bluuebunny/crossref_metadata_2025 huggingface dataset:
The rise and fall of breakpoint reuse depending on genome resolution
Authors: Attie Oliver , Darling Aaron E , Yancopoulos Sophia
Published: October 2011

Background

During evolution, large-scale genome rearrangements of chromosomes shuffle the order of homologous genome sequences ("synteny blocks") across species. Some years ago, a controversy erupted in genome rearrangement studies over whether rearrangements recur, causing breakpoints to be reused.

Methods

We investigate this controversial issue using the synteny block's for human-mouse-rat reported by Bourque et al. and a series of synteny blocks we generated using Mauve at resolutions ranging from coarse to very fine-scale. We conducted analyses to test how resolution affects the traditional measure of the breakpoint reuse rate.

Results

We found that the inversion-based breakpoint reuse rate is low at fine-scale synteny block resolution and that it rises and eventually falls as synteny block resolution decreases. By analyzing the cycle structure of the breakpoint graph of human-mouse-rat synteny blocks for human-mouse and comparing with theoretically derived distributions for random genome rearrangements, we showed that the implied genome rearrangements at each level of resolution become more “random” as synteny block resolution diminishes. At highest synteny block resolutions the Hannenhalli-Pevzner inversion distance deviates from the Double Cut and Join distance, possibly due to small-scale transpositions or simply due to inclusion of erroneous synteny blocks. At synteny block resolutions as coarse as the Bourque et al. blocks, we show the breakpoint graph cycle structure has already converged to the pattern expected for a random distribution of synteny blocks.

Conclusions

The inferred breakpoint reuse rate depends on synteny block resolution in human-mouse genome comparisons. At fine-scale resolution, the cycle structure for the transformation appears less random compared to that for coarse resolution. Small synteny blocks may contain critical information for accurate reconstruction of genome rearrangement history and parameters.
Changes in transcriptional orientation are associated with increases in evolutionary rates of enterobacterial genes
Authors: Lin Chieh-Hua , Lian Chun-Yi , Hsiung Chao Agnes , Chen Feng-Chi
Published: October 2011

Background

Changes in transcriptional orientation (“CTOs”) occur frequently in prokaryotic genomes. Such changes usually result from genomic inversions, which may cause a conflict between the directions of replication and transcription and an increase in mutation rate. However, CTOs do not always lead to the replication-transcription confrontation. Furthermore, CTOs may cause deleterious disruptions of operon structure and/or gene regulations. The currently existing CTOs may indicate relaxation of selection pressure. Therefore, it is of interest to investigate whether CTOs have an independent effect on the evolutionary rates of the affected genes, and whether these genes are subject to any type of selection pressure in prokaryotes.

Methods

Three closely related enterbacteria, Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium, were selected for comparisons of synonymous (dS) and nonsynonymous (dN) substitution rate between the genes that have experienced changes in transcriptional orientation (changed-orientation genes, “COGs”) and those that do not (same-orientation genes, “SOGs”). The dN/dS ratio was also derived to evaluate the selection pressure on the analyzed genes. Confounding factors in the estimation of evolutionary rates, such as gene essentiality, gene expression level, replication-transcription confrontation, and decreased dS at gene terminals were controlled in the COG-SOG comparisons.

Results

We demonstrate that COGs have significantly higher dN and dS than SOGs when a series of confounding factors are controlled. However, the dN/dS ratios are similar between the two gene groups, suggesting that the increase in dS can sufficiently explain the increase in dN in COGs. Therefore, the increases in evolutionary rates in COGs may be mainly mutation-driven.

Conclusions

Here we show that CTOs can increase the evolutionary rates of the affected genes. This effect is independent of the replication-transcription confrontation, which is suggested to be the major cause of inversion-associated evolutionary rate increases. The real cause of such evolutionary rate increases remains unclear but is worth further explorations.
Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm
Authors: Li Jinquan , Lühmann Ann-Katrin , Weißleder Knuth , Stich Benjamin
Published: October 2011

Background

Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i) explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii) investigate the genome-wide distribution of genetic diversity, and (iii) assess the extent and genome-wide distribution of linkage disequilibrium (LD) in elite sugar beet germplasm.

Results

A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact thatr2>0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping.

Conclusions

We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of genome-wide association mapping in sugar beet as well as the efficient organization of germplasm.
Design and development of a peptide-based adiponectin receptor agonist for cancer treatment
Authors: Otvos Laszlo , Haspinger Eva , La Russa Francesca , Maspero Federica , Graziano Patrizia , Kovalszky Ilona , Lovas Sandor , Nama Kaushik , Hoffmann Ralf , Knappe Daniel , Cassone Marco , Wade John , Surmacz Eva
Published: October 2011

Background

Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug.

