bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning and expression of a hypothetical Loosenin from Neurospora crassa
Authors: Campos-Oliver Aranzazu , Quiroz-Castañeda Rosa Estela , Ortiz-Suri Ernesto , Folch-Mallol Jorge Luis
Published: October 2014

Loosenin is a protein recently described which presents amorphogenic activity on cellulose. It was isolated from the Basidiomycete Bjerkandera adusta and it enhances sugar release from cellulosic fibers treated previously with it and then subjected to cellulase treatment. It can also bind to other polysaccharides like chitin and xylans but presents no hydrolytic activity itself. Blast analysis using the loosenin amino acid sequence retrieved a sequence from the Neurospora crassa genome that showed 59% similarity. In this work, we cloned, expressed and partially characterized a putative loosenin from N. crassa, since these proteins have a potential for pretreatment of lignocellulosic materials.
Plaguicidas en México: usos, riesgos y marco regulatorio
Authors: Ortíz Irmene , Avila-Chávez Marco A. , Torres Luis G.
Published: October 2014

El presente documento describe la situación actual referente a la reglamentación de la producción, distribución, almacenamiento y uso de los plaguicidas en México. Se muestran datos de morbilidad como consecuencia del uso de estos productos como un referente de sus efectos sobre la salud humana, así como, los sitios en la República Mexicana en donde la incidencia es mayor. Adicionalmente, se presenta una revisión de la regulación nacional e internacional sobre plaguicidas, así como, las distintas dependencias gubernamentales, organizaciones civiles y centros de investigación involucrados en el tema en México. La información presentada sugiere que a pesar de las regulaciones y restricciones de uso de los plaguicidas, éstos pueden representar un grave problema de salud para los trabajadores y poblaciones expuestas, así como, de contaminación de suelos y aguas en México.
Coupled estimation of surface heat fluxes and vegetation dynamics from remotely sensed land surface temperature and fraction of photosynthetically active radiation
Authors: Bateni S. M. , Entekhabi D. , Margulis S. , Castelli F. , Kergoat L.
Published: October 2014

Remotely sensed Land Surface Temperature (LST) and Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) are assimilated, respectively, into the Surface Energy Balance (SEB) equation and a Vegetation Dynamics Model (VDM) in order to estimate surface fluxes and vegetation dynamics. The problem is posed in terms of three unknown and dimensionless parameters: (1) neutral bulk heat transfer coefficient, which scales the sum of turbulent heat fluxes, (2) soil and canopy evaporative fractions that characterize partitioning among the turbulent heat fluxes over soil and vegetation, and (3) specific leaf area, which captures seasonal phenology and vegetation dynamics. The model is applied over the Gourma site in Mali, the northern region of the West African Monsoon (WAM) domain. The application of the model over the Gourma site shows that spaceborne LST observations can be used to constrain the SEB equation and obtain its key two unknown parameters (i.e., neutral bulk heat transfer coefficient and evaporative fraction). We demonstrate that the spatial patterns of estimated neutral bulk heat transfer coefficient and evaporative fraction resemble, respectively, those of independently observed vegetation index and soil moisture. The framework also yields estimates of surface energy balance components. The daily sensible, latent, and ground heat flux estimates at the Agoufou site that is located in the south of the Gourma region have, respectively, a root‐mean‐square error (RMSE) of 53.6, 34.4, and 45.1 Wm−2. The daily sensible heat flux estimates at the Bamba site, which is located in the north of the Gourma domain, have a RMSE of 42.6 Wm−2. The results also show that remotely sensed FPAR observations can constrain the VDM and retrieve its main unknown parameter (specific leaf area) over large‐scale domains without costly in situ measurements. The results indicate that the estimated specific leaf area values vary reasonably with the expected influential environmental variables such as precipitation, air temperature, and solar radiation. Assimilating FPAR observations into the VDM can also provide an estimate of Leaf Area Index (LAI) dynamics. The estimated LAI values are comparable in magnitude, spatial pattern and temporal evolution with satellite retrievals.
Stochastic temporal disaggregation of monthly precipitation for regional gridded data sets
Authors: Thober Stephan , Mai Juliane , Zink Matthias , Samaniego Luis
Published: October 2014

Weather generators are used for spatiotemporal downscaling of climate model outputs (e.g., precipitation and temperature) to investigate the impact of climate change on the hydrological cycle. In this study, a multiplicative random cascade model is proposed for the stochastic temporal disaggregation of monthly to daily precipitation fields, which is designed to be applicable to grids of any spatial resolution and extent. The proposed method uses stationary distribution functions that describe the partitioning of precipitation throughout multiple temporal scales (e.g., weekly and biweekly scale). Moreover, it explicitly considers the intensity and spatial covariance of precipitation in the disaggregation procedure, but requires no assumption about the temporal relationship and spatial isotropy of precipitation fields. A split sampling test is conducted on a high‐resolution (i.e., 4 × 4 km2 grid) daily precipitation data set over Germany (≈357,000 km2) to assess the performance of the proposed method during future periods. The proposed method has proven to consistently reproduce distinctive location‐dependent precipitation distribution functions with biases less than 5% during both a calibration and evaluation period. Furthermore, extreme precipitation amounts and the spatial and temporal covariance of the generated fields are comparable to those of the observations. Consequently, the proposed temporal disaggregation approach satisfies the minimum conditions for a precipitation generator aiming at the assessment of hydrological response to climate change at regional and continental scales or for generating seamless predictions of hydrological variables.
Outcome and survival of asymptomatic PML in natalizumab‐treated MS patients
Authors: Dong‐Si Tuan , Richman Sandra , Wattjes Mike P. , Wenten Made , Gheuens Sarah , Philip Jeffrey , Datta Shoibal , McIninch James , Bozic Carmen , Bloomgren Gary , Richert Nancy
Published: October 2014

Objective

As of 3 September 2013, 399 cases of natalizumab‐associated progressive multifocal leukoencephalopathy (PML) were confirmed in multiple sclerosis (MS) patients. We evaluated outcomes of natalizumab‐treated MS patients who were asymptomatic at PML diagnosis.

