bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathophysiology of prospective memory failure after diffuse axonal injury - Lesion-symptom analysis using diffusion tensor imaging
Authors: Kondo Keita , Maruishi Masaharu , Ueno Hiroki , Sawada Kozue , Hashimoto Yukari , Ohshita Tomohiko , Takahashi Tetsuya , Ohtsuki Toshiho , Matsumoto Masayasu
Published: November 2010

Background

Prospective memory (PM) is one of the most important cognitive domains in everyday life. The neuronal basis of PM has been examined by a large number of neuroimaging and neuropsychological studies, and it has been suggested that several cerebral domains contribute to PM. For these activation studies, a constellation of experimental PM trials was developed and adopted to healthy subjects. In the present study, we used a widely used clinical PM assessment battery to determine the lesions attributable to PM failure, with the hypothesis that lesion-symptom analysis using diffusion tensor imaging (DTI) in subjects with diffuse axonal injury (DAI) can reveal the neuronal basis of PM in everyday life.

Results

Fourteen DAI patients (age: range of 18-36, median 24) participated in this study. PM failure was scored in the range of 0-6 using three sub-tests of the Rivermead Behavioural Memory Test. The PM scores of DAI patients were in the range of 2-6 (median 4.5, inter-quartile range 2.25). The severity of axonal injury following DAI was examined using fractional anisotropy (FA), one of the DTI parameters, at voxel level in each subject. We then obtained clusters correlated with PM failure by conducting voxel-based regression analysis between FA values and PM scores. Three clusters exhibited significant positive correlation with PM score, the left parahippocampal gyrus, left inferior parietal lobe, and left anterior cingulate.

Conclusions

This is the first lesion-symptom study to reveal the neuronal basis of PM using DTI on subjects with DAI. Our findings suggest that the neuronal basis of PM is in the left parahippocampal gyrus, left inferior parietal lobe, and/or left anterior cingulate. These findings are similar to those of previous activation studies with loading experimental PM tasks.
The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers
Authors: Hong Seung-Jin , Oh Jung-Hwan , Jeon Eun-Jung , Min Ki-Ouk , Kang Moo-Il , Choi Sang-Wook , Rhyu Mun-Gan
Published: November 2010

Background

The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with Helicobacter pylori (H. pylori) and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH) events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements.

Methods

The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the H. pylori-negative gastric mucosa.

Results

The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the H. pylori-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the H. pylori-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner.

Conclusions

The overmethylated genes under the influence of retroelement methylation in the H. pylori-infected stomach are demethylated in the gastric cancers influenced by LOH.
The gene-reduction effect of chromosomal losses detected in gastric cancers
Authors: Hong Seung-Jin , Jeon Eun-Jung , Oh Jung-Hwan , Seo Eun-Joo , Choi Sang-Wook , Rhyu Mun-Gan
Published: November 2010

Background

The level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.

Methods

The pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).

Results

Most of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).

Conclusions

The cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.
Mechanical ventilation modulates Toll-like receptor-3-induced lung inflammation via a MyD88-dependent, TLR4-independent pathway: a controlled animal study
Authors: Chun Carrie D , Liles W Conrad , Frevert Charles W , Glenny Robb W , Altemeier William A
Published: November 2010

Background

Mechanical ventilation augments lung inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that ventilator-associated immune modulation requires MyD88-dependent signaling. Because MyD88 is a critical adapter protein utilized for pro-inflammatory signaling by all Toll-like receptors (TLRs), with the exception of TLR3, as well as by the IL-1 and IL-18 receptors, MyD88 dependence would implicate generation of an endogenous soluble ligand recognized by one or more of these receptors during mechanical ventilation and would provide an opportunity for a potential future therapeutic intervention.

Methods

We compared the effect of mechanical ventilation on lung inflammation and permeability between poly(I:C) exposed mice with or without expression of MyD88. Poly(I:C) is a synthetic ligand for TLR3, the only MyD88-independent TLR, allowing isolation of the effect of MyD88 deletion on ventilator-augmentation of lung inflammation. Lung inflammation was assessed by cytokine concentration in lung tissue homogenate and polymorphonuclear cell (PMN) number in bronchoalveolar lavage fluid (BALF). Lung permeability was assessed by total protein, IgM, and intravenously injected FITC-dextran concentrations in BALF.

