bluuebunny/crossref_metadata_2025 huggingface dataset:
Mean‐state acceleration of cloud‐resolving models and large eddy simulations
Authors: Jones C. R. , Bretherton C. S. , Pritchard M. S.
Published: October 2015

Large eddy simulations and cloud‐resolving models (CRMs) are routinely used to simulate boundary layer and deep convective cloud processes, aid in the development of moist physical parameterization for global models, study cloud‐climate feedbacks and cloud‐aerosol interaction, and as the heart of superparameterized climate models. These models are computationally demanding, placing practical constraints on their use in these applications, especially for long, climate‐relevant simulations. In many situations, the horizontal‐mean atmospheric structure evolves slowly compared to the turnover time of the most energetic turbulent eddies. We develop a simple scheme to reduce this time scale separation to accelerate the evolution of the mean state. Using this approach we are able to accelerate the model evolution by a factor of 2–16 or more in idealized stratocumulus, shallow and deep cumulus convection without substantial loss of accuracy in simulating mean cloud statistics and their sensitivity to climate change perturbations. As a culminating test, we apply this technique to accelerate the embedded CRMs in the Superparameterized Community Atmosphere Model by a factor of 2, thereby showing that the method is robust and stable to realistic perturbations across spatial and temporal scales typical in a GCM.
Burden of Comorbidity in Systemic Lupus Erythematosus in the UK, 1999–2012
Authors: Rees Frances , Doherty Michael , Grainge Matthew , Lanyon Peter , Davenport Graham , Zhang Weiya
Published: October 2015

Objective

To estimate the comorbidity associated with systemic lupus erythematosus (SLE) in the UK during 1999–2012.

Methods

A retrospective cohort study using the UK Clinical Practice Research Datalink was conducted. Prevalent cases of SLE were matched by age, sex, and practice to 4 controls. The incidence of cardiovascular disease (CVD), stroke, end‐stage renal failure (ESRF), cancer, osteoporosis, and infection were calculated per 1,000 person‐years during the study period and compared to controls using Poisson regression to obtain incidence rate ratios (IRRs). IRRs were adjusted for baseline age, sex, body mass index, smoking status, alcohol intake, hypertension, hyperlipidemia, Charlson Index scores, and prednisolone use. Age‐ and sex‐specific incidence rates were calculated.

Results

When comparing the 7,732 prevalent cases of SLE with 28,079 matched controls, the unadjusted IRR was 1.98 (95% confidence interval [95% CI] 1.69–2.31) for CVD, 1.81 (95% CI 1.49–2.19) for stroke, 7.81 (95% CI 4.68–13.05) for ESRF, 1.28 (95% CI 1.17–1.40) for cancer, 2.53 (95% CI 2.27–2.82) for osteoporosis, and 1.49 (95% CI 1.40–1.58) for infection. After adjustment, the rates remained significantly higher in cases. Men with SLE had higher rates of CVD, stroke, and cancer, whereas women had higher rates of infection and osteoporosis. Those at younger ages were at the greatest relative risk compared with controls. Cases had significantly higher Charlson Index scores at baseline.

Conclusion

People with SLE in the UK have a greater burden of comorbidity and are more likely to develop CVD, stroke, ESRF, cancer, osteoporosis, and infection than people of the same age and sex.
Clinical Efficacy of Celecoxib Compared to Acetaminophen in Chronic Nonspecific Low Back Pain: Results of a Randomized Controlled Trial
Authors: Bedaiwi Mohamed K. , Sari Ismail , Wallis Dinny , O'shea Finbar D. , Salonen David , Haroon Nigil , Omar Ahmed , Inman Robert D.
Published: October 2015

Objective

In this randomized controlled trial, we compared the effect of celecoxib and acetaminophen on pain and magnetic resonance imaging (MRI) scores in patients with chronic nonspecific low back pain.

Methods

A total of 50 patients with chronic nonspecific low back pain were blindly randomized into 2 groups treated with celecoxib (200 mg twice daily) or acetaminophen (500 mg twice daily). Outcome measures included total back pain, nocturnal back pain, Oswestry Disability Index (ODI) scores, the Short Form 36 health survey to assess physical and mental status, and patient global assessment. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Metrology Index scores were also assessed before and after the therapy. The Spondyloarthritis Research Consortium of Canada scoring method was used to evaluate spinal MRI changes.

Results

Celecoxib showed a superior effect on total back pain, ODI, BASDAI, nocturnal back pain, and patient global assessment, compared to acetaminophen (P < 0.05). The number of patients with a significant change in back pain scales was higher in the celecoxib arm (ODI 34.8% versus 4.5%, nocturnal back pain 41.7% versus 9.1%, total back pain 33.3% versus 9.1%, and BASDAI 30.4% versus 9.1%; P < 0.01 for all). The responsiveness to celecoxib, calculated by Guyatt's Responsiveness Index, was 1.62, 1.28, 1.27, and 0.58 for the ODI, total back pain, BASDAI, and nocturnal back pain, respectively. The MRI scores for sacroiliac joints and spine showed no significant change with either treatment when compared with baseline values (P > 0.05).

Conclusion

There was superior efficacy of celecoxib compared with acetaminophen in chronic nonspecific low back pain. Inflammatory lesions of sacroiliac joints and spine are commonly seen in nonspecific low back pain, but these lesions did not change with either celecoxib or acetaminophen treatments and were not associated with clinical response to either agent.
Association of Low B Cell Count and IgG Levels With Infection, and Poor Vaccine Response With All‐Cause Mortality in an Immunosuppressed Vasculitis Population
Authors: David Morgan Matthew , Richter Alex , Al‐Ali Samer , Flint Julia , Yiannakis Constantina , Drayson Mark , Goldblatt David , Harper Lorraine
Published: October 2015

Objective

Patients with systemic vasculitis (SV) have an increased risk of all‐cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death.