Methods

Analyses included data available as of 5 June 2013. Asymptomatic patients diagnosed with PML by magnetic resonance imaging (MRI) findings and JC virus DNA detection in the central nervous system were compared with patients presenting with symptoms at diagnosis. Demographics, MRI, and survival over 12 months were analyzed. Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores were recorded pre‐PML, at diagnosis, and at 6 and 12 months post‐diagnosis.

Results

A total of 372 PML cases were analyzed; 30 patients were asymptomatic and 342 were symptomatic at PML diagnosis. Classifications of PML lesions on MRI in asymptomatic versus symptomatic patients were unilobar in 68% versus 37%, multilobar in 21% versus 24%, and widespread in 11% versus 40%. In both groups with unilobar lesions, frontal lobe lesions predominated. Prior to PML, mean EDSS and KPS scores were similar for asymptomatic and symptomatic patients. At diagnosis, mean EDSS score was significantly lower for asymptomatic patients (4.1; n = 11) than for symptomatic patients (5.4; n = 193; P = 0.038). Six months after PML diagnosis, asymptomatic patients had less functional disability than symptomatic patients. As of 5 June 2013, 96.7% of asymptomatic patients and 75.4% of symptomatic patients were alive.

Interpretation

PML patients asymptomatic at diagnosis had better survival and less functional disability than those who were symptomatic at diagnosis.
HIP/PAP prevents excitotoxic neuronal death and promotes plasticity
Authors: Haldipur Parthiv , Dupuis Nina , Degos Vincent , Moniaux Nicolas , Chhor Vibol , Rasika Sowmyalakshmi , Schwendimann Leslie , le Charpentier Tifenn , Rougier Elodie , Amouyal Paul , Amouyal Gilles , Dournaud Pascal , Bréchot Christian , El Ghouzzi Vincent , Faivre Jamila , Fleiss Bobbi , Mani Shyamala , Gressens Pierre
Published: October 2014

Objectives

Excitotoxicity plays a significant role in the pathogenesis of perinatal brain injuries. Among the consequences of excessive activation of the N‐methyl‐d‐aspartate (NMDA)‐type glutamate are oxidative stress caused by free radical release from damaged mitochondria, neuronal death and subsequent loss of connectivity. Drugs that could protect nervous tissue and support regeneration are attractive therapeutic options. The hepatocarcinoma intestine pancreas protein/pancreatitis‐associated protein I (HIP/PAP) or Reg3α, which is approved for clinical testing for the protection and regeneration of the liver, is upregulated in the central nervous system following injury or disease. Here, we examined the neuroprotective/neuroregenerative potential of HIP/PAP following excitotoxic brain injury.

Methods

We studied the expression of HIP/PAP and two of its putative effectors, cAMP‐regulated phosphoprotein 19 (ARPP19) and growth‐associated protein 43 (GAP‐43), in the neonatal brain, and the protective/regenerative properties of HIP/PAP in three paradigms of perinatal excitotoxicity: intracerebral injection of the NMDA agonist ibotenate in newborn pups, a pediatric model of traumatic brain injury, and cultured primary cortical neurons.

Results

HIP/PAP, ARPP19, and GAP‐43 were expressed in the neonatal mouse brain. HIP/PAP prevented the formation of cortical and white matter lesions and reduced neuronal death and glial activation following excitotoxic insults in vivo. In vitro, HIP/PAP promoted neuronal survival, preserved neurite complexity and fasciculation, and protected cell contents from reactive oxygen species (ROS)‐induced damage.

Interpretation

HIP/PAP has strong neuroprotective/neuroregenerative potential following excitotoxic injury to the developing brain, and could represent an interesting therapeutic strategy in perinatal brain injury.
A Moldable Putty Containing Silk Fibroin Yolk Shell Particles for Improved Hemostasis and Bone Repair
Authors: Saran Kushagra , Shi Pujiang , Ranjan Shashi , Goh James C. H. , Zhang Yong
Published: October 2014

