bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors
Authors: Phababpha Suphawadee , Kukongviriyapan Upa , Pakdeechote Poungrat , Senggunprai Laddawan , Kukongviriyapan Veerapol , Settasatian Chatri , Tatsanavivat Pyatat , Intharaphet Phongsak , Senthong Vichai , Komanasin Nantarat , Settasatian Nongnuch , Greenwald Stephen E
Published: June 2013

Background

Increased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors.

Methods

A total of 208 Thai subjects, aged 35–75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated.

Results

Arterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype.

Conclusions

Our findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.
CYP450 phenotyping and metabolite identification of quinine by accurate mass UPLC-MS analysis: a possible metabolic link to blackwater fever
Authors: Marcsisin Sean R , Jin Xiannu , Bettger Theresa , McCulley Nicholas , Sousa Jason C , Shanks G Dennis , Tekwani Babu L , Sahu Rajnish , Reichard Gregory A , Sciotti Richard J , Melendez Victor , Pybus Brandon S
Published: June 2013

Background

The naturally occurring alkaloid drug, quinine is commonly used for the treatment of severe malaria. Despite centuries of use, its metabolism is still not fully understood, and may play a role in the haemolytic disorders associated with the drug.

Methods

Incubations of quinine with CYPs 1A2, 2C9, 2C19, 2D6, and 3A4 were conducted, and the metabolites were characterized by accurate mass UPLC-MSE analysis. Reactive oxygen species generation was also measured in human erythrocytes incubated in the presence of quinine with and without microsomes.

Results

The metabolites 3-hydroxyquinine, 2’-oxoquininone, and O-desmethylquinine were observed after incubation with CYPs 3A4 (3-hydroxyquinine and 2’-oxoquininone) and 2D6 (O-desmethylquinine). In addition, multiple hydroxylations were observed both on the quinoline core and the quinuclidine ring system. Of the five primary abundance CYPs tested, 3A4, 2D6, 2C9, and 2C19 all demonstrated activity toward quinine, while 1A2 did not. Further, quinine produced robust dose-dependent oxidative stress in human erythrocytes in the presence of microsomes.

Conclusions

Taken in context, these data suggest a CYP-mediated link between quinine metabolism and the poorly understood haemolytic condition known as blackwater fever, often associated with quinine ingestion.
TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease
Authors: Rayaprolu Sruti , Mullen Bianca , Baker Matt , Lynch Timothy , Finger Elizabeth , Seeley William W , Hatanpaa Kimmo J , Lomen-Hoerth Catherine , Kertesz Andrew , Bigio Eileen H , Lippa Carol , Josephs Keith A , Knopman David S , White Charles L , Caselli Richard , Mackenzie Ian R , Miller Bruce L , Boczarska-Jedynak Magdalena , Opala Grzegorz , Krygowska-Wajs Anna , Barcikowska Maria , Younkin Steven G , Petersen Ronald C , Ertekin-Taner Nilüfer , Uitti Ryan J , Meschia James F , Boylan Kevin B , Boeve Bradley F , Graff-Radford Neill R , Wszolek Zbigniew K , Dickson Dennis W , Rademakers Rosa , Ross Owen A
Published: June 2013

Background

A rare variant in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene has been reported to be a genetic risk factor for Alzheimer’s disease by two independent groups (Odds ratio between 2.9-4.5). Given the key role of TREM2 in the effective phagocytosis of apoptotic neuronal cells by microglia, we hypothesized that dysfunction of TREM2 may play a more generalized role in neurodegeneration. With this in mind we set out to assess the genetic association of the Alzheimer’s disease-related risk variant in TREM2 (rs75932628, p.R47H) with other related neurodegenerative disorders.

Results

The study included 609 patients with frontotemporal dementia, 765 with amyotrophic lateral sclerosis, 1493 with Parkinson’s disease, 772 with progressive supranuclear palsy, 448 with ischemic stroke and 1957 controls subjects free of neurodegenerative disease. A significant association was observed for the TREM2 p.R47H substitution in susceptibility to frontotemporal dementia (OR = 5.06; p-value = 0.001) and Parkinson’s disease (OR = 2.67; p-value = 0.026), while no evidence of association with risk of amyotrophic lateral sclerosis, progressive supranuclear palsy or ischemic stroke was observed.

Conclusions

Our results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson’s disease in addition to Alzheimer’s disease. These findings suggest a more general role for TREM2 dysfunction in neurodegeneration, which could be related to its role in the immune response.
Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids
Authors: Li Yunfeng , Guo Fengfeng , Zha Zhenggen , Wang Zhiyong
Published: June 2013

Background

The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable.

Results

In this manuscript, a novel method for synthesis of polysubstituted oxazoles was developed from metal-free decarboxylative cyclization of easily available primary α-amino acids with 2-bromoacetophenones.

