bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling Between Magnetic Exchange and Charge Activation in Cu‐Doped LaFeO3
Authors: Dogdibegovic Emir , Cai Qingsheng , James William J. , Yelon William B. , Anderson Harlan U. , Yang Jin‐Bo , Zhou Xiao‐Dong
Published: March 2016

Material research on perovskite‐type oxides (ABO3) has been driven by the recognition of their unique properties primarily attributed to the presence of oxygen octahedron (BO6). Since 2003, the discovery of strong coupling in TbMnO3 and BiFeO3 has stimulated new interests in understanding the relationship between magnetic and electric properties in perovskites. In this article, we report our recent work on the magnetic superexchange interaction and charge formation in copper‐doped LaFeO3 using high‐temperature neutron diffraction and thermoelectric measurements. In situ neutron diffraction measurements show a loss of antiferromagnetic ordering above 450°C. With an increase in Cu content, the (Fe, Cu)‐O bond length decreases and the (Fe, Cu)–O–(Fe, Cu) bond angle increases, which leads to an enhancement of the Fe–O–Fe superexchange interaction. Thermoelectric and electrical measurements show that the formation of electron holes in Cu‐doped LaFeO3 is a thermally activated process with two distinct regions with a transition temperature near 450°C, in congruence with the magnetic measurements. Our work show that Cu is in 3+ state in La(Fe,Cu)O3 at room temperature, resulting in the maximum superexchange interaction between Fe3+ ions.
ZrB2–SiC–G Composite Prepared by Spark Plasma Sintering of In‐Situ Synthesized ZrB2–SiC–C Composite Powders
Authors: Cheng YeHong , Qi Yushi , Hu Ping , Zhou Shanbao , Chen Guiqing , An Jiadong , Jin Kunfeng , Han Wenbo
Published: March 2016

To avoid introduction of milling media during ball‐milling process and ensure uniform distribution of SiC and graphite in ZrB2 matrix, ultrafine ZrB2–SiC–C composite powders were in‐situ synthesized using inorganic–organic hybrid precursors of Zr(OPr)4, Si(OC2H5)4, H3BO3, and excessive C6H14O6 as source of zirconium, silicon, boron, and carbon, respectively. To inhabit grain growth, the ZrB2–SiC–C composite powders were densified by spark plasma sintering (SPS) at 1950°C for 10 min with the heating rate of 100°C/min. The precursor powders were investigated by thermogravimetric analysis–differential scanning calorimetry and Fourier transform infrared spectroscopy. The ceramic powders were analyzed by X‐ray diffraction, X‐ray photoelectron spectroscopy, and scanning electron microscopy. The lamellar substance was found and determined as graphite nanosheet by scanning electron microscopy, Raman spectrum, and X‐ray diffraction. The SiC grains and graphite nanosheets distributed in ZrB2 matrix uniformly and the grain sizes of ZrB2 and SiC were about 5 μm and 2 μm, respectively. The carbon converted into graphite nanosheets under high temperature during the process of SPS. The presence of graphite nanosheets alters the load‐displacement curves in the fracture process of ZrB2–SiC–G composite. A novel way was explored to prepare ZrB2–SiC–G composite by SPS of in‐situ synthesized ZrB2–SiC–C composite powders.
Efficient Enhancement of Bismuth NIR Luminescence by Aluminum and Its Mechanism in Bismuth‐Doped Germanate Laser Glass
Authors: Wang Liping , Tan Linling , Yue Yuanzheng , Peng Mingying , Qiu Jianrong
Published: March 2016

As a new member of laser glass family, bismuth‐doped glasses have received rising interests due to the application of fiber amplifiers and laser sources in the new spectral range for the next‐generation optical communication system. For practical application of the glasses, it must be considered on how to improve the luminescence efficiency. Here, we demonstrate that addition of aluminum can enhance the bismuth near‐infrared luminescence by more than 10 000 times, which is right followed by the discussion on the mechanism on why this can happen. We believe this work can be helpful for designing bismuth‐doped multiple component laser glasses with high efficiency. In addition, because of high susceptibility of bismuth to local field change, it can be used as probe ion to envision glass structures. Using bismuth as a luminescent structural probe, we can see the modifier ions of Bi+ are not completely randomly distributed inside germanate glass and they prefer the residence around tetrahedral AlO4 sites.
Aminothiazoles inhibit RANKL‐ and LPS‐mediated osteoclastogenesis and PGE2 production in RAW 264.7 cells
Authors: Kats Anna , Norgård Maria , Wondimu Zenebech , Koro Catalin , Concha Quezada Hernán , Andersson Göran , Yucel‐Lindberg Tülay
Published: March 2016