During minimally invasive orthopedic surgeries, surgical intervention is required at two stages; to attain hemostasis and subsequently to implant the bone graft or its substitute. There is an apparent need for a material which can simultaneously control bone bleeding and provide support for bone repair. In this work, a moldable putty, which can be applied to bone defects (usually irregular in shape), was developed to address this need. It comprises of a hemostatic factor thrombin, osteoinductive “yolk‐shell” particles containing bone growth factor (BMP‐2), and an osteoconductive component hydroxyapatite. The yolk shell particles allowed controlled release of BMP‐2 and showed significantly enhanced osteogenic differentiation of C2C12 (mouse myoblast) cells as demonstrated by increased alkaline phosphatase (ALP) activity and relative gene expressions of osteogenic differentiation markers. These particles were assembled into a moldable putty by mixing them with hydroxyapatite and silk fibroin solution (binding agent) supplemented with thrombin. The putty showed non‐cytotoxicity, hemostatic ability, sustained release of BMP‐2 and induced increased mineralization in C2C12 cells. This putty, if applied to bone defects during surgeries, may help attain hemostasis and may enhance bone repair by providing sustained release of bone growth factors.
Die Bedeutung von Metallionen für die mechanischen Eigenschaften von Biomaterialien auf Proteinbasis
Authors: Degtyar Elena , Harrington Matthew J. , Politi Yael , Fratzl Peter
Published: October 2014

Protein‐Metall‐Wechselwirkungen wurden bisher vor allem hinsichtlich ihrer Bedeutung in Stoffwechselprozessen betrachtet. Aktuelle Forschungsergebnisse zeigen, dass sie auch die mechanischen Eigenschaften von Biomaterialien verbessern können, wie z. B. Härte, Zähigkeit, Haftung und die Fähigkeit zur Selbstheilung. Die zugrundeliegenden Prinzipien werden hier anhand einiger Beispiele, wie der Beißwerkzeuge von Arthropoden, der Byssusfäden von Miesmuscheln und des Zements von Sandburg‐Würmern, besprochen. Diese neuen Erkenntnisse können auch für die Entwicklung von bio‐inspirierten Metallopolymeren mit potentiellen Anwendungen in der Industrie und Biomedizin von Bedeutung sein.
The Mechanical Role of Metal Ions in Biogenic Protein‐Based Materials
Authors: Degtyar Elena , Harrington Matthew J. , Politi Yael , Fratzl Peter
Published: October 2014

Protein‐metal interactions—traditionally regarded for roles in metabolic processes—are now known to enhance the performance of certain biogenic materials, influencing properties such as hardness, toughness, adhesion, and self‐healing. Design principles elucidated through thorough study of such materials are yielding vital insights for the design of biomimetic metallopolymers with industrial and biomedical applications. Recent advances in the understanding of the biological structure–function relationships are highlighted here with a specific focus on materials such as arthropod biting parts, mussel byssal threads, and sandcastle worm cement.
Energy Storage Materials Synthesized from Ionic Liquids
Authors: Gebresilassie Eshetu Gebrekidan , Armand Michel , Scrosati Bruno , Passerini Stefano
Published: October 2014

The advent of ionic liquids (ILs) as eco‐friendly and promising reaction media has opened new frontiers in the field of electrochemical energy storage. Beyond their use as electrolyte components in batteries and supercapacitors, ILs have unique properties that make them suitable as functional advanced materials, media for materials production, and components for preparing highly engineered functional products. Aiming at offering an in‐depth review on the newly emerging IL‐based green synthesis processes of energy storage materials, this Review provides an overview of the role of ILs in the synthesis of materials for batteries, supercapacitors, and green electrode processing. It is expected that this Review will assess the status quo of the research field and thereby stimulate new thoughts and ideas on the emerging challenges and opportunities of IL‐based syntheses of energy materials.
New diurethane plasticizers for polyurethane thermoplastics and perspective functional composites
Authors: Tereshatov Vasiliy Vasilyevich , Senichev Valeriy Yulyevich
Published: October 2014

A method to synthesize low‐molecular‐mass diurethane compounds via reaction between diisocyanates and various primary and secondary alcohols was presented. A number of diurethanes with the melting points below 100oC were revealed. These diurethanes can be used as fusible plasticizers for thermoplastic polyurethanes (TPU) and for high‐filled composites based thereupon. TPU based on oligotetramethyleneoxide diol and on 4,4′‐diphenylmethane diisocyanate and containing 30% of fusible diurethanes were produced. In the presence of such plasticizers, a 3‐order increase in magnitude of the melt flow index was demonstrated. Data evincing significantly larger strength values of TPU and of tungsten‐containing high‐filled composites (94.2 wt %), comparing with thermoplastics plasticized with low‐molecular‐mass liquids, were presented. The mechanism of this phenomenon attributed to the partial crystallization of diurethanes in TPU compositions was described. Samples of low‐toxic thermoplastic polyurethane having density value of 9.4 g/cm3 and meant for protection of various facilities from radioactive radiation, instead of highly toxic metallic, lead, were prepared. Issues of improving the frost resistance of this new type of TPU were considered. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41481.
Lipid Profile Changes in Patients With Chronic Inflammatory Arthritis Treated With Biologic Agents and Tofacitinib in Randomized Clinical Trials: A Systematic Review and Meta‐Analysis
Authors: Souto Alejandro , Salgado Eva , Maneiro José Ramón , Mera Antonio , Carmona Loreto , Gómez‐Reino Juan J.
Published: October 2014

Objective

To analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs).

Methods

A systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta‐analyses were performed using random‐effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels.

