bluuebunny/crossref_metadata_2025 huggingface dataset:
Normas de Presentación de Artículos
Authors: . .
Published: September 2014

.
Pilot Plants
Authors: Palluzi Richard P.
Published: September 2014

The article contains sections titled:

1.
Introduction

2.
Classification of Pilot Plants

3.
Scale‐Up

4.
Planned Pilot Plant Experimentation

5.
Pilot Plant Design

6.
Methods of Estimating Pilot Plant Costs

7.
Pilot Plant Space

8.
Scheduling

9.
Pilot Plant Control System and Instrumentation

10.
Feed and Product Handling

11.
Pilot Plant Start‐Up

12.
Safety in Pilot Plant Design and Operation
Latitudinal GRBR‐TEC estimation in Southeast Asia region based on the two‐station method
Authors: Watthanasangmechai Kornyanat , Yamamoto Mamoru , Saito Akinori , Tsugawa Takuya , Yokoyama Tatsuhiro , Supnithi Pornchai , Yatini Clara Yono
Published: September 2014

Total electron content (TEC) is an important parameter for revealing latitudinal ionospheric structures, such as the equatorial ionization anomaly (EIA) in Southeast Asia. Understanding the EIA is beneficial for studying equatorial spread F. To reveal the structures, the absolute TEC as a function of latitude must be accurately determined. In early 2012, we expanded a GNU Radio Beacon Receiver (GRBR) network to provide latitudinal coverage in the Thailand‐Indonesia sector. We employed the GRBR network to receive VHF and UHF signals from polar low‐Earth‐orbit satellites. The TEC offset is an unknown parameter in the absolute TEC estimation process. We propose a new technique based on the two‐station method to estimate the offset for the latitudinal TEC estimation, and it works better than the original method for a sparse network. The TEC estimation system requires two iterations to minimize the root‐mean‐square error (RMSE). Once the RMSE reaches the global minimum, the absolute TECs are estimated simultaneously over five GRBR stations. GPS‐TECs from local stations are used as the initial guess of the offset estimation. The height of the ionospheric pierce point is determined from the ionosonde hmF2. As a result, the latitudinal GRBR‐TEC was successfully estimated from the polar orbit satellites. The two EIA humps were clearly captured by the GRBR‐TEC. The result was well verified with the TEC reconstructed from the C/NOFS density data and the ionosonde bottomside data. This is a significant step showing that the GRBR is a useful tool for the study of low‐latitude ionospheric features.
Forest Service Groundwater Plan Oversteps Bounds, Critics Say
Authors: Showstack Randy
Published: September 2014

The U.S. Forest Service (USFS) is at odds with some members of Congress and other critics about a proposed government directive on groundwater resource management. The USFS says the proposed directive is an innocuous internal measure to provide a consistent, systematic, and transparent agency‐wide approach to groundwater management. However, some participants in a 10 September congressional hearing questioned the directive, saying that the agency is overstepping its bounds.
Fossil snail shells tell story about Tibetan Plateau
Authors: Wendel JoAnna
Published: September 2014

Ancient and modern snail shells have given scientists a unique look at the evolution of the Tibetan Plateau, confirming that parts of the plateau have actually lost elevation over time, despite its immense height. A new paper detailing the research was published on 29 August in the Geological Society of America Bulletin (doi:10.1130/B31000.1).
Howard Receives 2013 G. K. Gilbert Award: Response
Authors: Howard Alan D.
Published: September 2014

I am deeply honored to receive this award associated with the luminous heritage of G. K. Gilbert. My interest in geology and, in particular, in landforms was triggered by family vacations in the western United States. These trips fostered the theme of the process controls of landscape morphology that has been central to my research.
How a change in slope affects lava flows
Authors: Schultz Colin
Published: September 2014

As soon as lava flows from a volcano, exposure to air and wind causes it to start to cool and harden. Rather than hardening evenly, the energy exchange tends to take place primarily at the surface. The cooling causes a crust to form on the outer edges of the lava flow, insulating the molten lava within. This hardened lava shell allows lava to travel much farther than it would otherwise, although cracks in the lava's crust can cause it to draw up short.
At what depths do magma‐water eruptions breach the surface?
Authors: Wendel JoAnna
Published: September 2014

When magma ascends upward in the Earth's crust, it can react violently with groundwater, leading to underground explosions or even full‐fledged eruptions. If they breach the surface, these phreatomagmatic eruptions leave debris that falls concentrically around the crater or cone. Previously, researchers have sought to determine the depth within the vent from which the eruption originated by looking at the types of ejected rocks and their original positions beneath the volcanoes, but Valentine et al. found that these two factors are not necessarily directly related.
Heterotrophic bacteria as major nitrogen fixers in the euphotic zone of the Indian Ocean
Authors: Shiozaki Takuhei , Ijichi Minoru , Kodama Taketoshi , Takeda Shigenobu , Furuya Ken
Published: September 2014