Conclusions

The method was simple, and this reaction could be carried out smoothly under mild and metal-free conditions. By virtue of this method, various polysubstituted oxazoles were obtained from the primary α-amino acids with moderate yields.
pKa determination of oxysophocarpine by reversed - phase high performance liquid chromatography
Authors: Huo Huiling , Li Tingting , Zhang Lei
Published: June 2013

Background

In this study, a RP - HPLC method was applied for determination of pKa value by using the dependence of the capacity factor (k) on the pH of the mobile phase for oxysophocarpine (OSP).

Findings

The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa value at different MeOH concentrations, ranging from 10 to 20% (v/v). Based on all pH - k curves plotted and pH values at inflection point calculated, experimental pKa value obtained for oxysophocarpine was 6.5.

Conclusion

This method was successfully applied to realize low sample consumption, rapid sample throughput, high sensitivity and precision.
Endogenous progesterone levels and frontotemporal dementia: modulation of TDP-43 and Tau levelsin vitroand treatment of the A315TTARDBPmouse model
Authors: Dang Theresa N. T. , Dobson-Stone Carol , Glaros Elias N. , Kim Woojin S. , Hallupp Marianne , Bartley Lauren , Piguet Olivier , Hodges John R. , Halliday Glenda M. , Double Kay L. , Schofield Peter R. , Crouch Peter J. , Kwok John B. J.
Published: June 2013

Frontotemporal dementia (FTD) is associated with motor neurone disease (FTD-MND), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Together, this group of disorders constitutes a major cause of young-onset dementia. One of the three clinical variants of FTD is progressive nonfluent aphasia (PNFA), which is focused on in this study. The steroid hormone progesterone (PROG) is known to have an important role as a neurosteroid with potent neuroprotective and promyelination properties. In a case-control study of serum samples (39 FTD, 91 controls), low serum PROG was associated with FTD overall. In subgroup analysis, low PROG levels were significantly associated with FTD-MND and CBS, but not with PSP or PNFA. PROG levels of >195 pg/ml were significantly correlated with lower disease severity (frontotemporal dementia rating scale) for individuals with CBS. In the human neuroblastoma SK-N-MC cell line, exogenous PROG (9300-93,000 pg/ml) had a significant effect on overall Tau and nuclear TDP-43 levels, reducing total Tau levels by ~1.5-fold and increasing nuclear TDP-43 by 1.7- to 2.0-fold. Finally, elevation of plasma PROG to a mean concentration of 5870 pg/ml in an Ala315Thr (A315T) TARDBP transgenic mouse model significantly reduced the rate of loss of locomotor control in PROG-treated, compared with placebo, mice. The PROG treatment did not significantly increase survival of the mice, which might be due to the limitation of the transgenic mouse to accurately model TDP-43-mediated neurodegeneration. Together, our clinical, cellular and animal data provide strong evidence that PROG could be a valid therapy for specific related disorders of FTD.
Non-invasive neural stem cells become invasive in vitro by combinatorial FGF2 and BMP4 signaling
Authors: Sailer Martin H. M. , Gerber Alexandra , Tostado Cristóbal , Hutter Gregor , Cordier Dominik , Mariani Luigi , Ritz Marie-Françoise
Published: June 2013

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study Sox2-positive NSCs from the E14.5 rat cortex were non-invasive and showed only limited migration in vitro. In contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of both factors FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR at the plasma membrane after exposure to FGF2 and BMP4. The combination FGF2 and BMP4 upregulated the expression of Msx1, Snail1, Snail2, p75NGFR, genes that are found in neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), but not in forebrain stem cells. Invasive cells downregulated the expression of Olig2, Sox10, EGFR, PDGFRalpha, Gsh1/Gsx1, and Gsh2/Gsx2. Migrating and invasive NSCs had elevated Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3 mRNA expression. Based on strongest upregulation in invasion-induced NSCs, we defined a group of 5 key invasion-related genes: p75NGFR, SPARC, Snail1, PDPN and TNC. These genes were found co-expressed and upregulated in 7 samples of glioblastoma multiforme (GBM) compared to normal human brain controls. Induction of invasion/migration lead to low expression of differentiation markers and repressed proliferation in NSCs. Our results indicate that normal forebrain stem cells have the inherent ability to adopt a glioma-like invasiveness. The results provide a novel in vitro system to study stem cell invasion and a novel glioma invasion model: tumoral abuse of the developmental dorsoventral identity regulation.
Resolvin D1 stimulates efferocytosis through p50/p50-mediated suppression of tumor necrosis factor-α expression
Authors: Lee Ha-Na , Kundu Joydeb Kumar , Cha Young-Nam , Surh Young-Joon
Published: June 2013