Results

Twenty‐five of 4,527 identified articles met the inclusion criteria. Compared with RA patients treated with placebo, those treated with tocilizumab were more likely to have hypercholesterolemia (odds ratio [OR] 4.64; 95% confidence interval [95% CI] 2.71, 7.95 [P < 0.001]), increased levels of high‐density lipoprotein (HDL) cholesterol (OR 2.25; 95% CI 1.14, 4.44 [P = 0.020]), and increased levels of low‐density lipoprotein (LDL) cholesterol (OR 4.80; 95% CI 3.27, 7.05 [P < 0.001]); this was not observed in patients treated with tumor necrosis factor (TNF) antagonists (OR 1.54; 95% CI 0.90, 2.66 [P = 0.119]) or tofacitinib (OR 3.4; 95% CI 0.62, 18.55 [P = 0.158]). Among patients receiving tofacitinib 5 mg twice daily, the mean percentage of increases in the HDL cholesterol level (weighted mean difference [WMD] 13.00 mg/dl; 95% CI 12.08, 13.93 [P < 0.001]) and the LDL cholesterol level (WMD 11.20 mg/dl; 95% CI 10.08, 12.32 [P < 0.001]) were higher than those in the comparator groups. Among patients treated with tofacitinib 10 mg twice daily, the mean percentage of increases in the HDL cholesterol level (WMD 15.21 mg/dl; 95% CI 13.28, 17.14 [P < 0.001]) and the LDL cholesterol level (WMD 15.42 mg/dl; 95% CI 11.77, 19.06 [P < 0.001]) were also higher than those in the comparator groups. No data were available for RA treated with other biologic agents or for SpA.

Conclusion

In patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.
Failed Degradation of JunB Contributes to Overproduction of Type I Collagen and Development of Dermal Fibrosis in Patients With Systemic Sclerosis
Authors: Ponticos Markella , Papaioannou Ioannis , Xu Shiwen , Holmes Alan M. , Khan Korsa , Denton Christopher P. , Bou‐Gharios George , Abraham David J.
Published: October 2014

Objective

The excessive deposition of extracellular matrix, including type I collagen, is a key aspect in the pathogenesis of connective tissue diseases such as systemic sclerosis (SSc; scleroderma). To further our understanding of the mechanisms governing the dysregulation of type I collagen production in SSc, we investigated the role of the activator protein 1 (AP‐1) family of transcription factors in regulating COL1A2 transcription.

Methods

The expression and nuclear localization of AP‐1 family members (c‐Jun, JunB, JunD, Fra‐1, Fra‐2, and c‐Fos) were examined by immunohistochemistry and Western blotting in dermal biopsy specimens and explanted skin fibroblasts from patients with diffuse cutaneous SSc and healthy controls. Gene activation was determined by assessing the interaction of transcription factors with the COL1A2 enhancer using transient transfection of reporter gene constructs, electrophoretic mobility shift assays, chromatin immunoprecipitation analysis, and RNA interference involving knockdown of individual AP‐1 family members. Inhibition of fibroblast mammalian target of rapamycin (mTOR), Akt, and glycogen synthase kinase 3β (GSK‐3β) signaling pathways was achieved using small‐molecule pharmacologic inhibitors.

Results

Binding of JunB to the COL1A2 enhancer was observed, with its coalescence directed by activation of gene transcription through the proximal promoter. Knockdown of JunB reduced enhancer activation and COL1A2 expression in response to transforming growth factor β. In SSc dermal fibroblasts, increased mTOR/Akt signaling was associated with inactivation of GSK‐3β, leading to blockade of JunB degradation and, thus, constitutively high expression of JunB.

Conclusion

In patients with SSc, the accumulation of JunB resulting from altered mTOR/Akt signaling and a failure of proteolytic degradation underpins the aberrant overexpression of type I collagen. These findings identify JunB as a potential target for antifibrotic therapy in SSc.
Anti–Ribosomal P Protein Autoantibodies From Patients With Neuropsychiatric Lupus Impair Memory in Mice
Authors: Bravo‐Zehnder Marcela , Toledo Enrique M. , Segovia‐Miranda Fabián , Serrano Felipe G. , Benito María J. , Metz Claudia , Retamal Claudio , Álvarez Alejandra , Massardo Loreto , Inestrosa Nibaldo C. , González Alfonso
Published: October 2014

Objective

To define whether anti‐ribosomal P (anti‐P) autoantibodies from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) impair the function of hippocampal neurons that express the neuronal surface P antigen (NSPA) when accessing the brain via circulating blood.

Methods

We used anti‐P antibodies from patients with NPSLE and rabbit‐generated anti‐P and anti‐NSPA antibodies. Primary hippocampal neurons from mice were analyzed to determine antibody cell surface binding (double immunofluorescence), intracellular calcium variations (Fura 2 AM), and apoptosis (caspase 3 activation). Hippocampal‐dependent spatial flexible memory was assessed in mice subjected to a water maze test 24 hours after an intravenous injection of anti‐P or anti‐NSPA, using lipopolysaccharide (LPS) to permeate the blood–brain barrier. Presence of antibodies and apoptosis in the hippocampus was studied using immunohistochemistry and TUNEL assays.

Results

Hippocampal neurons expressed NSPA on the cell surface, as revealed by anti‐P and anti‐NSPA staining colocalization, and responded to both anti‐P and anti‐NSPA by exhibiting increased intracellular calcium levels. Neuronal apoptosis was induced when anti‐P was directly injected by stereotaxis into the hippocampus or added to primary cultures. Upon LPS treatment, intravenously injected anti‐P impaired memory but did not elicit neuronal apoptosis in the hippocampus, where it was detectable in low amounts. Anti‐NSPA antibodies also impaired memory.