Diazotrophy in the Indian Ocean is poorly understood compared to that in the Atlantic and Pacific Oceans. We first examined the basin‐scale community structure of diazotrophs and their nitrogen fixation activity within the euphotic zone during the northeast monsoon period along about 69°E from 17°N to 20°S in the oligotrophic Indian Ocean, where a shallow nitracline (49–59 m) prevailed widely and the sea surface temperature (SST) was above 25°C. Phosphate was detectable at the surface throughout the study area. The dissolved iron concentration and the ratio of iron to nitrate + nitrite at the surface were significantly higher in the Arabian Sea than in the equatorial and southern Indian Ocean. Nitrogen fixation in the Arabian Sea (24.6–47.1 μmolN m−2 d−1) was also significantly greater than that in the equatorial and southern Indian Ocean (6.27–16.6 μmolN m−2 d−1), indicating that iron could control diazotrophy in the Indian Ocean. Phylogenetic analysis of nifH showed that most diazotrophs belonged to the Proteobacteria and that cyanobacterial diazotrophs were absent in the study area except in the Arabian Sea. Furthermore, nitrogen fixation was not associated with light intensity throughout the study area. These results are consistent with nitrogen fixation in the Indian Ocean, being largely performed by heterotrophic bacteria and not by cyanobacteria. The low cyanobacterial diazotrophy was attributed to the shallow nitracline, which is rarely observed in the Pacific and Atlantic oligotrophic oceans. Because the shallower nitracline favored enhanced upward nitrate flux, the competitive advantage of cyanobacterial diazotrophs over nondiazotrophic phytoplankton was not as significant as it is in other oligotrophic oceans.
The worst North American drought year of the last millennium: 1934
Authors: Cook Benjamin I. , Seager Richard , Smerdon Jason E.
Published: September 2014

During the summer of 1934, over 70% of western North America experienced extreme drought, placing this summer far outside the normal range of drought variability and making 1934 the single worst drought year of the last millennium. Strong atmospheric ridging along the West Coast suppressed cold season precipitation across the Northwest, Southwest, and California, a circulation pattern similar to the winters of 1976–1977 and 2013–2014. In the spring and summer, the drying spread to the Midwest and Central Plains, driven by severe precipitation deficits downwind from regions of major dust storm activity, consistent with previous work linking drying during the Dust Bowl to anthropogenic dust aerosol forcing. Despite a moderate La Niña, contributions from sea surface temperature forcing were small, suggesting that the anomalous 1934 drought was primarily a consequence of atmospheric variability, possibly amplified by dust forcing that intensified and spread the drought across nearly all of western North America.
Structural evolution triggers a dynamic reduction in active glacier length during rapid retreat: Evidence from Falljökull, SE Iceland
Authors: Phillips Emrys , Finlayson Andrew , Bradwell Tom , Everest Jez , Jones Lee
Published: September 2014

Over the past two decades Iceland's glaciers have been undergoing a phase of accelerated retreat set against a backdrop of warmer summers and milder winters. This paper demonstrates how the dynamics of a steep outlet glacier in maritime SE Iceland have changed as it adjusts to recent significant changes in mass balance. Geomorphological evidence from Falljökull, a high‐mass turnover temperate glacier, clearly shows that between 1990 and 2004 the ice front was undergoing active retreat resulting in seasonal oscillations of its margin. However, in 2004–2006 this glacier crossed an important dynamic threshold and effectively reduced its active length by abandoning its lower reaches to passive retreat processes. A combination of ice surface structural measurements with radar, lidar, and differential Global Navigation Satellite Systems data are used to show that the upper active section of Falljökull is still flowing forward but has become detached from and is being thrust over its stagnant lower section. The reduction in the active length of Falljökull over the last several years has allowed it to rapidly reequilibrate to regional snowline rise in SE Iceland over the past two decades. It is possible that other steep, mountain glaciers around the world may respond in a similar way to significant changes in their mass balance, rapidly adjusting their active length in response to recent atmospheric warming.
Observation, analysis, and modeling of deep radio occultation signals: Effects of tropospheric ducts and interfering signals
Authors: Sokolovskiy S. , Schreiner W. , Zeng Z. , Hunt D. , Lin Y.‐C. , Kuo Y.‐H.
Published: September 2014

GPS radio occultation (RO) signals are sometimes observed very deep in the Earth's shadow. To investigate these phenomena, one of the FORMOSAT‐3/COSMIC RO receivers was set to track RO signals deep below the limb, down to a height of straight line −350 km on 5–6 October 2010. Analysis of the spectrograms revealed the existence of two types of signals below −200 km, RO signals induced by tropospheric propagation and interfering signals not transmitted by the occulted GPS. The RO signals induced by tropospheric propagation arrive from impact heights corresponding to inversion layers. Wave optics modeling of RO signals showed that deep signals exist when the refractivity gradient exceeds critical (super‐refraction). The existence of such signals is a diffractional phenomenon, which offers a new quality control parameter to identify occultations that may be affected by super‐refraction. This is important for RO data assimilation in weather models in the moist lower troposphere because assimilation of RO data affected by super‐refraction is an ill‐conditioned problem. Detection of the tropospheric ducts also may be useful for evaluation of radio wave propagation conditions. For infinitely horizontally extended ducts, the deep signals are extended in duration, have amplitudes of about 0.1%, and exist for only elevated ducts. For ducts of limited horizontal extension, the deep signals are shorter in duration, have amplitude of about 1%, and may exist for both elevated and surface ducts. The interfering signals were found in about half of occultations. Based on frequency modeling, in most cases, the interfering signal was identified with non‐occulted GPS. The disturbance of retrieved bending angle induced by an interfering signal from a non‐occulted GPS in a region of strong defocusing and significant spectral spread of RO signal was modeled and determined to be quite large, up to 10% of bending angle. However, the probability of occurrence of such interference (not estimated), generally, must be low. Removal of the interfering signal by high‐pass filtering was tested, but it introduced a disturbance of bending angle of about the same magnitude as the interfering signal itself.
Association of Time to Kidney Transplantation With Graft Failure Among US Patients With End‐Stage Renal Disease Due to Lupus Nephritis
Authors: Plantinga Laura C. , Patzer Rachel E. , Drenkard Cristina , Kramer Michael R. , Klein Mitchel , Lim S. Sam , McClellan William M. , Pastan Stephen O.
Published: September 2014