Results

We found that MyD88 was required for mechanical ventilation augmentation of TLR3-induced lung inflammation and permeability. Because TLR4 is the most commonly reported receptor for endogenous ligands generated during tissue injury, we performed a second experiment comparing wildtype and TLR4-/- mice. We found that mechanical ventilation increased TLR3-mediated inflammation and permeability independent of TLR4.

Conclusion

These data support the hypothesis that mechanical ventilation with moderate tidal volumes generates an endogenous ligand(s) recognized by MyD88-dependent receptor(s) other than TLR4, and that this mechanism can contribute to the development of ventilator-associated lung inflammation and injury. Identification of these ligands and/or receptors could lead to new pharmacological treatments for ARDS.
Modulation of inhibitory activity of xylanase - α-amylase inhibitor protein (XAIP): binding studies and crystal structure determination of XAIP- II from Scadoxus multiflorus at 1.2 Å resolution
Authors: Kumar Sanjit , Singh Nagendra , Mishra Biswajit , Dube Divya , Sinha Mau , Singh S Baskar , Dey Sharmistha , Kaur Punit , Sharma Sujata , Singh Tej P
Published: November 2010

Background

Plants produce a wide range of proteinaceous inhibitors to protect themselves against hydrolytic enzymes. Recently a novel protein XAIP belonging to a new sub-family (GH18C) was reported to inhibit two structurally unrelated enzymes xylanase GH11 and α-amylase GH13. It was shown to inhibit xylanase GH11 with greater potency than that of α-amylase GH13. A new form of XAIP (XAIP-II) that inhibits α-amylase GH13 with a greater potency than that of XAIP and xylanase GH11 with a lower potency than that of XAIP, has been identified in the extracts of underground bulbs of Scadoxus multiflorus. This kind of occurrence of isoforms of inhibitor proteins is a rare observation and offers new opportunities for understanding the principles of protein engineering by nature.

Results

In order to determine the structural basis of the enhanced potency of XAIP-II against α-amylase GH13 and its reduced potency against xylanase GH11 as compared to that of XAIP, we have purified XAIP-II to homogeneity and obtained its complete amino acid sequence using cloning procedure. It has been crystallized with 0.1 M ammonium sulphate as the precipitating agent and the three-dimensional structure has been determined at 1.2 Å resolution. The binding studies of XAIP-II with xylanase GH11 and α-amylase GH13 have been carried out with surface plasmon resonance (SPR).

Conclusion

The structure determination revealed that XAIP-II adopts the well known TIM barrel fold. The xylanase GH11 binding site in XAIP-II is formed mainly with loop α3-β3 (residues, 102 - 118) which has acquired a stereochemically less favorable conformation for binding to xylanase GH11 because of the addition of an extra residue, Ala105 and due to replacements of two important residues, His106 and Asn109 by Thr107 and Ser110. On the other hand, the α-amylase binding site, which consists of α-helices α6 (residues, 193 - 206), α7 (residues, 230 - 243) and loop β6-α6 (residues, 180 - 192) adopts a stereochemically more favorable conformation due to replacements of residues, Ser190, Gly191 and Glu194 by Ala191, Ser192 and Ser195 respectively in α-helix α6, Glu231 and His236 by Thr232 and Ser237 respectively in α-helix α7. As a result, XAIP-II binds to xylanase GH11 less favorably while it interacts more strongly with α-amylase GH13 as compared to XAIP. These observations correlate well with the values of 4.2 × 10-6 M and 3.4 × 10-8 M for the dissociation constants of XAIP-II with xylanase GH11 and α-amylase GH13 respectively and those of 4.5 × 10-7 M and 3.6 × 10-6 M of XAIP with xylanase GH11 and α-amylase GH13 respectively.
PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients
Authors: Shen Tao , Zheng Jiajia , Xu Chunhui , Liu Jia , Zhang Weidong , Lu Fengmin , Zhuang Hui
Published: November 2010

Background

Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression.