Conclusion

Anti‐P antibodies interact with NSPA on the surface of hippocampal neurons leading to apoptotic death or to functional perturbations, results that are likely dependent on the concentration of these antibodies. Circulating anti‐P can access the hippocampus and impair memory without requiring neuronal death when the blood–brain barrier is disrupted. NSPA can mediate antibody‐driven diffuse brain dysfunction, and anti‐P might contribute to the cognitive impairment that is frequently observed in SLE.
Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease
Authors: Chen Juan , Doyle Tracy J. , Liu Yongliang , Aggarwal Rohit , Wang Xiaoping , Shi Yonghong , Ge Sheng Xiang , Huang Heqing , Lin Qingyan , Liu Wen , Cai Yongjin , Koontz Diane , Fuhrman Carl R. , Golzarri Maria F. , Liu Yushi , Hatabu Hiroto , Nishino Mizuki , Araki Tetsuro , Dellaripa Paul F. , Oddis Chester V. , Rosas Ivan O. , Ascherman Dana P.
Published: October 2014

Objective

Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA‐associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.

Methods

Patients with RA who were enrolled in a well‐characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high‐resolution computed tomography scans of the chest. Multiplex enzyme‐linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute‐phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA‐ILD and biomarkers of interest.

Results

MMP‐7 and interferon‐γ–inducible protein 10 (IP‐10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA‐ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA‐ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid‐phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA‐ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.

Conclusion

Levels of MMP‐7 and IP‐10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
Enhanced Chondrogenesis of Induced Pluripotent Stem Cells From Patients With Neonatal‐Onset Multisystem Inflammatory Disease Occurs via the Caspase 1–Independent cAMP/Protein Kinase A/CREB Pathway
Authors: Yokoyama Koji , Ikeya Makoto , Umeda Katsutsugu , Oda Hirotsugu , Nodomi Seishiro , Nasu Akira , Matsumoto Yoshihisa , Izawa Kazushi , Horigome Kazuhiko , Kusaka Toshimasa , Tanaka Takayuki , Saito Megumu K. , Yasumi Takahiro , Nishikomori Ryuta , Ohara Osamu , Nakayama Naoki , Nakahata Tatsutoshi , Heike Toshio , Toguchida Junya
Published: October 2014

Objective

Neonatal‐onset multisystem inflammatory disease (NOMID) is a dominantly inherited autoinflammatory disease caused by NLRP3 mutations. NOMID pathophysiology is explained by the NLRP3 inflammasome, which produces interleukin‐1β (IL‐1β). However, epiphyseal overgrowth in NOMID is resistant to anti–IL‐1 therapy and may therefore occur independently of the NLRP3 inflammasome. This study was undertaken to investigate the effect of mutated NLRP3 on chondrocytes using induced pluripotent stem cells (iPSCs) from patients with NOMID.

Methods

We established isogenic iPSCs with wild‐type or mutant NLRP3 from 2 NOMID patients with NLRP3 somatic mosaicism. The iPSCs were differentiated into chondrocytes in vitro and in vivo. The phenotypes of chondrocytes with wild‐type and mutant NLRP3 were compared, particularly the size of the chondrocyte tissue produced.

Results

Mutant iPSCs produced larger chondrocyte masses than wild‐type iPSCs owing to glycosaminoglycan overproduction, which correlated with increased expression of the chondrocyte master regulator SOX9. In addition, in vivo transplantation of mutant cartilaginous pellets into immunodeficient mice caused disorganized endochondral ossification. Enhanced chondrogenesis was independent of caspase 1 and IL‐1, and thus the NLRP3 inflammasome. Investigation of the human SOX9 promoter in chondroprogenitor cells revealed that the CREB/ATF‐binding site was critical for SOX9 overexpression caused by mutated NLRP3. This was supported by increased levels of cAMP and phosphorylated CREB in mutant chondroprogenitor cells.

Conclusion

Our findings indicate that the intrinsic hyperplastic capacity of NOMID chondrocytes is dependent on the cAMP/PKA/CREB pathway, independent of the NLRP3 inflammasome.
The Mediating Effect of Leptin on the Relationship Between Body Weight and Knee Osteoarthritis in Older Adults
Authors: Fowler‐Brown Angela , Kim Dae Hyun , Shi Ling , Marcantonio Edward , Wee Christina C. , Shmerling Robert H. , Leveille Suzanne
Published: October 2014

Objective

Obesity is associated with an increased risk of osteoarthritis (OA) of the knee. Emerging evidence suggests that adipokines, substances produced by adipose tissue, may play a role in the development of knee OA. The aim of this study was to determine whether the inflammatory adipokine leptin partially mediates the relationship between body mass index (BMI) and knee OA.

Methods

We used baseline data from 653 participants who were 70 years of age or older in the population‐based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly Boston Study. Height and weight were measured, and participants were assessed for knee OA using clinical criteria. Serum leptin was measured using a microsphere‐based assay.

