bluuebunny/crossref_metadata_2025 huggingface dataset:
Folate Receptor Alpha, Mesothelin and Megakaryocyte Potentiating Factor as Potential Serum Markers of Chronic Kidney Disease
Authors: Somers Elizabeth B. , O'Shannessy Daniel J.
Published: May 2014

Renal disease is the eighth leading cause of death in the United States. Early diagnosis is usually based on the detection of proteinuria or elevated serum creatinine, a relatively poor biomarker that does not accurately predict renal disease progression. As a result, more predictive biomarkers of renal function are sought. We present preliminary data on three protein biomarkers, folate receptor alpha (FRA), mesothelin (MSLN), and megakaryocyte potentiating factor (MPF), currently being pursued for applications in oncology diagnostics, and evaluate serum and urine levels in subjects with renal disease. Compared to healthy subjects, a significant ( P < 0.0001) increase in all three biomarkers in both serum and urine of subjects with renal disease was demonstrated. Further, serum levels of these three protein biomarkers increased with increasing stage of disease suggesting their potential value in predicting progression in subjects with renal disease and raising caution in interpretation of data in oncology applications.
Modeling the Altered Expression Levels of Genes on Signaling Pathways in Tumors as Causal Bayesian Networks
Authors: Neapolitan Richard , Xue Diyang , Jiang Xia
Published: May 2014

This paper concerns a study indicating that the expression levels of genes in signaling pathways can be modeled using a causal Bayesian network (BN) that is altered in tumorous tissue. These results open up promising areas of future research that can help identify driver genes and therapeutic targets. So, it is most appropriate for the cancer informatics community.

Our central hypothesis is that the expression levels of genes that code for proteins on a signal transduction network (STP) are causally related and that this causal structure is altered when the STP is involved in cancer. To test this hypothesis, we analyzed 5 STPs associated with breast cancer, 7 STPs associated with other cancers, and 10 randomly chosen pathways, using a breast cancer gene expression level dataset containing 529 cases and 61 controls. We identified all the genes related to each of the 22 pathways and developed separate gene expression datasets for each pathway. We obtained significant results indicating that the causal structure of the expression levels of genes coding for proteins on STPs, which are believed to be implicated in both breast cancer and in all cancers, is more altered in the cases relative to the controls than the causal structure of the randomly chosen pathways.
Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children
Authors: Kirino Eiji
Published: May 2014

Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.
Preliminary Findings for the Effectiveness of Whole Green Coffee Powder (WGCP) versus Placebo in a Double-blind Withdrawal Design Study with Young Adults on Three Tasks of Executive Function
Authors: Manos Michael J. , Sidol Craig A. , Monaco Alicia , Frazier Thomas W.
Published: May 2014

Objective

This study compared relative effects of whole green coffee powder (WGCP) on cognitive functioning in neurotypical adults under three treatment conditions: placebo (A), low-dose 889.9 mg WGCP (B1), and moderate-dose 1334.4 mg WGCP (B2).

Method

Fourteen adults aged 18–25 years, acted as their own controls in three treatment conditions within a seven-session withdrawal design. Participants completed the Cambridge Neuropsychological Test Automated Battery for attention-deficit/hyperactivity disorder (ADHD) at each session. The Side Effects Behavior Monitoring Scale (SEBMS), used to assess stimulant effects in individuals with ADHD, was a secondary outcome measure to assess adverse events associated with caffeine intake delivered by capsule. Self-report of qualitative effects was collected.

Results

Results indicated that moderate doses of WGCP significantly improved sustained attention (vs placebo and low dose) and working memory (vs low dose only) but had no effect on response inhibition. Low doses of WGCP showed decreased sustained attention. Fifty percent of subjects reported positive subjective improvement in well-being. No side effects were reported.

Conclusion

Commercially available WGCP (ie, sold as GoBean®) in moderate doses improved executive functioning for sustained attention and working memory but had no effect on response inhibition. Implications for individuals with attention difficulties are discussed.
Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa
Authors: Thakur Tanya J. , Guindo Aldiouma , Cullifer Londyn R. , Li Yi , Imumorin Ikhide G. , Diallo Dapa a. , Thomas Bolaji N.
Published: May 2014

Sickle cell disease shows marked variability in severity and pathophysiology among individuals, probably linked to differential expression of various adhesion molecules. In this study, we investigated the differential distribution, genomic diversity and haplotype frequency of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) polymorphisms, recently implicated as important in modification of disease severity. One hundred and forty five sickle cell disease patients (HbSS) and 244 adult and pediatric controls, without sickle cell disease (HbAA), were recruited from Mali. Genotypic analysis of the functionally significant eNOS variants (T786C, G894T and intron 4) and endothelin-1 (G5665T) was carried out with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our results show that the wild type alleles are the most frequent for all eNOS variants between cases and controls. Allelic and genotypic frequencies of eNOS polymorphic groups are not significantly different between cases and controls ( P ≫ 0.05). In addition, there is no association between eNOS variants and sickle cell disease, contrary to published reports. On the other hand, we report that endothelin-1 (G5665T) mutant variant had the lowest allelic frequency, and is significantly associated with sickle cell disease in Africa ( P < 0.05). Similarly, haplotype frequencies were the same between cases and controls, except for the haplotype combining all mutant variants (T, C, 4a; P = 0.01). eNOS polymorphic variants are less frequent, with no significance with sickle cell disease in Africa. On the other hand, endothelin-1 is associated with sickle cell disease, and has the capacity to redefine pathophysiology and possibly serve as modulator of disease phenotype.
Nutritional Effect of Oral Supplement Enriched in ω-3 Fatty Acids, Arginine, RNA on Immune Response and Leukocyte–platelet Aggregate Formation in Patients Undergoing Cardiac Surgery
Authors: Iwase Harunobu , Kariyazono Hiroko , Arima Junko , Yamamoto Hiroyuki , Nakamura Kazuo
Published: May 2014

