bluuebunny/crossref_metadata_2025 huggingface dataset:
NEDD8 ultimate buster‐1 regulates the abundance of TRF1 at telomeres by promoting its proteasomal degradation
Authors: Jeong Yu Young , Her Joonyoung , Chung In Kwon
Published: May 2016

The human telomeric protein TRF1 negatively regulates telomere length by inhibiting the access of telomerase to telomeres. Here, we describe a novel function of NEDD8 ultimate buster‐1 (NUB1) for regulating the levels of TRF1 at telomeres. NUB1 is a NEDD8‐interacting protein, which down‐regulates the NEDD8 conjugation system. We showed that NUB1 physically interacts with TRF1 and promotes its degradation by the proteasome in the absence of NEDD8 conjugation. We also demonstrated that TRF1 is conjugated to NEDD8, and that neddylated TRF1 is targeted to the proteasome for degradation in a NUB1‐dependent manner. These data suggest that NUB1 participates in telomere maintenance by regulating the levels of TRF1 at telomeres through both NEDD8‐dependent and NEDD8‐independent pathways.
High‐resolution regional modeling of summertime transport and impact of African dust over the Red Sea and Arabian Peninsula
Authors: Kalenderski Stoitchko , Stenchikov Georgiy
Published: May 2016

Severe dust outbreaks and high dust loading over Eastern Africa and the Red Sea are frequently detected in the summer season. Observations suggest that small‐scale dynamic and orographic effects, from both the Arabian and African sides, strongly contribute to dust plume formation. To better understand these processes, we present here the first high‐resolution modeling study of a dust outbreak in June 2012 developed over East Africa, the Red Sea, and the Arabian Peninsula. Using the Weather Research and Forecasting model coupled with Chemistry (WRF‐Chem) component, we identified several dust generating dynamical processes that range from convective to synoptic scales, including synoptic cyclones, nocturnal low‐level jets, and cold pools of mesoscale convective systems. The simulations reveal an eastward transport of African dust across the Red Sea. Over the northern part of the Red Sea, most of the dust transport occurs above 2 km height, whereas across the central and southern parts of the sea; dust is mostly transported below 2 km height. Dust is the dominant contributor (87%) to the aerosol optical depth, producing a domain average cooling effect of −12.1 W m−2 at the surface, a warming of 7.1 W m−2 in the atmosphere, and a residual cooling of −4.9 W m−2 at the top of the atmosphere. Both dry and wet deposition processes contribute significantly to dust removal from the atmosphere. Model results compare well with available ground‐based and satellite observations but generally underestimate the observed maximum values of aerosol optical depth. The satellite‐retrieved mean optical depth at some locations is underestimated by a factor of 2. A sensitive experiment suggests that these large local differences may result from poor characterization of dust emissions in some areas of the modeled domain. In this case study we successfully simulate the major fine‐scale dust generating dynamical processes, explicitly resolving convection and haboob formation. The future development of this novel approach will be beneficial for dust research, assuming steady growth of available computational power.
Onset and demise of Cretaceous oceanic anoxic events: The coupling of surface and bottom oceanic processes in two pelagic basins of the western Tethys
Authors: Gambacorta G. , Bersezio R. , Weissert H. , Erba E.
Published: May 2016

The upper Albian–lower Turonian pelagic successions of the Tethys record processes acting during the onset, core, and recovery from perturbed conditions across oceanic anoxic event (OAE) 1d, OAE 2, and the mid‐Cenomanian event I (MCE I) relative to intervening intervals. Five sections from Umbria‐Marche and Belluno Basins (Italy) were analyzed at high resolution to assess processes in surface and deep waters. Recurrent facies stacking patterns (SP) and their associations record periods of bottom current activity coupled with surface changes in trophic level. Climate changes appear to have been influential on deep circulation dynamics. Under greenhouse conditions, vigorous bottom currents were arguably induced by warm and dense saline deep waters originated on tropical shelves in the Tethys and/or proto‐Atlantic Ocean. Tractive facies postdating intermittent anoxia during OAE 1d and in the interval bracketed by MCE I and OAE 2 are indicative of feeble bottom currents, though capable of disrupting stratification and replenish deep water with oxygen. The major warming at the onset of OAE 2 might have enhanced the formation of warm salty waters, possibly producing local hiatuses at the base of the Bonarelli Level and winnowing at the seafloor. Hiatuses detected at the top of the Bonarelli Level possibly resulted from most effective bottom currents during the early Turonian thermal maximum. Times of minimal sediment displacement correlate with cooler climatic conditions and testify a different mechanism of deep water formation, as further suggested by a color change to reddish lithologies of the post‐OAE 1d and post‐OAE 2 intervals.
Analysis of reach‐scale elevation distribution in braided rivers: Definition of a new morphologic indicator and estimation of mean quantities
Authors: Redolfi M. , Tubino M. , Bertoldi W. , Brasington J.
Published: May 2016