Methods

PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied.

Results

Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was negatively correlated with HCV viral load.

Conclusion

PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.
Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10
Authors: Rodríguez-García Marta , Porichis Filippos , de Jong Olivier G , Levi Karen , Diefenbach Thomas J , Lifson Jeffrey D , Freeman Gordon J , Walker Bruce D , Kaufmann Daniel E , Kavanagh Daniel G
Published: November 2010

PD-1 plays an important role in T cell exhaustion during HIV infection. PD-1 has two ligands: PD-L1, expressed on hematopoietic and nonhematopoietic cells, and PD-L2, limited to DCs and macrophages. Little is known about PD-L1 expression and regulation in human macrophages. Previous reports have found few immediate effects of macrophage exposure to HIV, suggesting that macrophages lack PRRs for this virus. Using quantitative confocal microscopy and a multiplexed cytokine bead array, we measured induction of PD-L1, PD-L2, and innate response cytokines in human MDMs in response to chemically inactivated HIV virions. Consistent with previous reports, no cytokines were induced by HIV virion exposure. Whereas PD-L1 and PD-L2 had low baseline expression, TLR ligands (LPS and CL097) up-regulated PD-L1 but not PD-L2. Unlike what we found for cytokine expression, PD-L1 and PD-L2 were up-regulated in response to exposure with inactivated HIV virions or with replication-competent HIV. Expression of PD-L1 was differentially modulated by IL-10, which induced up-regulation of PD-L1 but not of PD-L2, and IL-10 blockade enhanced only PD-L2 expression. We discuss implications for innate recognition of HIV by macrophages and potential, different roles for PD-L1 and PD-L2 in immunity and pathogenesis.
Ligand-induced conformational capture of a synthetic tetracycline riboswitch revealed by pulse EPR
Authors: Wunnicke Dorith , Strohbach Denise , Weigand Julia E. , Appel Bettina , Feresin Emiliano , Suess Beatrix , Müller Sabine , Steinhoff Heinz-Jürgen
Published: November 2010

RNA aptamers are in vitro–selected binding domains that recognize their respective ligand with high affinity and specificity. They are characterized by complex three-dimensional conformations providing preformed binding pockets that undergo conformational changes upon ligand binding. Small molecule-binding aptamers have been exploited as synthetic riboswitches for conditional gene expression in various organisms. In the present study, double electron-electron resonance (DEER) spectroscopy combined with site-directed spin labeling was used to elucidate the conformational transition of a tetracycline aptamer upon ligand binding. Different sites were selected for post-synthetic introduction of either the (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl) methanethiosulfonate by reaction with a 4-thiouridine modified RNA or of 4-isocyanato-2,6-tetramethylpiperidyl-N-oxid spin label by reaction with 2′-aminouridine modified RNA. The results of the DEER experiments indicate the presence of a thermodynamic equilibrium between two aptamer conformations in the free state and capture of one conformation upon tetracycline binding.
Tandem affinity purification combined with inducible shRNA expression as a tool to study the maturation of macromolecular assemblies
Authors: Wyler Emanuel , Zimmermann Mirjam , Widmann Barbara , Gstaiger Matthias , Pfannstiel Jens , Kutay Ulrike , Zemp Ivo
Published: November 2010

Tandem affinity purification (TAP) is an efficient method for the purification and characterization of large macromolecular complexes. To elucidate the role of specific components of such complexes, it is important to address the question of how loss of a specific factor affects complex composition. Here, we introduce a method that combines TAP of large macromolecular assemblies with inducible shRNA-mediated protein depletion in human somatic cells. As a proof of principle, we have applied this method to the purification of human pre-ribosomal particles. Using inducible expression of ribosome assembly factors as bait proteins, different pre-40S particles could be isolated and characterized, revealing high conservation of the ribosome biogenesis pathway from yeast to human cells. Besides known ribosome maturation factors, C21orf70 was identified as a novel pre-40S component. By combining TAP of pre-40S particles with shRNA-mediated depletion of the pre-40S-associated protein kinase Rio2, we observed that increased levels of the nuclear HEAT-repeat protein Rrp12 are associated with 40S precursors in absence of Rio2. Further analyses revealed that Rrp12 is partially mislocalized to the cytoplasm and trapped on late 40S precursors upon loss of Rio2, and therefore fails to efficiently recycle to the nucleus. Thus, the combination of tandem affinity purification and shRNA induction provided further insights into late cytoplasmic 40S maturation steps, demonstrating the high potential of this method.
Psychological Heuristics for Making Inferences: Definition, Performance, and the Emerging Theory and Practice
Authors: Katsikopoulos Konstantinos V.
Published: November 2010