Results

We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH2). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1.In vivo, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice.

Conclusions

ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.
Concomitant pulmonary and thyroid tumors identified by FDG PET/CT and immunohistochemical techniques
Authors: Zhu Guangwen , Li Hong , Zhang Yanjun , Li Yaming , Liang Shujun , Liu Jia
Published: October 2011

Background

The exact diagnosis of double primary papillary adenocarcinoma of thyroid and lung is even rarer, to our knowledge no report in the literature by [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography/X-ray CT(FDG PET/CT) with surgical specimens immunohistochemistry(IHC). We report a patient with abnormal FDG PET/CT in thyroid and lung, this unusual presentation may lead to misdiagnosis without surgical specimens IHC.

Case presentation

A 56-year-old man with coughing three months. FDG PET/CT was performed, and resection specimens of lung and thyroid were detected by hematoxylin eosin staining (HE) and IHC. PET/CT: lung tumor SUVmax: 3.69, delay: 5.17; and thyroid tumor SUVmax 19.97. HE reveal papillary adenocarcinoma, but histological differentiation of primary pulmonary adenocarcinoma from metastatic adenocarcinoma is sometimes difficult because of their phenotypic similarities. So IHC was performed, the IHC of lung tumor: cytokeratin 20 (CK20)(-), thyroglobulin(Tg)(-), cytokeratin7(CK7)(+), thyroid transcription factor-1 (TTF-1)(+); thyroid tumor: CK7(+), TTF-1(+), thyroglobulin (+), CK20(-). Therefore, the final diagnosis was double primary adenocarcinomas of thyroid and lung.

Conclusion

FDG PET/CT has preliminary diagnostic capacity of multiple primary tumors; the final diagnosis should be adopted for specimens after tumor-specific markers IHC to obtain. Consequently, effective therapeutic approaches can be designed and conducted.
Controllable synthesis of flake-like Al-doped ZnO nanostructures and its application in inverted organic solar cells
Authors: Fan Xi , Fang Guojia , Guo Shishang , Liu Nishuang , Gao Huimin , Qin Pingli , Li Songzhan , Long Hao , Zheng Qiao , Zhao Xingzhong
Published: October 2011

Flake-like Al-doped ZnO (AZO) nanostructures including dense AZO nanorods were obtained via a low-temperature (100°C) hydrothermal process. By doping and varying Al concentrations, the electrical conductivity (σ) and morphology of the AZO nanostructures can be readily controlled. The effect of σ and morphology of the AZO nanostructures on the performance of the inverted organic solar cells (IOSCs) was studied. It presents that the optimized power conversion efficiency of the AZO-based IOSCs is improved by approximately 58.7% compared with that of un-doped ZnO-based IOSCs. This is attributed to that the flake-like AZO nanostructures of high σ and tunable morphology not only provide a high-conduction pathway to facilitate electron transport but also lead to a large interfacial area for exciton dissociation and charge collection by electrodes.
Thermoelectric properties of Ca0.8Dy0.2MnO3 synthesized by solution combustion process
Authors: Park Kyeongsoon , Lee Ga Won
Published: October 2011

High-quality Ca0.8Dy0.2MnO3 nano-powders were synthesized by the solution combustion process. The size of the synthesized Ca0.8Dy0.2MnO3 powders was approximately 23 nm. The green pellets were sintered at 1150-1300°C at a step size of 50°C. Sintered Ca0.8Dy0.2MnO3 bodies crystallized in the perovskite structure with an orthorhombic symmetry. The sintering temperature did not affect the Seebeck coefficient, but significantly affected the electrical conductivity. The electrical conductivity of Ca0.8Dy0.2MnO3 increased with increasing temperature, indicating a semiconducting behavior. The absolute value of the Seebeck coefficient gradually increased with an increase in temperature. The highest power factor (3.7 × 10-5 Wm-1 K-2 at 800°C) was obtained for Ca0.8Dy0.2MnO3 sintered at 1,250°C. In this study, we investigated the microstructure and thermoelectric properties of Ca0.8Dy0.2MnO3, depending on sintering temperature.
The enhancement of enzymatic hydrolysis of lignocellulosic substrates by the addition of accessory enzymes such as xylanase: is it an additive or synergistic effect?
Authors: Hu Jinguang , Arantes Valdeir , Saddler Jack N
Published: October 2011

Background

We and other workers have shown that accessory enzymes, such as β-glucosidase, xylanase, and cellulase cofactors, such as GH61, can considerably enhance the hydrolysis effectiveness of cellulase cocktails when added to pretreated lignocellulosic substrates. It is generally acknowledged that, among the several factors that hamper our current ability to attain efficient lignocellulosic biomass conversion yields at low enzyme loadings, a major problem lies in our incomplete understanding of the cooperative action of the different enzymes acting on pretreated lignocellulosic substrates.