Understanding the role of external controls on the morphology of braided rivers is currently limited by the dearth of robust metrics to quantify and distinguish the diversity of channel form. Most existing measures are strongly dependent on river stage and unable to account for the three‐dimensional complexity that is apparent in digital terrain models of braided rivers. In this paper, we introduce a simple, stage‐independent morphological indicator that enables the analysis of reach‐scale regime morphology as a function of slope, discharge, sediment size, and degree of confinement. The index is derived from the bed elevation frequency distribution and characterizes a statistical width‐depth curve averaged longitudinally over multiple channel widths. In this way, we define a “synthetic channel” described by a simple parameter that embeds information about the river morphological complexity. Under the assumption of uniform flow, this approach can be extended to provide estimates of the reach‐averaged shear stress distribution, bed load flux, and at‐a‐station‐variability of wetted width. We test this approach using data from a wide range of labile channels including 58 flume experiments and three gravel bed braided rivers. Results demonstrate a strong relationship between the unit discharge and the shape of the elevation distribution, which varies between a U shape for typical single‐thread confined channels and a Y shape for multithread reaches. Finally, we discuss the use of the metric as a diagnostic index of river condition that may be used to support inferences about the river morphological trajectory.
Developing the greatest Blue Economy: Water productivity, fresh water depletion, and virtual water trade in the Great Lakes basin
Authors: Mayer Alex , Mubako Stanley , Ruddell Benjamin L.
Published: May 2016

The Great Lakes basin hosts the world's most abundant surface fresh water reserve. Historically an industrial and natural resource powerhouse, the region has suffered economic stagnation in recent decades. Meanwhile, growing water resource scarcity around the world is creating pressure on water‐intensive human activities. This situation creates the potential for the Great Lakes region to sustainably utilize its relative water wealth for economic benefit. We combine economic production and trade datasets with water consumption data and models of surface water depletion in the region. We find that, on average, the current economy does not create significant impacts on surface waters, but there is some risk that unregulated large water uses can create environmental flow impacts if they are developed in the wrong locations. Water uses drawing on deep groundwater or the Great Lakes themselves are unlikely to create a significant depletion, and discharge of groundwater withdrawals to surface waters offsets most surface water depletion. This relative abundance of surface water means that science‐based management of large water uses to avoid accidentally creating “hotspots” is likely to be successful in avoiding future impacts, even if water use is significantly increased. Commercial water uses are the most productive, with thermoelectric, mining, and agricultural water uses in the lowest tier of water productivity. Surprisingly for such a water‐abundant economy, the region is a net importer of water‐derived goods and services. This, combined with the abundance of surface water, suggests that the region's water‐based economy has room to grow in the 21st century.
The last millennium climate reanalysis project: Framework and first results
Authors: Hakim Gregory J. , Emile‐Geay Julien , Steig Eric J. , Noone David , Anderson David M. , Tardif Robert , Steiger Nathan , Perkins Walter A.
Published: May 2016

An “offline” approach to DA is used, where static ensemble samples are drawn from existing CMIP climate‐model simulations to serve as the prior estimate of climate variables. We use linear, univariate forward models (“proxy system models (PSMs)”) that map climate variables to proxy measurements by fitting proxy data to 2 m air temperature from gridded instrumental temperature data; the linear PSMs are then used to predict proxy values from the prior estimate. Results for the LMR are compared against six gridded instrumental temperature data sets and 25% of the proxy records are withheld from assimilation for independent verification. Results show broad agreement with previous reconstructions of Northern Hemisphere mean 2 m air temperature, with millennial‐scale cooling, a multicentennial warm period around 1000 C.E., and a cold period coincident with the Little Ice Age (circa 1450–1800 C.E.). Verification against gridded instrumental data sets during 1880–2000 C.E. reveals greatest skill in the tropics and lowest skill over Northern Hemisphere land areas. Verification against independent proxy records indicates substantial improvement relative to the model (prior) data without proxy assimilation. As an illustrative example, we present multivariate reconstructed fields for a singular event, the 1808/1809 “mystery” volcanic eruption, which reveal global cooling that is strongly enhanced locally due to the presence of the Pacific‐North America wave pattern in the 500 hPa geopotential height field.
Size distribution and optical properties of African mineral dust after intercontinental transport
Authors: Denjean Cyrielle , Formenti Paola , Desboeufs Karine , Chevaillier Servanne , Triquet Sylvain , Maillé Michel , Cazaunau Mathieu , Laurent Benoit , Mayol‐Bracero Olga L. , Vallejo Pamela , Quiñones Mariana , Gutierrez‐Molina Ian E. , Cassola Federico , Prati Paolo , Andrews Elisabeth , Ogren John
Published: May 2016

The transatlantic transport of mineral dust from Africa is a persistent atmospheric phenomenon, clue for understanding the impacts of dust at the global scale. As part of the DUST Aging and Transport from Africa to the Caribbean (Dust‐ATTACk) intensive field campaign, the size distribution and optical properties of mineral dust were measured in June–July 2012 on the east coast of Puerto Rico, more than 5000 km from the west coast of Africa. During the recorded dust events, the PM10 (particulate matter 10 micrometers or less in diameter) concentrations increased from 20 to 70 µg m−3. Remote sensing observations and modeling analysis were used to identify the main source regions, which were found in the Western Sahara, Mauritania, Algeria, Niger, and Mali. The microphysical and optical properties of the dust plumes were almost independent of origin. The size distribution of mineral dust after long‐range transport may have modal diameters similar to those on the eastern side of the Atlantic short time after emission, possibly depending on height of transport. Additional submicron particles of anthropogenic absorbing aerosols (likely from regional marine traffic activities) can be mixed within the dust plumes, without affecting in a significant way the PM10 absorption properties of dust observed in Puerto Rico. The Dust‐ATTACk experimental data set may be useful for modeling the direct radiative effect of dust. For accurate representation of dust optical properties over the Atlantic remote marine region, we recommend mass extinction efficiency (MEE) and single‐scattering albedo values in the range 1.1–1.5 m2 g−1 and 0.97–0.98, respectively, for visible wavelengths.
SuperDARN backscatter during intense geomagnetic storms
Authors: Currie J. L. , Waters C. L. , Menk F. W. , Sciffer M. D. , Bristow W. A.
Published: May 2016

