiomyopathy (PPCM) are still unknown. We aimed to assess the usefulness of the wearable cardioverter/defibrillator (WCD) to bridge a potential risk for life‐threatening arrhythmic events in patients with early PPCM, severely reduced left ventricular ejection fraction (LVEF) and symptoms of heart failure.

Methods and results

Twelve consecutively admitted women with PPCM were included in this single‐centre, prospective observational study between September 2012 and September 2013. Patients with LVEF ≤35% were considered to use the WCD for 3 months or even 6 months when considered necessary for LVEF recovery. Nine of the 12 women had a severely reduced LVEF (mean 18.3%) at the time of study enrolment; seven women received a WCD, while two patients refused to wear a WCD. During a median WCD follow‐up of 81 days (range 25–345 days), we observed a total of four events of ventricular fibrillation with appropriate and successful WCD shocks in three of the seven women receiving a WCD. No syncope or sudden arrhythmic deaths occurred in women not using the WCD during a median follow‐up of 12 months (range 5–15 months). All women showed impressive improvement of LVEF during follow‐up.

Conclusion

PPCM patients with severely reduced LVEF have an elevated risk for ventricular tachyarrhythmias early after diagnosis. Therefore, use of the WCD should be considered in all women with early‐stage PPCM and severely reduced LVEF during the first 6 months after initiation of heart failure therapy.
Evaluation of the Formate Dehydrogenase Activity of Three‐Legged Pianostool Complexes in Dilute Aqueous Solution
Authors: Keller Sascha G. , Ringenberg Mark R. , Häussinger Daniel , Ward Thomas R.
Published: November 2014

Formic acid is an attractive means to reversibly store dihydrogen. In this context, d6 pianostool complexes rank among the most‐effective formate dehydrogenase catalysts. With biologically generated formic acid in mind, we evaluated the performances of iridium‐based pianostool complexes bearing a cooperative ligand, which are known to catalyze formate decomposition. Interestingly, the phenylpyrazole‐derived catalyst [Cp*Ir(phenpz)(OH2)]+ (7, Cp* = pentamethylcyclopentadienyl, phenpz = 1‐phenylpyrazole) compares favourably with the very best systems [Cp*Ir(phenpzCO2H)H2O]+ [8, phenpzCO2H = 4‐(pyrazol‐1‐yl)benzoic acid] and [Cp*Ir(imim)H2O]2+ [11, imim = 2,2′‐bis(4,5‐dimethylimidazole)]. These catalysts display remarkable air tolerance, recyclability and activity under dilute aqueous conditions.
An integrated analytical approach for the compositional evaluation of different stages of fully ripened Jatropha curcas seed oil
Authors: Porwal Jyoti , Behra Babita , Ponnekanti Nagendramma , Bangwal Dinesh , Kaul Savita
Published: November 2014

The present study aims to determine the compositional changes including physicochemical characterization of Jatropha seed oil at three different stages of ripening (green: JO‐I; yellow: JO‐II; and brown: JO‐III). The moisture and oil content of Jatropha seeds was 60.83–10.12% and 34–32 (wt%) for JO‐I to JO‐III stages, respectively. The moisture content and acid value (mg KOH/g) of the oil was 8.88–4.05% and 0.62–2.86. Fatty acid composition (wt%) of the oil (JO‐I‐III stage) showed that palmitic (C16:0) acid decreases from 16.98 to 14.40 while as stearic (C18:0) acid increases from 7.19 to 7.57. The content of the monounsaturated acid (wt%) oleic (9‐cis C18:1) acid was 53.13, 41.96, and 60.93, while a diunsaturated acid, linoleic (9‐cis 12‐cis C18:2) acid, was 12.39, 32.52, and 14.93 in the JO‐I to JO‐III stages respectively, which was also confirmed by 1H NMR. The percentage of diunsaturated (9‐cis 12‐cis C18:2) acid follows a reverse trend to the monounsaturated (9‐cis C18:1) acid. The stage JO‐II (yellow) seems to be a turning point in the seed development. The studies also revealed the presence of sterol glucosides in early stage (JO‐I) of seed development; which declined at later stages. The results showed that variation in fatty acid composition together with the physicochemical properties can be helpful in understanding the biosynthesis of seed development.