The aim of the present study was to investigate the influence of a supplement enriched in ω-3 fatty acids on immune responses and platelet–leukocyte complex formation in patients undergoing cardiac surgery. Patients in the supplement group ( n = 7) took a supplement enriched in ω-3 fatty acids (Impact®) in addition to a hospital diet for five successive days before surgery; those in the control group ( n = 7) took only hospital diet and did not take Impact®. Blood samples in both groups were collected at same time points. Before surgery, samples were collected five days before surgery, at the start of supplementation (baseline), and the end of supplementation (postoperative day (POD)-0). After surgery, samples were collected on POD-1 and POD-7. The expression of human leukocyte antigen (HLA)-DR, the ratio of CD4-/CD8-positive cells, the production of interferon (IFN)-γ by CD4-positive cells, plasma levels of cytokines, and leukocyte–platelet aggregates were measured. Before surgery (POD-0), the supplement caused significant increases in HLA-DR expression, CD4/CD8 ratio, and plasma levels of IFN-γ; these levels were significantly higher compared to those in the control group ( P < 0.05, respectively). After surgery (POD-1), all values dramatically decreased in comparison with those of POD-0; however, the values in the supplement group were significantly higher compared to their respective markers in the control group ( P < 0.05, respectively). Significant differences of HLA-DR expression and CD4/CD8 ratio persisted through POD-7. Before surgery (POD-0), plasma levels of interleukin (IL)-10 in the supplement group decreased significantly compared with those in the control group ( P < 0.05). After surgery (POD-1), plasma levels of IL-10 in both the control and supplement groups increased; these levels in the supplement group were significantly lower than those in the control group ( P < 0.05). Significant decreases in the percentage of leukocyte–platelet aggregates were found after supplementation; the difference between the supplement and the control groups was found on POD-0 and POD-1 ( P < 0.05, respectively). In conclusion, the dietary supplement increased HLA-DR expression, the CD4/CD8 ratio, and the production of IFN-γ by CD4-positive cells; conversely, the levels of IL-10 and the formation of leukocyte–platelet aggregates before and after surgery were suppressed. These beneficial effects may decrease the incidence of complications after surgery.
Atmospheric and ionospheric response to sudden stratospheric warming of January 2013
Authors: Jonah O. F. , de Paula E. R. , Kherani E. A. , Dutra S. L. G. , Paes R. R.
Published: May 2014

In this work, we examine the atmospheric and ionospheric responses to the January 2013 sudden stratospheric warming (SSW) event. To examine the atmospheric and ionospheric behavior during this event, three main parameters are used (1) Total Electron Content (TEC) collected from the International Global Positioning System and from the Brazilian Network of Continuous Monitoring stations, (2) daytime E × B vertical drift derived from the magnetometers located at the equatorial station Alta Floresta (9.9°S, 55.9°W, dip latitude 1.96°) and an off‐equatorial station Cuiaba (15.3°S, 56.0°W, dip latitude 7.10°), both in the Brazilian sector, (3) the mesosphere and lower thermosphere (MLT) meridional and zonal wind components measured by the Meteor Radar located at the southern midlatitude Santa Maria (29.4°S, 53.3°W, dip latitude 17.8°). We identify the anomalous variation in E × B drift based on later local‐time migration of peak value with SSW days. A novel feature of the present study is the identification of the similar migration pattern in the TEC anomaly, in spite that the simultaneous solar flux increases during the SSW event. Other novel features are the amplification of the 13–16 day period in the TEC anomaly during the SSW days and simultaneous amplification of this period in the meridional and zonal wind components in the MLT region, as far as 30°S. These aspects reveal the presence of coupled atmosphere‐ionosphere dynamics during the SSW event and the amplification of the lunar and/or solar tidal component, a characteristic which is recently reported from the electrojet current measurements.
The relationship between clouds and dynamics in Southern Hemisphere extratropical cyclones in the real world and a climate model
Authors: Govekar Pallavi D. , Jakob Christian , Catto Jennifer
Published: May 2014