Periodontitis is characterized by chronic inflammation and osteoclast‐mediated bone loss regulated by the receptor activator of nuclear factor‐κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). The aim of this study was to investigate the effect of aminothiazoles targeting prostaglandin E synthase‐1 (mPGES‐1) on RANKL‐ and lipopolysaccharide (LPS)‐mediated osteoclastogenesis and prostaglandin E2 (PGE2) production in vitro using the osteoclast precursor RAW 264.7 cells. RAW 264.7 cells were treated with RANKL or LPS alone or in combination with the aminothiazoles 4‐([4‐(2‐naphthyl)‐1,3‐thiazol‐2‐yl]amino)phenol (TH‐848) or 4‐(3‐fluoro‐4‐methoxyphenyl)‐N‐(4‐phenoxyphenyl)‐1,3‐thiazol‐2‐amine (TH‐644). Aminothiazoles significantly decreased the number of multinucleated tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclast‐like cells in cultures of RANKL‐ and LPS‐stimulated RAW 264.7 cells, as well as reduced the production of PGE2 in culture supernatants. LPS‐treatment induced mPGES‐1 mRNA expression at 16 hrs and the subsequent PGE2 production at 72 hrs. Conversely, RANKL did not affect PGE2 secretion but markedly reduced mPGES‐1 at mRNA level. Furthermore, mRNA expression of TRAP and cathepsin K (CTSK) was reduced by aminothiazoles in RAW 264.7 cells activated by LPS, whereas RANK, OPG or tumour necrosis factor α mRNA expression was not significantly affected. In RANKL‐activated RAW 264.7 cells, TH‐848 and TH‐644 down‐regulated CTSK but not TRAP mRNA expression. Moreover, the inhibitory effect of aminothiazoles on PGE2 production was also confirmed in LPS‐stimulated human peripheral blood mononuclear cell cultures. In conclusion, the aminothiazoles reduced both LPS‐ and RANKL‐mediated osteoclastogenesis and PGE2 production in RAW 264.7 cells, suggesting these compounds as potential inhibitors for treatment of chronic inflammatory bone resorption, such as periodontitis.
Heritability, evolvability, phenotypic plasticity and temporal variation in sperm‐competition success of Drosophila melanogaster
Authors: Dobler R. , Reinhardt K.
Published: March 2016

Sperm‐competition success (SCS) is seen as centrally important for evolutionary change: superior fathers sire superior sons and thereby inherit the traits that make them superior. Additional hypotheses, that phenotypic plasticity in SCS and sperm ageing explain variation in paternity, are less considered. Even though various alleles have individually been shown to be correlated with variation in SCS, few studies have addressed the heritability, or evolvability, of overall SCS. Those studies that have addressed found low or no heritability and have not examined evolvability. They have further not excluded phenotypic plasticity, and temporal effects on SCS, despite their known dramatic effects on sperm function. In Drosophila melanogaster, we found that both standard components of sperm competition, sperm defence and sperm offence, showed nonsignificant heritability across several offspring cohorts. Instead, our analysis revealed, for the first time, the existence of phenotypic plasticity in SCS across an extreme environment (5% CO2), and an influence of sperm ageing. Evolvability of SCS was substantial for sperm defence but weak for sperm offence. Our results suggest that the paradigm of explaining evolution by sperm competition is more complex and will benefit from further experimental work on the heritability or evolvability of SCS, measuring phenotypic plasticity, and separating the effects of sperm competition and sperm ageing.
Fibrinolysis Treatment for Cerebral Intraventricular Hemorrhage: A Temporal and Spatial Voxel‐Based Analysis
Authors: Strinitz Marc , Kuramatsu Joji , Kaschka Iris , Kloska Stephan , Dörfler Arnd , Schwab Stefan , Huttner Hagen B. , Seifert Frank
Published: March 2016

OBJECTIVE

A voxel‐based statistical approach on computer tomographic data in patients with intracerebral hemorrhage (ICH) and acute intraventricular hemorrhage (IVH) was used to evaluate spatial and temporal patterns of intraventricular blood in patients treated with intraventricular fibrinolysis (IVF) or without.

METHODS

IVH shapes were systematically assessed three dimensionally in patients with supratentorial ICH at three intervals of time (day of admission, day 4 ± 1, day 7+). The boundaries of the intraventricular blood clot were delineated on computed tomography (CT) scans using dedicated software. The CT scan and the IVH shape were transferred into stereotaxic space. In a second step, voxel‐based statistics on group level were used to correlate the distribution of intraventricular blood with the interval and the treatment group.

RESULTS

Altogether 45 patients, 29 with IVF therapy and 16 without, were eligible to be included into this study. We found significant (false discovery rate [FDR] correction, q < .05) reduction of the intraventricular blood between day of admission and day 7 + for the third and fourth ventricle and parts of both lateral ventricles. In addition, we were able to show a significant difference between the IVF therapy and the conventionally treated group at day 4 ± 1 for the third ventricle.

CONCLUSIONS

The data indicate that voxel‐based analysis on group level can be used to compare the time course and the distribution of intraventricular hemorrhage. This technique could be an interesting tool for future research on ICH with IVH.
Alpha-boswellic acid protects against ethanol-induced gastric injury in rats: involvement of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway
Authors: Zhang Yikai , Jia Jing , Ding Yi , Ma Yongzheng , Shang Peijin , Liu Tianlong , Hui Guangfei , Wang Lin , Wang Mingming , Zhu Zhihui , Li Yuwen , Wen Aidong
Published: March 2016

Objectives

The purpose of this study was to assess the gastroprotective properties of alpha-boswellic acid (α-BA), a pentacyclic triterpene compound from extracts of Frankincense.

Methods

The gastroprotection of α-BA was assessed with ethanol-induced gastric lesions model, by histopathological assessment and measuring gastric juice acidity (pH), gastric wall mucus (GWM), prostaglandins E2 (PGE-2), membrane lipids peroxidation (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity and amount of nitric oxide (NO). The gastroprotective effects of α-BA through the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) anti-oxidative pathway were presented and measured by immunohistochemistry and Western blot.

Key findings

The results showed that α-BA reduced injuries associated with the administration of ethanol, gastric juice acidity and the formation of MDA and increased CAT activity and SOD activity and the level of NO and PGE-2 in a dose-depended manner. The expression of both Nrf2 and HO-1 was significantly increased in the group treated with 200 mg/kg α-BA, which suggested that activation of the Nrf2/HO-1 pathway might be critical in α-BA's prevention of gastric ulcers.