Methods

Patients with SV in remission were vaccinated with pneumococcal 7‐valent conjugate, Haemophilus influenzae type b, and meningococcal group C conjugate vaccine and meningococcal polysaccharide groups A, C, Y, and W135 vaccines. Total IgG and antibody titers against specific antigens and lymphocyte subset analysis were performed before vaccination. Postvaccination antibody titers were measured at 4 weeks and 2 years, from which an antibody response score was calculated. Infections and death following vaccination were collected prospectively following vaccination.

Results

A total of 92 patients were safely vaccinated with no increase in disease relapse, median followup 4.6 years (interquartile range [IQR] 3.6–4.8 years). Eighteen patients died at a median of 2 years and the overall infection rate was 0.4 (IQR 0.2–1.3) infections/patient/year. Reduced serum IgG, B cell count, and CD4+ cell counts predicted poor vaccine response and infection but not death. The response rates to individual vaccine antigens was highly variable, with a median response rate of 46% (IQR 39–58%) of patients responding to each individual antigen. Vaccine response, age, and reduced renal function were independent predictors of all‐cause mortality in multivariate analysis.

Conclusion

Total IgG and B cell counts predict infection and response to vaccination. Vaccination in patients with SV in remission is safe and the response predicts all‐cause mortality. Vaccine response is a surrogate marker of immune system health.
Efficacy and Safety of Subcutaneous Golimumab in Methotrexate‐Naive Patients With Rheumatoid Arthritis: Five‐Year Results of a Randomized Clinical Trial
Authors: Emery Paul , Fleischmann Roy M. , Strusberg Ingrid , Durez Patrick , Nash Peter , Amante Eric Jason B. , Churchill Melvin , Park Won , Pons‐Estel Bernardo , Han Chenglong , Gathany Timothy A. , Xu Stephen , Zhou Yiying , Leu Jocelyn H. , Hsia Elizabeth C.
Published: October 2015

Objective

To evaluate the safety and efficacy of golimumab through 5 years in adults with active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX).

Methods

In the GO‐BEFORE study, 637 MTX‐naive adult patients with active RA were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4). Inadequate responders in groups 1, 2, and 3 entered early escape at week 28 to golimumab 50 mg + MTX, golimumab 100 mg + MTX, or golimumab 100 mg + MTX, respectively; remaining patients in group 1 could cross over to golimumab 50 mg + MTX at week 52. Assessments included the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response, the Disease Activity Score in 28 joints (DAS28) using C‐reactive protein (CRP) level, and the modified Sharp/van der Heijde score (SHS). Efficacy was analyzed using an intent‐to‐treat (ITT) analysis. Pharmacokinetics and immunogenicity were evaluated at selected visits.

Results

A total of 422 patients completed golimumab treatment through week 256. At week 256, 72.8%, 54.6%, and 38.0% of all patients in the full ITT population (n = 637) had an ACR20/50/70 response, respectively; 84.1% had a good or moderate DAS28‐CRP response; and 72.7% had a clinically meaningful improvement in physical function. Radiographic progression was minimal in all treatment groups through week 256, and the overall mean change from baseline in SHS was 1.36. Serum trough golimumab concentrations were approximately dose proportional and maintained through week 256. Antibodies to golimumab occurred in 9.6% of patients through week 256. Infections were the most common type of adverse event (AE); 204 of 616 patients (33.1%) had ≥1 serious AE.

Conclusion

Clinical efficacy with golimumab treatment was maintained through week 256 of the GO‐BEFORE trial of MTX‐naive RA patients. No unexpected AEs occurred; safety results through 5 years are consistent with earlier reports.
Patient‐Reported Outcomes From a Two‐Year Head‐to‐Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis
Authors: Fleischmann Roy , Weinblatt Michael E. , Schiff Michael , Khanna Dinesh , Maldonado Michael A. , Nadkarni Anagha , Furst Daniel E.
Published: October 2015

Objective

To report 2‐year patient‐reported outcomes (PROs) from the head‐to‐head Abatacept versus Adalimumab Comparison in Biologic‐Naive RA Subjects with Background Methotrexate (MTX) (AMPLE) trial.

Methods

AMPLE was a phase IIIb, randomized, investigator‐blinded trial. Biologic‐naive patients with rheumatoid arthritis (RA) and an inadequate response to MTX were randomized to subcutaneous (SC) abatacept (125 mg/week) or adalimumab (40 mg every 2 weeks) with background MTX. PROs (pain, fatigue, ability to perform work, and ability to perform daily activities) were compared up to year 2 for patients in each treatment group, as well as those who achieved low disease activity at both years 1 and 2 (responders) and those who did not (nonresponders).

Results

A total of 646 patients were randomized and treated with SC abatacept (n = 318) or adalimumab (n = 328). Baseline characteristics were balanced between the 2 treatment arms. Comparable improvements in PROs were observed in the abatacept and adalimumab groups over 2 years, with both groups achieving clinically meaningful improvements in PROs from baseline. At year 2, fatigue improved by 23.4 mm and 21.5 mm on a 100‐mm visual analog scale with abatacept and adalimumab, respectively. Clinical responders achieved greater improvements in PROs than nonresponders.

Conclusion

In biologic‐naive patients with active RA, despite prior MTX, treatment with SC abatacept or adalimumab with background MTX resulted in comparable improvements in PROs, which were highly correlated with physician‐reported clinical response end points.
Sex Variations in the Effects of Arthritis and Activity Limitation on First Heart Disease Event Occurrence in the Canadian General Population: Results From the Longitudinal National Population Health Survey
Authors: Schieir Orit , Hogg‐Johnson Sheilah , Glazier Richard H. , Badley Elizabeth M.
Published: October 2015

Objective

To estimate sex‐specific effects of arthritis and activity limitation on incident heart disease in a nationally representative, Canadian longitudinal population‐based survey.