The representation of clouds over the Southern Ocean in contemporary climate models remains a major challenge. A major dynamical influence on the structure of clouds is the passage of extratropical cyclones. They exert significant dynamical influences on the clouds in the dynamically active frontal regions as well as in the dynamically suppressed regions ahead and behind the cyclones. A cyclone compositing methodology is applied to a reanalysis and vertical profiles of cloudiness from CloudSat/CALIPSO to quantify the relationship between clouds and dynamics in extratropical cyclones over the Southern Ocean. It is found that the range of cloud fraction, vertical motion, and relative humidity changes considerably with height. There is a strong quasi‐linear relationship between the three variables which changes with altitude. After establishing the observed relationships, the methodology is applied to the Australian Community Climate and Earth System Simulator to evaluate the model's ability to simulate the identified cloud‐dynamics relationships. While the model is able to qualitatively reproduce the overall cloud structure, the circulation around the cyclone is generally too weak. As a result, the model fails to represent the observed cloud to dynamics relationship. This wrong relationship in the model leads to a misrepresentation of the cloud field manifested as either an error in the cloud fraction or as simulating the “right” clouds for the “wrong” reason. The result underscores the importance of relationship‐oriented model evaluation techniques over simple right or wrong assessments.
Long‐term trends and the effect of solar cycle variations on mesospheric winter temperatures over Longyearbyen, Svalbard (78°N)
Authors: Holmen Silje E. , Dyrland Margit E. , Sigernes Fred
Published: May 2014

This paper gives an update on the long‐term trend in hydroxyl (OH*) airglow winter temperatures measured by a 1 m Ebert‐Fastie spectrometer in Longyearbyen, Svalbard (78°N, 16°E), from 1983 to 2013. The temperatures are derived through synthetic fits of measured airglow spectra of the OH*(6‐2) vibrational state. The data set is corrected for seasonal variations by subtracting the mean climatology. Also, solar cycle dependence is investigated. A solar response coefficient of 3.6 K ± 4.0 K/100 solar flux units (SFU) is calculated from F10.7 cm solar radio flux data. After subtraction of the climatology and solar response, the remaining long‐term trend is a near‐zero trend, −0.2 K ± 0.5 K/decade. Trend analysis of monthly temperatures indicates positive trends for November, January, and February and a negative trend for December, but the uncertainties are high.
Family predictors of continuity and change in social and physical aggression from ages 9 to 18
Authors: Ehrenreich Samuel E. , Beron Kurt J. , Brinkley Dawn Y. , Underwood Marion K.
Published: May 2014

This research examined developmental trajectories for social and physical aggression for a sample followed from age 9 to 18, and investigated possible family predictors of following different trajectory groups. Participants were 158 girls and 138 boys, their teachers, and their parents (21% African American, 5.3% Asian, 51.6% Caucasian, and 21% Hispanic). Teachers rated children's social and physical aggression yearly in grades 3–12. Participants' parent (83% mothers) reported on family income, conflict strategies, and maternal authoritarian and permissive parenting styles. The results suggested that both social and physical aggression decline slightly from middle childhood through late adolescence. Using a dual trajectory model, group‐based mixture modeling revealed three trajectory groups for both social and physical aggression: low‐, medium‐, and high‐desisting for social aggression, and stably‐low, stably‐medium, and high‐desisting for physical aggression. Membership in higher trajectory groups was predicted by being from a single‐parent family, and having a parent high on permissiveness. Being male was related to both elevated physical aggression trajectories and the medium‐desisting social aggression trajectory. Negative interparental conflict strategies did not predict social or physical aggression trajectories when permissive parenting was included in the model. Permissive parenting in middle childhood predicted following higher social aggression trajectories across many years, which suggests that parents setting fewer limits on children's behaviors may have lasting consequences for their peer relations. Future research should examine transactional relations between parenting styles and practices and aggression to understand the mechanisms that may contribute to changes in involvement in social and physical aggression across childhood and adolescence. Aggr. Behav. 40:421–439, 2014. © 2014 Wiley Periodicals, Inc.
“Stiffness Has Different Meanings, I Think, to Everyone”: Examining Stiffness From the Perspective of People Living With Rheumatoid Arthritis
Authors: Orbai Ana‐Maria , Smith Katherine C. , Bartlett Susan J. , De Leon Elaine , Bingham Clifton O.
Published: May 2014

Objective

Stiffness is a well‐recognized symptom of rheumatoid arthritis (RA). It is frequently queried during clinic visits as an indicator of disease activity and was included in the 1961 and 1987 RA classification criteria. Little is known about how people with RA experience stiffness and its impact on their lives.

Methods

We conducted 4 focus groups including 20 people with RA (4–6 participants per group) from 1 academic clinical practice and 1 private practice to generate accounts of stiffness experiences. Qualitative inductive thematic data analysis was conducted.

Results

Five overarching themes were identified: relationship of stiffness with other symptoms, exacerbating or alleviating factors and self‐management, stiffness timing and location, individual meanings of stiffness experiences, and impact of stiffness on daily life.