Conclusions

These findings demonstrate that α-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of α-BA in ethanol-induced gastric injury in rats.
Influence of 5% dextrose volume on amphotericin B deoxycholate preparation
Authors: Sun Pingping , Chen Jie , Zhang Zhihao , Gao Xiang , Chen Pan , Li Shuxia
Published: March 2016

Objectives

Preparation of amphotericin B deoxycholate (AmB-d) in different volumes of 5% dextrose (D5W) was studied to investigate a interesting phenomenon that AmB-d was easy to bring pipe blockage when diluted in 500 ml but not in 50 ml.

Methods

AmB-d (25 mg/vial) in 50 ml, 250 ml or 500 ml D5W was prepared. Fluids were collected before and after infusion, then were assayed by validated high-performance liquid chromatography (HPLC) method. Light obscuration assay was used to detect the particles in transfusions.

Key findings

pH values of different volumes of D5W were all about 3.7, which was lower than the requirement of AmB-d package insert (pH > 4.2). The number of insoluble particles >10 μm/25 μm in 25 mg/500 ml infusions exceeded China Pharmacopoeia limit. Filters in 25 mg/500 ml infusion set were full of AmB-d after dripping slowly for 6 h, and 331.3 ml solution was left in the bottles and only 11.3% of AmB-d could flow out. Whereas the AmB-d infusion consists of 25 mg/50 ml, 25 mg/250 ml and 50 mg/500 ml could meet with China Pharmacopoeia standards, and they flowed out easily and completely.

Conclusions

In practice, 25 mg/250 ml and 50 mg/500 ml would be more suitable for clinical use, rather than 25 mg/500 ml. We provided a convenient method for AmB-d preparation.
Effects of different strategies of mineral supplementation (marine algae alone or combined with rumen boluses) in organic dairy systems
Authors: López‐Alonso M. , Rey‐Crespo F. , Orjales I. , Rodríguez‐Bermúdez R. , Miranda M.
Published: March 2016

This study was designed to evaluate the effect of marine algae supplementation alone or in combination with a regular mineral supplement (rumen boluses) to improve the mineral status in organic dairy cattle and their effect on the milk mineral composition, milk production, composition (% of fat and protein) and quality (SCC). Thirty‐two Holstein Friesian lactating cows were randomly selected and assigned to the algae (A), boluses (B), algae+boluses (AB) and control group (C). For the algae groups (A, AB), a supplement composed of Sea Lettuce (80%), Japanese Wireweed (17.5%) and Furbelows (2.5%) was formulated to be given to the cows at the rate of 100 g/animal per day (A1) for the length of 4 weeks. In the second half of the experiment (weeks 5–8), the algae mixture was reformulated and the proportion of Furbelows was increased from 2.5% to 5.0% with a subsequent decrease of Lettuce to 77.5% (A2). In the boluses group (B), each cow received 2 boluses after calving. Blood (serum) and milk samples were collected at 2 and 4 week intervals, respectively, and analysed for trace element concentrations by ICP‐MS. Information related to the milk composition and SCC during a 305‐day lactation for each animal were obtained from the Dairy Records Management System. The supplementation with algae, boluses or the combination of both treatments showed a statistically significant effect on the iodine (algae), selenium (boluses) and cobalt (algae+boluses) status of the animals. In milk, treatments had a statistical significant increase on iodine, and a tendency to increase selenium concentrations. The assayed algae mixture combined with another source of selenium could be an effective tool to improve the mineral status in serum and milk.
Effects of beta‐glucans ingestion (Saccharomyces cerevisiae) on metabolism of rats receiving high‐fat diet
Authors: de Araújo T. V. , Andrade E. F. , Lobato R. V. , Orlando D. R. , Gomes N. F. , de Sousa R. V. , Zangeronimo M. G. , Pereira L. J.
Published: March 2016

We investigated the effects of beta‐glucans (Saccharomyces cerevisiae) ingestion on metabolic parameters of Wistar rats receiving high‐fat diet. The experimental period was divided into two stages: in the first one, the animals were divided into two groups containing 12 animals each. The first group received commercial feed and the second received high‐fat diet containing 20% of pork fat during 60 days. At the end of this period, body weight, blood glucose and Lee index were assessed. In the second stage, those 24 animals were redivided into four groups: (C) – control diet; (CB) – control diet and treated with Beta‐glucan (BG); (O) – obese animals and (OB) – obese animals treated with BG. Animals from groups CB and OB received 30 mg/kg of BG dissolved in saline solution by gavage. Animals from groups C and O received only saline solution for 28 days. The design used was totally randomized in 2 × 2 factorial scheme. Data were submitted to analysis of variance (anova). Animals from OB group showed inferior levels (p < 0.05) of total cholesterol (13.33%), triacylglycerols (16.77%) and blood glucose (23.97%) when compared to the animals from group O. The use of BG has provided smaller increase in Lee index (p < 0.05), without promoting alteration in feed and water consumption, organs weight, HDL‐C, LDL+VLDL‐C, carcass composition, villus/crypt ratio, and pancreas, kidney and stomach histology. BG from S. cerevisiae promoted beneficial metabolic effects in rats receiving high‐fat diet.
Determination of sulfadiazine, trimethoprim, and N4‐acetyl‐sulfadiazine in fish muscle plus skin by Liquid Chromatography–Mass Spectrometry. Withdrawal‐time calculation after in‐feed administration in gilthead sea bream (Sparus aurata L.) fed two different diets
Authors: Zonaras V. , Tyrpenou A. , Alexis M. , Koupparis M.
Published: March 2016