Study describes the compositional changes including physicochemical characterization of Jatropha seed oil at three different stages of ripening (green: JO‐I; yellow: JO‐II; and brown: JO‐III) using integrated analytical techniques (i.e. 1H, 13C NMR, GC).
Practical Access to Aromatic Thiocyanates by CuCN‐Mediated Direct Aerobic Oxidative Cyanation of Thiophenols and Diaryl Disulfides
Authors: Castanheiro Thomas , Gulea Mihaela , Donnard Morgan , Suffert Jean
Published: November 2014

The practical and mild aerobic oxidative CuCN‐mediated cyanation of thiophenols and diaryl disulfides was investigated. The reaction was performed in air at room temperature and reached aromatic thiocyanates in moderate to good yields starting from a broad range of diversely functionalized substrates.
Isometric exercises reduce temporal summation of pressure pain in humans
Authors: Vaegter H.B. , Handberg G. , Graven‐Nielsen T.
Published: November 2014

Background

Aerobic and isometric exercises are known to decrease pain sensitivity. The effect of different types of exercise on central mechanisms such as temporal summation of pain (TSP) is less clear. This study hypothesized that both aerobic and isometric exercises would increase pressure pain tolerance (PTT) and reduce TSP with greater effects after higher‐intensity exercises.

Methods

One hundred thirty‐six healthy subjects (18–65 years; 68 women) participated in two randomized crossover experiments with trials on two different days. PTT and TSP were assessed before and after bicycling and a non‐exercise condition (experiment 1), and after low‐ and high‐intensity bicycling and low‐ and high‐intensity isometric arm and leg exercises with the dominant arm/leg (experiment 2). PTT and TSP were assessed before and after each exercise condition on the non‐dominant arm and leg by computer‐controlled cuff algometry. TSP was assessed by visual analogue scale (VAS) scores of the pain intensity during sequential cuff‐pressure stimulation at the pain tolerance intensity related to that specific time point.

Results

In experiment 1, bicycling, but not the non‐exercise condition, slightly increased PTT when assessed at the leg (p < 0.05). In experiment 2, isometric arm and leg exercises increased PTT and reduced VAS scores to sequential stimulation at the arm and leg (p < 0.05). No systematic difference was found between low‐ and high‐intensity exercises.

Conclusions

Different manifestations of hypoalgesia between aerobic and isometric exercises were found. Isometric exercises reduced temporal summation illustrating the potential for exercise as a rehabilitation procedure also targeting the central mechanisms.
Plants as river system engineers: further comments
Authors: Gurnell Angela
Published: November 2014

This paper is a response to commentary on the review by Gurnell (Plants as river system engineers. Earth Surface Processes and Landforms 39: 4–25, 2014). It covers three themes. First, it explains how the review focused on physical ecosystem engineering by plants, particularly in the northern humid temperate zone. Second, it explains how the review was structured to address that theme and why annual species were not highlighted. Within the humid temperate zone, mature plants of annual species are not present during the seasons of the year when fluvial processes are most active: they survive as seeds or young seedlings, and so their ability to act as river ecosystem engineers is limited. Third, some comments are made regarding the annual species, Himalayan balsam (Impatiens glandulifera), including the traits that enable it to be successful in riparian environments, its competitive ability, its potential role in influencing fluvial sediment dynamics, and the need for controlled experiments to characterize and quantify the latter over one or more complete years. Copyright © 2014 John Wiley & Sons, Ltd.
No observable effect of a glyphosate-based herbicide on two top predators of temporal water bodies
Authors: Ujszegi János , Gál Zoltán , Mikó Zsanett , Hettyey Attila
Published: November 2014