Conclusion

Focus group discussions revealed individual stiffness experiences as diverse and complex. Several stiffness features were endorsed by a majority of participants, but few, if any, were universally experienced; thus, the significance of stiffness as an expression of the disease varied widely. Discussions yielded descriptions of how individual limits imposed by RA in general and stiffness in particular may change over time and were intertwined with adaptations to preserve participation in valued life activities. These results concerning the diversity of the stiffness experience, consequential adaptations, and its impact suggest that a more individualized approach to stiffness measurement may be needed to improve stiffness assessments.
A Colorimetric Hydrocarbon Sensor Employing a Swelling‐Induced Mechanochromic Polydiacetylene
Authors: Park Dong‐Hoon , Hong Jaesung , Park In Sung , Lee Chan Woo , Kim Jong‐Man
Published: May 2014

Exceptional challenges have confronted the rational design of colorimetric sensors for saturated aliphatic hydrocarbons (SAHCs). The main reasons for this difficulty are the extremely nonpolar nature of these targets and their lack of functional groups that can interact with probes. By taking advantage of a mechanochromic conjugated polydiacetylene (PDA) and the hydrocarbon‐induced swelling properties of polydimethylsiloxane (PDMS), a sensor film that enables simple, colorimetric differentiation between a variety of C5 to C14 aliphatic hydrocarbons is fabricated. The unprecedented PDA–PDMS composite sensor undergoes a blue‐to‐red colorimetric transition on a timescale that is dependent on the chain length of the hydrocarbon target. In addition, the development of the red color is directly proportional to the swelling ratio of the film. This straightforward approach enables naked‐eye differentiation between n‐pentane and n‐heptane. The versatility of the sensor system is demonstrated by using it for the colorimetric determination of kerosene in adulterated diesel oil. Finally, the observation that a PDA microcrystal in the film undergoes significant expansion and tearing in concert with a blue‐to‐red colorimetric transition during the swelling process provides direct evidence for the mechanism for the mechanochromic behavior of the PDA.
Direct and Enantioselective Vinylogous Michael Addition of α‐Alkylidenepyrazolinones to Nitroolefins Catalyzed by Dual Cinchona Alkaloid Thioureas
Authors: Rassu Gloria , Zambrano Vincenzo , Pinna Luigi , Curti Claudio , Battistini Lucia , Sartori Andrea , Pelosi Giorgio , Casiraghi Giovanni , Zanardi Franca
Published: May 2014

While several protocols exist for the asymmetric functionalization of pyrazolinones at the α‐position relying on nucleophilic addition or annulation procedures, use of α‐alkylidene electron‐rich analogues in asymmetric vinylogous coupling to carbon electrophiles is substantially an uncharted domain. We now report, for the first time, that alkylidenepyrazolinones carrying an enolizable carbon at the γ‐position efficiently participate in direct and asymmetric, catalytic vinylogous Michael‐type additions to nitroolefins providing the expected adducts in high yields, with complete γ‐site selectivity and with extraordinary levels of enantio‐, diastereo‐, and geometrical selectivities. Both enantiomeric adducts were equally accessed by employing a quasi‐enantiomeric quinine‐ or quinidine‐based thiourea catalyst pair.

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H‐Phosphonate‐Mediated Amination of Quinoline N‐Oxides with Tertiary Amines: A Mild and Metal‐Free Synthesis of 2‐Dialkylaminoquinolines
Authors: Chen Xiaolan , Li Xu , Qu Zhibo , Ke Diandian , Qu Lingbo , Duan Likun , Mai Wenpeng , Yuan Jinwei , Chen Jianyu , Zhao Yufen
Published: May 2014

A synthetic strategy has been developed for the synthesis of 2‐dialkylaminoquinolines from easily available quinoline N‐oxides, tertiary amines, diisopropyl H‐phosphonate and carbon tetrachloride (CCl4) in one pot under metal‐free conditions at room temperature.

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Palladium/Copper Bimetallic System‐Mediated Cross‐Coupling of Alkynes and Alkenes: Two Strategies to Suppress β‐H Elimination on Alkyl‐Palladium Center
Authors: Huang Liangbin , Wang Qian , Wu Wanqing , Jiang Huanfeng
Published: May 2014

This paper describes two efficient strategies to suppress β‐H elimination during the palladium/copper bimetallic system‐mediated cross‐coupling between alkynamides and alkenes. Remote donor groups with the terminal olefins, such as toluenesulfonamide, phosphate, sulfone, etc., cooperate with the amide of alkynamides and chelate the palladium active center, to promote C(sp3)O bond formation by suppressing the β‐H elimination. Another strategy uses the rigid structure of norbornene to make an intermediate without a syn‐β‐hydrogen to achieve reductive elimination of the CCl bond.