Results

The average BMI and the average serum leptin level were 27.5 kg/m2 and 589 pM, respectively; the prevalence of knee OA was 24.7%. In regression models adjusted for covariates, we found that a 5‐kg/m2 increase in BMI was associated with 32% increased odds of knee OA (odds ratio [OR] 1.32, 95% confidence interval [95% CI] 1.10, 1.58); a 200‐pM increase in serum leptin levels was associated with 11% increased odds of knee OA (OR 1.11, 95% CI 1.05, 1.17). The ratio of the standardized coefficients for the indirect:total effect calculated using the product‐of‐coefficients method was 0.49, suggesting that approximately half of the total effect of BMI on knee OA may be mediated by serum leptin. The estimated 95% CIs for the mediated effect suggest that this effect is statistically significant. Similarly, mediation analysis using a counterfactual approach suggested that the effect of leptin mediation was statistically significant.

Conclusion

We found that almost half of the association between elevated BMI and knee OA could be explained by the inflammatory adipokine leptin.
Chemical Approach to a New Crystal Structure: Phase Control of Manganese Oxide on a Carbon Sphere Template
Authors: Nam Ki Min , Park Joon T.
Published: October 2014

The stabilization and growth of a non‐native structure, hexagonal wurtzite MnO (h‐MnO), is explored via kinetic control of manganese precursor on a carbon sphere template. MnO is most stable in the cubic rock‐salt structure (c‐MnO), and a number of studies have focused on the synthesis and properties of this rock‐salt phase. However, h‐MnO has not been fully characterized before our work. Prolonged heating at a relatively low temperature yields c‐MnO, whereas rapid heating of the reaction mixture at reflux produces h‐MnO in the presence of carbon spheres. The effect of benzyl amine concentration on the formation of two different oxidation states (c‐MnO and t‐Mn3O4) was examined as well. Moreover, the structural stability of the manganese oxides and phase transition of MnO in terms of the wurtzite to rock‐salt structural transformation have been investigated.
Multivariable Output Feedback Adaptive Terminal Sliding Mode Control for Underwater Vehicles
Authors: Wang Yaoyao , Gu Linyi , Gao Ming , Zhu Kangwu
Published: October 2014

For the four degrees of freedom (4‐DOF) trajectory tracking control problem of underwater vehicles in the presence of parametric uncertainties and external disturbances, a novel multivariable output feedback adaptive nonsingular terminal sliding mode control (ANTSMC) approach is proposed based on the equivalent output injection adaptive sliding mode observer (ASMO) and ANTSMC method. The ASMO is applied to reconstruct the full states in finite time and the ANTSMC method is designed to stabilize the trajectory tracking error to a small field in finite time. The proposed output feedback ANTSMC approach, using the adaptive technology, does not require the bound information of parametric uncertainties or external disturbances which successfully achieves the decrease of undesired chattering effectively. Corresponding stability analysis is presented. Comparative numerical simulation results are presented to validate the effectiveness of the proposed approach.
Congestion avoidance in city traffic
Authors: Kala Rahul , Warwick Kevin
Published: October 2014

The number of vehicles on the road (worldwide) is constantly increasing, causing traffic jams and congestion especially in city traffic. Anticipatory vehicle routing techniques have thus far been applied to fairly small networked traffic scenarios and uniform traffic. We note here a number of limitations of these techniques and present a routing strategy on the assumption of a city map that has a large number of nodes and connectivity and where the vehicles possess highly varying speed capabilities. A scenario of operation with such characteristics has not previously been sufficiently studied in the literature. Frequent short‐term planning is preferred as compared with infrequent planning of the complete map. Experimental results show an efficiency boost when single‐lane overtaking is allowed, traffic signals are accounted for and every vehicle prefers to avoid high traffic density on a road by taking an alternative route. Comparisons with optimistic routing, pessimistic routing and time message channel routing are given. Copyright © 2014 John Wiley & Sons, Ltd.
Interactions of amelogenin with phospholipids
Authors: Bekshe Lokappa Sowmya , Balakrishna Chandrababu Karthik , Dutta Kaushik , Perovic Iva , Spencer Evans John , Moradian‐Oldak Janet
Published: October 2014

Amelogenin protein has the potential to interact with other enamel matrix proteins, mineral, and cell surfaces. We investigated the interactions of recombinant amelogenin rP172 with small unilamellar vesicles as model membranes, toward the goal of understanding the mechanisms of amelogenin–cell interactions during amelogenesis. Dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), and nuclear magnetic resonance (NMR) were used. In the presence of phospholipid vesicles, a blue shift in the Trp fluorescence emission maxima of rP172 was observed (∼334 nm) and the Trp residues of rP172 were inaccessible to the aqueous quencher acrylamide. DLS studies indicated complexation of rP172 and phospholipids, although the possibility of fusion of phospholipids following amelogenin addition cannot be ruled out. NMR and CD studies revealed a disorder–order transition of rP172 in a model membrane environment. Strong fluorescence resonance energy transfer from Trp in rP172 to DNS‐bound‐phospholipid was observed, and fluorescence polarization studies indicated that rP172 interacted with the hydrophobic core region of model membranes. Our data suggest that amelogenin has ability to interact with phospholipids and that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 96–108, 2015.
Training situational awareness to reduce surgical errors in the operating room
Authors: Graafland M , Schraagen J M C , Boermeester M A , Bemelman W A , Schijven M P
Published: October 2014

Background

Surgical errors result from faulty decision-making, misperceptions and the application of suboptimal problem-solving strategies, just as often as they result from technical failure. To date, surgical training curricula have focused mainly on the acquisition of technical skills. The aim of this review was to assess the validity of methods for improving situational awareness in the surgical theatre.