Laypeople as well as professionals such as business managers and medical doctors often use psychological heuristics. Psychological heuristics are models for making inferences that (1) rely heavily on core human capacities (such as recognition, recall, or imitation); (2) do not necessarily use all available information and process the information they use by simple computations (such as lexicographic rules or aspiration levels); and (3) are easy to understand, apply, and explain. Psychological heuristics are a simple alternative to optimization models (where the optimum of a mathematical function that incorporates all available information is computed). I review studies in business, medicine, and psychology where computer simulations and mathematical analyses reveal conditions under which heuristics make better inferences than optimization and vice versa. The conditions involve concepts that refer to (i) the structure of the problem, (ii) the resources of the decision maker, or (iii) the properties of the models. I discuss open problems in the theoretical study of the concepts. Finally, I organize the current results tentatively in a tree for helping decision analysts decide whether to suggest heuristics or optimization to decision makers. I conclude by arguing for a multimethod, multidisciplinary approach to the theory and practice of inference and decision making.
Opportunity Spaces in Innovation: Empirical Analysis of Large Samples of Ideas
Authors: Kornish Laura J. , Ulrich Karl T.
Published: November 2010

A common approach to innovation, parallel search, is to identify a large number of opportunities and then to select a subset for further development, with just a few coming to fruition. One potential weakness with parallel search is that it permits repetition. The same, or a similar, idea might be generated multiple times, because parallel exploration processes typically operate without information about the ideas that have already been identified. In this paper we analyze repetition in five data sets comprising 1,368 opportunities and use that analysis to address three questions: (1) When a large number of efforts to generate ideas are conducted in parallel, how likely are the resulting ideas to be redundant? (2) How large are the opportunity spaces? (3) Are the unique ideas more valuable than those similar to many others? The answer to the first question is that although there is clearly some redundancy in the ideas generated by aggregating parallel efforts, this redundancy is quite small in absolute terms in our data, even for a narrowly defined domain. For the second question, we propose a method to extrapolate how many unique ideas would result from an unbounded effort by an unlimited number of comparable idea generators. Applying that method, and for the settings we study, the estimated total number of unique ideas is about one thousand for the most narrowly defined domain and greater than two thousand for the more broadly defined domains. On the third question, we find a positive relationship between the number of similar ideas and idea value: the ideas that are least similar to others are not generally the most valuable ones.

This paper was accepted by Lee Fleming, entrepreneurship and innovation.
Recruiting for Ideas: How Firms Exploit the Prior Inventions of New Hires
Authors: Singh Jasjit , Agrawal Ajay
Published: November 2010

When firms recruit inventors, they acquire not only the use of their skills but also enhanced access to their stock of ideas. But do hiring firms actually increase their use of new recruits' prior inventions? Our estimates suggest they do, quite significantly in fact, by approximately 219% on average. However, this does not necessarily reflect widespread “learning by hiring.” In fact, we estimate that a recruit's exploitation of her own prior ideas accounts for almost half of the above effect, with much of the diffusion to others being limited to the recruit's immediate collaborative network. Furthermore, although one might expect the recruit's role to diminish rapidly as her tacit knowledge diffuses across her new firm, our estimates indicate that her importance is surprisingly persistent over time. We base these findings on an empirical strategy that exploits the variation over time in hiring firms' citations to the recruits' premove patents. Specifically, we employ a difference-in-differences approach to compare premove versus postmove citation rates for the recruits' prior patents and corresponding matched-pair control patents. Our methodology has three benefits compared to previous studies that also examine the link between labor mobility and knowledge flow: (1) it does not suffer from the upward bias inherent in the conventional cross-sectional comparison, (2) it generates results that are robust to a more stringently matched control sample, and (3) it enables a temporal examination of knowledge flow patterns.