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Improved magnetic particle tracking technique in dense gas fluidized beds
Authors: Buist Kay A. , van der Gaag Alex C. , Deen Niels G. , Kuipers Johannes A. M.
Published: May 2014

Noninvasive monitoring of multiphase flow is rapidly gaining increased interest. More specifically noninvasive particle tracking techniques have received a lot of attention in recent years to study dense granular flow. However, these techniques are usually quite expensive and require strict safety measures. An improved magnetic particle tracking (MPT) technique for dense granular flow will be presented in this article. The improvements of the analysis technique for MPT will be demonstrated and rigorously tested with a three‐dimensional system and two‐dimensional sensor system. The strengths and limitations of the MPT technique will also be reported. Finally, the results of the MPT are compared with data obtained from a combined particle image velocimetry and digital image analysis technique. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3133–3142, 2014
A mechanistic growth model for inorganic crystals: Growth mechanism
Authors: Dandekar Preshit , Doherty Michael F.
Published: May 2014

Inorganic crystals grown from solution find wide application. A mechanistic growth model based on the spiral growth mechanism that operates at low supersaturation on inorganic crystal surfaces is presented. The long‐range electrostatic interactions on inorganic crystal surfaces are captured by methods developed in our previous article (Dandekar and Doherty, AIChE J., in press). The interactions of kink site growth units with the solvent molecules partially determine the growth kinetics. Relevant experimental parameters are systematically accounted for in the expression for the kink incorporation rate along step edges on the crystal surfaces. The growth model accurately predicts the asymmetric growth spirals on the
surface of calcite crystals. The effect of supersaturation and ionic activity ratio on the step velocities of the acute and obtuse spiral edges is also correctly captured. This model can be used to predict the shapes of solution grown inorganic crystals and to engineer the growth process to design inorganic solids with functionally desirable shapes. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3720–3731, 2014
Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: A case of gonadal mosaicism
Authors: Dhamija Radhika , Kirmani Salman , Wang Xiangling , Ferber Matthew J. , Wieben Eric D. , Lazaridis Konstantinos N. , Babovic‐Vuksanovic Dusica
Published: May 2014

Hartsfield syndrome has been recently reported to be associated with mutations in FGFR1 however, to this date; no familial cases have been reported. In this report, we describe two siblings with Hartsfield syndrome and a novel de novo FGFR1 mutation suggesting gonadal mosaicism. The proband presented at our institution at age 6 years with a clinical diagnosis of Hartsfield syndrome and requesting further genetic evaluation. Previous studies included a normal karyotype, oligonucleotide array, and single gene testing for nonsyndromic holoprosencephaly (SHH, SIX3, ZIC2, TGIF). At the age of 6 years, exome sequencing was performed and a de novo novel missense variant was identified in FGFR1 (coding for fibroblast growth factor‐1) on chromosome 8p12: c.1880G>C (p.R627T). Subsequently, a younger sibling was born with the same phenotype (holoprosencephaly, ectrodactyly of bilateral hands and feet and bilateral cleft lip and palate). Targeted sequencing of FGFR1 revealed the identical variant that was previously identified in the proband. To our knowledge this observation is the first documentation of familial recurrence of Hartsfield syndrome. As both parents were negative for the sequence variant in FGFR1 gene by testing peripheral blood samples, this suggests gonadal mosaicism. The frequency of gonadal mosaicism in Hartsfield syndrome is not known however given our case, this possibility should be taken in to consideration for recurrence risk estimation in children of clinically unaffected parents. © 2014 Wiley Periodicals, Inc.
Asymmetrische Palladium‐katalysierte allylische Alkylierung mit Dialkylzinkreagentien: ein bemerkenswerter Ligandeneffekt
Authors: Misale Antonio , Niyomchon Supaporn , Luparia Marco , Maulide Nuno
Published: May 2014

Wir berichten hier über eine zufällig entdeckte Palladium‐katalysierte asymmetrische allylische Alkylierung mit Diorganozinkreagentien, die eine breite Kompatibilität mit funktionellen Gruppen zeigt. Diese neuartige Transformation basiert auf einem bemerkenswerten Ligandeneffekt, der die Standard‐Umpolungsreaktivität von Allylpalladiumintermediaten in Gegenwart von Dialkylzinkverbindungen unterbindet. Die milden Bedingungen ermöglichen enantioselektive allylische Alkylierungen von racemischen Allyl‐Elektrophilen in Gegenwart empfindlicher funktioneller Gruppen.
Eine nachhaltige Synthese von Formiaten: Kombination der katalytischen Methanol‐Dehydrierung und Hydrogencarbonat‐Hydrierung
Authors: Liu Qiang , Wu Lipeng , Gülak Samet , Rockstroh Nils , Jackstell Ralf , Beller Matthias
Published: May 2014

Formiatsalze sind wichtige Chemikalien, die in alltäglichen Produkten verwendet werden. Allerdings erfordert die aktuelle industrielle Großproduktion von Formiaten hohe CO‐Drücke und drastische Reaktionsbedingungen. Wir beschreiben hier einen neuen Prozess zur Synthese von Formiaten, der ohne die Verwendung gefährlicher Gase und Chemikalien auskommt. Mit Ruthenium‐Pincerkomplexen gelingt die gleichzeitige Methanol‐Dehydrierung und Hydrogencarbonat‐Hydrierung als ein “grüner” Prozess zu Formiaten mit exellenten TON (>18 000), TOF (>1300 h−1) und Ausbeuten (>90 %).
Terminologie von Metall‐organischen Gerüstverbindungen und Koordinationspolymeren (IUPAC‐Empfehlungen 2013)
Authors: Fischer Roland A. , Schwedler Inke
Published: May 2014