Objective

Providers recommend waiting to transplant patients with end‐stage renal disease (ESRD) secondary to lupus nephritis (LN), to allow for quiescence of systemic lupus erythematosus (SLE)–related immune activity. However, these recommendations are not standardized, and we sought to examine whether duration of time to transplant was associated with risk of graft failure in US LN‐ESRD patients.

Methods

Using national ESRD surveillance data (United States Renal Data System), we identified 4,743 US patients with LN‐ESRD who received a first transplant on or after January 1, 2000 (followup through September 30, 2011). The association of wait time (time from ESRD start to transplant) with graft failure was assessed with Cox proportional hazards models, with splines of the exposure to allow for nonlinearity of the association and with adjustment for potential confounding by demographic, clinical, and transplant factors.

Results

White LN‐ESRD patients who were transplanted later (versus at <3 months receiving dialysis) were at increased risk of graft failure (3–12 months: adjusted hazard ratio [HR] 1.23, 95% confidence interval [95% CI] 0.93–1.63; 12–24 months: adjusted HR 1.37, 95% CI 0.92–2.06; 24–36 months: adjusted HR 1.34, 95% CI 0.92–1.97; and >36 months: adjusted HR 1.98, 95% CI 1.31–2.99). However, no such association was seen among African American recipients (3–12 months: adjusted HR 1.07, 95% CI 0.79–1.45; 12–24 months: adjusted HR 1.01, 95% CI 0.64–1.60; 24–36 months: adjusted HR 0.78, 95% CI 0.51–1.18; and >36 months: adjusted HR 0.74, 95% CI 0.48–1.13).

Conclusion

While future studies are needed to examine the potential confounding effect of clinically recognized SLE activity on the observed associations, these results suggest that longer wait times to transplant may be associated with equivalent or worse, not better, graft outcomes among LN‐ESRD patients.
Metal Nanowire Networks: The Next Generation of Transparent Conductors
Authors: Ye Shengrong , Rathmell Aaron R. , Chen Zuofeng , Stewart Ian E. , Wiley Benjamin J.
Published: September 2014

There is an ongoing drive to replace the most common transparent conductor, indium tin oxide (ITO), with a material that gives comparable performance, but can be coated from solution at speeds orders of magnitude faster than the sputtering processes used to deposit ITO. Metal nanowires are currently the only alternative to ITO that meets these requirements. This Progress Report summarizes recent advances toward understanding the relationship between the structure of metal nanowires, the electrical and optical properties of metal nanowires, and the properties of a network of metal nanowires. Using the structure–property relationship of metal nanowire networks as a roadmap, this Progress Report describes different synthetic strategies to produce metal nanowires with the desired properties. Practical aspects of processing metal nanowires into high‐performance transparent conducting films are discussed, as well as the use of nanowire films in a variety of applications.
HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders
Authors: Reuter Miriam S. , Sass Jörn Oliver , Leis Thomas , Köhler Julia , Mayr Johannes A. , Feichtinger René G. , Rauh Manfred , Schanze Ina , Bähr Luzy , Trollmann Regina , Uebe Steffen , Ekici Arif B. , Reis André
Published: September 2014

HIBCH (3‐hydroxyisobutyryl‐CoA hydrolase) deficiency (MIM #250620) is a rare autosomal recessive inborn error of metabolism, leading to a block in the catabolic pathway of the amino acid valine and presumably to accumulation of toxic valine metabolites in mitochondria. Only three families with HIBCH deficiency and biallelic HIBCH mutations have been described. We report on a further patient, first child of healthy consanguineous parents, with severe developmental delay, seizures, hyperintensities of the basal ganglia on magnetic resonance imaging (MRI), progressive brain atrophy, optic nerve atrophy, repeatedly elevated blood lactate, and respiratory chain complexes I, I + III and cytochrome c oxidase deficiencies with borderline depletion of mitochondrial DNA in muscle tissue. Laboratory findings in blood and skeletal muscle were inconsistent and did not allow a definite diagnosis, but supported the hypothesis of mitochondrial dysfunction. Homozygosity mapping and whole‐exome sequencing revealed a homozygous one‐base pair insertion in HIBCH. Deficiency of enzyme activity was confirmed in cultured fibroblasts. Although relatively unspecific, the clinical features were similar to those of the previously reported cases. Given the clinical variability and large number of differential diagnoses, the prevalence of HIBCH deficiency is probably underestimated. Next‐generation sequencing approaches are an effective tool for identifying the underlying genetic basis in patients suspected of mitochondrial disorders. © 2014 Wiley Periodicals, Inc.
Intragenic duplication—A novel causative mechanism for SATB2‐associated syndrome
Authors: Liedén Agne , Kvarnung Malin , Nilssson Daniel , Sahlin Ellika , Lundberg Elisabeth Syk
Published: September 2014