Phagocytosis of apoptotic neutrophils, termed efferocytosis, is essential for the resolution of inflammation as it prevents the exposure of surrounding tissues at the inflamed site to toxic contents of lytic cells. Resolvin D1 (RvD1), endogenously generated from docosahexaenoic acid during resolution of inflammation, is known to stimulate efferocytosis. However, the molecular mechanism underlying RvD1-mediated enhancement of efferocytosis remains largely unresolved. In the present study, murine macrophage-like RAW264.7 cells treated with lipopolysaccharide (LPS) exhibited markedly reduced efferocytic activity, but this was restored by the co-incubation with RvD1. RvD1-induced restoration of the efferocytic activity appears to be mediated by down-regulating the LPS-induced TNF-α expression. The inhibitory effect of RvD1 on LPS-induced TNF-α expression was associated with enhanced nuclear localization of p50/p50 homodimer and concomitant reduction of p65/p50 heterodimer accumulation in the nucleus. RvD1 triggered phosphorylation and proteasomal degradation of nuclear factor κB1 (NF-κB1) p105 to generate p50, which was subsequently translocated to nucleus as p50/p50 homodimer. Knockdown of NF-κB p50 abolished the ability of RvD1 to suppress TNF-α expression and also to restore efferocytosis, suggesting that the replacement of p65/p50 with p50/p50 homodimer in the nucleus is critical for RvD1-mediated stimulation of efferocytosis. In a murine peritonitis model, intraperitoneal administration of RvD1 abrogated the zymosan A-induced TNF-α production, thereby stimulating efferocytosis. Taken together, these findings indicate that RvD1 expedites the resolution of inflammation through induction of efferocytosis by p50/p50 homodimer-mediated repression of TNF-α production.
Changes in the expression and current of the Na+/K+ pump in the snail nervous system after exposure to static magnetic field
Authors: Nikolic Ljiljana M. , Bataveljic Danijela , Andjus Pavle R. , Nedeljkovic Miodrag , Todorovic Dajana , Janac Branka
Published: June 2013

Compelling evidence confirms the use of moderate static magnetic field (SMF) for therapeutic purposes. In order to provide an insight into the mechanisms underlying SMF treatment, it is essential to examine the cellular responses elicited by therapeutically applied SMF, especially in the nervous system. The Na+/K+ pump, by creating and maintaining the gradient of Na+ and K+ ions across the plasma membrane, regulates the physiological properties of neurons. In this study, we examined the expression of the Na+/K+ pump in isolated brain-subesophageal ganglion complex of the garden snail Helix pomatia, along with the immunoreactivity and current of the Na+/K+ pump in isolated snail neurons after 15 min exposure to the moderate 10 mT SMF. Western blot and immunofluorescence analysis revealed that 10 mT SMF did not significantly change the expression of Na+/K+ pump α subunit in the snail brain and neuronal cell body, respectively. However, our immunofluorescence data showed that SMF treatment induced a significant increase in the Na+/K+ pump α subunit expression in the neuronal plasma membrane area. This change in the Na+/K+ pump expression was reflected in the pump activity as demonstrated by the pump current measurements. Whole-cell patch-clamp recordings from isolated snail neurons revealed that Na+/K+ pump current density is significantly increased after the 10 mT SMF treatment. SMF induced increase was different in the two groups of control snail neurons defined by the pump current level. Obtained results could represent physiologically important response of neurons to the 10 mT SMF comparable in strength to therapeutic applications.
Ventilation patterns of the songbird lung/air sac system during different behaviors
Authors: Mackelprang Rebecca , Goller Franz
Published: June 2013

Unidirectional, continuous airflow through the avian lung is achieved through an elaborate air sac system with a sequential, posterior to anterior ventilation pattern. This classical model was established through various approaches spanning passively ventilated systems to mass spec analysis of tracer gas flow into various air sacs during spontaneous breathing in restrained ducks. Information on flow patterns in other bird taxa is missing, and these techniques do not permit direct tests of whether the basic flow pattern can change during different behaviors. Here we use thermistors implanted into various locations of the respiratory system to detect small pulses of tracer gas (helium) to reconstruct airflow patterns in quietly breathing and behaving (calling, wing flapping) songbirds (zebra finch and yellow-headed blackbird). The results illustrate that the basic pattern of airflow in these two species is largely consistent with the model. However, two notable differences emerged. (1) Some tracer gas arrived in the anterior set of air sacs during the inspiration during which it was inhaled, suggesting a more rapid throughput through the lung than previously assumed. (2) Differences in ventilation between the two anterior air sacs emerged during calling and wing flapping, indicating that adjustments in the flow pattern occur during dynamic behaviors. It is unclear whether this modulation in ventilation pattern is passive or active. This technique for studying ventilation patterns during dynamic behaviors proves useful for establishing detailed timing of airflow and modulation of ventilation in the avian respiratory system.
On how whales avoid decompression sickness and why they sometimes strand
Authors: Blix Arnoldus S. , Walloe Lars , Messelt Edward
Published: June 2013