Im Folgenden werden Begriffe, Definitionen und Empfehlungen für die Klassifizierung von Koordinationspolymeren, Netzwerken und Metall‐organischen Gerüstverbindungen (MOFs) erläutert. Es wird eine hierarchische Terminologie empfohlen, die vom Koordinationspolymer als Oberbegriff ausgeht. Koordinationsnetzwerke sind dann eine Untergruppe der Koordinationspolymere und MOFs wiederum eine Untergruppe der Koordinationsnetzwerke. Eines der Kriterien für MOFs sind potenzielle Hohlräume, ohne dass physikalische Messungen der Porosität oder anderer Eigenschaften per se erforderlich sind. Die Verwendung von Topologien und Topologiedeskriptoren wird zur Verbesserung der Kristallstrukturbeschreibung von MOFs und 3D‐Koordinationspolymeren dringend empfohlen.
Asymmetric Palladium‐Catalyzed Allylic Alkylation Using Dialkylzinc Reagents: A Remarkable Ligand Effect
Authors: Misale Antonio , Niyomchon Supaporn , Luparia Marco , Maulide Nuno
Published: May 2014

A serendipitously discovered palladium‐catalyzed asymmetric allylic alkylation reaction with diorganozinc reagents, which displays broad functional group compatibility, is reported. This novel transformation hinges on a remarkable ligand effect which overrides the standard “umpolung” reactivity of allyl–palladium intermediates in the presence of dialkylzincs. Owing to its mild conditions, enantioselective allylic alkylations of racemic allylic electrophiles are possible in the presence of sensitive functional groups.
Multifunctional Redox Polymers: Electrochrome, Polyelectrolyte, Sensor, Electrode Modifier, Nanoparticle Stabilizer, and Catalyst Template
Authors: Deraedt Christophe , Rapakousiou Amalia , Wang Yanlan , Salmon Lionel , Bousquet Melanie , Astruc Didier
Published: May 2014

Simple “click” polycondensation metallopolymers of redox‐robust bis(ethynyl)biferrocene (biFc) and di(azido) poly(ethylene glycol) (PEG400 and PEG1000) were designed for multiple functions including improvement of water solubility and biocompatibility, the introduction of mixed valency and sensing capabilities, and as nanoparticle stabilizers for catalysis.
Dative or Not Dative?
Authors: Himmel Daniel , Krossing Ingo , Schnepf Andreas
Published: May 2014

Is a meatball an animal praline? The authors of the Essay Dative Bonds in Main‐Group Compounds: A Case for Fewer Arrows! respond to the criticism of Gernot Frenking and correct one point in their original Essay.
Development of polynorbornene as a structural material for microfluidics and flexible BioMEMS
Authors: Hess‐Dunning Allison E. , Smith Russell L. , Zorman Christian A.
Published: May 2014

Polynorbornene is a class of polymer that exhibits significant potential as a structural material in microelectromechanical systems owing to its dielectric constant and compatibility with silicon‐based microfabrication processes. A commercially available version of PNB (AvatrelTM 2585P) is particularly attractive for bioMEMS applications because of its low moisture absorption characteristics, photodefinability, and potential biocompatibility. This study furthers the advancement of PNB as an enabling structural material for microfluidics and flexible bioMEMS applications by developing the following key processing techniques: (1) oxygen plasma‐based surface modification for bonding PNB layers to glass substrates, and (2) the monolithic fabrication of free‐standing, mechanically flexible electrode arrays using silicon wafers as mechanical supports during fabrication. To further develop PNB for flexible, implantable bioMEMS applications, this study also includes an evaluation of: (1) the tensile properties of free standing structures after accelerated lifetime testing in phosphate‐buffered saline, and (2) the in vitro performance of free‐standing, mechanically flexible neural microelectrode array‐based neural interfaces. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40969.
High‐performance thermosetting films based on an amino‐functionalized poly(ether sulfone)
Authors: Lin Ching Hsuan , Chen Jui Chun , Huang Chu Ming , Juang Tzong Yuan
Published: May 2014

We have developed a sequence‐dependent synthesis of the amino‐functionalized poly(ether sulfone) P2. The amino groups of P2 act as reactive sites toward epoxy resins. After curing P2 with diglycidyl ether of bisphenol A (DGEBA) and cresol novolac epoxy (CNE), we obtained the flexible, light‐yellow, transparent, epoxy thermosetting films P2/DGEBA, and P2/CNE, respectively, having glass transition temperatures (Tg) of 258 and 274°C, respectively. In addition, we also prepared a flexible film after condensation of the amino groups of P2 with the anhydride groups of 4,4′‐oxydiphthalic anhydride (ODPA); after imidization at 300°C for 1 h, the resulting P2/ODPA thermosetting film possessed a value of Tg of 340°C. These three thermosetting films also exhibited flame retardancy with a UL‐94 VTM‐0 grade. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40980.
Treg Cell Function in Rheumatoid Arthritis Is Compromised by CTLA‐4 Promoter Methylation Resulting in a Failure to Activate the Indoleamine 2,3‐Dioxygenase Pathway
Authors: Cribbs Adam P. , Kennedy Alan , Penn Henry , Read Jordan E. , Amjadi Parisa , Green Patricia , Syed Khaja , Manka Szymon W. , Brennan Fionula M. , Gregory Bernard , Williams Richard O.
Published: May 2014

Objective

Functionally impaired Treg cells expressing abnormally low levels of CTLA‐4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA‐4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function.