It is often stated that high‐frequency radars experience a loss of backscatter during geomagnetic storm events. The occurrence of backscatter during 25 intense geomagnetic storms was examined using data from the Bruny Island and Kodiak radars and a superposed epoch analysis. It was found that while a reduction of backscatter occurred in the middle to far ranges, there was an increase in the amount of backscatter from close range following storm onset. Ray tracing showed that an enhanced charge density in the E region can reduce the chance of F region and increase the chance of E region backscatter. It was also shown that reduction in backscatter cannot be explained by D region absorption. Using a normalized SYM‐H value, percentage time through recovery phase can be estimated during storm progression which allows a prediction of backscatter return in real time that accounts for varying storm recovery phase duration.
Reply to comment by Keith E. Schilling on “Climate and agricultural land use change impacts on streamflow in the upper Midwestern United States”
Authors: Gupta Satish C. , Kessler Andrew C. , Brown Melinda K. , Schuh William M.
Published: May 2016

This reply addresses concerns raised by Schilling (2016, doi:10.1002/2015WR018482) on Gupta et al. (2015a, doi: 10.1002/2015WR017323, 2015b, doi:10.1002/2015WR017323). To this end, we provide additional analysis of the Raccoon River flows in Iowa and show that both annual streamflow and baseflow are mainly controlled by precipitation.
High Surface Area MoS2/Graphene Hybrid Aerogel for Ultrasensitive NO2 Detection
Authors: Long Hu , Harley‐Trochimczyk Anna , Pham Thang , Tang Zirong , Shi Tielin , Zettl Alex , Carraro Carlo , Worsley Marcus A. , Maboudian Roya
Published: May 2016

A MoS2/graphene hybrid aerogel synthesized with two‐dimensional MoS2 sheets coating a high surface area graphene aerogel scaffold is characterized and used for ultrasensitive NO2 detection. The combination of graphene and MoS2 leads to improved sensing properties with the graphene scaffold providing high specific surface area and high electrical and thermal conductivity and the single to few‐layer MoS2 sheets providing high sensitivity and selectivity to NO2. The hybrid aerogel is integrated onto a low‐power microheater platform to probe the gas sensing performance. At room temperature, the sensor exhibits an ultralow detection limit of 50 ppb NO2. By heating the material to 200 °C, the response and recovery times to reach 90% of the final signal decrease to <1 min, while retaining the low detection limit. The MoS2/graphene hybrid also shows good selectivity for NO2 against H2 and CO, especially when compared to bare graphene aerogel. The unique structure of the hybrid aerogel is responsible for the ultrasensitive, selective, and fast NO2 sensing. The improved sensing performance of this hybrid aerogel also suggests the possibility of other 2D material combinations for further sensing applications.
Synergism between sinusoidal‐50 Hz magnetic field and formaldehyde in triggering carcinogenic effects in male Sprague–Dawley rats
Authors: Soffritti Morando , Tibaldi Eva , Padovani Michela , Hoel David G. , Giuliani Livio , Bua Luciano , Lauriola Michelina , Falcioni Laura , Manservigi Marco , Manservisi Fabiana , Belpoggi Fiorella
Published: May 2016

Background

Experimental rodent bioassays performed up to now have failed to provide conclusive confirmation of the carcinogenicity of extremely low frequency magnetic fields (ELFMF).

Objectives

To evaluate the potential synergistic carcinogenic effects of concurrent exposure to ELFMF and formaldehyde in four groups of male and female Sprague–Dawley rats.

Methods

One group was exposed from prenatal life until natural death to S‐50 Hz MF and to formaldehyde in drinking water from 6 weeks of age for 104 weeks, two groups were treated only with formaldehyde or only with MF and one group served as untreated control.

Results

Compared to untreated controls, exposure to MF and formaldehyde causes in males a statistically significant increased incidence of malignant tumors (P ≤ 0.01), thyroid C‐cell carcinomas (P ≤ 0.01), and hemolymphoreticular neoplasias (P ≤ 0.05). No statistically significant differences were observed among female groups.

Conclusions

Life‐span exposure to MF and formaldehyde induces statistically significant carcinogenic effects in male rats. Am. J. Ind. Med. 59:509–521, 2016. © 2016 Wiley Periodicals, Inc.
Ranking occupational contexts associated with risk of non‐Hodgkin lymphoma
Authors: Rieutort Delphine , Moyne Oriane , Cocco Pierluigi , de Gaudemaris Régis , Bicout Dominique J.
Published: May 2016

Background

Risk factors associated with non‐Hodgkin lymphoma (NHL) remain unknown, but certain occupational contexts (OCs) have been implicated. The objective of this study was to inventory, from the accumulated knowledge, associations between OCs and NHL risk.

Methods

Literature was used to identify the NHL‐associated OCs. For each context, items were ranked both by scientific interest and the association strength.

Results

Three ranked lists of OCs related to NHL were constructed. We found that NHL was associated with 31 occupational activities, 91 occupational exposures, and 35 occupational activity–exposure combinations. Among them, 5 activities, 2 exposures, and 3 combinations, involving agricultural or industrial sector and solvents or pesticides, were highlighted with the highest publications number and the strongest association with NHL risk.