Previous studies have shown that genetic aberrations involving the special AT‐rich sequence‐binding protein 2 (SATB2) gene result in a variable phenotype of syndromic intellectual disability. Although only a small number of patients have been described, there is already considerable variation in regard to the underlying molecular mechanism spanning from structural variation to point mutations. We here describe a male patient with intellectual disability, speech and language impairment, cleft palate, malformed teeth, and oligodontia. Array CGH analysis identified a small intragenic duplication in the SATB2 gene that included three coding exons. The result was confirmed by multiplex ligation‐dependent probe amplification and low coverage whole genome mate pair sequencing. WGS breakpoint analysis directly confirmed the duplication as intragenic. This is the first reported patient with an intragenic duplication in SATB2 in combination with a phenotype that is highly similar to previously described patients with small deletions or point mutations of the same gene. Our findings expand the spectra of SATB2 mutations and confirm the presence of a distinct SATB2‐phenotype with severe ID and speech impairment, cleft palate and/or high arched palate, and abnormalities of the teeth. For patients that present with this clinical picture, a high‐resolution exon targeted array CGH and/or WGS, in addition to sequencing of SATB2, should be considered. © 2014 Wiley Periodicals, Inc.
Synthesis of cyclic carbonates from epoxides catalyzed by metal–BINOL complexes
Authors: Bai Dongsheng , Wang Guangjian , Ma Fang , Wang Juangang , Wang Kuai , Yang Zijing
Published: September 2014

Synthesis of cyclic carbonates from CO2 and terminal epoxides catalyzed by Mg, Ca and In BINOL complexes was achieved without organic solvents. Effects of temperature, CO2 pressure, reaction time and co‐catalyst on the cycloaddition were investigated. Propylene carbonate was obtained under a CO2 pressure of 1.2 MPa within 10 hours in a yield of 98% catalyzed by Ca–BINOL at 120°C. The order of catalytic activity of the metal center is Ca > In > Mg. Copyright © 2014 John Wiley & Sons, Ltd.
Screening of N,N‐bidentate and N,N,N‐tridentate pyridine‐based ligands in the catalytic allylic oxidation of cyclic olefins
Authors: Solinas Maurizio , Sechi Barbara , Chelucci Giorgio
Published: September 2014

A variety of chiral N,N‐bidentate and N,N,N‐tridentate ligands based on the pyridine framework, namely C2‐symmetric dipyridylmethane and terpyridine, N‐(p‐toluensulfinyl)iminopyridines and two kinds of iminopyridines, has been assessed in the asymmetric copper(I)‐catalysed allylic oxidation of cyclic olefins. Catalytic activity and enantioselectivity were found to be highly dependent upon the framework of the ligands, which afforded cycloalkenyl benzoates in low to moderate yields and enantioselectivities. The best yields (up to 70%) and enantioselectivities (up to 53% enantiomeric excess) were obtained with an iminopyridine based on camphane and quinoline skeletons. Copyright © 2014 John Wiley & Sons, Ltd.
Comparison of the initial reactant structure and crosslinked network of poly(dimethyl siloxane) membranes from different macromonomers
Authors: Singh Puyam S. , Jadav Ghanshyam L. , Aswal Vinod K. , Das Arun K. , Kumar Sugam , Kansara Ankit M. , Chaudhri Sanjay G. , Brahmbhatt Harshad
Published: September 2014

Some of the best entities for the removal of volatile organic pollutants from water, poly(dimethyl siloxane) (PDMS) membranes from two types of initial PDMS precursors, were thoroughly investigated. In both the cases, the sizes of the initial macromonomers increased because of the crosslinking in the liquid state, and they exhibited Gaussian chain statistics, which were condensed by further crosslinking to the formation of the membranes. The structures of both the membrane types exhibited large interchain spacing on swelling; this implied a high degree of chain mobility. Their structural properties were corroborated by their separation performances. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41461.
Five‐Year Followup of Knee Joint Cartilage Thickness Changes After Acute Rupture of the Anterior Cruciate Ligament
Authors: Eckstein F. , Wirth W. , Lohmander L. S. , Hudelmaier M. I. , Frobell R. B.
Published: September 2014

Objective

Anterior cruciate ligament (ACL) rupture involves an increased risk of osteoarthritis. The purpose of this study was to explore changes in cartilage thickness over 5 years after ACL rupture.

Methods

A total of 121 young active adults (ages 18–35 years; 26% women) from the Knee ACL, Nonsurgical versus Surgical Treatment (KANON) study, who had acute traumatic rupture of the ACL were studied. Sagittal magnetic resonance images were acquired within 4 weeks of ACL rupture (baseline) and at the 2‐year and 5‐year followup assessments. Medial and lateral femorotibial cartilage was segmented (with blinding to acquisition order), and the mean cartilage thickness was computed across 16 femorotibial subregions. Total femorotibial cartilage thickness change was the primary analytic focus. Maximal subregional mean cartilage thickness loss (ordered value 1 [OV1]) and gain (ordered value 16 [OV16]), independent of its specific location in individual knees, were the secondary analytic focus.

Results

Overall femorotibial cartilage thickness increased by 31 μm/year over 5 years (95% confidence interval 18, 44). The increase was similar in men and women and was significantly greater in those younger, as compared with those older, than the median age (25.3 years). The rate of total cartilage thickness change did not differ significantly between the first 2 years and the later 3 years. However, the maximal annualized subregional cartilage loss (OV1) and gain (OV16) were both significantly greater (P < 0.001 and P < 0.05, respectively) during the earlier interval than during the later interval (−115 versus −54 μm [OV1] and 116 versus 69 μm [OV16]).