Methods

CTLA‐4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry. Methylation of the CTLA‐4 gene promoter was analyzed by bisulfite‐specific PCR, followed by sequencing. Methylation‐dependent transcriptional activity of the CTLA‐4 gene promoter was measured by luciferase assay, and NF‐AT binding to the CTLA‐4 gene promoter was determined by chromatin immunoprecipitation. The role of CTLA‐4 expression in controlling Teff cells was analyzed using an autologous mixed lymphocyte reaction.

Results

Down‐regulation of CTLA‐4 expression in Treg cells from RA patients was caused by methylation of a previously unidentified NF‐AT binding site within the CTLA‐4 gene promoter. As a consequence, Treg cells were unable to induce expression and activation of the tryptophan‐degrading enzyme indoleamine 2,3‐dioxygenase (IDO), which in turn resulted in a failure to activate the immunomodulatory kynurenine pathway.

Conclusion

We show for the first time that epigenetic modifications contribute to defective Treg cell function in RA through an inability to activate the IDO pathway. Therefore, this study sets a precedent for investigating potential therapeutic strategies aimed at reinforcing the IDO pathway in RA patients.
Symptomatic Efficacy of Etanercept and Its Effects on Objective Signs of Inflammation in Early Nonradiographic Axial Spondyloarthritis: A Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Dougados Maxime , van der Heijde Désirée , Sieper Joachim , Braun Jürgen , Maksymowych Walter P. , Citera Gustavo , Miceli‐Richard Corinne , Wei James Cheng‐Chung , Pedersen Ron , Bonin Randi , Rahman Mahboob U. , Logeart Isabelle , Wajdula Joseph , Koenig Andrew S. , Vlahos Bonnie , Alvarez Daniel , Bukowski Jack F.
Published: May 2014

Objective

To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA).

Methods

The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double‐blind study); during the subsequent open‐label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.

Results

One hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA–B27 positive, and 174 (81%) had MRI‐confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 [32%] versus 17 of 108 [16%]; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI‐based scores for sacroiliac joint inflammation (−46.9% versus −10.9%; P < 0.001) and spinal inflammation (−45.4% versus −33.4%; P = 0.04) compared with placebo‐treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C‐reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.

Conclusion

In patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.
Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund's Adjuvant–Induced Arthritis
Authors: Garrison Sheldon R. , Stucky Cheryl L.
Published: May 2014

Objective

To investigate age‐related differences in mechanical sensitivity to inflammatory pain and determine the contribution of transient receptor potential ankyrin 1 (TRPA1) to mechanical hypersensitivity during chronic inflammation in young and aged mice with complete Freund's adjuvant (CFA)–induced arthritis.

Methods

Mechanical sensitivity in young (3‐month‐old) and aged (24‐month‐old) wild‐type (TRPA1+/+) mice and TRPA1‐deficient (TRPA1−/−) mice was measured behaviorally for 8 weeks following injection of CFA into the plantar hind paw. The severity of inflammation was evaluated by histologic analyses and hind‐paw measurements. Ex vivo preparations of the skin saphenous nerve from mice were assessed for C‐fiber sensitivity.

Results

Among naive (uninjured) wild‐type mice, aged animals were less sensitive than young animals to mechanical stimuli. Afferent recordings of C‐fibers from TRPA1−/− mice indicated that TRPA1 contributes to the normal mechanical sensitivity in both age groups. Following injection of CFA, both young and aged TRPA1+/+ mice exhibited mechanical hypersensitivity. In young TRPA1−/− mice injected with CFA, peak development of mechanical hypersensitivity was delayed until week 4, when they exhibited a sharp decrease (9‐fold) in the mechanical paw withdrawal threshold, whereas aged TRPA1−/− mice did not exhibit mechanical hypersensitivity at any time during the 8 weeks after CFA injection. Recordings of C‐fibers from the saphenous nerve supported these findings, with results indicating that both young and aged TRPA1+/+ mice exhibited increased action potential firing at 8 weeks after CFA injection (increases of 25% and 60%, respectively). Interestingly, among TRPA1−/− mice injected with CFA, mechanical firing was increased markedly in the C‐fibers of young mice (increase of 80%) but not in the C‐fibers of aged mice.