Conclusion

These results could be useful in both providing a ranked inventory of OCs associated with NHL risk and highlighting “hot” occupational activities and exposures. Am. J. Ind. Med. 59:561–574, 2016. © 2016 Wiley Periodicals, Inc.
Synthesis and Photophysical Properties of Substituted 2,2′:6′,2′′‐Terpyridine Derivatives and Analogous Compounds with a Central Thiophene Ring
Authors: Hommes Paul , Reissig Hans‐Ulrich
Published: May 2016

New 2,2′:6′,2′′‐terpyridine derivatives were prepared by Suzuki–Miyaura coupling of the corresponding 4,4′′‐bis(nonaflate) with the appropriate boronic acid derivatives. The corresponding 4,4′′‐diazido terpyridine derivative allowed a copper(I)‐promoted click reaction with phenyl acetylene to provide the bis(triazolyl)‐substituted terpyridine in excellent yield. For comparison, analogs or terpyridines with a central thiophene ring were synthesized by applying the well proven cyclocondensation reaction of the bis(β‐ketoenamide) derived from 2,5‐thiophenedicarboxylic acid. The UV/Vis spectra as well as the fluorescence spectra of these new compounds were recorded and compared with related heterocycles.
Synthesis of Five‐Porphyrin Nanorings by Using Ferrocene and Corannulene Templates
Authors: Liu Pengpeng , Hisamune Yutaka , Peeks Martin D. , Odell Barbara , Gong Juliane Q. , Herz Laura M. , Anderson Harry L.
Published: May 2016

The smallest and most strained member of a family of π‐conjugated cyclic porphyrin oligomers was synthesized by using pentapyridyl templates based on ferrocene and corannulene. Both templates are effective for directing the synthesis of the butadiyne‐linked cyclic pentamer, despite the fact that the radii of their N5 donor sets are too small by 0.5 Å and 0.9 Å, respectively (from DFT calculations). The five‐porphyrin nanoring exhibits a structured absorption spectrum and its fluorescence extends to 1200 nm, reflecting strong π conjugation and Herzberg–Teller vibronic coupling.
One‐Pot N2C/C2C/N2N Ligation To Trap Weak Protein–Protein Interactions
Authors: Zhao Lei , Ehrt Christiane , Koch Oliver , Wu Yao‐Wen
Published: May 2016

Weak transient protein–protein interactions (PPIs) play an essential role in cellular dynamics. However, it is challenging to obtain weak protein complexes owing to their short lifetime. Herein we present a general and facile method for trapping weak PPIs in an unbiased manner using proximity‐induced ligations. To expand the chemical ligation spectrum, we developed novel N2N (N‐terminus to N‐terminus) and C2C (C‐terminus to C‐terminus) ligation approaches. By using N2C (N‐terminus to C‐terminus), N2N, and C2C ligations in one pot, the interacting proteins were linked. The weak Ypt1:GDI interaction drove C2C ligation with t1/2 of 4.8 min and near quantitative conversion. The Ypt1‐GDI conjugate revealed that binding of Ypt1 G‐domain causes opening of the lipid‐binding site of GDI, which can accommodate one prenyl group, giving insights into Rab membrane recycling. Moreover, we used this strategy to trap the KRas homodimer, which plays an important role in Ras signaling.
CuO nanoparticle‐catalyzed diaminations for synthesis of benzimidazole derivatives
Authors: Yu Dan , You Qing , Zhang Xinming , Tao Guide , Zhang Wu
Published: May 2016

Copper oxide nanoparticles have been applied as an efficient catalyst for the formation of C–N bonds. They can catalyze diaminations for the regiospecific synthesis of 1,2‐disubstituted benzimidazoles from 1,2‐dihaloarenes and N‐arylamidines. The best performance has been achieved using CuO nanoparticles with average diameter of 6.5 nm. In addition, the catalyst can be recycled and reused without any significant decrease in catalytic activity. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis, characterization and biological evaluation of a cobalt(II) complex with 5‐chloro‐8‐hydroxyquinoline as anticancer agent
Authors: Zhang Hai‐Rong , Meng Ting , Liu Yan‐Cheng , Chen Zhen‐Feng , Liu You‐Nian , Liang Hong
Published: May 2016

A new cobalt(II) complex (1) of 5‐chloro‐8‐hydroxyquinoline was prepared and structurally characterized using infrared spectroscopy, electrospray ionization mass spectrometry, elemental analysis, single‐crystal X‐ray diffraction as well as powder X‐ray diffraction. Its biological activities including DNA binding and anticancer activity were investigated. The DNA binding study of complex 1 suggested that it interacted with calf thymus DNA mainly via an intercalative binding mode. The in vitro anticancer activity of complex 1 was screened against a series of tumor cell lines as well as the normal liver cell line HL‐7702 using MTT assay. complex 1 showed much higher cytotoxicity than corresponding metal salt and ligand towards the five tested tumor cell lines, in which T‐24 was the most sensitive tumor cell line towards 1, with IC50 value of 7.04 ± 0.06 μM. complex 1 was found to greatly induce cell cycle arrest in T‐24 cells at S phase, and consequently to induce cell apoptosis in a dose‐dependent mode suggested by cell apoptosis analysis via Hoechst 33258 and acridine orange/ethidium bromide staining assays. The cell apoptosis mechanism of 1 was studied targeting the mitochondrion‐mediated pathway, since the apoptotic mechanism in the T‐24 cells treated by 1 was investigated by reactive oxygen species (ROS) detection, intracellular calcium concentration measurement and caspase‐9/3 activity assay. The results suggested that the cell apoptosis induced by 1 was closely related to the loss of mitochondrial membrane potential, ROS production and enhancement of intracellular [Ca2+], which would trigger the caspase‐9/3 activation via a mitochondrial dysfunction pathway. Copyright © 2016 John Wiley & Sons, Ltd.
Seasonal movements of immature Kemp's ridley sea turtles (Lepidochelys kempii) in the northern gulf of Mexico
Authors: Coleman Andrew T. , Pitchford Jonathan L. , Bailey Helen , Solangi Moby
Published: May 2016

Seasonal movements and core habitat areas of immature Kemp's ridley sea turtles (Lepidochelys kempii) in the northern Gulf of Mexico were tracked via satellite telemetry. Tagged turtles were incidentally captured by recreational fishermen and rehabilitated at the Institute for Marine Mammal Studies in Gulfport, Mississippi.