Whales are unique in that the supply of blood to the brain is not by the internal carotid arteries, but by way of thoracic and intra-vertebral arterial retia. We found in the harbour porpoise (Phocoena phocoena) that these retia split up into smaller anastomosing vessels and thin-walled sinusoid structures that are embedded in fat. The solubility of nitrogen is at least 6 times larger in fat than in water, and we suggest that nitrogen in supersaturated blood will be absorbed in the fat, by diffusion, during the very slow passage of the blood through the arterial retia. Formation of nitrogen bubbles that may reach the brain is thereby avoided. We also suggest that mass strandings of whales may be due to disturbances to their normal dive profiles resulting in extra release of nitrogen that may overburden the nitrogen 'trap' and allow bubbles to reach the brain and cause abnormal behaviour.
Tissue specific ionomotive enzyme activity and K+ reabsorption reveal the rectum as an important ionoregulatory organ in larvalChironomous ripariusexposed to varying salinity
Authors: Jonusaite Sima , Kelly Scott P. , Donini Andrew
Published: June 2013

A role for the rectum in the ionoregulatory homeostasis of larval Chironomus riparius was revealed by rearing animals in different saline environments and examining: (1) the spatial distribution and activity of keystone ionomotive enzymes Na+-K+-ATPase (NKA) and V-type H+-ATPase (VA) in the alimentary canal and (2) rectal K+ transport with scanning ion-selective electrode technique (SIET). NKA and VA activity were measured in four distinct regions of the alimentary canal as follows: the combined foregut and anterior midgut (FAMG), the posterior midgut (PMG), the Malpighian tubules (MT) and the hindgut (HG). Both enzymes exhibited 10 - 20 times greater activity in the HG relative to all other areas. When larvae were reared in either ion-poor water (IPW) or freshwater (FW), no significant difference in HG enzyme activity was observed. However, in brackish water (BW) reared animals, NKA and VA activity in the HG significantly decreased. Immunolocalization of NKA and VA in the HG revealed that the bulk of protein was located in the rectum. Therefore K+ transport across the rectum was examined using SIET. Measurement of K+ flux along the rectum revealed a net K+ reabsorption which was reduced four-fold in BW-reared larvae versus larvae reared in FW or IPW. Inhibition of NKA with ouabain, VA with bafilomycin and K+ channels with charybdotoxin, diminished rectal K+ reabsorption in FW- and IPW-reared larvae, but not BW-reared larvae. Data suggest that the rectum of C. riparius plays an important role in allowing these larvae to cope with dilute as well as salinated environmental conditions.
Limits to sustained energy intake XX: body temperatures and physical activity of female mice during lactation
Authors: Gamo Yuko , Troup Claire , Mitchell Sharon , Hambly Catherine , Vaanholt Lobke , Speakman John
Published: June 2013

Lactating animals consume greater amounts of food than non-reproductive animals but energy intake appears to be limited in late lactation. The heat dissipation limit theory suggests that the food intake of lactating mice is limited by the capacity of the mother to dissipate heat. Lactating mice should therefore have high body temperatures (Tb), and changes in energy intake, during lactation, should be reflected in variation in Tb. To investigate these predictions, 26 mice (Mus musculus) were monitored daily throughout lactation for food intake, body mass, litter size and litter mass. After weaning, 21 days postpartum, maternal food intake and body mass were monitored for another 10 days. Maternal activity and Tb were recorded every minute for 23 hours a day using implanted transmitters (vital view). Energy intake increased to a plateau in late lactation (days 13-17). Daily gain in pup mass declined during this same period, suggesting a limit on maternal energy intake. Litter size, and litter mass, were positively related to maternal energy intake and body mass. Activity levels were constantly low, and mice with the largest increase in energy intake at peak lactation had the lowest activity. Tb rose sharply after parturition and the circadian rhythm became compressed within a small range. Tb during the light period increased considerably (1.1 °C higher than in baseline), and lactating mice faced chronic hyperthermia, despite their lower activity levels in lactation being approximately halved. Average T b increased in relation to energy intake as lactation progressed, but there was no relationship between litter size or litter mass and the mean Tb at peak lactation. These data are consistent with the heat dissipation limit theory which suggests performance in late lactation is constrained by the ability to dissipate body heat.
Thermal Annealing Effects on the Photocarrier Dynamics in PCBM Films
Authors: Ambe Christopher E , Wakikawa Yusuke , Ikoma Tadaaki
Published: June 2013

The thermal annealing effects on the photocarrier dynamics in thin films of [6,6]-phenyl C61 butyric acid methyl ester (PCBM) on quartz substrates are investigated. Both the photocarrier generation via charge-transfer state and the charge transport in PCBM films are studied by time-resolved photoconductance (PC) measurement. More than 90% of external photocarrier generation efficiency relative to the non-annealed film is reduced upon annealing of the PCBM film at high temperatures. Excitation light power dependence of PC indicates that the photocarrier in the non-annealed film is generated by a one-photon process, while photons of more than one are required in highly annealed films. The multiphotonic process for carrier generation and the substantial reduction of carrier density caused by the thermal treatment are associated with trap formation. The density of photoinjected carrier is also affected by applying external magnetic field. The observed positive magnetophotoconductance (MPC) in non-annealed film is understood in terms of the incoherent spin conversion in nongeminate electron–hole (e–h) pairs with a selective recombination from singlet e–h pairs. In highly annealed film, the broad magnetic field dependence of MPC with negative phase is suggested to originate from the detrapping of trapped carrier assisted by collision with the triplet exciton.
U.S. High School Graduation Rates: Patterns and Explanations
Authors: Murnane Richard J
Published: June 2013