Conclusion

These findings reveal marked differences in the long‐term mechanical behavioral sensitivity of aged and young mice, and suggest that TRPA1 may be a key contributor to the transition from acute to chronic inflammatory pain in response to mechanical stimuli as well as to the development of nociceptor sensitization selectively in aged mice.
Brief Report: Involvement of TNFRSF11A Molecular Defects in Autoinflammatory Disorders
Authors: Jéru Isabelle , Cochet Emmanuelle , Duquesnoy Philippe , Hentgen Véronique , Copin Bruno , Mitjavila‐Garcia Maria Teresa , Sheykholeslami Shayan , Le Borgne Gaëlle , Dastot‐Le Moal Florence , Malan Valérie , Karabina Sonia , Mahevas Mathieu , Chantot‐Bastaraud Sandra , Lecron Jean‐Claude , Faivre Laurence , Amselem Serge
Published: May 2014

Objective

Autoinflammatory disorders are caused by a primary dysfunction of the innate immune system. Among these disorders are hereditary recurrent fevers, which are characterized by recurrent episodes of fever and inflammatory manifestations affecting multiple tissues. Hereditary recurrent fevers often lack objective diagnostic criteria, thereby hampering the identification of disease‐causing genes. This study was undertaken to identify a gene responsible for hereditary recurrent fevers.

Methods

Copy number variations and point mutations were sought by array‐comparative genomic hybridization and polymerase chain reaction sequencing, respectively. Serum cytokine levels were measured using Luminex technology. The effect of TNFRSF11A molecular defects on NF‐κB signaling in cells expressing wild‐type and mutated forms of the receptor was evaluated by luciferase assay.

Results

A patient with multiple congenital anomalies and hereditary recurrent fever was found to carry a de novo heterozygous complex chromosomal rearrangement encompassing a duplication of TNFRSF11A, a gene known to regulate fever in rodents. We also identified a heterozygous frameshift mutation (p.Met416Cysfs*110) in TNFRSF11A in a mother and daughter with isolated hereditary recurrent fever. This mutation was associated with increased secretion of several inflammatory cytokines (tumor necrosis factor α [TNFα], interleukin‐18 [IL‐18], IL‐1 receptor antagonist, interferon‐γ) and altered the biologic effects of the receptor on NF‐κB signaling. The disease in the patients described herein exhibits striking clinical similarities to TNF receptor–associated periodic syndrome, another hereditary recurrent fever involving a gene of the same family (TNFRSF1A).

Conclusion

The involvement of TNFRSF11A in hereditary recurrent fever highlights the key role of this receptor in innate immunity. The present results also suggest that TNFRSF11A screening could serve as a new diagnostic test for autoinflammatory disorders.
Emerging roles of metal solute carriers in cancer mechanisms and treatment
Authors: Jong Nancy N. , McKeage Mark J.
Published: May 2014

The literature concerning the roles of metal transporting solute carriers in the development and progression of human cancer, and in the delivery of metal‐containing anticancer drugs, chemical carcinogens and imaging agents, is reviewed. A range of different solute carrier families, including members from the SLC2A, SLC11A, SLC22A, SLC25A, SLC30A, SLC31A, SLC39A, SLC40A, SLC47A and SLCO1B families, and various metal substrates, including arsenic, copper, gadolinium, iron, platinum and zinc, have been implicated in these cancer‐related transport processes. For example, the transport of platinum‐based anticancer drugs has been reported to be influenced by the expression and activities of OCT1‐3 (SLC22A1‐3), OCTN1/2 (SLC22A4/5), CTR1/2 (SLC31A1/2) and MATE1/2 (SLC47A1/2) solute carriers. As another example, solute carriers mediate control over the availability of endogenous metal ions, such as copper, iron and zinc, may have key roles in regulating tumour angiogenesis, cell proliferation, epithelial‐to‐mesenchymal transition and aberrant MAPK and STAT‐3 signal transduction in cancer. In conclusion, emerging mechanisms involving metal transporting solute carriers are being defined and seem likely to make major contributions to cancer development and progression, and to the delivery of anticancer and tumour imaging agents. Copyright © 2014 John Wiley & Sons, Ltd.
Induction of ganoderic acid biosynthesis by Mn2+ in static liquid cultivation of Ganoderma lucidum
Authors: Xu Yi‐Ning , Xia Xiao‐Xia , Zhong Jian‐Jiang
Published: May 2014

Metal ions affect cell physiology and metabolism significantly, but the role of Mn2+ in the secondary metabolism of mushrooms is yet unclear. In static liquid cultivation of Ganoderma lucidum for producing antitumor ganoderic acids (GAs), the Mn2+ addition was performed. Addition of 10 mM Mn2+ at the start of the static liquid cultivation resulted in 2.2‐fold improvement of total GAs production. The expression levels of GA biosynthetic and Ca2+ sensors' genes were up‐regulated with Mn2+ induction while down‐regulated by adding cyclosporin A (calcineurin inhibitor), suggesting that higher GA production might result from calcineurin signal regulation. Intracellular Ca2+ imaging and calcineurin inhibitor study revealed that addition of Mn2+ led to Ca2+ influx from medium to the cells to trigger calcineurin signals. Mn2+ addition was therefore an efficient induction strategy for improving GAs production, whose regulation mechanism was via calcineurin signaling transduction. Biotechnol. Bioeng. 2014;111: 2358–2365. © 2014 Wiley Periodicals, Inc.