Conclusion

Cartilage thickening was observed over 5 years following ACL injury, particularly in the medial femorotibial compartment and in younger subjects. Major perturbations in cartilage homeostasis were seen over the first 2 years after ACL rupture, with simultaneous subregional thinning and thickening occurring within the same cartilage plate or compartment.
Mechanisms of Tumor Necrosis Factor α Antagonist–Induced Lupus in a Murine Model
Authors: Xu Yuan , Zhuang Haoyang , Han Shuhong , Liu Chao , Wang Hai , Mathews Clayton E. , Massini John , Yang Lijun , Reeves Westley H.
Published: September 2014

Objective

Tumor necrosis factor α (TNFα) antagonists are effective for treating rheumatoid arthritis and other inflammatory diseases, but their use can be complicated by the development of lupus‐like phenomena. This study was undertaken to investigate the role of TNFα in a murine model of lupus.

Methods

Toll‐like receptor 7 (TLR‐7) ligand–driven lupus was induced by injection of pristane into C57BL/6 (B6) mice deficient in TNFα (TNFα−/−) or TNFα‐intact B6 mice as wild‐type controls. Autoantibody and type I interferon (IFN) production was measured in each group of mice, and the effects of the presence or absence of TNFα on type I IFN–producing plasmacytoid dendritic cells (PDCs), Ly‐6Chigh monocytes, and TNFα‐producing neutrophils were determined.

Results

TNFα−/− mice did not spontaneously develop autoantibodies or clinical manifestations of lupus, suggesting that TNFα deficiency alone is insufficient to cause lupus. Although the levels of type I IFN were comparable between untreated TNFα−/− and wild‐type control mice, untreated TNFα−/− mice had increased circulating levels of PDCs and PDC‐like cells, which enhanced the potential for production of type I IFN. When treated with pristane, TNFα−/− mice developed more severe lupus compared to pristane‐treated controls, characterized by increased levels of anti‐Sm/RNP autoantibodies, type I IFN, PDCs, and peritoneal inflammatory (Ly‐6Chigh) monocytes. In pristane‐treated TNFα−/− mice, the numbers of neutrophils, a cell type that promotes resolution of inflammation, were decreased considerably, whereas the responses of inflammatory monocytes and PDCs and the production of type I IFN were increased and prolonged.

Conclusion

Low levels of TNFα will increase the number of circulating PDCs in mice, thereby enhancing the potential to produce type I IFN. However, this does not necessarily lead to type I IFN production or autoimmunity unless there is concomitant exposure to endogenous TLR‐7 ligands, which are released from dead cells following pristane treatment. In humans, the rate of clearance of dead cells, along with the levels of TNFα, may influence who will develop lupus following treatment with TNFα inhibitors.
Effects of Low‐Dose Embryonic Thyroid Disruption and Rearing Temperature on the Development of the Eye and Retina in Zebrafish
Authors: Reider Masha , Connaughton Victoria P.
Published: September 2014

Thyroid hormones are required for vertebrate development, and disruption of the thyroid system in developing embryos can result in a large range of morphologic and physiologic changes, including in the eye and retina. In this study, our anatomic analyses following low‐dose, chronic thyroid inhibition reveal that both methimazole (MMI) exposure and rearing temperature affect eye development in a time‐ and temperature‐dependent fashion. Maximal sensitivity to MMI for external eye development occurred at 65 hr postfertilization (hpf) for zebrafish reared at 28°C, and at 69 hpf for those reared at 31°C. Changes in eye diameter corresponded to changes in thickness of two inner retinal layers: the ganglion cell layer and the inner plexiform layer, with irreversible MMI‐induced decreases in layer thickness observed in larvae treated with MMI until 66 hpf at 28°C. We infer that maximal sensitivity to MMI between 65 and 66 hpf at 28°C indicates a critical period of thyroid‐dependent eye and retinal development. Furthermore, our results support previous work that shows spontaneous escape from MMI‐induced effects potentially due to embryonic compensatory actions, as our data show that embryos treated beyond the critical period generally resemble controls
Evaluation of Bupropion Hydrochloride Developmental Cardiotoxic Effects in Chick Cardiomyocyte Micromass Culture and stem cell derived Cardiomyocyte Systems
Authors: Shaikh Qureshi W. M. , Latif Muhammad Liaque , Parker Terry L. , Pratten Margaret K.
Published: September 2014

The use of antidepressant drug bupropion hydrochloride (BPN) during pregnancy results in increased cardiovascular anomalies. In this study, BPN developmental cardiotoxic effects in in vitro system were evaluated using chick cardiomyocyte micromass (MM) culture system and mouse embryonic stem cell derived cardiomyocyte (ESDC) system. In MM system, the cardiomyocyte contractile activity significantly decreased only at BPN 200 μM, while in ESDC system BPN concentration above 75 μM resulted in decreased contractile activity. The increase in drug concentration also affected the cardiomyocyte viability and total cellular protein content in both systems, but in ESDC system the cell viability failed to attain significant difference. The drug failed to induce reactive oxygen species production in both systems, but has affected the cardiac connexin43 expression especially in MM system. We observed that BPN showed developmental cardiotoxic effects irrespective of the stage of cardiac development in both in vitro systems
Relationship Between Bent Long Bones, Bent Scapulae, and Wavy Ribs: Malformations or Variations?
Authors: Kimmel Carole A. , Garry Michael R. , DeSesso John M.
Published: September 2014

BACKGROUND

Shortened and bent long bones and bent scapulae are sometimes reported in fetuses with wavy ribs (Carney and Kimmel, ). Wavy ribs are typically seen in the presence of maternal and developmental toxicity, are transient and reversible postnatally, and are considered to be variations rather than malformations.