This study presents a depletion study for sulfadiazine and trimethoprim in muscle plus skin of gilthead sea bream (Sparus aurata L.). N4‐acetyl‐sulfadiazine, the main metabolite of sulfadiazine (SDZ), was also examined. The fish were held in seawater at a temperature of 24–26 °C. SDZ and trimethoprim (TMP) were administered orally with medicated feed for five consecutive days at daily doses of 25 mg SDZ and 5 mg TMP per kg of fish body weight per day. Two different diets, fish oil‐ and plant oil‐based diets, were investigated. Ten fish were sampled at each of the days 1, 3, 5, 6, 8, 9, 10, and 12 after the start of veterinary medicine administration. However for the calculation of the withdrawal periods, sampling day 1 was set as 24 h after the last dose of the treatment. Fish samples were analyzed for SDZ, TMP, and acetyl‐sulfadiazine (AcSDZ) residues by liquid chromatography–mass spectrometry. SDZ and TMP concentrations declined rapidly from muscle plus skin. Considering a maximum residue limit of 100 μg/kg for the total of sulfonamides and 50 μg/kg for TMP residues in fish muscle plus skin, the withdrawal periods of the premix trimethoprim‐sulfadiazine 50% were calculated as 5 and 6 days, at 24–26 °C, in fish oil (FO) and plant oil (PO) groups, respectively. The investigation of this work is important to protect consumers by controlling the undesirable residues in fish.
Does a mouse have a friend? Mixed evidence for individual recognition in the African striped mouse (Rhabdomys pumilio)
Authors: Brunner P. , Schoepf I. , Yuen C. H. , König B. , Schradin C.
Published: March 2016

Individual recognition, the ability to discriminate between members of a social group according to their distinctive characteristics, is a sophisticated form of social recognition. Several laboratory studies demonstrated individual recognition in rodents, but not under natural conditions. We combined behavioral observations and an experiment to assess individual recognition in free‐living African striped mice Rhabdomys pumilio. Striped mice live in groups that share a nest, but forage alone during the day. Interactions among group members are typically amicable and take place at the nest. In order to determine whether striped mice have individualized relationships, we analyzed whether focal mice interacted repeatedly more often with one specific group member. Data from 58 focal individuals from 15 groups revealed that the individual with which amicable interactions occurred the most was often alone in one mode of the data distribution, indicating that behavior toward this specific individual differed compared to the behavior to all other group members. Striped mice consistently preferred this specific individual during the following weeks. Preferred social partners of both breeders and younger non‐breeders were young non‐breeders. Sex‐specific effects were obtained only for young adult males and breeding females, which both associated more often with the opposite sex. For 11 young adults from 11 groups, the preferred social partner was trapped and removed, either overnight (experiment) or only during the day (control), when striped mice forage solitarily and usually do not interact with group members. Striped mice interacted on average more with their preferred social partner after it returned in the experimental group compared to the control (7 of 11 experiments), but the difference was not significant (P = 0.16). Our study indicates that striped mice might have individualized relationships, although they failed to significantly indicate individual recognition during experimental removals. Future studies will have to test the adaptive function of individualized relationships in African striped mice.
The ability of Hepascore to predict liver fibrosis in chronic liver disease: a meta‐analysis
Authors: Huang Yi , Adams Leon A. , Joseph John , Bulsara Max K. , Jeffrey Gary P.
Published: March 2016

Background & Aims

Hepascore is a serum model that was developed to assess the severity of liver fibrosis. It has been well validated in common causes of chronic liver disease. This study performed a meta‐analysis to evaluate the pooled diagnostic performance of Hepascore and to compare it for different aetiologies of chronic liver disease.

Methods

Two reviewers searched electronic databases from October 2005 to September 2015 for studies that evaluated the diagnostic performance of Hepascore for liver fibrosis in chronic liver disease.

Results

21 studies were included. The AUROC was adjusted according to the distribution of fibrosis stages. The mean adjusted AUROC was 0.83 (95% CI, 0.81–0.85) for significant fibrosis, 0.89 (95% CI, 0.85–0.92) for advance fibrosis and 0.93 (95% CI, 0.91–0.95) for cirrhosis. A cut point of 0.50–0.55 achieved a summary sensitivity of 70% and a summary specificity of 79% to predict significant fibrosis. A cut point of 0.50–0.61 had a summary sensitivity of 81% and a summary specificity of 74% to predict advanced fibrosis. A cut point of 0.80–0.84 had a summary sensitivity of 72% and a summary specificity of 0.88% to predict cirrhosis. The accuracy of Hepascore was similar among all disease aetiologies for the prediction of cirrhosis. However, Hepascore had better diagnostic ability for significant and advanced fibrosis in chronic hepatitis C, chronic hepatitis B and alcoholic liver disease than for non‐alcoholic fatty liver disease and HIV co‐infected viral hepatitis.

Conclusions

Hepascore is a clinically useful measure of liver fibrosis in patients with common causes of chronic liver disease.
Grade of soluble inflammatory response is mainly affected by circulating bacterial DNA concentrations in cirrhosis
Authors: Caro Elena , Francés Rubén , Zapater Pedro , Pascual Sonia , Bellot Pablo , Such José
Published: March 2016

Background & Aims

Patients with decompensated cirrhosis show a marked innate immune response that shows a wide variability. The reasons for this fact have not been previously evaluated. This investigation was undertaken to study factors influencing the immune response intensity in both serum and ascitic fluid in patients with cirrhosis and ascites with presence of bactDNA.