Results

The reported work assessed the interaction between cellulase and xylanase enzymes and their potential to improve the hydrolysis efficiency of various pretreated lignocellulosic substrates when added at low protein loadings. When xylanases were added to the minimum amount of cellulase enzymes required to achieve 70% cellulose hydrolysis of steam pretreated corn stover (SPCS), or used to partially replace the equivalent cellulase dose, both approaches resulted in enhanced enzymatic hydrolysis. However, the xylanase supplementation approach increased the total protein loading required to achieve significant improvements in hydrolysis (an additive effect), whereas the partial replacement of cellulases with xylanase resulted in similar improvements in hydrolysis without increasing enzyme loading (a synergistic effect). The enhancement resulting from xylanase-aided synergism was higher when enzymes were added simultaneously at the beginning of hydrolysis. This co-hydrolysis of the xylan also influenced the gross fiber characteristics (for example, fiber swelling) resulting in increased accessibility of the cellulose to the cellulase enzymes. These apparent increases in accessibility enhanced the steam pretreated corn stover digestibility, resulting in three times faster cellulose and xylan hydrolysis, a seven-fold decrease in cellulase loading and a significant increase in the hydrolysis performance of the optimized enzyme mixture. When a similar xylanase-aided enhancement strategy was assessed on other pretreated lignocellulosic substrates, equivalent increases in hydrolysis efficiency were also observed.

Conclusions

It was apparent that the 'blocking effect' of xylan was one of the major mechanisms that limited the accessibility of the cellulase enzymes to the cellulose. However, the synergistic interaction of the xylanase and cellulase enzymes was also shown to significantly improve cellulose accessibility through increasing fiber swelling and fiber porosity and also plays a major role in enhancing enzyme accessibility.
Global discourses and experiential speculation: Secondary and tertiary graduate Malawians dissect the HIV/AIDS epidemic
Authors: Myroniuk Tyler W
Published: October 2011

Background

Since the beginning of the HIV/AIDS epidemic, the perspectives of secondary and tertiary school graduates in sub‐Saharan Africa regarding the effectiveness of government and international HIV/AIDS policies and programmes have not been thoroughly examined. When extensive monetary aid is directed toward “development” in a country like Malawi, it is the educated elites ‐ secondary and tertiary graduates who are heavily involved and influential in the domestic re‐distribution and implementation of millions of dollars worth of aid ‐ on whom international expectations fall to decrease the transmission of HIV. Many Malawian jobs related to public health and HIV/AIDS are created as a direct result of this funding and are occupied by the few secondary and tertiary graduates. Thus, it is a practical venture to understand their perspectives on highly contentious and heavily funded HIV/AIDS issues that affect their nation.

Methods

Qualitative data was collected in this study in efforts to discover in‐depth perspectives on the HIV/AIDS epidemic. Thirty‐eight secondary and tertiary graduate Malawians took part in semi‐structured interviews. Data was analysed using an early grounded theory approach and subsequent themes of “global discourses” and “experiential knowledge of HIV/AIDS” emerged.

Results

This group of Malawians frequently responded to questions regarding healthcare and access to medicine, sexual behaviours and methods of reducing the spread of HIV/AIDS by citing and explaining the widespread, international and “proper” responses. The secondary and tertiary graduate Malawians also discussed these same topics in terms of what they perceive or have experienced. Experiential responses, such as the counter‐productivity of circumcision and condoms, the overestimation of HIV/AIDS prevalence, and calls for more authoritarian policing of commercial sex work, were remarkably divergent from the HIV/AIDS discourse.

Conclusions

The opinions of this group of secondary and tertiary graduate Malawians do not always coincide with the current literature and policies. They give deeper insight into what is perceived and what may be taking place, and hint at what the future holds for their people. The widespread and divergent perspectives must be seriously considered because these experiences describe the potential positive and negative consequences that occur on the ground throughout Malawi as a result of HIV/AIDS policies.
Poly(A) Tail Length of Neurohypophysial Hormones Is Shortened Under Endoplasmic Reticulum Stress
Authors: Morishita Yoshiaki , Arima Hiroshi , Hiroi Maiko , Hayashi Masayuki , Hagiwara Daisuke , Asai Naoya , Ozaki Nobuaki , Sugimura Yoshihisa , Nagasaki Hiroshi , Shiota Akira , Takahashi Masahide , Oiso Yutaka
Published: October 2011

Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of arginine vasopressin (AVP), an antidiuretic hormone. Although the carriers are normal at birth, polyuria and polydipsia appear several months or years later. Previously, we made mice possessing a mutation causing FNDI and reported that the mice manifested progressive polyuria as do the patients with FNDI. Here, we report that decreases in AVP mRNA expression in the supraoptic nucleus were accompanied by shortening of the AVP mRNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons. Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors (thapsigargin and tunicamycin) caused shortening of the poly(A) tail length of AVP and oxytocin mRNA, accompanied by decreases in their expression. On the other hand, an ER stress-reducing molecule (tauroursodeoxycholate) increased the poly(A) tail length as well as the expression levels of AVP and oxytocin mRNA. These data reveal a novel mechanism by which ER stress decreases poly(A) tail length of neurohypophysial hormones, probably to reduce the load of unfolded proteins.
Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin
Authors: Córdoba-Chacón José , Gahete Manuel D. , Pozo-Salas Ana I. , Martínez-Fuentes Antonio J. , de Lecea Luis , Gracia-Navarro Francisco , Kineman Rhonda D. , Castaño Justo P. , Luque Raul M.
Published: October 2011

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.
Orexins/Hypocretins Act in the Posterior Paraventricular Thalamic Nucleus During Repeated Stress to Regulate Facilitation to Novel Stress
Authors: Heydendael Willem , Sharma Kanika , Iyer Vikram , Luz Sandra , Piel David , Beck Sheryl , Bhatnagar Seema
Published: October 2011

Orexins/hypocretins heavily innervate the posterior division of the paraventricular nucleus of the thalamus (pPVT), which expresses both orexin receptor types. The pPVT is important for adaptations to repeated stress, particularly the ability to facilitate to novel stress after repeated stress exposure. Here, we examined how orexins acting in the pPVT regulate facilitation of hypothalamic-pituitary-adrenal (HPA) responses to novel restraint after 4 d of repeated swim stress. Blockade of orexin receptors in the pPVT with SB334867 before novel restraint did not change the facilitated HPA response. However, blockade of orexin receptors before each of four daily swim exposures prevented the facilitated ACTH and facilitated hypothalamic c-Fos response to restraint as well as the repeated swim stress-induced increase in CRH mRNA in the paraventricular hypothalamus. These results suggest that orexin actions in the pPVT during the 4 d of swim, but not during restraint, are necessary for the facilitated HPA response to heterotypic restraint. Exposure to the fourth swim produced a shift in orexin1 receptors from membrane to cytosolic fractions. OrexinA also changed the firing patterns of pPVT cells to be more responsive in repeatedly swim stressed rats compared with nonstressed rats. Together, the results suggest that orexin actions in the pPVT, mediated by orexin1 receptors, are important for the ability to adapt to repeated stress.
Dihedral Angle Dependence of Transfer Integrals in Organic Semiconductors with Herringbone Structures
Authors: Kojima Hirotaka , Mori Takehiko
Published: October 2011

The herringbone structure is a representative molecular packing in organic semiconductors, but there are some modifications with largely different dihedral angles ranging from 40 to 130°. Dihedral angle θ dependence of the transfer integrals is systematically investigated on the basis of the molecular orbital calculations for various organic semiconductors including pentacene, picene, oligothiophene, fused thiophene, tetrathiafulvalenes (TTF), and benzothienobenzothiophene (BTBT). In the conventional organic semiconductors such as pentacene and oligothiophene, the transfer integral is a monotonously decreasing function of θ starting from the stacking geometry, and smaller θ provides more two-dimensional bands. When the molecules are slipped along the molecular long axis D, these compounds show characteristic oscillating structure of the transfer integrals depending on D, which is called D-modulation. Contrarily, TTF derivatives show oscillating structure of the transfer integrals depending on θ (θ-modulation) due to interaction at the side position. BTBT exhibits a pattern much different from the conventional organic semiconductors, and a considerable magnitude of transfer integrals is expected in the large θ region. These systematic investigations demonstrate that the θ-dependence of the charge transport largely depends on the original molecular orbital symmetry.
Getting “Messy” with Problems: The Challenges of Teaching “Soft” OR
Authors: Ackermann Fran
Published: October 2011

For many, teaching soft “OR” or problem structuring methods (PSMs) within the constraints of a degree program can be a challenge. For example, effort is needed in managing student expectations—particularly as problem structuring methods typically do not give “a single right answer.” Then there is the requirement of working interactively with groups—a daunting task to many! Finally, adding the extra consideration of teaching distance-learning students just exacerbates the situation—or does it? However, despite these challenges PSMs clearly provide benefit to many and are a valuable part of an operational researcher's armoury. This paper reflects on a selection of the challenges faced by those teaching such methods, and provides some insights into their management.
Teaching Problem Structuring Methods: Improving Understanding Through Meaningful Learning
Authors: Carreras Ashley L. , Kaur Parmjit
Published: October 2011

This paper examines how Novak's concept (Novak, J. D. 1998. Learning, Creating and Using Knowledge: Concept Maps as Facilitative Tools in Schools and Corporations. Lawrence Erlbaum, Mahwah, NJ) of “meaningful learning” can help teachers using an “experiential” approach to teaching problem structuring methods (PSMs) help students acquire an understanding of how these methods might aid group decision making.