METHODS

We further assessed the literature cited in Kimmel and Carney () as well as papers published since then to determine under what conditions bent long bones in the absence of gross limb defects and bent scapulae were reported and whether information was available on the transient or permanent nature of these effects.

RESULTS

Long bone and/or scapular changes almost always occurred at a lower incidence than wavy ribs. In every case, maternal and fetal toxicity occurred at the same dose levels. In a few studies, pups were followed sequentially after birth and bent long bones and scapulae were transient in nature and appeared normal by the time of weaning. Rabbits were much less likely to show wavy ribs or long bone and scapular changes at birth, even in the presence of severe maternal and fetal toxicity. This species difference may be due in part to the great increase in bone mass and remodeling that occurs during the first few postnatal weeks in rodents, but which takes place during the longer fetal period in rabbits.

CONCLUSION

Our conclusion from this review is that bent long bones and scapulae, like wavy ribs, appear to be secondary to maternal and developmental toxicity, are transient, and like wavy ribs should be considered variations rather than malformations
Chimeric murine interferon regulatory factor‐2 (IRF‐2) binds to IRF‐E (IRF binding element), VREβ (virus response element) but not to VREα1
Authors: Prakash Krishna , Kumar Pardeep , Mukherjee Somnath , Rath P.C.
Published: September 2014

Interferon regulatory factor‐2 (IRF‐2) is a multifunctional transcription factor having gene activation, repression and synergistic effect in conjunction with IRF‐1. IRF‐2 is also involved in type I IFN signalling by repressing INFβ gene. So far, the molecular mechanism of its DNA binding activity remains elusive. We have carried out molecular sub‐cloning, expression and electrophoretically mobility shift assay study of chimeric murine IRF‐2. Here, we report expression of chimeric murine IRF‐2 as GST‐IRF‐2 fusion protein in Escherichia coli/BL21 cells and demonstrated DNA binding activity by gel retardation technique using radio 32P‐labelled IRF‐E motif (GAAAGT)4, virus response element (VRE) of human INFβ and IFNα1 gene. We observed five different masses DNA/GST‐IRF‐2 complexes (1–5) with IRF‐E motif, three different masses DNA/GST‐IRF‐2 complexes (1–3) with VREß, but we could not observe any complex of DNA/GST‐IRF‐2 with VREα1. The specific binding on IRF‐E motif was confirmed by carrying out 100‐X fold cold competition with 32P‐labelled IRF‐E motif. In contrast to specific binding on VREß, we used negative control where we observed no binding complex, but we observed complexes with clones IPTG‐induced extract. As far as binding on VREα1 is concerned, we could not observe any complex in negative control as well as in IPTG‐inducible clones extract. Chimeric IRF‐2 binds with IRF‐E motif and VREβ but not with VREα1. This study is first of its kind and paves the way to understand the differential DNA binding and molecular mechanism of DNA binding activity of the IRF‐2 molecule, which is crucial for its function(s). Copyright © 2014 John Wiley & Sons, Ltd.
Characterization of human adipose tissue‐derived stromal cells isolated from diabetic patient's distal limbs with critical ischemia
Authors: Kočí Zuzana , Turnovcová Karolína , Dubský Michal , Baranovičová Lenka , Holáň Vladimír , Chudíčková Milada , Syková Eva , Kubinová Šárka
Published: September 2014

Adipose tissue is an abundant source of autologous adult stem cells that may bring new therapeutic perspectives on the treatment of diabetes and its complications. It is unclear whether adipose tissue‐derived stromal cells (ASCs) of diabetic patients, constantly influenced by hyperglycaemia, have the same properties as non‐diabetic controls. As an alternative source of ASCs, adipose tissue from distal limbs of diabetic patients with critical ischemia was isolated. ASCs were characterized in terms of cell surface markers, multilineage differentiation and the expression of vascular endothelial growth factor (VEGFA), chemokine‐related genes and compared with non‐diabetic controls. Flow cytometry analysis confirmed mesenchymal phenotypes in both diabetic and non‐diabetic ASCs. Nevertheless, 40% of diabetic and 20% of non‐diabetic ASC samples displayed high expressions of fibroblast marker, which inversely correlated with the expression of CD105. In diabetic patients, significantly decreased expression of VEGFA and chemokine receptor CXCR4 was found in fibroblast‐positive ASCs, compared with their fibroblast‐negative counterparts. Reduced osteogenic differentiation and the downregulation of chemokine CXCL12 were found in fibroblast‐negative diabetic ASCs. Both diabetic and non‐diabetic ASCs were differentiated into adipocytes and chondrocytes and did not reveal islet‐like cell differentiation. According to this study, adipose tissue from distal limbs of diabetic patients is not satisfactory as an autologous ASC source. Copyright © 2014 John Wiley & Sons, Ltd.