The average size of the core habitat areas (50% KDE (kernel density estimation)) was 1660.2 km2 ± 3438.2 SD. Turtles displayed strong intra‐ and inter‐annual site fidelity to the Mississippi Sound during the spring, summer, and autumn months. During the winter months, most turtles, probably influenced by water temperatures, migrated to nearshore waters of Louisiana on either side of the Mississippi River Delta. However, other migration strategies were also observed.

Overall, these data indicate that the Mississippi Sound is an important developmental habitat for this critically endangered species. In addition, their wintering grounds in Louisiana are utilized by adult Kemp's ridleys and other sea turtle species as foraging grounds and migratory corridors. The high use of these areas by sea turtle populations increases the potential for negative impacts from anthropogenic disturbances (e.g. shrimp trawling, oil production, hypoxia) that occur there.

Copyright © 2016 John Wiley & Sons, Ltd.
Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis
Authors: Viatte Sebastien , Lee James C. , Fu Bo , Espéli Marion , Lunt Mark , De Wolf Jack N. E. , Wheeler Lily , Reynolds John A. , Castelino Madhura , Symmons Deborah P. M. , Lyons Paul A. , Barton Anne , Smith Kenneth G. C.
Published: May 2016

Objective

Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte‐driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis.

Methods

Collagen‐induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss‐of‐function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C‐reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA.

Results

Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin‐6 in the blood. Similarly, rs12212067 (a single‐nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores.

Conclusion

Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage.
Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments
Authors: Xie Fenglong , Yun Huifeng , Bernatsky Sasha , Curtis Jeffrey R.
Published: May 2016

Objective

To evaluate gastrointestinal (GI) perforation in rheumatoid arthritis (RA) patients receiving tofacitinib, tocilizumab, or other biologic agents.

Methods

Using health plan data from 2006 through 2014, RA patients without prior GI perforation were identified. Those in whom treatment with tofacitinib or a biologic agent was being initiated were followed up for incident GI perforation with hospitalization. Crude incidence rates were calculated by exposure. Adjusted Cox proportional hazards models were used to evaluate the association between GI perforation and exposures. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated.

Results

A cohort of 167,113 RA patients was analyzed. Among them, 4,755 began treatment with tofacitinib, 11,705 with tocilizumab, 115,047 with a tumor necrosis factor inhibitor (TNFi), 31,214 with abatacept, and 4,392 with rituximab. Compared to TNFi recipients, abatacept recipients were older, tofacitinib and rituximab recipients were younger, and tocilizumab recipients were similar in age. Patients beginning treatment with a non‐TNFi agent were more likely to have previously received biologic agents than patients beginning treatment with a TNFi. The incidence of GI perforation per 1,000 patient‐years was 0.86 (tofacitinib), 1.55 (tocilizumab), 1.07 (abatacept), 0.73 (rituximab), and 0.83 (TNFi). Most perforations occurred in the lower GI tract: the incidence of lower GI tract perforation per 1,000 patient‐years was 0.86 (tofacitinib), 1.26 (tocilizumab), 0.76 (abatacept), 0.48 (rituximab), and 0.46 (TNFi). Lower GI tract perforation risk was significantly elevated with tocilizumab treatment, and numerically elevated with tofacitinib treatment, versus treatment with TNFi. Adjusted HRs were 2.51 (95% CI 1.31–4.80) for tocilizumab and 1.94 (95% CI 0.49–7.65) for tofacitinib. Older age (HR 1.16 per 5 years [95% CI 1.10–1.22]), diverticulitis/other GI conditions (HR 3.25 [95% CI 1.62–6.50]), and prednisone use at >7.5 mg/day (HR 2.29 [95% CI 1.39–3.78]) were associated with lower GI tract perforation. The incidence of upper GI tract perforation was similar among all drug exposures.

Conclusion

The risk of lower GI tract perforation associated with tocilizumab treatment, and possibly tofacitinib treatment, is elevated compared to that associated with TNF blockade.
Brief Report: HLA–DRB1, DQA1, and DQB1 in Juvenile‐Onset Systemic Sclerosis
Authors: Stevens Anne M. , Kanaan Sami B. , Torok Kathryn S. , Medsger Thomas A. , Mayes Maureen D. , Reveille John D. , Klein‐Gitelman Marisa , Reed Ann M. , Lee Tzielan , Li Suzanne C. , Henstorf Gretchen , Luu Christine , Aydelotte Tessa , Nelson J. Lee
Published: May 2016

Objective

Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study was undertaken to investigate HLA class II alleles in juvenile‐onset SSc.

Methods

DRB1, DQA1, and DQB1 alleles were determined by DNA‐based HLA typing. Analyses were conducted comparing Caucasian patients with juvenile‐onset SSc (n = 76) to healthy Caucasian controls (n = 581).