Experiential learning is seen as a necessary foundation for the building of a student's understanding of PSMs if they are to fully appreciate the potential of the techniques. It is argued that if the affective mode of functioning (relating to moods, feelings, and attitudes) is triggered, the student is more likely to choose to engage in meaningful learning, and thereby gain an enhanced appreciation of how the methods work. An example of a causal mapping workshop is evaluated, with the findings, although limited in their validity for generalisation, pointing to a clear and direct positive link between meaningful learning and understanding by the learner.
A Comparison of Anticipatory Algorithms for the Dynamic and Stochastic Traveling Salesman Problem
Authors: Ghiani Gianpaolo , Manni Emanuele , Thomas Barrett W.
Published: October 2011

Advances in information technology and telecommunications, together with ever-growing amounts of data, offer opportunities for transportation companies to improve the quality of the service that they provide to their customers. This paper compares two methods motivated by the opportunity that the availability of data and technology gives to improve on current practice. In particular, the two solution approaches are explored in the context of a dynamic and stochastic routing problem in which a single, uncapacitated vehicle serves a set of known customers locations. One approach, sample-scenario planning, offers the potential for higher-quality solutions, but at the expense of greater computational effort. On the other hand, anticipatory insertion offers reduced computation and increased managerial ease, but with the potential for reduced solution quality due to restrictions on solution structure. Our results show that anticipatory insertion can often match the quality of sample-scenario planning, particularly when the degree of dynamism is low.
Graphite Furnace Atomic Absorption Spectrometry for the Analysis of Petroleum Products and Lubricants
Authors: Tittarelli Paolo
Published: October 2011

Since the pioneering work carried out by Boris V. L'Vov [1], graphite furnace atomic absorption spectrometry (GFAAS) represents a powerful tool for the determination of trace elements at ppb concentrations [2].
Energy Dispersive X-ray Fluorescence and Its Applications in the Field of Petroleum Products and Lubricants
Authors: Petiot C. A. , Pohl M. C.
Published: October 2011

Henry Moseley was perhaps the father of the X-ray fluorescence (XRF) technique. He was the first to build an X-ray tube that could be used to bombard samples with high-energy electrons. In 1925, Coster and Nishina [1] began using the X-rays coming from the bombardment of an electrode to excite an actual sample. Glocker and Schreiber [2] attempted to use the infant technique for quantitative analysis in 1928. Poor quality detector tubes made this nearly impossible until the late 1940s. The first commercially available instruments were offered in the 1950s. In 1970, the lithium drifted silicon detector was developed and it is still in use today!
Low-Power Monochromatic Wavelength-Dispersive X-ray Fluorescence-Principle and Applications in Petroleum Products
Authors: Chen Z. W. , Wei Fuzhong
Published: October 2011

X-ray fluorescence (XRF) using polychromatic X-rays is a powerful elemental analysis tool for petroleum products. XRF with an energy dispersive spectrometer (EDS) provides rapid multielement analysis in oil, lubricants, and raw materials. Energy dispersive XRF (EDXRF) systems can be compact and robust. Several ASTM methods are based on EDXRF techniques, including D4294, D6445, D6481, and D7212. However, the limitations of an EDXRF system include 1) susceptibility to elemental interference due to relatively poor energy resolution, and 2) low limit of detection (LOD) in the range of 5 to 10 ppm for sulfur, chlorine, and phosphorus in low atomic number matrix, which is not adequate for trace-level analysis. Another option, wavelength-dispersive XRF (WDXRF), provides superior energy resolution and lower LOD. A high-power WDXRF system has an LOD of about 0.5 ppm for sulfur, chlorine, and other elements. Several ASTM methods are well established for petroleum applications, including D2622, D6334, and D6376. The disadvantage of a WDXRF system is that it typically requires a high-power X-ray tube in a sophisticated system involving precision alignment and scanning. It is also bulky and not suitable for field testing.
Spectroscopic Analysis of Biofuels and Biolubes
Authors: Nadkarni R. A. Kishore
Published: October 2011