SIGNIFICANCE OF THE STUDY

Hyperglycaemic milieu as well as other metabolic disorders linked to diabetes may have an influence on endogenous stem cell properties. The present study investigated the feasibility of autologous stem cell therapy in diabetic patients. ASCs isolated from the ischemic limb of diabetic patients were found to be less potent when compared phenotypically and functionally to control non‐diabetic counterparts with no signs of limb ischemia. High expression of fibroblast markers associated with reduced expression of VEGFA as well as reduced osteogenic differentiation may have an impact on the effectiveness of autologous cell therapies in diabetic patients.
Kinesin‐12 influences axonal growth during zebrafish neural development
Authors: Xu Man , Liu Dong , Dong Zhangji , Wang Xin , Wang Xueqian , Liu Yan , Baas Peter W. , Liu Mei
Published: September 2014

Kinesin‐12 (also called KIF15) is a microtubule‐based motor protein best known for its role in cell division. We previously reported that kinesin‐12 is robustly expressed in developing terminally post‐mitotic neurons, with levels diminishing as neurons reach maturity. We found that axons of cultured rodent neurons grow faster and longer if kinesin‐12 is experimentally depleted, leading us to conclude that kinesin‐12 plays a role in modulating axonal growth. Here we used zebrafish to explore whether these results apply to an in vivo system and whether they apply across different kinds of vertebrates. In whole mount in situ hybridization, kinesin‐12 mRNA was detectable at 2‐cell and 1K‐cell stages. At 5.3 and 8 hours post‐fertilization (hpf), hybridization signal for kinesin‐12 mRNA was observed in the ectoderm. From 14 to 36 hpf, the signal had expanded to the central nervous system. At 60 hpf, the hybridization signal was concentrated in the brain. After 5 days post‐fertilization, kinesin‐12 expression was reduced. Kinesin‐12 knockdown resulted in notably longer fast‐growing axons with fewer branches by injection of a splice‐blocking morpholino into Tg(huC:egfp) or Tg(hb9:gfp) zebrafish embryos. Kinesin‐12 overexpression resulted in shorter axons than controls. These results are consistent with our previous observations on rodents using primary cultures for the experimental manipulations, and suggest a key role of kinesin‐12 as a modulator of axonal development. © 2014 Wiley Periodicals, Inc.
Identification of novel mutations by exome sequencing in African American colorectal cancer patients
Authors: Ashktorab Hassan , Daremipouran Mohammad , Devaney Joe , Varma Sudhir , Rahi Hamed , Lee Edward , Shokrani Babak , Schwartz Russell , Nickerson Michael L. , Brim Hassan
Published: September 2014

BACKGROUND

The purpose of this study was to identify genome‐wide single nucleotide variants and mutations in African American patients with colorectal cancer (CRC). There is a need of such studies in African Americans, because they display a higher incidence of aggressive CRC tumors.

METHODS

We performed whole exome sequencing (WES) on DNA from 12 normal/tumor pairs of African American CRC patient tissues. Data analysis was performed using the software package GATK (Genome Analysis Tool Kit). Normative population databases (eg, 1000 Genomes SNP database, dbSNP, and HapMap) were used for comparison. Variants were annotated using analysis of variance and were validated via Sanger sequencing.

RESULTS

We identified somatic mutations in genes that are known targets in CRC such as APC, BRAF, KRAS, and PIK3CA. We detected novel alterations in the Wnt pathway gene, APC, within its exon 15, of which mutations are highly associated with CRC.

CONCLUSIONS

This WES study in African American patients with CRC provides insight into the identification of novel somatic mutations in APC. Our data suggest an association between specific mutations in the Wnt signaling pathway and an increased risk of CRC. The analysis of the pathogenicity of these novel variants may shed light on the aggressive nature of CRC in African Americans. Cancer 2015;121:34–42. © 2014 American Cancer Society.
Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy‐resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo
Authors: English Diana P. , Bellone Stefania , Schwab Carlton L. , Roque Dana M. , Lopez Salvatore , Bortolomai Ileana , Cocco Emiliano , Bonazzoli Elena , Chatterjee Sudeshna , Ratner Elena , Silasi Dan‐Arin , Azodi Masoud , Schwartz Peter E. , Rutherford Thomas J. , Santin Alessandro D.
Published: September 2014

BACKGROUND

Solitomab is a novel, bispecific, single‐chain antibody that targets epithelial cell adhesion molecule (EpCAM) on tumor cells and also contains a cluster of differentiation 3 (CD3) (T‐cell coreceptor) binding region. The authors evaluated the in vitro activity of solitomab against primary chemotherapy‐resistant epithelial ovarian carcinoma cell lines as well as malignant cells in ascites.

METHODS

EpCAM expression was evaluated by flow cytometry in 5 primary ovarian cancer cell lines and in 42 fresh ovarian tumor cell cultures in ascites from patients with mainly advanced or recurrent, chemotherapy‐resistant disease. The potential activity of solitomab against EpCAM‐positive tumor cells was evaluated by flow cytometry, proliferation, and 4‐hour chromium‐release, cell‐mediated cytotoxicity assays.