Results

Initial analyses focused on HLA class II associations previously reported in adult Caucasian patients with SSc. The frequency of DRB1*11 was not significantly increased in juvenile‐onset SSc (22.4% of patients with juvenile‐onset SSc versus 17.6% of controls; odds ratio [OR] 1.35, P = 0.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult men with SSc, was increased in patients with juvenile‐onset SSc versus controls (57.9% versus 44.1%; OR 1.76, P = 0.027), as was DRB1*03 (34.2% versus 22.5%; OR 1.79, P = 0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of patients with juvenile‐onset SSc versus 1.5% of controls; OR 7.48, P = 0.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant (P = 0.003). Also, a lower frequency of DRB1*01 was observed in patients with juvenile‐onset SSc who were younger at disease onset (OR 0.06, P = 0.01) and in those with antibodies to topoisomerase (OR 0.14, P = 0.024).

Conclusion

Associations of HLA alleles with juvenile‐onset SSc differed from associations with SSc in women, but were similar to associations with SSc in men. Additionally, a novel association with DRB1*10 was observed in children. The greatest proportion of genetic risk of SSc is contributed by the HLA complex, and the current study reveals the importance of the association of HLA class II genes in juvenile‐onset SSc.
On a uniform mixture model
Authors: Gupta A. K. , Miyawaki T.
Published: May 2016

Estimation of the parameters of a mixture of two rectangular distributions is investigated. The method of moments estimators have been derived and their properties studied. The limiting distribution of these estimators is also derived. Then the maximum likelihood estimators are obtained in some cases and their properties are also studied. Some relevant testing of hypotheses problems in this context are also explored.
Small sample results for partial classification with the studentized statisticW
Authors: McLachlan G. J.
Published: May 2016

In this paper an investigation is undertaken of the performance in small samples of a partial allocation procedure appropriate for imposing upper confidence bounds on both types of conditional errors of allocation associated whith the linear discriminant function. The underlying assumption is that there are two populations wich are multivariate normal with a common covariance matrix. It is concluded from a series of simulation experiments that the procedure can be applied with reasonable precision in small samples.
Inference on trends in several poisson or binomial populations
Authors: Bauer P. , Hackl P.
Published: May 2016

It is assumed that either the means of several Poisson, or the parameters of several binomial populations are linear functions of a regressor variable such as time. If samples from the different populations are given at several values of the regressor variable, the maximum likelihood solution exists for a reasonable set of hypotheses. It can be found by a necessarily converging, iterative procedure of successively solving single equations. Two examples are given, one dealing with suicide numbers in the different districts of Vienna over the years 1966–1974 and one with proportions of stillbirths among all births in different areas of Austria during the years 1951–1960; on the basis of these data three different solution algorithms are compared.
Test of the hypothesis about the same degree of association inr× 2‐contingency tables
Authors: Knauer S.
Published: May 2016

In addition to the enumeration of some test criteria for testing the hypothesis about the same degree of association ink2 × 2‐contingency tables used in the literature the present paper derives a test criterion for testing a corresponding hypothesis ink r×2‐contingency tables.
Comparison of missing plot techniques
Authors: Burns W. D. , Charlton P. J. , Li W. K.
Published: May 2016

Three methods are considered for the analysis of incomplete data from designed experiments. One is to analyse the data as they stand, a second is to fit missing plot values and a third is to fit such values approximately and to adjust by the analysis of covariance. Examination of the first leads to a method for identifying the contrast affected. The second causes overestimation of the treatment sum of squares, but a formula is given. A numerical example is included.
Combinatorial evolution of phosphotriesterase toward a robust malathion degrader by hierarchical iteration mutagenesis
Authors: Luo Xiao‐Jing , Zhao Jian , Li Chun‐Xiu , Bai Yun‐Peng , Reetz Manfred T. , Yu Hui‐Lei , Xu Jian‐He
Published: May 2016

Malathion is one of the most widely used organophosphorus pesticides in the United States and developing countries. Herein, we enhanced the degradation rate of malathion starting with a phosphotriesterase PoOPHM2 while also considering thermostability. In the first step, iterative saturation mutagenesis at residues lining the binding pocket (CASTing) was employed to optimize the enzyme active site for substrate binding and activity. Hot spots for enhancing activity were then discovered through epPCR‐based random mutagenesis, and these beneficial mutations were then recombined by DNA shuffling. Finally, guided by in silico energy calculations (FoldX), thermostability of the variant was improved. The mutations extend from the core region to the enzyme surface during the evolutionary pathway. After screening <9,000 mutants, the best variant PoOPHM9 showed 25‐fold higher activity than wild‐type PoOPHM2, with a thermostability (T5015) of 67.6°C. Thus, PoOPHM9 appears to be an efficient and robust candidate for malathion detoxification. Biotechnol. Bioeng. 2016;113: 2350–2357. © 2016 Wiley Periodicals, Inc.
In VitroPET/MRI Diagnosis and Targeted Chemotherapy for Cancer Using Radiolabeled Nanoprobe : A Theragnostic Approach
Authors: Cho Bo‐Bae , Moon Mi Mi , Chellan Justin Raj , Hwang Sang Hyuck , Lee Jung Hoon , Jung Soon Jae , Kim Byung Chul , Yu Kook Hyun
Published: May 2016