As crude oil stocks around the world slowly dwindle and the prices of crude oil and gasoline at the pump skyrocket, serious attention is being given to developing alternative fuels for the internal combustion engines. The more prominent among these alternative fuels is one derived from biomass, which a majority of oil-consuming countries have an abundance of. Whether biofuels will truly deliver the consumers from dependence on foreign oils is a matter of debate. The United States went through a similar scenario in the 1980s after Arab oil embargos, when concentrated efforts were dedicated by all major oil companies and nations to produce synthetic oil from coal and oil shale. Although technically successful, those efforts came to nothing when the crude oil price tumbled to about $5 a barrel in 1985 and all research and development efforts on synthetic fuels were abandoned. But at least at the moment, with encouragement from state and federal governments, a big push is on the way to commercialize biofuels. Worldwide investment in biofuels rose from $5 billion in 1995 to $38 billion in 2005 and is expected to top $100 billion by 2010. ASTM International is working toward standardizing or developing test methods for the characterization of these biofuels and biolubes.
Calibration and Quality Control Standards and Reference Materials for Spectroscopic Analysis of Petrochemical Products
Authors: Nadkarni R. A. Kishore
Published: October 2011

Calibration and quality control form an integral part of all analyses, including spectroscopic analysis of petroleum products and lubricants. All apparatus and instruments used in a laboratory for such analysis require calibration or verification before an instrument can be used for producing reliable data. A perfect analysis needs a perfect calibration as a first step and perfect quality control as perhaps the last step in the sequence of analytical events. Often this cycle is depicted as [1]: 1Calibration→Sample Analysis→QC Analysis→Calibration→
Wavelength Dispersive X-ray Spectrometry
Authors: Vrebos Bruno A. R. , Glose Timothy L.
Published: October 2011

The wavelength range of interest in X-ray fluorescence (XRF) spectrometry is roughly the range between 0.04 and 2 nm. This allows the analysis of the elements from fluorine upward to the transuranics, either on their K or L characteristic lines. Using special precautions and dedicated multilayers (see section on “Diffraction and the Analyzing Crystal”), the range can be enlarged to 11 nm, including the characteristic lines of beryllium. Energy and wavelength are related according to the following equation: 1E=hcλ where E is the photon energy; h is Planck's constant (6.626 10−34 J s, or 4.135 10−15 eV s); c is the speed of light in vacuum (3×108m/s); and λ is wavelength. By substituting these values in Eq 1, and expressing photon energy in kiloelectronvolts and wavelength in nanometres, the following is obtained: 2E=1.24λ or 3λ=1.24E
Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors
Authors: Fisher Daniel , Xing Bin , Dill John , Li Hui , Hoang Hai Hiep , Zhao Zhenze , Yang Xiao-Li , Bachoo Robert , Cannon Stephen , Longo Frank M. , Sheng Morgan , Silver Jerry , Li Shuxin
Published: October 2011

Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix molecules with various functions in regulating tissue morphogenesis, cell division, and axon guidance. A number of CSPGs are highly upregulated by reactive glial scar tissues after injuries and form a strong barrier for axonal regeneration in the adult vertebrate CNS. Although CSPGs may negatively regulate axonal growth via binding and altering activity of other growth-regulating factors, the molecular mechanisms by which CSPGs restrict axonal elongation are not well understood. Here, we identified a novel receptor mechanism whereby CSPGs inhibit axonal growth via interactions with neuronal transmembrane leukocyte common antigen-related phosphatase (LAR). CSPGs bind LAR with high affinity in transfected COS-7 cells and coimmunoprecipitate with LAR expressed in various tissues including the brain and spinal cord. CSPG stimulation enhances activity of LAR phosphatasein vitro. Deletion of LAR in knock-out mice or blockade of LAR with sequence-selective peptides significantly overcomes neurite growth restrictions of CSPGs in neuronal cultures. Intracellularly, CSPG–LAR interaction mediates axonal growth inhibition of neurons partially via inactivating Akt and activating RhoA signals. Systemic treatments with LAR-targeting peptides in mice with thoracic spinal cord transection injuries induce significant axon growth of descending serotonergic fibers in the vicinity of the lesion and beyond in the caudal spinal cord and promote locomotor functional recovery. Identification of LAR as a novel CSPG functional receptor provides a therapeutic basis for enhancing axonal regeneration and functional recovery after CNS injuries in adult mammals.
Grasp Movement Decoding from Premotor and Parietal Cortex
Authors: Townsend Benjamin R. , Subasi Erk , Scherberger Hansjörg
Published: October 2011