Methods

77 patients with cirrhosis and presence of bactDNA fragments in blood and ascitic fluid were included. Identification of bactDNA was evaluated by 16SrRNA gene PCR followed by nucleotide sequencing and by species‐specific PCR. Concentration of amplified bacterial‐DNA, bacteria identification, LPS, TNF‐alpha, IFN‐gamma, Interleukin 12 and nitric oxide in serum and ascitic fluid were evaluated as factors related to intensity of the immune response.

Results

Serum and AF levels of bactDNA, TNF‐α, IFN‐γ and nitric oxide concentration were higher in patients with presence of bactDNA from gram negative bacteria. Serum TNF‐α levels showed a significant correlation with concentrations of bactDNA (r = 0.88; P = 0.001) and LPS (r = 0.28; P = 0.016). Serum nitric oxide levels were also significantly correlated with concentrations of bactDNA (r = 0.761; P = 0.001) but not with LPS levels. Levels of INF‐γ and IL‐12 were not significantly correlated with either bactDNA nor LPS levels. Plasmatic concentration of bactDNA was the most accurately correlated factor with the inflammatory response (ancova model included only levels of bactDNA (r2 = 0.87, P = 0.047 for TNF‐α; r2 = 0.45, P = 0.03 for NOx).

Conclusions

Bacterial‐DNA concentration is the most influencing variable associated with serum TNF‐α and nitric oxide response.
2‐phenylethynesulphonamide (PFT‐μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP‐AUY922 in melanoma, by reducing GSH levels
Authors: Yeramian Andree , Vea Alvar , Benítez Sandra , Ribera Joan , Domingo Mónica , Santacana Maria , Martinez Montserrat , Maiques Oscar , Valls Joan , Dolcet Xavier , Vilella Ramón , Cabiscol Elisa , Matias‐Guiu Xavier , Marti Rosa M.
Published: March 2016

Heat shock proteins (HSPs), are molecular chaperones that assist the proper folding of nascent proteins. This study aims to evaluate the antitumour effects of the hsp90 inhibitor NVP‐AUY922 in melanoma, both in vitro and in vivo. Our results show that NVP‐AUY922 inhibits melanoma cell growth in vitro, with down regulation of multiple signalling pathways involved in melanoma progression such as NF‐ĸB and MAPK/ERK. However, NVP‐AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP‐AUY922 and PFT‐μ, a dual inhibitor of both hsp70 and autophagy, induced a synergistic increase of cell death in vitro, and delayed tumour formation in A375M xenografts. PFT‐μ depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT‐μ further enhanced NVP‐AUY922‐induced cytotoxic effects. These data suggest a potential therapeutic role for NVP‐AUY922 used in combination with PFT‐μ, in melanoma.
Multi‐Echelon Inventory Management under Short‐Term Take‐or‐Pay Contracts
Authors: Goh Joel , Porteus Evan L.
Published: March 2016

We extend the Clark–Scarf serial multi‐echelon inventory model to include procuring production inputs under short‐term take‐or‐pay contracts at one or more stages. In each period, each such stage has the option to order/process at two different cost rates; the cheaper rate applies to units up to the contract quantity selected in the previous period. We prove that in each period and at each such stage, there are three base‐stock levels that characterize an optimal policy, two for the inventory policy and one for the contract quantity selection policy. The optimal cost function is additively separable in its state variables, leading to conquering the curse of dimensionality and the opportunity to manage the supply chain using independently acting managers. We develop conditions under which myopic policies are optimal and illustrate the results using numerical examples. We establish and use a generic one‐period result, which generalizes an important such result in the literature. Extensions to cover variants of take‐or‐pay contracts are included. Limitations are discussed.
Dutch elm disease in New Zealand: impacts from eradication and management programmes
Authors: Ganley R. J. , Bulman L. S.
Published: March 2016

Ophiostoma novo‐ulmi, the cause of the current pandemic of Dutch elm disease, is considered one of the 20 worst pests to have been introduced to New Zealand. An attempt to eradicate the pathogen came close to success, but was eventually stopped and replaced by management programmes. These programmes are slowing the spread of the pathogen. If left uncontrolled it is likely that New Zealand will lose 90% of its elm trees. Although elms are exotic trees in New Zealand, the loss of such a large number of popular amenity trees is likely to have numerous social, cultural, environmental and economic effects. It is estimated that this disease could cost public and councils over NZD $350 million in tree removal and replacement costs. Control of O. novo‐ulmi is limited, but biological control using d‐factor viruses has been proposed. Although O. novo‐ulmi was not eradicated from New Zealand, the eradication programme had many successes; in particular, the effective interaction of good management and science in the early years of the campaign. Also highlighted in this review are several tactics and steps that could be applied to eradication attempts for other species.
Normlessness, Anomie, and the Emotions
Authors: TenHouten Warren D.
Published: March 2016