The 68Ga‐labeled iron oxide (Fe3O4
) nanocomposites (
68Ga(NF)HFCNP) have been fabricated for positron emission tomography (PET)/magnetic resonance imaging (MRI) diagnosis and targeted cancer therapy. These radioisotopes labeled nanocomposites with folate conjugation have improved the targeting property toward cancer cells. The chemotherapeutic drug doxorubicin (DOX) was loaded with
68Ga‐labeled Fe3O4
nanoparticles (
68Ga(NF)HFCNP) via intermediate DOX–Fe2+ complex. The average loading efficiency of DOX was 35% for NFHFCNP and 41% for HFCNP, respectively. In drug release profile, the release rate of DOX from the nanocomposite was increased with respect to time. The cell lines, KB and A549 treated with
68Ga(NF)HFCNP showed high cell viability and excellent cell uptake. Meanwhile, the DOX‐loaded nanocomposites exhibit high cytotoxicity toward these cell lines. These properties make
68Ga(NF)HFCNP nanocomposite as a potential dual theragnostic probe for PET/MRI and targeted chemotherapy for cancer cells.
A DFT Study on the Reaction Mechanism of the Pd(II)‐catalyzed Cycloisomerization of 4‐Aza‐1‐cyclopropyl‐1,6‐enyne: A Solvent Effect
Authors: Park Ji Eun , Kang Youn Kyung
Published: May 2016

The solvent effect on the reaction mechanism of the Pd(II)‐catalyzed cycloisomerization of 4‐aza‐1‐cyclopropyl‐1,6‐enyne toward 3‐aza‐bicyclo[4.1.0]heptene and homo‐ene product was investigated via density functional theory. Four different Pd complexes, PdCl2
{P(OPh)3}, PdCl2
(PPh3
), Pd{P(OPh)3}, and Pd(PPh3
) as hypothetical active catalyst species were applied to (E)‐N‐(but‐2‐ynyl)‐N‐(3‐cyclopropylallyl)amine model substrate in 1,4‐dioxane and dichloroethane solvent environment. Reaction pathways toward (Z)‐3‐((Z)‐buta‐1,3‐dien‐1‐yl)‐4‐ethylidenepyrrolidine (homo‐ene product) and 7‐cyclopropyl‐6‐methyl‐3‐azabicyclo[4.1.0]hept‐4‐ene were obtained and energetic differences were compared. The selective formation of 3‐aza‐bicyclo[4.1.0]heptenes in toluene at 130°C that was not reproduced in other solvents at lower temperatures was likely because of the catalyst effect rather than the solvent effect.
Application of a LC–MS/MS method developed for the determination of p‐phenylenediamine, N‐acetyl‐p‐phenylenediamine and N,N‐diacetyl‐p‐phenylenediamine in human urine specimens
Authors: Mohamed Khaled M. , Steenkamp Vanessa
Published: May 2016

Cases of poisoning by p‐phenylenediamine (PPD) are detected sporadically. Recently an article on the development and validation of an LC–MS/MS method for the detection of PPD and its metabolites, N‐acetyl‐p‐phenylenediamine (MAPPD) and N,N‐diacetyl‐p‐phenylenediamine (DAPPD) in blood was published. In the current study this method for detection of these compounds was validated and applied to urine samples. The analytes were extracted from urine samples with methylene chloride and ammonium hydroxide as alkaline medium. Detection was performed by LC–MS/MS using electrospray positive ionization under multiple reaction‐monitoring mode. Calibration curves were linear in the range 5–2000 ng/mL for all analytes. Intra‐ and inter‐assay imprecisions were within 1.58–9.52 and 5.43–9.45%, respectively, for PPD, MAPPD and DAPPD. Inter‐assay accuracies were within −7.43 and 7.36 for all compounds. The lower limit of quantification was 5 ng/mL for all analytes. The method, which complies with the validation criteria, was successfully applied to the analysis of PPD, MAPPD and DAPPD in human urine samples collected from clinical and postmortem cases.
Monte Carlo method to explain the probabilistic interpretation of atomic quantum mechanics
Authors: Coto Baudilio , Arencibia Amaya , Suárez Inmaculada
Published: May 2016

Quantum mechanics description of physical and chemical systems is included in books of Physics, General Chemistry or Physical Chemistry including mathematical, graphical, and conceptual descriptions. Mathematical calculations are complex and are covered only in advanced courses. Main problem in the first degree courses is the understanding of the probabilistic interpretation of quantum mechanics. The Monte Carlo method is based on probabilistic concepts and its application to quantum calculations can be carried out quite straightforward. In this work, a simple Monte Carlo method was used to obtain a sequence of random electron coordinates according to the probability given by the wave function. Electron is seen as a shot whose appearance is only accepted and plotted when probability is high enough. Hydrogen atom was studied as it is a familiar system for most students and its description can be easily related to previous knowledge of atomic orbitals. The objective of the present work is to supply all the crucial points that students need to create their own program to plot atomic orbitals according to the above ideas. All the numerical details are indicated in order to get the proposed programming project as a simple task. Student should be able to generate random electron coordinates, to compute wave functions and probabilities, and to obtain plots according to the right probabilistic interpretation of quantum mechanics. In order to show the quantitative obtained plots some results were shown. Typical s, p, and d orbitals were obtained and compared to the usual angular and radial representation. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:765–774, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21749
Sodium nitrite enhances generation of reactive oxygen species that decrease antioxidant power and inhibit plasma membrane redox system of human erythrocytes
Authors: Ansari Fariheen Aisha , Mahmood Riaz
Published: May 2016