Methods

A search was conducted in PubMed, Embase, the Cochrane Library and PsycINFO® using predefined inclusion criteria, up to June 2014. All study types were considered eligible. The primary endpoint was validity for improving situational awareness in the surgical theatre at individual or team level.

Results

Nine articles were considered eligible. These evaluated surgical team crisis training in simulated environments for minimally invasive surgery (4) and open surgery (3), and training courses focused at training non-technical skills (2). Two studies showed that simulation-based surgical team crisis training has construct validity for assessing situational awareness in surgical trainees in minimally invasive surgery. None of the studies showed effectiveness of surgical crisis training on situational awareness in open surgery, whereas one showed face validity of a 2-day non-technical skills training course.

Conclusion

To improve safety in the operating theatre, more attention to situational awareness is needed in surgical training. Few structured curricula have been developed and validation research remains limited. Strategies to improve situational awareness can be adopted from other industries.
Screening for medullary carcinoma of the thyroid
Authors: Niederle B
Published: October 2014

Could potentially reduce mortality and morbidity
A validated LC‐MS/MS assay for simultaneous quantification of methotrexate and tofacitinib in rat plasma: application to a pharmacokinetic study
Authors: Sharma Kuldeep , Giri Kalpeshkumar , Dhiman Vinay , Dixit Abhishek , Zainuddin Mohd , Mullangi Ramesh
Published: October 2014

A highly sensitive, specific and rapid LC‐ESI‐MS/MS method has been developed and validated for simultaneous quantification of methotrexate (MTX) and tofacitinib (TFB) in rat plasma (50 μL) using phenacetin as an internal standard (IS), as per the US Food and Drug Administration guidelines. After a solid‐phase extraction procedure, the separation of the analytes and IS was performed on a Chromolith RP18e column using an isocratic mobile phase of 5 m m ammonium acetate (pH 5.0) and acetonitrile at a ratio of 25:75 (v/v) using flow‐gradient with a total run time of 3.5 min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 455.2 → 308.3, m/z 313.2 → 149.2 and m/z 180.3 → 110.2 for MTX, TFB and IS, respectively. The calibration curves were linear over the range of 0.49–91.0 and 0.40–74.4 ng/mL for MTX and TFB, respectively. The intra‐ and interday accuracy and precision values for MTX and TFB were <15% at low quality control (QC), medium QC and high QC and <20% at lower limit of quantification. The validated assay was applied to derive the pharmacokinetic parameters for MTX and TFB post‐dosing of MTX and TFB orally and intravenously to rats. Copyright © 2014 John Wiley & Sons, Ltd.
Validation of HPLC‐UV method for determination of minor glycosides contained in Stevia rebaudiana Bertoni leaves
Authors: Aranda‐González Irma , Moguel‐Ordoñez Yolanda , Betancur‐Ancona David
Published: October 2014

Leaves of Stevia rebaudiana contain glycosides with sweetness and biological activity. However besides the major glycosides, there are other glycosides within extracts that may contribute to its activity, and therefore it is important to quantify them. In this work, an isocratic HPLC method was validated for determination of dulcoside A, steviolbioside, rebaudioside C and rebaudioside B. An HPLC method was performed using a C18 column (250 × 4.6 mm, particle size 5 µm) and a UV detector set at 210 nm. The mobile phase consisted of a 32:68 (v/v) mixture of acetonitrile and sodium phosphate buffer (10 mmol/L, pH 2.6), set to a flow rate of 1.0 mL/min. The calculated parameters were: sensitivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision. The calibration curves were linear over the working range 25–150 µg/mL, with coefficient of correlation of ≥0.99 and coefficient of determination of ≥0.98. The LOD was 5.68–8.81 µg/mL, while the LOQ was 17.21–26.69 µg/mL. The percentage recoveries of fortified samples were 100 ± 10% and precision, relative standard deviation, was <10%. The method validation showed accuracy, linearity and precision; therefore this method can be applied for quantitative analysis of minor steviol glycosides in S. rebaudiana leaves. Copyright © 2014 John Wiley & Sons, Ltd.
Assessment of Waste Treatment Options: The New VDI Guideline 3925 for Decision Support
Authors: Simon Franz‐Georg , Hiebel Markus
Published: October 2014

Die neue VDI Richtlinie 3925 stellt Bewertungswerkzeuge vor, die es erlauben, ökologische, ökonomische und inzwischen auch soziale Aspekte und Auswirkungen verschiedener Abfallbehandlungsverfahren miteinander zu vergleichen. Die Richtlinie verfolgt das Ziel, die Anwendung von geeigneten wissenschaftlich‐technischen Bewertungsmethoden auf abfallwirtschaftliche Fragen zu beschreiben. Die Methoden, deren Einsatz, Anwendung, Komplexität, Möglichkeiten und Grenzen werden anhand von Praxisbeispielen erläutert.
On the Determination of Bubble Volumes
Authors: Nüllig Marius , Peters Franz
Published: October 2014