InSuicide, Durkheim described two qualitatively different experiences of normative anomie, each with a distinct affective basis: an intentional, if not ruthless, disdain for society's normative order; and an unintentional disregard for, or confusion about, norms or rules of conduct. We generalize Durkheim's classification of the socioaffective aspects of anomic suicide, and present two theoretical models of normlessness‐anomie and the emotions. These models posit that intentional anomie involves the primary emotions anger, disgust, and joy‐happiness; these emotions can combine to form the secondary emotions contempt, pride, and derisiveness. Unintentional, passive anomie rather involves the emotions surprise, fear, and sadness; these can combine to form the secondary emotions disappointment, shame, and alarm. We additionally hypothesize that each kind of anomie has distinct potential behavioral consequences: intentional anomie can result in immorality, shamelessness, acquisitiveness, and premeditated homicidality; unintentional anomie, in depression, confusion, uncertainty, unpremeditated homicidality, and suicidality.
Limitations of Majority Agreement in Crowdsourced Image Interpretation
Authors: Salk Carl F , Sturn Tobias , See Linda , Fritz Steffen
Published: March 2016

Crowdsourcing can efficiently complete tasks that are difficult to automate, but the quality of crowdsourced data is tricky to evaluate. Algorithms to grade volunteer work often assume that all tasks are similarly difficult, an assumption that is frequently false. We use a cropland identification game with over 2,600 participants and 165,000 unique tasks to investigate how best to evaluate the difficulty of crowdsourced tasks and to what extent this is possible based on volunteer responses alone. Inter‐volunteer agreement exceeded 90% for about 80% of the images and was negatively correlated with volunteer‐expressed uncertainty about image classification. A total of 343 relatively difficult images were independently classified as cropland, non‐cropland or impossible by two experts. The experts disagreed weakly (one said impossible while the other rated as cropland or non‐cropland) on 27% of the images, but disagreed strongly (cropland vs. non‐cropland) on only 7%. Inter‐volunteer disagreement increased significantly with inter‐expert disagreement. While volunteers agreed with expert classifications for most images, over 20% would have been mis‐categorized if only the volunteers’ majority vote was used. We end with a series of recommendations for managing the challenges posed by heterogeneous tasks in crowdsourcing campaigns.
Initial in vitro studies on tissues and cells from GTKO/CD46/NeuGcKO pigs
Authors: Lee Whayoung , Hara Hidetaka , Ezzelarab Mohamed B. , Iwase Hayato , Bottino Rita , Long Cassandra , Ramsoondar Jagdeece , Ayares David , Cooper David K.C.
Published: March 2016

Absract

Background

The impact that the absence of expression of NeuGc in pigs might have on pig organ or cell transplantation in humans has been studied in vitro, but only using red blood cells (pRBCs) and peripheral blood mononuclear cells (pPBMCs) as the target cells for immune assays. We have extended this work in various in vitro models and now report our initial results.

Methods

The models we have used involve GTKO/hCD46 and GTKO/hCD46/NeuGcKO pig aortas and corneas, and pRBCs, pPBMCs, aortic endothelial cells (pAECs), corneal endothelial cells (pCECs), and isolated pancreatic islets. We have investigated the effect of the absence of NeuGc expression on (i) human IgM and IgG binding, (ii) the T‐cell proliferative response, (iii) human platelet aggregation, and (iv) in an in vitro assay of the instant blood‐mediated inflammatory reaction (IBMIR) following exposure of pig islets to human blood/serum.

Results

The lack of expression of NeuGc on some pig tissues (aortas, corneas) and cells (RBCs, PBMCs, AECs) significantly reduces the extent of human antibody binding. In contrast, the absence of NeuGc expression on some pig tissues (CECs, isolated islet cells) does not reduce human antibody binding, possibly due to their relatively low NeuGc expression level. The strength of the human T‐cell proliferative response may also be marginally reduced, but is already weak to GTKO/hCD46 pAECs and islet cells. We also demonstrate that the absence of NeuGc expression on GTKO/hCD46 pAECs does not reduce human platelet aggregation, and nor does it significantly modify the IBMIR to pig islets.

Conclusion

The absence of NeuGc on some solid organs from GTKO/hCD46/NeuGcKO pigs should reduce the human antibody response after clinical transplantation when compared to GTKO/hCD46 pig organs. However, the clinical benefit of using certain tissue (e.g., cornea, islets) from GTKO/hCD46/NeuGcKO pigs is questionable.
Inherent envelope fluctuations in forward maskers: Effects of masker-probe delay for listeners with normal and impaired hearing
Authors: Svec Adam , Dubno Judy R. , Nelson Peggy B.
Published: March 2016

Forward-masked thresholds increase as the magnitude of inherent masker envelope fluctuations increase for both normal-hearing (NH) and hearing-impaired (HI) adults for a short masker-probe delay (25 ms). The slope of the recovery from forward masking is shallower for HI than for NH listeners due to reduced cochlear nonlinearities. However, effects of hearing loss on additional masking due to inherent envelope fluctuations across masker-probe delays remain unknown. The current study assessed effects of hearing loss on the slope and amount of recovery from forward maskers that varied in inherent envelope fluctuations. Forward-masked thresholds were measured at 2000 and 4000 Hz, for masker-probe delays of 25, 50, and 75 ms, for NH and HI adults. Four maskers at each center frequency varied in inherent envelope fluctuations: Gaussian noise (GN) or low-fluctuation noise (LFN), with 1 or 1/3 equivalent rectangular bandwidths (ERBs). Results suggested that slopes of recovery from forward masking were shallower for HI than for NH listeners regardless of masker fluctuations. Additional masking due to inherent envelope fluctuations was greater for HI than for NH listeners at longer masker-probe delays, suggesting that inherent envelope fluctuations are more disruptive for HI than for NH listeners for a longer time course
Giant atom-smasher gears up to chase whiff of new physics
Authors: Cho Adrian
Published: March 2016