Nitrite/nitrate salts are used in fertilizers and as food preservatives. Human exposure to high levels of nitrite results in its uptake and subsequent entry into blood where it can interact with erythrocytes. We show that treatment of human erythrocytes with sodium nitrite (NaNO2) results in a dose‐dependent increase in the production of reactive oxygen species. This was accompanied by a decrease in the antioxidant power which lowered the free radical quenching and metal‐reducing ability. NaNO2 treatment also inhibited plasma membrane redox system (PMRS) of erythrocytes. These changes increase the susceptibility of erythrocytes to oxidative damage, decrease the antioxidant power of whole blood, and can be a major cause of nitrite‐induced cellular toxicity.
Ozonation of Pyrolytic Aqueous Phase: Changes in the Content of Phenolic Compounds and Color
Authors: Liaw Shi‐Shen , Justo Oselys Rodriguez , Perez Victor Haber , Zhou Shuai , Garcia‐Perez Manuel
Published: May 2016

Ozonation on the phenols present in pyrolytic aqueous phases attained from biomass thermochemical conversion was evaluated. During ozonation, the dark color of original samples was found to decrease as a function of ozonation time. The oxidation kinetics of phenols was quantified by a method based on the color changes of samples. The oxidation profiles showed different behaviors and in some cases the phenols presented a positive correlation with the relative R color parameter, except eugenol, syringol, and vanillin which were markedly different. Finally, the color changes observed seem to be associated with the changes in the overall content of phenols and with the change in the molecular weight of the heavy fractions that include lignin oligomers.
Harnessing C−H Activation of Benzhydroxamates as a Macrocyclization Strategy: Synthesis of Structurally Diverse Macrocyclic Isoquinolones
Authors: Krieger Jean‐Philippe , Ricci Gino , Lesuisse Dominique , Meyer Christophe , Cossy Janine
Published: May 2016

Macrocycles are arising considerable interest in medicinal chemistry. With the goal of harnessing C−H activation reactions for the development of efficient macrocyclization processes, the ruthenium(II)‐catalyzed cyclization of O‐methyl benzhydroxamates possessing an ω‐acetylenic chain was investigated to access new structurally diverse macrocyclic isoquinolones. A slow addition of the substrate and the presence of Cu(OAc)2⋅H2O as an additive were crucial for the success of the macrocyclization that features an excellent functional‐group compatibility, as illustrated by the successful synthesis of a library of 21 macrocyclic isoquinolones of different ring sizes and substitution patterns. These results contribute to significantly highlight the synthetic interest of C−H activation‐mediated processes for the synthesis of new macrocyles incorporating heterocyclic scaffolds of potential interest in medicinal chemistry.
ChemInform Abstract: Photocatalytic Reduction of Mercury(II) Ions in Aqueous Suspensions of Titanium Dioxide and Tungsten Trioxide.
Authors: DOMENECH J. , ANDRES M.
Published: May 2016

It is shown that UV irradiation of aqueous suspensions of TiO2 and WO3 containing Hg(II) results in the formation of Hg deposits on both semiconductor particles.
ChemInform Abstract: Transformation of But‐1‐ene into Aromatic Hydrocarbons Over ZSM‐5 Zeolites.
Authors: ONO Y. , KITAGAWA H. , SENDODA Y.
Published: May 2016

The yield of aromatic hydrocarbons from but‐1‐ene increases greatly when Zn cations are incorporated into ZSM‐5 zeolites.
ChemInform Abstract: Effects of Sterically Remote Substituents on π‐Facial Stereoselectivity in Additions to Methylenecyclohexanes.
Authors: JOHNSON C. R. , TAIT B. D. , CIEPLAK A. S.
Published: May 2016

In addition to the reaction shown in the scheme, the oxidation of (I) with m‐chloroperoxybenzoic acid followed by reduction and the catalytic osmylation of (I) with subsequent methylation of the resulting diols lead to the methyl carbinols (II) and (III).
ChemInform Abstract: The Oxidation of Secondary and Tertiary Alcohols by Nitrous Acid.
Authors: MOODIE R. B. , RICHARDS S. N. , THORNE M. P.
Published: May 2016

Treatment of the 1‐phenylethanols (II) with nitrous acid in aqueous sulfuric acid results in two competitive processes: direct dehydrogenation, yielding the acetophenones (I), or dehydration to give the intermediate styrenes (III) which are oxidatively cleaved, forming the benzaldehydes (IV).
ChemInform Abstract: Elucidation of a Side Reaction During Acylation of Primary Amines with Fatty Acid Chlorides.
Authors: METZGER J. , JUNG G.
Published: May 2016

The acylation of the cystine diester (I) with palmitoyl chloride (II) in the presence of a tert. base affords a by‐product (IIIb) along with the regular acylation product (IIIa).
ChemInform Abstract: Reactions of Polyfluoro‐arenols and ‐heteroarenols with Activated Dimethyl Sulfoxide. Facile (2,3)‐Sigmatropic Rearrangement Reactions Giving Dearomatized Products.
Authors: BROOKE G. M. , FERGUSON J. A. K. J.
Published: May 2016

Activation of DMSO using DCC/H3PO4 or, preferably, trifluoroacetic anhydride, and reaction with polyfluorophenols (I) yields mixtures of (III)‐(V) with (IV) being formed from (III) by the title rearrangement.
ChemInform Abstract: Structure of 2,3‐Butanedione Dihydrazone and IR Study of Higher Polyazines: A New Class of Polymeric Conductors.
Authors: HAUER C. R. , KING G. S. , MCCOOL E. L. , EULER W. B. , FERRARA J. D. , YOUNGS W. J.
Published: May 2016

The preparation and IR spectra for a series of polyazines (III) are reported.