Methods

Information on sociodemographic variables, self‐reported physician‐diagnosed chronic conditions (including arthritis and heart disease), activity limitations, and traditional risk factors was collected every 2 years from 1994–1995 through 2010–2011 as part of the longitudinal Canadian National Population Health Survey. Deaths due to ischemic heart disease (International Classification of Diseases, Tenth Revision [ICD‐10] codes I20–I25) and heart failure (ICD‐10 codes I50.0–I50.9) were confirmed against the Canadian Vital Statistics Database. Discrete‐time survival analysis stratified by sex was used to estimate effects of arthritis and activity limitation on first heart disease event occurrence.

Results

The study included 12,591 participants with no prior history of heart disease and 1,783 incident heart disease events. After adjusting for common risk factors, arthritis was associated with a significant increased risk of incident heart disease in women (adjusted odds ratio [OR] 1.58, 95% confidence interval [95% CI] 1.23–2.02). Even higher risks were reported in women with arthritis and activity limitation (OR 2.19, 95% CI 1.61–2.97). Arthritis was not associated with incident heart disease in men, except for when also reported with activity limitation (OR 1.60, 95% CI 1.14–2.26).

Conclusion

Women with arthritis, and men with arthritis and activity limitation, have significant excess risks for developing heart disease in the general population. These findings point to the need for improved access to arthritis care, cardiovascular prevention strategies, particularly in women with arthritis, and directed interventions toward prevention of activity limitation.
Skin Telangiectasia and the Identification of a Subset of Systemic Sclerosis Patients With Severe Vascular Disease
Authors: Hurabielle Charlotte , Avouac Jérôme , Lepri Gemma , de Risi Tullia , Kahan André , Allanore Yannick
Published: October 2015

Objective

Cutaneous telangiectasia (CT) are common in systemic sclerosis (SSc) patients, but their ability to stratify patients by risk is poorly known. We aimed to determine whether the number and size of CT were associated with the pattern of microvascular lesions assessed by nailfold videocapillaroscopy (NVC) and markers reflecting the severity of SSc‐related vasculopathy.

Methods

We performed a cross‐sectional study, including consecutive SSc patients over a 6‐month period. We also considered 3 predefined subsets of patients according to the number of hand or face CT: absence, ≤10, or >10 hand or face CT (profuse CT). Pseudotumoral CT were defined as CT with >5 mm diameter.

Results

A total of 87 patients were included, of whom 75 (86%) had CT (27 with profuse and 19 with pseudotumoral CT). Profuse and pseudotumoral CT were both associated with capillary loss (P < 0.001 and P = 0.002, respectively) and severe neoangiogenesis (P = 0.015 and P = 0.041, respectively), 2 hallmarks of the late NVC pattern. In multivariate analysis, profuse CT were independently associated with past or current digital ulcers (odds ratio [OR] 2.95 [95% confidence interval (95% CI) 1.09–19.63]), and pseudotumoral CT were independently associated with the late NVC pattern (OR 4.84 [95% CI 1.32–26.19]) and with precapillary pulmonary hypertension (OR 12.60 [95% CI 1.68–94.53]).

Conclusion

We demonstrate that the number and size of CT are associated with the most severe NVC pattern. In addition, profuse and pseudotumoral CT identify a subset of patients with a more severe vascular phenotype. Further prospective studies should determine whether CT number and size could serve as an early clinical biomarker for the development of severe vascular disease.
Design and Characterization of a Multifunctional pH‐Triggered Peptide C8 for Selective Anticancer Activity
Authors: Lu Sheng , Bennett W. F. Drew , Ding Yong , Zhang Lei , Fan Helen Y. , Zhao Danyang , Zheng Tao , Ouyang Ping‐Kai , Li Jason , Wu Yan , Xu Wen , Chu Dafeng , Yuan Yongfang , Heerklotz Heiko , Karttunen Mikko , Chen P.
Published: October 2015

Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on‐demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH‐triggered anticancer peptide, is developed by incorporating histidine‐mediated pH‐sensitivity, amphipathic helix, and amino acid pairing self‐assembly design. We designed C8 to function as a pH‐responsive nanostructure whose cytotoxicity can be switched on and off by its self‐assembly: Noncytotoxic β‐sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore‐forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH‐responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self‐assembling peptides for therapeutic and drug delivery applications.
An Abnormal N‐Heterocyclic Carbene‐Based Palladium Dimer: Aqueous Oxidative Heck Coupling Under Ambient Temperature
Authors: Hota Pradip Kumar , Vijaykumar Gonela , Pariyar Anand , Sau Samaresh Chandra , Sen Tamal K. , Mandal Swadhin K.
Published: October 2015

Herein we report the synthesis of a new abnormal N‐heterocyclic carbene (aNHC)‐based ligand and its use in synthesizing an acetate bridged CH activated palladium dimer (1). In complex 1, the carbene ligand displays an abnormal mode of binding with the palladium(II) ion. We used complex 1 as a catalyst for the oxidative Heck coupling reaction of arylboronic acids with electron‐deficient as well as electron‐rich olefins at ambient temperature in water to produce selectively the β‐arylated products in good to excellent yields.

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Iodine‐Promoted Metal‐Free Aromatization: Synthesis of Biaryls, Oligo p‐Phenylenes and A‐Ring Modified Steroids
Authors: Domingo Victoriano , Prieto Consuelo , Castillo Alexis , Silva Lucia , Quílez del Moral José F. , Barrero Alejandro F.
Published: October 2015

We describe efficient procedures based on the use of iodine for the synthesis of biaryls from arylcyclohexenols or arylcyclohexanols using sub‐stoichiometric/catalytic iodine and dimethyl sulfoxide (DMSO) as oxidant. Heteroarylcyclohexanols also produced the corresponding biaryl products. It was proven that biphenyl can also be efficiently obtained when the quantity of iodine was reduced to 0.05 equiv. The method is compatible with different functional groups in the aromatic ring (either electron‐donating or electron‐withdrawing groups). For substrate scope, apart from cyclohexanone and cyclohexenone, some substituted cyclohexanones were also used to synthesize the starting arylcyclohexanols. The process was applied to the synthesis of oligo p‐phenylenes and A‐ring aromatized steroids, where the combined use of I2/DMSO not only provoked the necessary migration of the methyl group at C‐10, but also further extended the conjugation.