This paper was accepted by Kamalini Ramdas, entrepreneurship and innovation.
An Investigation of Earnings Management Through Marketing Actions
Authors: Chapman Craig J. , Steenburgh Thomas J.
Published: November 2010

Prior research hypothesizes managers use “real actions,” including the reduction of discretionary expenditures, to manage earnings to meet or beat key benchmarks. This paper examines this hypothesis by testing how different types of marketing expenditures are used to boost earnings for a durable commodity consumer product that can be easily stockpiled by end consumers. Combining supermarket scanner data with firm-level financial data, we find evidence that differs from prior literature. Instead of reducing expenditures to boost earnings, soup manufacturers roughly double the frequency and change the mix of marketing promotions (price discounts, feature advertisements, and aisle displays) at the fiscal quarter-end when they have greater incentive to boost earnings. Our results confirm managers' stated willingness to sacrifice long-term value in order to smooth earnings and their stated preference to use real actions to boost earnings to meet different types of earnings benchmarks. We estimate that marketing actions can be used to boost quarterly net income by up to 5% depending on the depth and duration of promotion. However, there is a price to pay, with the cost in the following period being approximately 7.5% of quarterly net income. Finally, a unique aspect of the research setting allows tests of who is responsible for the earnings management. Although firms appear unable to increase the frequency of aisle display promotions in the short run, they can reallocate these promotions within their portfolio of brands. Results show firms shifting display promotions away from smaller revenue brands toward larger ones following periods of poor financial performance. This indicates the behavior is determined by parties above brand managers in the firm. These findings are consistent with firms engaging in real earnings management and suggest that effects on subsequent reporting periods and competitor behavior are greater than previously documented.

This paper was accepted by Stefan Reichelstein, accounting.
Competing to Be Certain (But Wrong): Market Dynamics and Excessive Confidence in Judgment
Authors: Radzevick Joseph R. , Moore Don A.
Published: November 2010

In this paper, we investigate how market competition contributes to the expression of overconfidence among those competing for influence. We find evidence that market competition exacerbates the tendency to express excessive confidence. This evidence comes from experiments in which advisors attempt to sell their advice. In the first, advisors must compete with other advice sellers. In the second, advisors and their customers are paired. Advisors are overconfident in both studies and it helps advisors sell their advice. However, competition between advisors in the market further exacerbates overconfidence. In a third study, we demonstrate that the market competition drives overconfidence even when advisors vary in quality. We also investigate the strategic expressions and interpretations of confidence by both sides in the exchange.

This paper was accepted by Peter Wakker, decision analysis.
Modeling Network Transition Constraints with Hypergraphs
Authors: Harrod Steven
Published: November 2010

Discrete time dynamic graphs are frequently used to model multicommodity flows or activity paths through constrained resources, but simple graphs fail to capture the interaction effects of resource transitions. The resulting schedules are not operationally feasible, and return inflated objective values. A directed hypergraph formulation is derived to address railway network sequencing constraints, and an experimental problem sample solved to estimate the magnitude of objective inflation when interaction effects are ignored. The model is used to demonstrate the value of advance scheduling of train paths on a busy North American railway.
Optimal Allocation of Protective Resources in Shortest-Path Networks
Authors: Cappanera Paola , Scaparra Maria Paola
Published: November 2010