It has been implied that the application of pesticides is involved in the world-wide decline of biodiversity, but little is known about the influence of these chemicals on key predators of temporary wetlands. The direct impacts were examined of a frequently applied glyphosate-based herbicide on larval Aeshna cyanea (Müller, 1764; Odonata, Insecta) and adult male Lissotriton vulgaris (Linnaeus, 1758; Caudata, Amphibia), 2 top predators of Central European ephemeral ponds. The effects of herbicide exposure were measured on survival, behavior, body mass change, and predatory activity in an outdoor mesocosm experiment lasting for 17 d. No significant effects of exposure were observed in either predator species. The results suggest that the herbicide has no immediate effect on the predators studied at environmentally relevant concentrations and that these predators can also fulfill their top-down regulatory role in contaminated ecosystems. Environ Toxicol Chem 2014;9999:1–7. © 2014 SETAC
Investigation of cell association techniques in uplink cloud radio access networks
Authors: Yan Shi , Wang Wenbo , Zhao Zhongyuan , Ahmed Abana
Published: November 2014

Cloud radio access networks (C‐RANs) have been proposed as promising solutions to increase both the spectrum and energy‐efficiency performances in the fifth generation wireless communication systems. Many published works have discussed the concrete implementation technology to justify the huge development potential of C‐RAN. However, few litterateurs focused on characterising the cell association in the uplink. In this paper, we study the cell association techniques in uplink C‐RAN systems. Three received power based cell association techniques, namely the single best, N‐best and N‐th best, are presented and analysed. To characterise the random deployment of remote radio heads (RRHs) with multiple antenna configuration, stochastic geometry is used to evaluate the proposals' ergodic capacity, and the corresponding closed‐form expressions are derived. For the received power based cell association techniques, both analytical and simulation results demonstrate that the ergodic capacity gain from an increase in RRH density is larger than that of increasing the number of antennas per RRH. Copyright © 2014 John Wiley & Sons, Ltd.
Responses to Discrimination: Relationships Between Social Support Seeking, Core Self‐Evaluations, and Withdrawal Behaviors
Authors: Wagstaff María Fernanda , del Carmen Triana María , Kim Sihyun , Al‐Riyami Said
Published: November 2014

Drawing from the theory of conservation of resources (Hobfoll, 1989), we examined relationships between social support seeking as a response to perceived discrimination from supervisors, core self‐evaluations, and withdrawal behaviors. We further studied how the relationship between social support seeking and withdrawal behaviors was moderated by core self‐evaluations. With two different samples, we found, as expected, that social support seeking in response to discrimination from supervisors is positively related to employee withdrawal behaviors, and core self‐evaluations is negatively related to withdrawal behaviors. Across the two samples, we also found evidence that the relationship between social support seeking and withdrawal behaviors was weaker when core self‐evaluations were high compared to low. We discuss implications of our results in the context of past research. © 2014 Wiley Periodicals, Inc.
An antifungal mechanism of curcumin lies in membrane‐targeted action within Candida albicans
Authors: Lee Wonyoung , Lee Dong Gun
Published: November 2014

The aim of this study is to investigate the antifungal mechanism of curcumin. This polyphenolic compound has been used traditionally in Asia for medicinal, culinary, and other purposes. Although antifungal effect of curcumin has been reported, this is the first study for its mode of action underlying disruption of plasma membrane in Candida albicans. The leakage of potassium ion from the fungal cytosol and dissipation in membrane potential was detected by bis‐(1,3‐dibutylbarbituric acid)trimethine oxonol [DiBAC4] staining. We also investigated an increase in membrane permeability in curcumin‐treated C. albicans with influx of propidium iodide assay. Fluorescence analysis with 1,6‐diphenyl‐1,3,5‐hexatriene supported the membrane‐targeted mechanism of action indicating membrane disruption. On the basis of these results, we studied the effects of curcumin treatment on model membrane to elucidate its antifungal mechanism. Using calcein leakage assays from curcumin‐treated large unilamellar vesicles and giant unilamellar vesicles, we found that curcumin has membrane‐active mechanism inducing leakage of intracellular component through the flappy membrane. Therefore, this study suggests that curcumin exerts antifungal activity via inducing disruption of fungal plasma membrane. © 2014 IUBMB Life, 66(11):780–785, 2014
INTEGRATED APPLICATION OF RISK MANAGEMENT AND COST OF QUALITY
Authors: Brekka Lawrence T. , Picardal Chelo , Vlay George J.
Published: November 2014