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Nitrative Cyclization of 1‐Ethynyl‐2‐(vinyloxy)benzenes to Access 1‐[2‐(Nitromethyl)benzofuran‐3‐yl] Ketones Through Dioxygen Activation
Authors: Hu Ming , Liu Bang , Ouyang Xuan‐Hui , Song Ren‐Jie , Li Jin‐Heng
Published: October 2015

A new metal‐free method for the nitrative cyclization of 1‐ethynyl‐2‐(vinyloxy)benzenes with tert‐butyl nitrite (t‐BuONO), air and water at room temperature is presented, in which an oxygen atom is introduced into the carbon‐carbon triple bond to form a new carbonyl group through dioxygen activation.

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The Squaramide‐Catalyzed 1,3‐Dipolar Cycloaddition of Nitroalkenes with N‐2,2,2‐Trifluoroethylisatin Ketimines: An Approach for the Synthesis of 5′‐Trifluoromethyl‐spiro[pyrrolidin‐3,2′‐oxindoles]
Authors: Sun Quantao , Li Xiaoyuan , Su Jinhuan , Zhao Long , Ma Mingxia , Zhu Yuanyuan , Zhao Yanyan , Zhu Ranran , Yan Wenjin , Wang Kairong , Wang Rui
Published: October 2015

A Cinchona alkaloid‐derived squaramide‐catalyzed asymmetric cycloaddition of trfluoromethyl‐containing azomethine ylides with β‐nitroalkenes was realized under mild conditions. A series of biologically important 5′‐trifluoromethyl‐ spiro[pyrrolidin‐3,2′‐oxindoles] was synthesized efficiently by this process in excellent yields, enantioseletivities and diastereoselectivities.

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Hemin‐Catalyzed, Cyclodextrin‐Assisted Insertion of Carbenoids into NH Bonds
Authors: Xu Xiaofei , Li Chang , Tao Zhihao , Pan Yuanjiang
Published: October 2015

An aqueous hemin‐catalyzed, cyclodextrin‐assisted NH insertion reaction of α‐diazo ester into aromatic amines is described here. This aqueous catalytic system showed good compatibility with various arylamines, with yields up to 96%. A size‐controlled reaction phenomenon by different cyclodextrins (CDs) was also observed when ethyl diazoacetate (EDA) was used. The reaction mechanism was also preliminarily proposed on the basis of designed control experiments.

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Copper(I) Complexes Bearing Carbenes Beyond Classical N‐Heterocyclic Carbenes: Synthesis and Catalytic Activity in “Click Chemistry”
Authors: Bidal Yannick D. , Lesieur Mathieu , Melaimi Mohand , Nahra Fady , Cordes David B. , Athukorala Arachchige Kasun S. , Slawin Alexandra M. Z. , Bertrand Guy , Cazin Catherine S. J.
Published: October 2015

The synthesis and characterization of abnormal N‐heterocyclic carbene, cyclic (alkyl)(amino)carbene, and mesoionic carbene copper(I) complexes are reported. These organometallic species are obtainedviaa versatile and inexpensive synthetic pathway using readily available reactants, namely copper oxide and iminium salts. The catalytic activity of this series of complexes was evaluated in the [3+2] cycloaddition of alkynes with azides (CuAAC). Outstanding catalytic properties were observed for the abnormal NHC‐ and triazolylidene‐based copper(I) complexes.

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Catalytic Aerobic Oxidation of Arylhydrazides with Iron Phthalocyanine
Authors: Hashimoto Takuma , Hirose Daisuke , Taniguchi Tsuyoshi
Published: October 2015

A convenient method for the synthesis of 2‐arylazocarboxylates from 2‐arylhydrazinecarboxylates by aerobic oxidation with iron phthalocyanine is described. The reaction is applicable to oxidative activation of 1‐acyl‐2‐phenylhydrazines. Some preliminary experiments suggest Michaelis–Menten kinetics and participation of radical species in the reaction mechanism.

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Synthesis of O,S‐Containing Polycycles via One‐Pot Michael Addition–Cycloacetalisation Cascade
Authors: Bankar Siddheshwar K. , Shirke Rajendra P. , Ramasastry S. S. V.
Published: October 2015

An efficient diversity‐oriented approach for the synthesis of previously unknown di‐, tri‐, tetra‐ and spirocyclic pyrano‐1,4‐dioxinones, pyrano‐1,4‐dithiinones and pyrano‐1,4‐oxathiinones from readily available starting compounds has been described. Cascade Michael addition–cycloacetalisation of acetoxy‐, alkoxy‐, and aryloxypyranones and 1,2‐dinucleophiles under mild Lewis acidic conditions provides a direct access to oxygen and sulfur‐containing complex heterocycles. Mechanistic aspects of the cascade process were elucidated in light of experimental facts. The methodology described herein shows high promise for the synthesis of several bioactive natural products as well as pharmaceutically important compounds.

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Stannylation and Stille Coupling of Base‐Sensitive Tetrahydroxanthones to Heteromeric Biaryls
Authors: Lindner Stephanie , Nieger Martin , Bräse Stefan
Published: October 2015

Herein, the synthesis of heteromeric tetrahydroxanthone biaryls is described, a widespread core structure of many natural products. The development of both stannylation and Stille coupling procedures of base‐sensitive tetrahydroxanthones enabled their coupling with benzene derivatives as well as with xanthenes. These methods provide access to structures that are analogous to parnafungins as well as to dimeric compounds similar to secalonic acids or phomoxanthones.