I survey the evidence on patterns in U.S. high school graduation rates over the period 1970–2010 and report the results of new research conducted to fill in holes in the evidence. I begin by pointing out the strengths and limitations of existing data sources. I then describe six striking patterns in graduation rates. They include stagnation over the last three decades of the twentieth century, significant race-, income-, and gender-based gaps, and significant increases in graduation rates over the first decade of the twenty-first century, especially among blacks and Hispanics. I then describe the models economists use to explain the decisions of individuals to invest in schooling, and examine the extent to which the parameters of the models explain recent patterns in graduation rates. I find that increases in the nonmonetary costs of completing high school and the increasing availability of the GED credential help to explain stagnation in the face of substantial gaps between the wages of high school graduates and school dropouts. I point out that there are several hypotheses, but to date, very little evidence to explain the increases in high school graduation rates over the first decade of the twenty-first century. I conclude by reviewing the evidence on effective strategies to increase high school graduation rates, and explaining why the causal evidence is quite modest. (JEL I21, J15, J16)
Boundedly Rational versus Optimization-Based Models of Strategic Thinking and Learning in Games
Authors: Crawford Vincent P
Published: June 2013

Harstad and Selten's article in this forum performs a valuable service by highlighting the dominance of optimization-based models over boundedly rational models in modern microeconomics, and questioning whether optimization-based models are a better way forward than boundedly rational models. This article complements Rabin's response to Harstad and Selten, focusing on modeling strategic behavior. I consider Harstad and Selten's examples and proposed boundedly rational models in the light of modern behavioral economics and behavioral game theory, commenting on the challenges that remain and the most promising ways forward. (JEL B40, C72, D01, D03, D80)
A novel insight into the mechanism of mammalian selenoprotein synthesis
Authors: Kossinova Olga , Malygin Alexey , Krol Alain , Karpova Galina
Published: June 2013

The amino acid selenocysteine is encoded by UGA, usually a stop codon, thus requiring a specialized machinery to enable its incorporation into selenoproteins. The machinery comprises the tRNASec, a 3′-UTR mRNA stem–loop termed SElenoCysteine Insertion Sequence (SECIS), which is mandatory for recoding UGA as a Sec codon, the SECIS Binding Protein 2 (SBP2), and other proteins. Little is known about the molecular mechanism and, in particular, when, where, and how the SECIS and SBP2 contact the ribosome. Previous work by others used the isolated SECIS RNA to address this question. Here, we developed a novel approach using instead engineered minimal selenoprotein mRNAs containing SECIS elements derivatized with photoreactive groups. By cross-linking experiments in rabbit reticulocyte lysate, new information could be gained about the SBP2 and SECIS contacts with components of the translation machinery at various translation steps. In particular, we found that SBP2 was bound only to the SECIS in 48S pre-initiation and 80S pretranslocation complexes. In the complex where the Sec-tRNASecwas accommodated to the A site but transpeptidation was blocked, SBP2 bound the ribosome and possibly the SECIS element as well, and the SECIS had flexible contacts with the 60S ribosomal subunit involving several ribosomal proteins. Altogether, our findings led to broadening our understanding about the unique mechanism of selenocysteine incorporation in mammals.
Minotaur is critical for primary piRNA biogenesis
Authors: Vagin Vasily V. , Yu Yang , Jankowska Anna , Luo Yicheng , Wasik Kaja A. , Malone Colin D. , Harrison Emily , Rosebrock Adam , Wakimoto Barbara T. , Fagegaltier Delphine , Muerdter Felix , Hannon Gregory J.
Published: June 2013

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of theDrosophilaglycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur.
A new genus of Amycterini from the Pilbara region of Western Australia (Coleoptera: Curculionidae: Cyclominae)
Authors: Peterson Magnus
Published: June 2013

Xenommamycterus gen. nov. is described/diagnosed, and Talaurinus capito Pascoe, 1874 is designated its type-species. This genus is considered monospecific at present. Its distribution appears to be restricted to the tropical rock desert of the western Pilbara region of Western Australia, based on available specimens. Evidence suggests that F.H. DuBoulay collected the holotype of T. capito, and that its type-locality of “Champion Bay” is in error for Nickol Bay. Limited observations on its imaginal food-plants, behaviour, habitat preferences and relationships are provided, as well as possible reasons for the evolution of its unusual eye structure.
Advancing User Experience Research to Facilitate and Enable Patient Centered
Research: Current State and Future Directions
Authors: Payne Philip
Published: June 2013