Hints of a massive new particle at the Large Hadron Collider have physicists abuzz —and eager to follow up.
Five matings for moderns, Neandertals
Authors: Gibbons Ann
Published: March 2016

Powerful genetic studies pin down multiple trysts on different continents.
Europe on course for a neutron drought
Authors: Cartlidge Edwin
Published: March 2016

Billion-euro accelerator won't make up the shortfall, experts say.
The maternal microbiota drives early postnatal innate immune development
Authors: Gomez de Agüero Mercedes , Ganal-Vonarburg Stephanie C. , Fuhrer Tobias , Rupp Sandra , Uchimura Yasuhiro , Li Hai , Steinert Anna , Heikenwalder Mathias , Hapfelmeier Siegfried , Sauer Uwe , McCoy Kathy D. , Macpherson Andrew J.
Published: March 2016

Mom's bugs shape of spring immunity

In utero, babies are relatively microbe-free but are quickly colonized at birth. These early microbial residents help to shape our immune systems. Gomez de Agüeroet al.wondered whether the maternal microbiome also affects the of springs' immune system during gestation. To do this, they transiently colonized otherwise microbe-free pregnant mice. Compared to those born to microbe-free moms, pups born to colonized moms had increased numbers of certain innate immune cells and different patterns of gene expression in their guts.

Science, this issue p.1296
Quantum criticality with two length scales
Authors: Shao Hui , Guo Wenan , Sandvik Anders W.
Published: March 2016

Describing an exotic magnetic transition

Phase transitions can be caused by temperature fluctuations or, more exotically, by quantum fluctuations at zero temperature. To describe some of these quantum phase transitions, researchers came up with a complex theory called deconfined quantum criticality.

However, subsequent numerical simulations were inconsistent with some of the predictions of the theory, leading to a debate on its validity. By using quantum Monte Carlo simulations, Shao
et al.
show that it is possible to reconcile numerics with the theory for a specific model of 2D quantum magnetism.

Science
, this issue p.
213
Fine-tuning of a radical-based reaction by radical
S
-adenosyl-L-methionine tryptophan lyase
Authors: Sicoli Giuseppe , Mouesca Jean-Marie , Zeppieri Laura , Amara Patricia , Martin Lydie , Barra Anne–Laure , Fontecilla-Camps Juan C. , Gambarelli Serge , Nicolet Yvain
Published: March 2016

A radical carboxyl migration

The antibiotic nosiheptide, produced by
Streptomyces actuosus
, has high activity against multidrug-resistant pathogens. The enzymes involved in its biosynthesis include NosL, which cannibalizes tryptophan and forms a methylindolic acid precursor. Although NosL is included in a growing family of remarkable radical SAM enzymes, the mechanism by which it functions has been dif cult to identify. Using spectroscopic and theoretical approaches, Sicoli
et al.
show that an unexpected radical intermediate forms during the course of the reaction (see the Perspective by Bridwell-Rabb and Drennan). Unlike similar known enzymes, NosL cleaves a Cα-C bond, which results in the migration of tryptophan's carboxyl group to its side-chain indole.

Science
, this issue p.
1320
; see also p.
1266
Prostaglandin E
2
constrains systemic inflammation through an innate lymphoid cell–IL-22 axis
Authors: Duffin Rodger , O’Connor Richard A. , Crittenden Siobhan , Forster Thorsten , Yu Cunjing , Zheng Xiaozhong , Smyth Danielle , Robb Calum T. , Rossi Fiona , Skouras Christos , Tang Shaohui , Richards James , Pellicoro Antonella , Weller Richard B. , Breyer Richard M. , Mole Damian J. , Iredale John P. , Anderton Stephen M. , Narumiya Shuh , Maizels Rick M. , Ghazal Peter , Howie Sarah E. , Rossi Adriano G. , Yao Chengcan
Published: March 2016

A prostaglandin barrier to inflammation

Blood-borne bacterial infections and severe trauma can send the immune system into overdrive, causing it to pump out inflammatory mediators, sometimes at lethal doses. Duffin
et al.
now report on a role for prostaglandins in keeping systemic inflammation in check. Systemic inflammation correlates with decreased production of the prostaglandin E2 (PGE2). Blocking PGE2 signaling in mice led to severe inflammation associated with the translocation of gut bacteria. PGE2 acts on innate lymphoid cells, which produce interleukin-22, a secreted protein that helps promote intestinal integrity.

Science
, this issue p.
1333
C9orf72
is required for proper macrophage and microglial function in mice
Authors: O’Rourke J. G. , Bogdanik L. , Yáñez A. , Lall D. , Wolf A. J. , Muhammad A. K. M. G. , Ho R. , Carmona S. , Vit J.P. , Zarrow J. , Kim K. J. , Bell S. , Harms M. B. , Miller T. M. , Dangler C. A. , Underhill D. M. , Goodridge H. S. , Lutz C. M. , Baloh R. H.
Published: March 2016

Linking neurodegeneration and immune cells

The expansion of a repetitive DNA sequence in the C9orf72 gene is the major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Although the expansion decreases C9orf72 expression, most research has focused on the toxic RNA and protein products it creates in neurons. O'Rourke
et al.
found that C9orf72 unexpectedly plays a key role in innate immune cells. Loss of C9orf72 in mice led to macrophage and microglial dysfunction and age-related neuroinflammation. This raises the possibility of a “dual-effect” disease mechanism, in which toxic byproducts in neurons are combined with microglial dysfunction from decreased C9orf72 expression, together promoting neurodegeneration.