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Oxidative Alkene Cleavage Catalysed by Manganese‐Dependent Cupin TM1459 from Thermotoga maritima
Authors: Hajnal Ivan , Faber Kurt , Schwab Helmut , Hall Mélanie , Steiner Kerstin
Published: October 2015

A novel biocatalytic oxidative alkene cleavage activity was identified in protein TM1459 from Thermotoga maritima, a so far uncharacterised metalloprotein with a cupin fold, which preferentially binds manganese (over iron and zinc). Various styrene derivatives were converted with high chemoselectivity to the corresponding carbonyl compounds by the manganese‐containing protein, using organic hydroperoxide and molecular oxygen as oxidant. 4‐Chloroacetophenone could be obtained in 40% conversion from 4‐chloro‐α‐methylstyrene (50 mM) in a biphasic system using ethyl acetate as organic cosolvent (5% v/v), while 76% conversion was obtained at a lower substrate concentration (10 mM). This novel biocatalyst can be easily over‐expressed in Escherichia coli in exceptionally high yield and purified, and thus may offer a valuable and safer alternative in oxidative CC bond cleavage reactions for synthetic applications.

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Enantioselective Nickel‐Catalyzed Hydrocyanation using Chiral Phosphine‐Phosphite Ligands: Recent Improvements and Insights
Authors: Falk Anna , Cavalieri Alberto , Nichol Gary S. , Vogt Dieter , Schmalz Hans‐Günther
Published: October 2015

The asymmetric hydrocyanation of vinylarenes was investigated using hydrogen cyanide (HCN) in the presence of 5 mol% of a catalyst prepared from a phenol‐derived chiral phosphine‐phosphite ligand and bis(cyclooctadiene)nickel [Ni(cod)2]. The reactions were performed in tetrahydrofuran (THF) at room temperature to give exclusively the branched nitriles with superior enantioselectivities of 88–99% ee for vinylarenes and 74–94% ee for vinylheteroarenes, respectively. Using styrene as a model substrate it was shown that the catalyst loading could be decreased to 0.42 mol% without any loss of selectivity (88% ee). The structure of the pre‐catalyst, i.e., a tetrahedral Ni(0)(P,P‐chelate)(cod) complex, was proven by X‐ray and NMR analysis. Additional insight into the reaction course was gained by monitoring the hydrocyanation of styrene‐d8 by means of 2D NMR spectroscopy.

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Asymmetric Hydrogenation of β‐Secondary Amino Ketones Catalyzed by a Ruthenocenyl Phosphino‐oxazoline‐ruthenium Complex (RuPHOX‐Ru): the Synthesis of γ‐Secondary Amino Alcohols
Authors: Wang Jianxia , Wang Yanzhao , Liu Delong , Zhang Wanbin
Published: October 2015

A ruthenocenyl phosphino‐oxazoline‐ruthenium complex (RuPHOX‐Ru) was applied successfully to the asymmetric hydrogenation of β‐secondary amino ketones, directly affording the corresponding chiral γ‐secondary amino alcohols in up to 99% yield and with 99% ee. Reaction with β‐(benzylamino)‐1‐phenylpropan‐1‐one could be performed on a gram‐scale with a relatively low catalyst loading (up to 2000 S/C). The resulting hydrogenated product could be used for the synthesis of synthetically useful compounds.

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Synthesis and Evaluation of Organic–Inorganic Hybrid Molecularly Imprinted Monolith Column for Selective Recognition of Acephate and Phosphamidon in Vegetables
Authors: Wang Qingqing , Zhang Xin , Li Jie , Xu Zhixiang
Published: October 2015

In this study, a molecularly imprinted capillary monolithic column that can recognize the acephate and phosphamidon was synthesized by the molecular imprinting technique combined with a nonhydrolytic sol–gel process using intermediate 4‐(dimethoxyphosphorothioylamino)butanoic acid as the template molecule. The resulting material was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The potential of the prepared imprinted monolithic columns used as the stationary phase for capillary electrochromatography (CEC) was evaluated. The effects of operating voltage, pH, and acetonitrile content on the electroosmotic flow of the imprinted monolithic columns were evaluated in CEC. Under optimal conditions, the cucumber and lettuce samples spiked with acephate and phosphamidon were extracted and analyzed by this method with satisfactory recoveries ranging from 79.7 to 94.4%. The relative standard deviation for five replicates of 0.1 mg/L mixed solution of acephate and phosphamidon was in the range of 2.7–4.6%.
Parental counseling in trisomy 18: Novel insights in prenatal features and postnatal survival
Authors: Russo Francesca M. , Pozzi Elisa , Verderio Maria , Bernasconi Davide P. , Giardini Valentina , Colombo Carla , Maitz Silvia , Vergani Patrizia
Published: October 2015

Data on the outcome of trisomy T18 (T18) when diagnosed during pregnancy are lacking. We performed a retrospective study of pregnancies complicated by T18 diagnosed at our center and a literature search for publications on the topic, with pooled estimates of survival rates at different gestational and post‐natal ages. In our series, all the 60 patients included in the analysis had prenatally detected ultrasound anomalies, which were evidenced in the first trimester or at the second trimester scan in 73% of cases. In the continued pregnancies, ultrasound findings did not correlate with prenatal or post‐natal outcome. A meta‐analysis of available literature and our data showed that 48% [37–60%] of fetuses were live born, and among these 39% [11–72%] survived beyond 48 hr and 11% [3–21%] beyond 1 month. Our results confirm that prenatal ultrasound has high sensitivity in detection of T18 but is not predictive of the outcome of the continued pregnancies. The data on survival support that T18, even when antenatally diagnosed, cannot be considered as a uniformly lethal syndrome. © 2015 Wiley Periodicals, Inc.
Aortic coarctation and carotid artery aneurysm in a patient with hardikar syndrome: Cardiovascular implications for affected individuals
Authors: Ryan Kaitlin M. , Ellis Alexander R. , Raafat Reem , Bhoj Elizabeth J. , Hakonarson Hakon , Li Dong , Schrier Vergano Samantha
Published: October 2015