Human beings possess well-documented strengths in pattern recognition and
higher-order reasoning. This allows individuals to interpret complex data sets in ways
that remain difficult to reproduce using computers. Given these capabilities, it is
important to present data in a manner that supports such human-computer interaction, and
is pertinent to patient-centered research, where investigators frequently need to
analyze multidimensional data sets derived from a variety of heterogeneous sources. An
overarching domain of innovation focusing on user experience(UX), which can include
areas such as human factors, workflow evaluation, human-computer interaction, and data
visualization, has the potential to support the aforementioned needs. However, a review
of available data concerning the state of UX research as it relates to patient centered
research demonstrates a concerning low level of investment and knowledge generation in
this area. In response to these concerns, this report explores potential explanations
for these trends and then presents a set of recommendations to advance UX innovation in
the context of patient centered research. Ultimately, the hope is to catalyze a
community-wide dialogue concerning future directions for these important areas.
Poverty Orderings with Asymmetric Attributes
Authors: Garcia-Diaz Rocio
Published: June 2013

We provide a theorem that lists the necessary and sufficient dominance conditions for the poverty comparisons of the bivariate distributions function when considering an asymmetric treatment of attributes. The normative justification for an asymmetric treatment is based on the compensation principle proposed by Muller and Trannoy (2012), under which it makes sense to use one attribute to compensate another. The formulation results in a generalization of the needs approach in poverty analysis proposed by Atkinson (1992). The dominance conditions we found lie between those obtained by Bourguignon and Chakravarty (2002) and Duclos, Sahn, and Younger (2006a) when attributes are symmetric and those obtained within the needs framework by Atkinson (1992) and Jenkins and Lambert (1993) when attributes are asymmetric, but one is of discrete nature.
Deoxyadenosine family: improved synthesis, DNA damage and repair, analogs as drugs
Authors: Biswas Himadri , Kar Indrani , Chattopadhyaya Rajagopal
Published: June 2013

Improved synthesis of 2′-deoxyadenosine using Escherichia coli overexpressing some enzymes and gram-scale chemical synthesis of 2′-deoxynucleoside 5′-triphosphates reported recently are described in this review. Other topics include DNA damage induced by chromium(VI), Fenton chemistry, photoinduction with lumazine, or by ultrasound in neutral solution; 8,5′-cyclo-2′-deoxyadenosine isomers as potential biomarkers; and a recapitulation of purine 5′,8-cyclonucleoside studies. The mutagenicities of some products generated by oxidizing 2′-deoxyadenosine 5′-triphosphate, nucleotide pool sanitization, and translesion synthesis are also reviewed. Characterizing cross-linking between nucleosides in opposite strands of DNA and endonuclease V-mediated deoxyinosine excision repair are discussed. The use of purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias is reviewed. Some analogs at the C8 position induced delayed polymerization arrest during HIV-1 reverse transcription. The susceptibility of clinically metronidazole-resistant Trichomonas vaginalis to two analogs, toyocamycin and 2-fluoro-2′-deoxyadenosine, were tested in vitro. GS-9148, a dAMP analog, was translocated to the priming site in a complex with reverse transcriptase and double-stranded DNA to gain insight into the mechanism of reverse transcriptase inhibition.
Perelman's entropy functional at Type I singularities of the Ricci flow
Authors: Mantegazza Carlo , Müller Reto
Published: June 2013

We study blow-ups around fixed points at Type I singularities of the Ricci flow on closed manifolds using Perelman's 𝒲-functional. First, we give an alternative proof of the result obtained
by Naber (2010) and Enders–Müller–Topping (2011) that blow-up limits are non-flat gradient shrinking Ricci solitons. Our second and main result relates a limit 𝒲-density at a Type I singular point to the entropy of the limit gradient shrinking soliton
obtained by blowing-up at this point. In particular, we show that no entropy is lost at infinity during the blow-up process.
Plant derived alternatives for hormone replacement therapy (HRT)
Authors: Seidlova-Wuttke Dana , Jarry Hubertus , Wuttke Wolfgang
Published: June 2013