Despite recent advances in harnessing cortical motor-related activity to control computer cursors and robotic devices, the ability to decode and execute different grasping patterns remains a major obstacle. Here we demonstrate a simple Bayesian decoder for real-time classification of grip type and wrist orientation in macaque monkeys that uses higher-order planning signals from anterior intraparietal cortex (AIP) and ventral premotor cortex (area F5). Real-time decoding was based on multiunit signals, which had similar tuning properties to cells in previous single-unit recording studies. Maximum decoding accuracy for two grasp types (power and precision grip) and five wrist orientations was 63% (chance level, 10%). Analysis of decoder performance showed that grip type decoding was highly accurate (90.6%), with most errors occurring during orientation classification. In a subsequent off-line analysis, we found small but significant performance improvements (mean, 6.25 percentage points) when using an optimized spike-sorting method (superparamagnetic clustering). Furthermore, we observed significant differences in the contributions of F5 and AIP for grasp decoding, with F5 being better suited for classification of the grip type and AIP contributing more toward decoding of object orientation. However, optimum decoding performance was maximal when using neural activity simultaneously from both areas. Overall, these results highlight quantitative differences in the functional representation of grasp movements in AIP and F5 and represent a first step toward using these signals for developing functional neural interfaces for hand grasping.
Cortical Projections of Functionally Identified Thalamic Trigeminovascular Neurons: Implications for Migraine Headache and Its Associated Symptoms
Authors: Noseda Rodrigo , Jakubowski Moshe , Kainz Vanessa , Borsook David , Burstein Rami
Published: October 2011

This study identifies massive axonal arbors of trigeminovascular (dura-sensitive) thalamic neurons in multiple cortical areas and proposes a novel framework for conceptualizing migraine headache and its associated symptoms. Individual dura-sensitive neurons identified and characterized electrophysiologically in first-order and higher-order relay thalamic nuclei were juxtacellularly filled with an anterograde tracer that labeled their cell bodies and processes. First-order neurons located in the ventral posteromedial nucleus projected mainly to trigeminal areas of primary (S1) as well as secondary (S2) somatosensory and insular cortices. Higher-order neurons located in the posterior (Po), lateral posterior (LP), and lateral dorsal (LD) nuclei projected to trigeminal and extra-trigeminal areas of S1 and S2, as well as parietal association, retrosplenial, auditory, ectorhinal, motor, and visual cortices. Axonal arbors spread at various densities across most layers of the different cortical areas. Such parallel network of thalamocortical projections may play different roles in the transmission of nociceptive signals from the meninges to the cortex. The findings that individual dura-sensitive Po, LP, and LD neurons project to many functionally distinct and anatomically remote cortical areas extend current thinking on projection patterns of high-order thalamic neurons and position them to relay nociceptive information directly rather than indirectly from one cortical area to another. Such extensive input to diverse cortical areas that are involved in regulation of affect, motor function, visual and auditory perception, spatial orientation, memory retrieval, and olfaction may explain some of the common disturbances in neurological functions during migraine.
Alpha Oscillations Related to Anticipatory Attention Follow Temporal Expectations
Authors: Rohenkohl Gustavo , Nobre Anna C.
Published: October 2011

Temporal expectations have been shown to enhance visual analysis of task-relevant events, especially when these are coupled with spatial expectations. Oscillatory brain activity, particularly in the alpha band, has been implicated in regulating excitability in visual areas as a function of anticipatory spatial attention. Here we asked whether temporal expectations derived from regular, rhythmic events can modulate ongoing oscillatory alpha-band activity, so that the changes in cortical excitability are focused over the time intervals at which target events are expected. The task we used involved making a perceptual discrimination about a small target stimulus that reappeared from “behind” a peripheral occluding band. Temporal expectations were manipulated by the regular, rhythmic versus irregular, arrhythmic approach of the stimulus toward the occluding band. Alpha-band activity was measured during the occlusion period, in which no stimulus was presented, but target reappearance was anticipated in conditions of high versus low temporal expectation. Time–frequency analysis showed that the amplitude of alpha-desynchronization followed the time course of temporal expectations. Alpha desynchronization increased rhythmically, peaking just before the expected reappearance of target times. Analysis of the event-related potentials evoked by the subsequent target stimuli showed enhancement of processing at both visual and motor stages. Our findings support a role for oscillations in regulating cortical excitability and suggest a plausible mechanism for biasing perception and action by temporal expectations.
Chronic Stress Exacerbates Tau Pathology, Neurodegeneration, and Cognitive Performance through a Corticotropin-Releasing Factor Receptor-Dependent Mechanism in a Transgenic Mouse Model of Tauopathy
Authors: Carroll Jenna C. , Iba Michiyo , Bangasser Debra A. , Valentino Rita J. , James Michael J. , Brunden Kurt R. , Lee Virginia M.-Y. , Trojanowski John Q.
Published: October 2011