Hardikar syndrome is a multiple congenital anomaly syndrome first characterized in 1992 by Hardikar et al. to describe two individuals with cholestasis, cleft lip/palate, retinal pigmentation, intestinal abnormalities, and genitourinary anomalies. Between 1992 and 2002, four individuals with Hardikar syndrome were reported in the literature. The fourth individual [Maluf et al. (2002), Transplantation 74:1058–1061; Poley and Proud (2008) Am J Med Genet Part A 146A:2473–2479], who had progressive cholestatic liver disease ultimately requiring liver transplantation, has continued to be followed at our institution. Recently, at the age of 14 years, during an evaluation for refractory hypertension, she was found to have developed coarctation of the aorta that was treated with aortic angioplasty and stenting, dramatically improving her hypertension. Further vascular investigation also revealed a small aneurysm of her carotid artery requiring neurosurgical evaluation and anticoagulant therapy. To our knowledge, these vascular anomalies have not been reported in Hardikar syndrome and the high association of congenital heart disease in the individuals with Hardikar syndrome has not been further addressed. Herein, we discuss this additional clinical information, speculate briefly on possible molecular etiologies, and discuss potential cardiac surveillance recommendations. We hope that broadening the known phenotype of this very rare disorder will further aid clinicians in their management and surveillance for these individuals. © 2015 Wiley Periodicals, Inc.
Recognition and prevention of child abuse in the child with disability
Authors: Nowak Catherine Bearce
Published: October 2015

Children with disabilities (CWD) are victims of abuse more frequently than children in the general population. The features of their underlying conditions make it more difficult to detect abuse and on occasion can be mistaken for abuse. Thus, the expertise of the clinical geneticist is often vital to properly identifying maltreatment in this vulnerable population. The purpose of this article is to review the magnitude of abuse in the population of CWD, to identify the aggravating factors, and to suggest practice changes in order to both diagnose and reduce the likelihood of abuse in CWD. © 2015 Wiley Periodicals, Inc.
Triphenylphosphine/Triethylamine‐Mediated Decarboxylation of α‐Oxocarboxylic Acids and Application in a One‐Pot Synthesis of Deuterated Aldehydes.
Authors: Niu Guang‐Hao , Huang Pei‐Ru , Chuang Gary Jing
Published: October 2015

A simple method for synthesizing aldehydes from α‐oxocarboxylic acids via decarboxylation in the presence of PPh3 and Et3N is reported. The decarboxylation can be performed on a wide range of α‐oxocarboxylic acids; electron‐rich/electron‐deficient aryl, heteroaryl, as well as alkyl α‐oxocarboxylic acids. This method also provides a convenient procedure for the synthesis of deuterated aldehydes using D2O as deuterium source in a facile one‐pot process.
Standing on the shoulders of apes: Analyzing the form and function of the hominoid scapula using geometric morphometrics and finite element analysis
Authors: Püschel Thomas A. , Sellers William I.
Published: October 2015

Objective

The aim was to analyze the relationship between scapular form and function in hominoids by using geometric morphometrics (GM) and finite element analysis (FEA).

Methods

FEA was used to analyze the biomechanical performance of different hominoid scapulae by simulating static postural scenarios. GM was used to quantify scapular shape differences and the relationship between form and function was analyzed by applying both multivariate‐multiple regressions and phylogenetic generalized least‐squares regressions (PGLS).

Results

Although it has been suggested that primate scapular morphology is mainly a product of function rather than phylogeny, our results showed that shape has a significant phylogenetic signal. There was a significant relationship between scapular shape and its biomechanical performance; hence at least part of the scapular shape variation is due to non‐phylogenetic factors, probably related to functional demands.

Discussion

This study has shown that a combined approach using GM and FEA was able to cast some light regarding the functional and phylogenetic contributions in hominoid scapular morphology, thus contributing to a better insight of the association between scapular form and function. Am J Phys Anthropol 159:325–341, 2016. © 2015 Wiley Periodicals, Inc.
Non‐interacting single‐impurity Anderson model: solution without using the equation‐of‐motion method
Authors: Mahmoud Zakaria M.M. , Gebhard Florian
Published: October 2015

Ground‐state properties of the non‐interacting symmetric single‐impurity Anderson model (SIAM) are derived from the corresponding eigenenergy equation. Explicit formulae are given for the ground‐state energy, the hybridization, and the momentum distribution that are essential quantities for variational approaches to the interacting model. Various spectral functions, e.g., the total density of states, the phase shift function, and the impurity spectral function, are shown to agree with those obtained from the equation‐of‐motion method (see supplementary material). For a constant hybridization strength and a semi‐elliptic host density of states it is seen that the impurity spectral function builds up weight at the band edges.

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Direkte Modulation von Aktivität und Funktion kleiner GTPasen
Authors: Cromm Philipp M. , Spiegel Jochen , Grossmann Tom N. , Waldmann Herbert
Published: October 2015