This article introduces a game-theoretic approach for allocating protection resources among the components of a network so as to maximize its robustness to external disruptions. Specifically, we consider shortest-path networks where disruptions may result in traffic flow delays through the affected components or even in the complete loss of some elements. A multilevel program is proposed to identify the set of components to harden so as to minimize the length of the shortest path between a supply node and a demand node after a worst-case disruption of some unprotected components. An implicit enumeration algorithm is then developed to solve the multilevel problem to optimality. The approach is streamlined by solving the lower-level interdiction problem heuristically at each node of an enumeration tree and by using some variable fixing rules to reduce the dimension of the lower-level problems. A thorough computational investigation demonstrates that the proposed solution method is able to identify optimal protection strategies for networks of significant size. The paper is concluded with a study of the sensitivity of the solution approach to variations of the problem parameters such as the level of disruption and protective resources and the distribution of the arc lengths and delays.
“A Note on the Entropy Solutions of the Hydrodynamic Model of Traffic Flow” Revisited
Authors: Herbin Raphaèle , Leclercq Ludovic
Published: November 2010

This note revisits a paper from Velan and Florian (Velan, S., M. Florian. 2002. A note on the entropy solutions of the hydrodynamic model of traffic flow. Transportation Sci. 36(4) 435–446) dealing with the entropy condition in traffic flow models. It aims to clarify the application of this condition for nondifferentiable fundamental diagrams and then to correct some misunderstandings that appear in the above-mentioned paper. This note clearly exhibits that the nonsmoothness of the fundamental diagram does not change the properties of the Lighthill-Whitham-Richards (LWR) solutions: (i) existence of a unique entropy solution and (ii) nonuniqueness of weak solutions. These precisions are important because piecewise linear fundamental diagrams appear to accurately fit with experimental observations and cannot be disproved on an alleged mathematical basis.
Biofunctionalization of gold nanorods
Authors: Hwang Sung-Yeon , Tao Andrea R.
Published: November 2010

Gold nanorods (NRs) are promising nanomaterials for biotechnology innovations that include photoassisted drug delivery, gene therapy, noninvasive cancer detection, and ultrasensitive biodetection. Owing to their unique geometry, Au NRs exhibit surface plasmon (SP) modes in the near-infrared (IR) wavelength range—ideal for carrying out optical measurements in biological fluids and tissue. Because NR interactions highly depend on the chemical nature of their solvent-accessible interface, it is necessary to carry out specific postsynthetic chemical modifications of the Au surface to create NRs that are biocompatible and biofunctional. In this review, we discuss various NR surface chemistries that have successfully enabled the integration of Au NRs into biological environments, as well as current challenges in designing the biofunctional NR interface for in vivo applications.
Tricellulin Is Expressed in Autotypic Tight Junctions of Peripheral Myelinating Schwann Cells
Authors: Kikuchi Shin , Ninomiya Takafumi , Tatsumi Haruyuki , Sawada Norimasa , Kojima Takashi
Published: November 2010

Autotypic tight junctions are formed by tight junction-like structures in three regions of myelinating Schwann cells, the paranodal loops, Schmidt–Lanterman incisures, and outer/inner mesaxons, and various tight junction molecules, including claudin-19 and junctional adhesion molecule (JAM)-C. Our findings demonstrate the identification and subcellular distribution of a novel tricellular tight junction protein, tricellulin (TRIC), in the autotypic tight junctions of mouse myelinating Schwann cells, compared with the autotypic adherens junction protein E-cadherin and the autotypic tight junction protein JAM-C, which are expressed in the paranodal loops, Schmidt–Lanterman incisures, and mesaxons. In realtime RT-PCR, the expression level of TRIC mRNA was about 10-fold higher in the sciatic nerve than in the spinal cord or cerebrum. In immunostaining, TRIC signals were completely restricted to the peripheral nervous system (PNS) and strongly concentrated at the paranodal loops, Schmidt–Lanterman incisures, and mesaxons of myelinating Schwann cells. In addition, TRIC was expressed in the thin region of the paranode and there was a gap between TRIC and the Na+ channel. Furthermore, TRIC was more distally located from the node than E-cadherin and was colocalized with JAM-C. It is possible that TRIC may be a component to maintain the integrity for PNS myelin function and morphology. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials. (J Histochem Cytochem 58:1067–1073, 2010)
Commutability Limitations Influence Quality Control Results with Different Reagent Lots
Authors: Miller WGreg , Erek Aybala , Cunningham Tina D , Oladipo Olajumoke , Scott Mitchell G , Johnson Robert E
Published: November 2010

BACKGROUND

Good laboratory practice includes verifying that each new lot of reagents is suitable for use before it is put into service. Noncommutability of quality control (QC) samples with clinical patient samples may preclude their use to verify consistency of results for patient samples between different reagent lots.