Because overactivation of the hypothalamic–pituitary–adrenal (HPA) axis occurs in Alzheimer's disease (AD), dysregulation of stress neuromediators may play a mechanistic role in the pathophysiology of AD. However, the effects of stress on tau phosphorylation are poorly understood, and the relationship between corticosterone and corticotropin-releasing factor (CRF) on both β-amyloid (Aβ) and tau pathology remain unclear. Therefore, we first established a model of chronic stress, which exacerbates Aβ accumulation in Tg2576 mice and then extended this stress paradigm to a tau transgenic mouse model with the P301S mutation (PS19) that displays tau hyperphosphorylation, insoluble tau inclusions and neurodegeneration. We show for the first time that both Tg2576 and PS19 mice demonstrate a heightened HPA stress profile in the unstressed state. In Tg2576 mice, 1 month of restraint/isolation (RI) stress increased Aβ levels, suppressed microglial activation, and worsened spatial and fear memory compared with nonstressed mice. In PS19 mice, RI stress promoted tau hyperphosphorylation, insoluble tau aggregation, neurodegeneration, and fear–memory impairments. These effects were not mimicked by chronic corticosterone administration but were prevented by pre-stress administration of a CRF receptor type 1 (CRF1) antagonist. The role for a CRF1-dependent mechanism was further supported by the finding that mice overexpressing CRF had increased hyperphosphorylated tau compared with wild-type littermates. Together, these results implicate HPA dysregulation in AD neuropathogenesis and suggest that prolonged stress may increase Aβ and tau hyperphosphorylation. These studies also implicate CRF in AD pathophysiology and suggest that pharmacological manipulation of this neuropeptide may be a potential therapeutic strategy for AD.
Combustion Chemistry of the Butane Isomers in Premixed Low-Pressure Flames
Authors: Oßwald Patrick , Kohse-Höinghaus Katharina , Struckmeier Ulf , Zeuch Thomas , Seidel Lars , Leon Larisa , Mauss Fabian
Published: October 2011

The combustion chemistry of the two butane isomers represents a subset in a comprehensive description of C1–C4 hydrocarbon and oxygenated fuels. A critical examination of combustion models and their capability to predict emissions from this class of fuels must rely on high-quality experimental data that address the respective chemical decomposition and oxidation pathways, including quantitative intermediate species mole fractions. Premixed flat low-pressure (40 mbar) flames of the two butane isomers were thus studied under identical, fuel-rich (φ=1.71) conditions. Two independent molecular-beam mass spectrometer (MBMS) set-ups were used to provide quantitative species profiles. Both data sets, one from electron ionization (EI)-MBMS with high mass resolution and one from photoionization (PI)-MBMS with high energy resolution, are in overall good agreement. Simulations with a flame model were used to analyze the respective reaction pathways, and differences in the combustion behavior of the two isomers are discussed.
Friend of GATA suppresses the GATA-induced transcription of hepcidin in hepatocytes through a GATA-regulatory element in the HAMP promoter
Authors: Bagu Edward T , Santos Manuela M
Published: October 2011

Hepcidin is an antimicrobial peptide hormone involved in the metabolism of iron, encoded for by theHAMPgene mainly in hepatocytes. It's expressed at lower levels in other cells such as the macrophages. The mechanisms that determine tissue-specific expression of hepcidin remain unclear. GATA- and its co-factor Friend of GATA (FOG) modulate the tissue-specific transcription of other genes involved in the metabolism of iron. GATA proteins are group of evolutionary conserved transcriptional regulators that bind to the consensus motif –WGATAR– in the promoter. We characterized a 1.3 kb fragment of the 5′-flanking sequence of theHAMPgene in Huh7 cells, which expressHAMP. Transfection of 5′-deletions of theHAMPpromoter in Huh7 cells revealed two regions, −932/−878 and −155/−96, that when deleted decreased promoter activity. Using site-directed mutations in theHAMPpromoter region −155/−96 we identified two subregions, −138/−125 and −103/−98, which when mutated suppressed promoter activity by 70 and 90% respectively. Site −103/−98 with a sequence –TTATCT– to which endogenous GATA proteins 4 and 6 bind and transactivateHAMPis a GATA-regulatory element (RE). Mutation of the GATA-RE abrogated binding of GATA proteins 4 and 6 to the promoter and blunted the GATA transactivation ofHAMP. FOG proteins 1 and 2 suppressed the endogenous and exogenous GATA activation of theHAMPpromoter. We concluded that the GATA-RE, –TTATCT– in theHAMPpromoter region −103/−98 is crucial for the GATA-4 and GATA-6 driven transcription of hepcidin in Huh7 cells and that FOG proteins moderate the transcription by suppressing the GATA transactivation ofHAMP.