Kleine GTPasen bilden eine Familie von GDP‐/GTP‐bindenden Proteinen, die als biomolekulare Schalter innerhalb von Zellen wirken. Fehlfunktionen oder Fehlregulierungen kleiner GTPasen stehen in Verbindung mit zahlreichen menschlichen Erkrankungen, was diese Proteine zu einem vielversprechenden Ziel der pharmazeutischen Forschung macht. Allerdings werden kleine GTPasen oftmals als pharmakologisch nicht adressierbar klassifiziert, da jahrzehntelange Bemühungen keinerlei klinisch relevante Verbindungen liefern konnten, die die Aktivität kleiner GTPasen direkt modulieren. Die Entdeckung neuer, transienter Bindetaschen an den Proteinoberflächen und die Anwendung neuartiger Techniken haben dem Feld jedoch kürzlich neuen Schwung verliehen. Neben Ras‐Proteinen rücken zudem vermehrt andere kleine GTPasen in den Fokus der Forschung. Dieser Artikel bietet einen Überblick über die relevanten Aspekte der Superfamilie kleiner GTPasen und fasst die jüngsten Fortschritte und Perspektiven für die direkte Modulierung dieser herausfordernden Proteinklasse zusammen.
Funktionelle Synthese des Lichtsammelkomplexes II in Polymermembran‐Architekturen
Authors: Zapf Thomas , Tan Cherng‐Wen Darren , Reinelt Tobias , Huber Christoph , Shaohua Ding , Geifman‐Shochat Susana , Paulsen Harald , Sinner Eva‐Kathrin
Published: October 2015

Eines der wirkungsvollsten Konzepte der Natur ist die Aufnahme und Umwandlung von Sonnenenergie durch den Lichtsammelkomplex II (LHCII). Dieser Protein‐Pigment‐Komplex mit seinen zugehörigen Pigmenten ist der Hauptsonnenenergiekollektor in Pflanzen. Unser Ziel ist es, ein stabiles, reproduzierbares und ressourcenschonendes LHCII‐Pigment‐Material außerhalb der pflanzlichen Zelle zu generieren, das genauso bereit und in der Lage zur Aufnahme von Sonnenenergie ist. Wir verwendeten dafür ein konventionelles, zellfreies Proteinsynthesesystem aus Weizenkeimen und beobachteten eine cotranslationale Insertion von LHCII‐Proteinen in die Polymermembranen, die als Polymersomen der Synthesemischung zugegeben worden waren. Eine einheitliche Insertionsrichtung der Proteine in den Polymermembranen konnten wir durch einen Protease‐Assay nachweisen. Die Gegenwart des LHCII bewirkte einen Anstieg der Chlorophyllkonzentration in den Polymermembranen, und die Oberflächenplasmonen‐verstärkte Fluoreszenzspektroskopie (SPFS) ermöglichte die Messung des Energietransfers von Chl b nach Chl a, was als Indikator für die native Faltung des LHC‐Proteins gilt.
Ultrafine Molybdenum Carbide Nanoparticles Composited with Carbon as a Highly Active Hydrogen‐Evolution Electrocatalyst
Authors: Ma Ruguang , Zhou Yao , Chen Yongfang , Li Pengxi , Liu Qian , Wang Jiacheng
Published: October 2015

The replacement of platinum with non‐precious‐metal electrocatalysts with high efficiency and superior stability for the hydrogen‐evolution reaction (HER) remains a great challenge. Herein, we report the one‐step synthesis of uniform, ultrafine molybdenum carbide (Mo2C) nanoparticles (NPs) within a carbon matrix from inexpensive starting materials (dicyanamide and ammonium molybdate). The optimized catalyst consisting of Mo2C NPs with sizes lower than 3 nm encapsulated by ultrathin graphene shells (ca. 1–3 layers) showed superior HER activity in acidic media, with a very low onset potential of −6 mV, a small Tafel slope of 41 mV dec−1, and a large exchange current density of 0.179 mA cm−2, as well as good stability during operation for 12 h. These excellent properties are similar to those of state‐of‐the‐art 20 % Pt/C and make the catalyst one of the most active acid‐stable electrocatalysts ever reported for HER.
Entschlüsselung einer repetitiven Amyloidsequenz: Korrelation von Biofilm‐extrahierten und segmental markierten Curli‐Fimbrien mittels Festkörper‐NMR‐Spektroskopie
Authors: Schubeis Tobias , Yuan Puwei , Ahmed Mumdooh , Nagaraj Madhu , van Rossum Barth‐Jan , Ritter Christiane
Published: October 2015

Curli sind funktionelle bakterielle Amyloide, die durch eine ausgefeilte Biogenesemaschinerie hergestellt werden. Einblicke in ihre Faltung und Regulierung kann unser Verständnis der Amyloidbildung erweitern. Allerdings ist die Aufklärung hochaufgelöster Strukturen von Amyloiden aufgrund ihrer Tendenz zu strukturellen Polymorphismen weiterhin eine Herausforderung. Hier vergleichen wir qualitativ hochwertige Festkörper‐NMR‐Spektren von Curli, die aus Biofilmen isoliert wurden, mit rekombinant hergestellten Curli, und zeigen so, dass sie eine ähnliche, gut definierte β‐Solenoid‐Struktur annehmen. Curli‐Untereinheiten bestehen aus fünf repetitiven Sequenzwiederholungen, die in den NMR‐Spektren zu einer starken Resonanzüberlagerung führen. Durch die Anwendung segmentaler Isotopenmarkierung ist es gelungen, die Signale einer einzelnen Sequenzwiederholung eindeutig zuzuordnen. Die gewonnenen Sekundärstrukturinformationen zeigen, dass alle Wiederholungen höchstwahrscheinlich strukturell äquivalent sind.
Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A
Authors: Wada Hiroki , Williams Huw E. L. , Moody Christopher J.
Published: October 2015

The power of rhodium–carbene methodology in chemistry is demonstrated by the synthesis of a structurally complex polyazole antibiotic. Plantazolicin A, a novel soil‐bacterium metabolite, comprises a linear array of 10 five‐membered rings in two pentacyclic regions that derive from ribosomal peptide synthesis followed by extensive posttranslational modification. The compound possesses potent antimicrobial activity, and is selectively active against the anthrax‐causing organism. A conceptually different synthesis of plantazolicin A is reported in which the key steps are the use of rhodium(II)‐catalyzed reactions of diazocarbonyl compounds to generate up to six of the seven oxazole rings of the antibiotic. NMR spectroscopic studies and molecular modeling reveal a likely dynamic hairpin conformation with a hinge region around the two isoleucine residues. The compound has modest activity against methicillin‐resistant Staphylococcus aureus (MRSA).
Nanoporous Graphene with Single‐Atom Nickel Dopants: An Efficient and Stable Catalyst for Electrochemical Hydrogen Production
Authors: Qiu H.‐J. , Ito Yoshikazu , Cong Weitao , Tan Yongwen , Liu Pan , Hirata Akihiko , Fujita Takeshi , Tang Zheng , Chen Mingwei
Published: October 2015