Science
, this issue p.
1324
Back to nature
Half-Earth Our Planet's Fight for Life
Edward O. Wilson
Liveright, 2016. 261 pp.
Authors: Griffiths Christine J.
Published: March 2016

Could committing half of Earth's surface to conservation stave off the next mass extinction?
Quantum dynamics in the smallest water droplet
Authors: Clary David C.
Published: March 2016

Two hydrogen bonds in a six-molecule water cluster break simultaneously in a concerted set of movements

[Also see Report by

Richardson
et al.

]
A radically unexpected mechanism
Authors: Bridwell-Rabb Jennifer , Drennan Catherine L.
Published: March 2016

Biosynthesis of the antibiotic nosiheptide proceeds via unforeseen radical intermediates

[Also see Report by

Sicoli
et al.

]
A satiating signal
Authors: Schwartz Gary J.
Published: March 2016

A glycosylation enzyme in specific brain neurons is a nutrient sensor that controls body weight

[Also see Research Article by

Lagerlöf
et al.

]
Complete Genome Sequence of
Alternanthera mosaic virus
, Isolated from
Achyranthes bidentata
in Asia
Authors: Iwabuchi Nozomu , Yoshida Tetsuya , Yusa Akira , Nishida Shuko , Tanno Kazuyuki , Keima Takuya , Nijo Takamichi , Yamaji Yasuyuki , Namba Shigetou
Published: March 2016

Alternanthera mosaic virus
(AltMV) infecting
Achyranthes bidentata
was first detected in Asia, and the complete genome sequence (6,604 nucleotides) was determined. Sequence identity analysis and phylogenetic analysis confirmed that this isolate is the most phylogenetically distant AltMV isolate worldwide.
Complete Genome Sequence of
Aggregatibacter actinomycetemcomitans
Serotype g Strain NUM4039 (JCM 30399)
Authors: Saito Masanori , Hirasawa Masaaki , Kuwahara Noriko , Okada Tamami , Umezawa Koji , Kobayashi Taira , Okamoto Masaaki , Naito Mariko , Hirasawa Masatomo , Takada Kazuko
Published: March 2016

Aggregatibacter actinomycetemcomitans
is considered to be a major etiological agent of aggressive periodontitis and includes serotype a to g strains. We herein report the first complete genome sequence of
A. actinomycetemcomitans
serotype g strain NUM4039. The genome is 2,382,853 bp in length with a G+C content of 44.34%.
A case of psoriasis pustolosa palmaris induced by cetuximab
Authors: Marinello Elena , Pastorelli Davide , Alaibac Mauro
Published: March 2016

Cetuximab is a monoclonal antibody that competitively inhibits the epidermal growth factor receptor (EGFR). It is used for the treatment of metastatic colorectal cancer after first-line therapy. We report the first case of a pustular psoriasiform drug eruption induced by cetuximab in a patient with colorectal cancer. This paradoxical side effect could be the result of an imbalance in downstream molecular pathways due to the EGFR signal blockade that could, in selected patients, induce alternative signalling pathways related to keratinocyte proliferation.
Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease
Authors: Nascimbeni Fabio , Aron-Wisnewsky Judith , Pais Raluca , Tordjman Joan , Poitou Christine , Charlotte Frederic , Bedossa Pierre , Poynard Thierry , Clément Karine , Ratziu Vlad ,   for the LIDO study Group
Published: March 2016

Background

Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion.

Aim

We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF).

Methods

We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2–4 Kleiner's stages.

Results

84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60%vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57%vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022).

Conclusions

Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high-risk population.
Trial protocol to compare the efficacy of a smartphone-based blood glucose management system with standard clinic care in the gestational diabetic population
Authors: Mackillop Lucy H , Bartlett Katy , Birks Jacqueline , Farmer Andrew J , Gibson Oliver J , Kevat Dev A , Kenworthy Yvonne , Levy Jonathan C , Loerup Lise , Tarassenko Lionel , Velardo Carmelo , Hirst Jane E
Published: March 2016

Introduction

The prevalence of gestational diabetes mellitus (GDM) is rising in the UK. Good glycaemic control improves maternal and neonatal outcomes. Frequent clinical review of patients with GDM by healthcare professionals is required owing to the rapidly changing physiology of pregnancy and its unpredictable course. Novel technologies that allow home blood glucose (BG) monitoring with results transmitted in real time to a healthcare professional have the potential to deliver good-quality healthcare to women more conveniently and at a lower cost to the patient and the healthcare provider compared to the conventional face-to-face or telephone-based consultation. We have developed an integrated GDm-health management system and aim to test the impact of using this system on maternal glycaemic control, costs, patient satisfaction and maternal and neonatal outcomes compared to standard clinic care in a single large publicly funded (National Health Service (NHS)) maternity unit.

Methods and analysis

Women with confirmed gestational diabetes in a current pregnancy are individually randomised to either the GDm-health system and half the normal clinic visits or normal clinic care. Primary outcome is mean BG in each group from recruitment to delivery calculated, with adjustments made for number of BG measurements, proportion of preprandial and postprandial readings and length of time in study, and compared between the groups. The secondary objective will be to compare the two groups for compliance to the allocated BG monitoring regime, maternal and neonatal outcomes, glycaemic control using glycated haemoglobin (HbA1c) and other BG metrics, and patient attitudes to care assessed using a questionnaire and resource use.

Ethics and dissemination

Thresholds for treatment, dietary advice and clinical management are the same in both groups. The results of the study will be published in a peer-reviewed journal and disseminated electronically and in print.

Trial registration number

NCT01916694; Pre-results.