Hormone replacement therapy (HRT) has undisputable positive effects on climacteric complaints, in the bone and on body weight but also several undesired side effects. Therefore, plant-derived alternatives are currently promoted. Phytoestrogens – primarily the isoflavones genistein, daidzein and coumestrol, stemming from soy (Glycine max) or red clover (Trifolium pratense) – were suggested to have the desired but not the undesired effects of estrogens. Most recently published placebo-controlled studies question the beneficial effects. When taken at the time of puberty however, phytoestrogens appear to protect against mammary cancer later in life. Extracts from the rhizome of Cimicifuga racemosa (black cohosh) have no estrogenic effects. In a narrow dose range they have beneficial effects on climacteric complaints, which are due to several compounds with dopaminergic, noradrenergic, serotoninergic and GABAergic actions that act together in the hypothalamus. Ecdysone is produced by several plants, including spinach (Spinacia oleracea) and was very early on shown to increase muscle mass. Later it became apparent that spinach extracts containing ecdysone decreased body fat load, thereby reducing secretion of proinflammatory cytokines by visceral adipocytes and oxidative stress. This had beneficial effects on body weight and serum lipids not only in obese postmenopausal but also in premenopausal women and in men. For the above-described plant extracts, solid placebo-controlled clinical trials are available. For other plant extracts claiming beneficial effects on climacteric complaints or postmenopausal diseases, no solid data are available.
Endothelial progenitor cells in coronary artery disease
Authors: Donahue Michael , Quintavalle Cristina , Chiariello Giovanni Alfonso , Condorelli Gerolama , Briguori Carlo
Published: June 2013

In the last two decades a great deal of evidence has been collected on the key role of endothelial progenitor cells (EPC) in the mechanisms of vascular healing. The role of EPC as a marker of vascular health and prognosis of cardiovascular disease is already consolidated. This review aims to examine and evaluate recent data regarding EPC, as biomarkers, prognostic factor and potential therapy in cardiovascular disease.
Obtention of Rosemary Essential Oil Concentrates by Molecular Distillation and Free Radical Scavenging Capacity Analysis
Authors: Mezza Gabriela Natalia , Borgarello Ana V. , Daguero Jorge D. , Pramparo Maria C.
Published: June 2013

Rosemary essential oil is used in pharmaceutical, cosmetic and food industries. Due to its constituents’ chemical activity, it is also used as antioxidant to preserve foods and as antibacterial and antifungal agents.The most abundant components of rosemary essential oil used in this work are α-pinene, myrcene, 1,8-cineole and camphor, which respond to 1,8-cineole chemotype. Two sets of molecular distillation experience were conducted. Antioxidant power of distillates and residues obtained was quantified, and the residues obtained from molecular distillation have more antioxidant power than distillates and rosemary essential oil.The results of this study show that it is feasible to use molecular distillation operation to obtain concentrates of rosemary essential oil. Residues collected present higher antioxidant power than rosemary essential oil, probably due to the presence of camphor, linalool, linalyl acetate and α-terpineol, which are present in higher proportion in the residues.
Moment methods for C/SiC woven composite components reliability and sensitivity analysis
Authors: Kong Chunyuan , Sun Zhigang , Niu Xuming , Song Yingdong
Published: June 2013

A kind of reliability analysis method for C/SiC woven composite components was proposed, which is based on moment methods. Moment methods combining with perturbation method, the central difference method, as well as the Edgeworth series are applied to calculate the reliability of complex component for its effectivity and accuracy. The results computed by moment methods are sensitive to the distribution of parameters; thus, reliability sensitivity analysis has been performed. The reliability and sensitivity information of the complex components can be accurately and quickly obtained using a practical computer program. Finally, the proposed reliability-sensitivity analysis method is applied to CMCs components design. By comparing with Monte Carlo simulation, the numerical results demonstrate that the proposed approach provides accurate, convergent, and computationally efficient for finite element method-based reliability analysis in engineering practice.
Impact response of composite plates manufactured with stitch-bonded non-crimp glass fiber fabrics
Authors: Bektaş Numan Behlül , Ağır İnan
Published: June 2013

This experimental study deals with the impact response of composite plates manufactured with stitch-bonded non-crimp glass fiber fabrics. Three kinds of fabrics – biaxial, triaxial, and quadraxial – are used as reinforcing material. Polyester resin is used as a matrix material in the composition of composite plates. An instrumented drop weight impact testing machine, Instron-Dynatup 9250 HV, is used for impact testing. Impact tests are performed under various impact energies, ranging from damage initiation to final perforation. An energy profiling method, showing the relation between impact energy and absorbed energy, was used together with load-deflection curves to determine the penetration and perforation thresholds of those composites. The failure processes of damaged specimens for different impact energies were evaluated by comparing load-deflection curves and images of damaged samples taken from the impacted and non-impacted sides. All types of composites have obvious penetration and perforation thresholds. The perforation threshold of triaxial/polyester composite is approximately 27% and 22% higher than that of the quadraxial and biaxial/polyester composites, respectively.
The effects of different dusty aggregate on bituminous hot mixtures
Authors: Akbulut Hüseyin , Gürer Cahit , Çetin Sedat , Doğan Hasan
Published: June 2013