Single‐atom nickel dopants anchored to three‐dimensional nanoporous graphene can be used as catalysts of the hydrogen evolution reaction (HER) in acidic solutions. In contrast to conventional nickel‐based catalysts and graphene, this material shows superior HER catalysis with a low overpotential of approximately 50 mV and a Tafel slope of 45 mV dec−1 in 0.5 M H2SO4 solution, together with excellent cycling stability. Experimental and theoretical investigations suggest that the unusual catalytic performance of this catalyst is due to sp–d orbital charge transfer between the Ni dopants and the surrounding carbon atoms. The resultant local structure with empty C–Ni hybrid orbitals is catalytically active and electrochemically stable.
Membrane Disruption and Enhanced Inhibition of Cell‐Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin‐Resistant Bacteria
Authors: Yarlagadda Venkateswarlu , Samaddar Sandip , Paramanandham Krishnamoorthy , Shome Bibek R. , Haldar Jayanta
Published: October 2015

Resistance to glycopeptide antibiotics, the drugs of choice for life‐threatening bacterial infections, is on the rise. In order to counter the threat of glycopeptide‐resistant bacteria, we report development of a new class of semi‐synthetic glycopeptide antibiotics, which not only target the bacterial membrane but also display enhanced inhibition of cell‐wall biosynthesis through increased binding affinity to their target peptides. The combined effect of these two mechanisms resulted in improved in vitro activity of two to three orders of magnitude over vancomycin and no propensity to trigger drug resistance in bacteria. In murine model of kidney infection, the optimized compound was able to bring bacterial burden down by about 6 logs at 12 mg kg−1 with no observed toxicity. The results furnished in this report emphasize the potential of this class of compounds as future antibiotics for drug‐resistant Gram‐positive infections.
Meltable Spin Transition Molecular Materials with Tunable Tc and Hysteresis Loop Width
Authors: Romero‐Morcillo Tania , Seredyuk Maksym , Muñoz M. Carmen , Real Jose A.
Published: October 2015

Herein, we report a way to achieve abrupt high‐spin to low‐spin transition with controllable transition temperature and hysteresis width, relying not on solid‐state cooperative interactions, but utilizing coherency between phase and spin transitions in neutral FeII meltable complexes.
Metal‐Free Hydrosilylation Polymerization by Borane Catalyst
Authors: Kim Dong Wook , Joung Seewon , Kim Jeung Gon , Chang Sukbok
Published: October 2015

The first example of metal‐free hydrosilylation polymerization between dienes and disilanes is developed by using a borane catalyst, B(C6F5)3to replace precious transition‐metal‐based systems. Under the easy‐to‐handle and mild conditions, a step‐growth polymerization of two readily available diene and disilane units was achieved with high degrees of polymerization. Various combinations of dienes and disilanes produced polycarbosilanes with a broad range of structures and properties.
Facile Synthesis of N‐Carboranyl Amines through an ortho‐Carboryne Intermediate
Authors: Cheng Ruofei , Zhang Jie , Zhang Jiji , Qiu Zaozao , Xie Zuowei
Published: October 2015

The efficient o‐carboryne precursor 1‐Li‐2‐OTf‐o‐C2B10H10 reacts with lithium amides at room temperature to give a series of N‐carboranyl amines in moderate to high isolated yields. This reaction is compatible with a broad substrate scope from primary to secondary, alkyl to aryl amines. The reaction mechanism is also proposed on the basis of experimental results and DFT calculations. This represents the first general and efficient method for the synthesis of 1‐NR1R2‐o‐carboranes.
Cobalt‐katalysierte Alkylierung von aromatischen Aminen durch Alkohole
Authors: Rösler Sina , Ertl Michael , Irrgang Torsten , Kempe Rhett
Published: October 2015

Die Implementierung von preiswerten, auf der Erde häufig vorkommenden Metallen in Edelmetall‐vermittelten Reaktionen ist ein zentrales Ziel in der homogenen Katalyse. Eine nachhaltige oder grüne Reaktion, die große Aufmerksamkeit in den letzten Jahren erhalten hat und vorzugsweise durch Ir‐ oder Ru‐Komplexe katalysiert wird, ist die Alkylierung von Aminen durch Alkohole. Sie basiert auf dem “Borrowing‐Hydrogen”‐ oder “Hydrogen‐Auto‐Transfer”‐Konzept. Wir berichten hier über die Co‐vermittelte Alkylierung von aromatischen Aminen durch Alkohole. Die Reaktion läuft unter milden Bedingungen ab und selektiv monoalkylierte Amine werden erhalten. Die beobachtete Selektivität ermöglicht die Synthese von unsymmetrisch substituierten Diaminen. Ein neuartiger PN5P‐Ligand stabilisierter Co‐Komplex katalysiert die Reaktionen am effizientesten.
Direct Trifluoromethylthiolation and Perfluoroalkylthiolation of C(sp2)H Bonds with CF3SO2Na and RfSO2Na
Authors: Jiang Lvqi , Qian Jinlong , Yi Wenbin , Lu Guoping , Cai Chun , Zhang Wei
Published: October 2015

A new method for CF3SO2Na‐based direct trifluoromethylthiolation of C(sp2)H bonds has been developed. CF3SSCF3 is generated in situ from cheap and easy‐to‐handle CF3SO2Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using RfSO2Na.