Zur Untersuchung von Mehrphasenströmungen wird u. a. das Volumen individueller Blasen benötigt. Natürliche Asymmetrien und Schwankungen der Blasenform legen eine sehr aufwändige 3D‐Formanalyse nahe. An drei Beispielen mit ansteigendem Schwierigkeitsgrad wird gezeigt, dass bereits digitale 2D‐Aufnahmen die Ermittlung des Blasenvolumens erlauben, wenn zuvor eine Kalibration durchgeführt wird. In der Kalibration wird die Analyse der digitalen Bilder auf Bilder genau bekannter Blasengrößen normiert. Bei starken Formschwankungen werden statistische Mittelwerte gebildet, die das richtige Volumen ergeben.
Seasonal and Spatial Variations of Metals in Melen Watershed Groundwater, Turkey
Authors: Çelebi Ahmet , Şengörür Bülent , Kløve Bjørn
Published: October 2014

Effective groundwater monitoring and status assessment is vital in the management and protection of groundwater systems according to e.g., the European Groundwater Directive. This study determined metal concentrations in groundwater in the Melen watershed close to Istanbul and assessed land use effects on groundwater status. In the monitoring period (2010–2011), elevated metal concentrations were observed in regions close to industrial zones and seasonally in agricultural fields. The highest values of metals (As, Mn, Zn, V, Cu, Na and Ba) concentrations were found in autumn and winter, when groundwater recharge occurs. Detectable levels of dissolved metals, such as Cr and Cd, were only found close to industrial zones. The aquifer can be considered to be in good qualitative status regarding some metals. However, As, Mn and Zn are present in concentrations higher than approved by international standards and pose a risk to human health. Therefore, measures to prevent metal contamination close to potential sources and good watershed management are needed.
Studies on Dye Decolorization by Ultrasound Assisted Electrocoagulation
Authors: Vianney Mujyambere Jean Marie , Muthukumar Karuppan
Published: October 2014

This study presents the removal of azo dyes (Congo red, Methyl red, and Eriochrome black T) from aqueous solutions by ultrasound assisted electrocoagulation (UE). In this method, dye solutions were simultaneously sonicated and electrolyzed. The effect of various operating parameters such as intensity of irradiation, pH, current intensity, initial concentration of the dye, and temperature on the performance of the process was investigated. The reduction in chemical oxygen demand, biological oxygen demand, hardness, and alkalinity were assessed. The kinetic analysis of the data showed a pseudo‐first order degradation for all three dyes. The results showed that UE is an effective method for the destruction of dyes.
Graphene Oxide Nanosheets at the Water–Organic Solvent Interface: Utilization in One‐Pot Adsorption and Reactive Extraction of Dye Molecules
Authors: Sharma Ponchami , Borah Dipankar J. , Das Manash R.
Published: October 2014

Graphene oxide (GO) is amphiphilic in nature, due to its structure, which consists of hydrophilic oxygen‐containing functional groups and a hydrophobic basal plane of polyaromatic benzene rings. Due to this amphiphilicity, GO can create stable bubbles at water–organic solvent interfaces. In this study, the formation of bubbles at aqueous–organic interfaces in the presence of GO is investigated with different organic solvents. Bubble formation and transfer of GO from water to the organic phase is more prominent in aromatic solvents compared to aliphatic solvents, due to π–π interactions. Maximum transfer of GO from the aqueous to the organic phase is achieved at pH 2, and decreases with rising pH of the aqueous phase. Based on this property, and the ability of GO to adsorb cationic and anionic dye molecules, its application as a carrier for reactive extraction of cationic and anionic dye molecules is explored in toluene, kerosene, and carbon tetrachloride at pH 2 and 25 °C. The kinetics of the adsorption of the dyes onto GO nanosheets that takes place in the aqueous phase is also evaluated with different models, and a pseudo‐second‐order (linear) model is found to be the best fit. The adsorption isotherm data are also analyzed with different isotherm models. The electrostatic interaction and π–π interaction between the dye molecules and GO nanosheets leads to dye extraction of up to 98.2 % using this technique. The dye extraction is maximum in toluene and at low dye concentration.
Differentiation of South American crack and domestic (US) crack cocaine via headspace‐gas chromatography/mass spectrometry
Authors: Colley Valerie L. , Casale John F.
Published: October 2014

South American ‘crack’ cocaine, produced directly from coca leaf, can be distinguished from US domestically produced crack on the basis of occluded solvent profiles. In addition, analysis of domestically produced crack indicates the solvents that were used for cocaine hydrochloride (HCl) processing in South America. Samples of cocaine base (N=3) from South America and cocaine from the USA (N=157 base, N=88 HCl) were analyzed by headspace‐gas chromatography‐mass spectrometry (HS‐GC‐MS) to determine their solvent profiles. Each cocaine HCl sample was then converted to crack cocaine using the traditional crack production method and re‐examined by HS‐GC‐MS. The resulting occluded solvent profiles were then compared to their original HCl solvent profiles. Analysis of the corresponding crack samples confirmed the same primary processing solvents found in the original HCl samples, but at reduced levels. Domestically seized crack samples also contained reduced levels of base‐to‐HCl conversion solvents. In contrast, analysis of South American crack samples confirmed the presence of low to high boiling hydrocarbons and no base‐to‐HCl conversion solvents. The presented study showed analysis of crack cocaine samples provides data on which processing solvents were originally utilized in the production of cocaine HCl in South America, prior to conversion to crack cocaine. Determination of processing solvents provides valuable information to the counter‐drug intelligence community and assists the law enforcement community in determining cocaine distribution and trafficking routes throughout the world. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.