Adhesion between aggregate and bitumen is an important parameter of the performance of bituminous hot mix pavements. Dust on the aggregate surface adversely affects bituminous hot mix pavement performance and leads to some types of deterioration, such as raveling, rutting, stripping, and segregation, decreasing long-term pavement performance. The main objective of this study is to determine the effects of different dust contents of the aggregate surface on the bituminous hot mixture. Two separate aggregate specimens with contents of three different dusts were used to produce bituminous hot mixture specimens. Specific gravity, unit weight, gradation analysis, water absorption, Los Angeles abrasion, aggregate impact, freezing and thawing, Nicholson stripping, and Vialit adhesion tests were performed as aggregate tests, whereas Marshall stability and flow, Marshall mechanical immersion, and indirect tensile tests were performed as bituminous hot mixture tests. The study results show that dust content on the aggregate surface weakens adhesion, leading to the gradual deterioration of the characteristics of the hot bituminous mixtures. Because dust contents on the aggregate surface can vary according to the aggregate type, the progression of the deterioration of bituminous hot mixtures can also vary.
A mesh-free simulation of mode I delamination of composite structures
Authors: Hesar Goudarz Ghanizadeh , Pekbey Yeliz , Yildiz Hasan , Maleiki Farshid Khosravi
Published: June 2013

A numerical and experimental investigation for the analysis of delamination problem under mode I loading in composite material is presented. Firstly, the simulation of the delamination under mode I loading and failure of composite materials based on the cohesive segments model is investigated by using the meshfree method. With the partition of unity of moving least-squares shape functions, the discontinuities at the cohesive segments are approximated with additional degrees of freedom at the nodes. An iterative solution scheme between the continuous and discontinuous fields is presented to solve mode I delamination growth. Secondly, to verify the meshfree method’s results, an experimental investigation and the finite element method were used for the simulation of delamination. The experimental study used a double-cantilever beam made of carbon/epoxy laminate (AS4/3501-6) which consists of 10 plies in [0]10 and [0/90/0/90/0]s layup with delamination inserted in the middle of the laminate. The critical fracture force, which can be experimentally measured, was used to calculate the mode I delamination fracture toughness of the carbon/epoxy laminate. Results obtained from the meshfree method showed very good agreement with experimental data for single-mode delamination under mode I loading. The meshfree method could also be used effectively to produce delamination growth in composite laminates and is especially suitable for the simulation of complex delamination patterns that are difficult to model using traditional numerical methods.
The Logics of Materials Innovation
Authors: Lécuyer Christophe , Ueyama Takahiro
Published: June 2013

This article examines the rise of gallium nitride as a major semiconductor material at the center of a new industry, solid-state lighting. It argues that the development of gallium nitride was shaped by the interplay of three contextual logics: material logic (the materiality of substances, tools, and fabrication techniques); market logic (the needs, demands, and interests of intended users); and competitive logic (the competitive tensions among laboratories, firms, and nations). For nearly forty years, chemists, physicists, and engineers in the United States and Japan struggled with the persistent material challenges presented by gallium nitride to meet the needs of potential markets in lighting and consumer electronics. Competition among firms and the technological and economic rivalry between the U.S. and Japan led to significant material developments and to the shaping of gallium nitride into a critical material for the manufacture of light emitting diodes. This article is intended to contribute to recent interest in the history of advanced materials and to the larger question of the determinants of innovation in technoscience.
The Einstein-Picasso Question
Authors: Pyenson Lewis
Published: June 2013

The theories of relativity in physics and the style known as Cubism in painting found a favorable reception by theoretical physicists, on the one hand, and avant-garde art dealers and patrons, on the other hand, across the seven years before the First World War. The climate in bourgeois Europe contributing to this rapid assimilation of revolutionary, intellectual work is examined from the point of view of material culture. Emphasis is placed on Neo-Idealist abstraction in urban decoration and design, with a focus on Oriental carpets, wallpaper, and electrical lighting. Elements from all three domains are found in Cubism, and relativity assimilated both vocabulary and images from newly electrified cities.
Essential Fatty Acids, Prostaglandins, and Respiratory Distress Syndrome of the Newborn
Authors: Friedman Zvi , Demers Laurence M.
Published: June 2013

The lungs are a major metabolic site for the synthesis, release, and degradation of prostaglandins. Prostaglandins of the E and F series exert a potent physiological effect on the smooth muscle of blood vessels and the tracheobronchial tree; prostaglandin E dilates while prostaglandin F constricts. Thus, altered prostaglandin metabolism may contribute to the pathophysiology of respiratory distress syndrome (RDS). Twenty-one infants with RDS and ten age- and weight-matched controls were studied by analyzing their plasma for prostaglandins and their precursor essential fatty acids. The two groups showed no differences in the essential fatty acid prostaglandin precursors, dihomo-γ-linolenic and arachidonic acids. During the acute phase of RDS, plasma levels of the primary prostaglandins E and F are significantly elevated compared with control values and the ratio of prostaglandin E to prostaglandin F significantly reduced. Prostaglandins E and F returned to control values oIl recovery from the acute stage of the disease. Two infants with persistent patent ductus arteriosus had significantly elevated prostaglandin E values in their plasma compared with controls. The elevated levels of circulating plasma prostaglandins E and F and the reversal of their ratio during the acute phase of RDS may have adverse pulmonary and multisystem effects.