Risk management and cost of quality are two management methodologies that are receiving increasing attention from organizations concerned with the management of large, complex design, development, manufacturing, and operational programs. Typically these two methodologies are treated as separate functions and are executed independently of each other. In fact, cost of quality determines information critical in identifying and assessing risks in a program, and risk management provides procedures for monitoring and mitigating the risks that are identified with that information. Program management will be enhanced by the coordinated application of cost of quality and risk management. Clear program management responsibilities among the system engineer, program control manager, and program manager ensure effective, coordinated application of the two methodologies.
A RISK MANAGEMENT PROGRAM FOR A TASK‐ORDER CONTRACT
Authors: Ramchandani C. , Ligon W. , Rabenstine D. , Bhatia K.
Published: November 2014

This paper describes a risk management program that Computer Sciences Corporation (CSC) developed for a NASA Goddard Space Flight Center (GSFC) task‐order contract. The program uses a closed‐loop risk management process, supported by a spreadsheet‐based tool to standardize the information that task managers must enter and to facilitate risk impact calculations. The paper addresses the challenges of developing and deploying a risk management program for a diverse task‐order contract. The paper also describes process improvement actions taken to maximize program acceptance among CSC task managers.
A CUSTOMER ORIENTED APPROACH TO OPTIMIZING SUBALLOCATIONS OF SYSTEM REQUIREMENTS
Authors: Hadel J. J. , Lakey P.
Published: November 2014

A proper Systems Engineering approach to aircraft requirements allocation demands that upper‐level performance requirements be flowed down and allocated to lower‐level subfunctions in a logical, traceable, structured process. Normally it is not in the customer's best interest to contractually specify suballocated values developed from the top requirement because such action borders on dictating hardware design solutions instead of focusing on communicating customer overall needs to the contractor. Because of this, the requirement flowdown process appears to offer opportunities for multiple feasible solutions which are all capable of meeting the customers top level requirement. Thus, there is need for a systems engineering process which is capable of identifying a “best choice” among these selections. At McDonnell Douglas, a creative approach to resolve this requirements flowdown issue has been developed. The approach provides guid‐ance identifying and rank ordering preferred design choices, developing requirements flowdown, and documenting rationale behind identification and selection of optimal choices. The process focuses on a guidance philosophy which identifies customer needs using Quality Function Deployment assessments in combination with linear optimization analyses to perform numerical suballocation of top requirements. The approach provides guidance towards solutions which protect the customer's interests without the need for the customer to dictate design solutions and contractual requirements at these suballocated levels of detail. An application of this process to the diagnostic requirements area has been packaged by McDonnell Douglas as a single integrated set of software modules which fit on a floppy disk capable of operating on a desktop PC.
REQUIREMENTS FOR DEVELOPMENT OF SOFTWARE REQUIREMENTS
Authors: Mar Brian W.
Published: November 2014