RESULTS

EpCAM expression was detected by flow cytometry in approximately 80% of the fresh ovarian tumors and primary ovarian tumor cell lines tested. EpCAM‐positive, chemotherapy‐resistant cell lines were identified as resistant to natural killer cell‐mediated or T‐cell–mediated killing after exposure to peripheral blood lymphocytes in 4‐hour chromium‐release assays (mean±standard error of the mean, 3.6%±0.7% of cells killed after incubation of EpCAM‐positive cell lines with control bispecific antibody). In contrast, after incubation with solitomab, EpCAM‐positive, chemotherapy‐resistant cells became highly sensitive to T‐cell cytotoxicity (mean±standard error of the mean, 28.2%±2.05% of cells killed; P<.0001) after exposure to peripheral blood lymphocytes. Ex vivo incubation of autologous tumor‐associated lymphocytes with EpCAM‐expressing malignant cells in ascites with solitomab resulted in a significant increase in T‐cell activation markers and a reduction in the number of viable ovarian tumor cells in ascites (P<.001).

CONCLUSIONS

Solitomab may represent a novel, potentially effective agent for the treatment of chemotherapy‐resistant ovarian cancers that overexpress EpCAM. Cancer 2015;121:403–412. © 2014 American Cancer Society.
An historic step for advanced cytopathology training in Canada
Authors: Auger Manon , Islam Shahidul , Weir Michele
Published: September 2014

Advanced cytopathology training has finally obtained official recognition in Canada, having recently been assigned the newly developed status of “Area of Focused Competence” by the Royal College of Physicians and Surgeons of Canada. It is hoped that the trainees who graduate from these programs in cytopathology will be provided with the leadership and consultant skills to allow them to adapt and respond competently to the rapid evolving field of cytopathology.
Differential susceptibility in a developmental perspective: DRD4 and maternal sensitivity predicting externalizing behavior
Authors: Windhorst Dafna A. , Mileva‐Seitz Viara R. , Linting Mariëlle , Hofman Albert , Jaddoe Vincent W.V. , Verhulst Frank C. , Tiemeier Henning , van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J.
Published: September 2014

This study is the first to investigate the longitudinal effects of gene–environment interplay between DRD4 genotype and maternal sensitivity on child externalizing behavior. Multiple measures of maternal sensitivity (14, 36, and 48 months) and externalizing behavior (18 months, 36 months, and 5 years) were assessed in a large cohort study (N = 548). Early maternal insensitivity (14 months) was associated with early externalizing behavior (18 months) in a for better and for worse manner, but only in children with at least one DRD4 7‐repeat, consistent with a differential susceptibility model. Later insensitivity (48 months) predicted externalizing behavior at age 5 independent of DRD4 genotype. A structural equation model including all measures across time supported the differential susceptibility model: The overall effect of early maternal sensitivity on later externalizing behavior was significant only for children with a DRD4 7‐repeat allele. The results highlight the importance of studying gene–environment interactions across development. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 35–49, 2015.
The Effect of Leisure‐Time Physical Activity on Obesity, Diabetes, High BP and Heart Disease Among Canadians: Evidence from 2000/2001 to 2005/2006
Authors: Sarma Sisira , Devlin Rose Anne , Gilliland Jason , Campbell M. Karen , Zaric Gregory S.
Published: September 2014

Although studies have looked at the effect of physical activity on obesity and other health outcomes, the causal nature of this relationship remains unclear. We fill this gap by investigating the impact of leisure‐time physical activity (LTPA) and work‐related physical activity (WRPA) on obesity and chronic conditions in Canadians aged 18–75 using instrumental variable and recursive bivariate probit approaches. Average local temperatures surrounding the respondents' interview month are used as a novel instrument to help identify the causal relationship between LTPA and health outcomes. We find that an active level of LTPA (i.e. walking ≥1 h/day) reduces the probability of obesity by five percentage points, which increases to 11 percentage points if also combined with some WRPA. WRPA exhibits a negative effect on the probability of obesity and chronic conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Primary extradural meningioma presenting as a neck mass: Case report and review of the literature
Authors: Saade Rami , Hessel Amy , Ginsberg Lawrence , Fuller Greg , Bell Diana
Published: September 2014

Background

Primary extradural meningiomas (PEMs) are rare, particularly those involving the paraspinal cervical area, so little is known about them. We identified a new case and compared it with 10 previous cases, addressed the diagnostic challenges, and highlighted the clinical and pathologic characteristics.

Methods

We conducted a case report and literature review of PEM cases reported since 1976.

Results

A 59‐year‐old man presented with right neck stiffness and discomfort that was present over the last several months, which is consistent with other cases. CT scan and MRI revealed a paraspinal cervical mass. Fine‐needle aspiration (FNA) and core biopsy revealed spindle cells with whorling consistent with meningioma. The patient underwent complete en bloc resection of the tumor. The PEM was histologically benign.

Conclusion

Cervical PEMs should be considered in the differential diagnosis of a deep neck mass. These tumors are typically benign and are surgically resected. © 2014 Wiley Periodicals, Inc. Head Neck 37: E92–E95, 2015
CHOOSING THE VARIABLES TO ESTIMATE SINGULAR DSGE MODELS
Authors: Canova Fabio , Ferroni Filippo , Matthes Christian
Published: September 2014

We propose two methods to choose the variables to be used in the estimation of the structural parameters of a singular DSGE model. The first selects the vector of observables that optimizes parameter identification; the second selects the vector that minimizes the informational discrepancy between the singular and non‐singular model. An application to a standard model is discussed and the estimation properties of different setups compared. Practical suggestions for applied researchers are provided. Copyright © 2014 John Wiley & Sons, Ltd.