This paper (1) describes what the current literature identifies as qualities of good software requirements, (2) identifies and examines different categories of software requirement methods, and (3) concludes that methods used to develop software requirements, though not perfect, have advantages that can improve the development of requirements for any type of system. Twelve requirement qualities were identified from the literature and these were used to establish evaluation criteria for software requirement development methods. Three methods selected for evaluation were the Hatley‐Pirbhai method (1988), the CoRE (Consortium Requirements Engineering, SPC, 1992), and Requirements State Machine Language (RSML) develop by Leveson (1990). None of these method stands out as being superior and each have strengths and weaknesses depending upon the application, but each offers improvements over the text based methods used in traditional systems engineering efforts to create function/requirement sets.
TEACHING THE GENERATION OF OPERATIONS BASED REQUIREMENTS
Authors: DeFoe Joseph C.
Published: November 2014

This paper presents specific recommendations that have been found effective within IBM (now Loral) Federal Systems for teaching the process of generating operations‐based requirements. Specific recommendations include:

Base the workshop on a holistic, flexible process

Base exercises on a problem the students can relate to as a user

Ensure the students understand the needs the entity addresses before allowing them to begin requirements analysis

Have all exercises involve teams

Have at least two exercises using each critical method or technique covered in the workshop

Have multiple teams work the same problem

Construct class requirements definition examples such that there is at least one with a clearly superior resolution, and one with number of nearly equivalent “okay” resolutions
HOW TO DO AND USE REQUIREMENTS TRACEABILITY EFFECTIVELY
Authors: Curtis A. Scott
Published: November 2014

Every customer wants good requirements traceability when they start a new program. They want to ensure their contractor provide “tops down” traceability when deriving lower‐level requirements to ensure the original customer requirements are met thus avoid what is commonly called “requirements creep”. However, most customers are soon disappointed about the methodology their contractors use when trying to actually implement requirements traceability. After a while most contractors persuade their customers to relax their expectations and finally drop the requirements traceability task and say “Let's just design and build it, we're just wasting time.”

This paper will present a “how‐to‐do” requirements traceability more efficiently as well as “how‐to‐use” the information more effectively once you've done all that work. Topics include customer requirements traceability; derived requirements traceability; requirements allocation traceability; design compliance traceability; verification traceability; product sell‐off traceability; and operational lessons learned traceability. Real experience and lessons learned from many programs are revealed to help avoid some of the pitfalls and provide more efficient methods for performing these tasks. A generic, multi‐user requirements traceability database is discussed to describe how to automate the requirements traceability process for increased productivity.
RESPONSIVE CONSTRUCTIVIST REQUIREMENTS ENGINEERING: A PARADIGM
Authors: Mayhew Michael E. , Alessi R. Samuel
Published: November 2014

Poor requirements can lead to cost and schedule overruns and are therefore a source of low quality products and stressful work environments. This paper introduces a “responsive constructivist” paradigm for use by systems engineers to address these concerns. The paradigm is “responsive” to stakeholder statements in a nonlinear but methodological manner. “Constructivist” refers to the abstract construction of problem space based on a linguistic understanding of the various stakeholder's worldview of the problem, not necessarily upon the “preordinate positivist” beliefs of science. This paradigm asserts the necessity of approaching requirements such that the human component is more formally embraced. This challenges requirements engineers to evaluate their own stance of curiosity and neutrality. Additionally, questioning types and patterns aid to gather different views of the problem. This responsive constructivist systems engineering paradigm can improve the quality of interpersonal communications, thereby resulting in higher quality requirements and alternate problem abstractions.
Using Rapid Prototypes for Early Requirements Validation
Authors: Andrews Blake A. , Goeddel William C.
Published: November 2014

Using rapid prototypes for early validation can accelerate product development in all phases of the development life cycle. The most obvious benefit is the ability to evaluate requirements for applicability and unanticipated errors early in the development life cycle. However, additional benefits can also be realized during the follow‐on phases of the development life cycle. These benefits are often not considered as a part of the planning and decision making process regarding systems modeling tools. During the development of the 777 Autopilot Flight Director System (AFDS), system engineers at Collins Air Transport Division (CATD) evaluated both a conventional approach and a rapid prototyping approach in the development of two complex system functions. The lessons learned from this exercise could significantly change the way CATD system engineering teams approach system development in future projects.