METHODS

Patient sample results and QC data were obtained from reagent lot change verification records for 18 QC materials, 661 reagent lot changes, 1483 reagent lot change–QC events, 82 analytes, and 7 instrument platforms. The significance of between-lot differences in the results for QC samples compared with those for patient samples was assessed by a modified 2-sample t test adjusted for heterogeneity of QC and patient sample measurement variances.

RESULTS

Overall, 40.9% of reagent lot change–QC events had a significant difference (P < 0.05) between results for QC samples compared with results for patient samples between 2 reagent lots. For QC results with differences <1.0 SD interval (83.1% of total), 37.7% were significantly different from the changes observed for patient samples. For QC results with differences ≥1.0 SD interval (16.9% of total), 57.0% were significantly different from those for patient samples.

CONCLUSIONS

Occurrence of noncommutable results for QC materials was frequent enough that the QC results could not be used to verify consistency of results for patient samples when changing lots of reagents.
Inverse Log-Linear Relationship between Thyroid-Stimulating Hormone and Free Thyroxine Measured by Direct Analog Immunoassay and Tandem Mass Spectrometry
Authors: van Deventer Hendrick E , Mendu Damodara R , Remaley Alan T , Soldin Steven J
Published: November 2010

BACKGROUND

Accurate measurement of free thyroxine (FT4) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT4 by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT4 and thyroid-stimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT4 assays.

METHODS

The study included 109 participants for whom FT4 measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT4 and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT4 was also measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) (MS-FT4).

RESULTS

The inverse log-linear correlation coefficient between TSH and FT4 was significantly better (P < 0.0001) for MS-FT4 (0.84, 95% CI, 0.77–0.88) than for IA-FT4 (0.45, 95% CI, 0.29–0.59). IA-FT4 showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29–0.5, P < 0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05–0.41, P = 0.02). In contrast, FT4 measurement by LC-MS/MS did not show a significant correlation with albumin or TBG.

CONCLUSIONS

The inverse log-linear relationship between FT4 and TSH was significantly better for FT4 measured by LC-MS/MS than by IA. The MS-FT4 method therefore provides FT4 results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT4 with albumin and TBG suggests that this FT4 method depends on binding protein concentrations and consequently does not accurately reflect FT4.
Mathematical Modeling and Computer Simulation of Fatigue Properties of Quenched and Tempered Steel
Authors: Smoljan Božo , Iljkić Dario , Traven Furio , Mrša Josipa
Published: November 2010

The engineering and economical aspects of the optimization of steel shaft quenching and tempering were investigated. The mathematical model and method of computer simulation for the prediction of fatigue properties of quenched and tempered steel were developed. Computer simulation of the fatigue properties of quenched and tempered steel was applied in the optimization of quenching and tempering of steel shafts. The proper heat treatment process was accepted based on economical analysis. Fatigue properties of quenched and tempered steel were predicted based on microstructure composition and yield strength. Microstructure composition and yield strength were predicted based on as-quenched hardness. The distribution of as-quenched hardness in the workpiece was predicted through computer simulation of steel quenching using a finite volume method. The as-quenched hardness was estimated based on time of cooling and on Jominy test results. It was taken into account that the mechanical properties of quenched steel directly depend on the hardness, degree of hardening, and microstructural constituents. Using a numerical simulation of microstructure and mechanical properties, it was found out that the investigated shaft has the best fatigue properties in cases when the shaft was machined or formed on proper geometry before proper quenching and tempering. Through economical analysis of the investigated shaft manufacturing, it was found out that the most suitable shaft manufacture process is to manufacture the shaft from the quenched and tempered bar. But in this case, heterogeneous microstructures of ferrite, perlite, bainite, and martensite with very low fatigue limits could appear at some critical locations.
Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes
Authors: Eising Stefanie , Nilsson Anita , Carstensen Bendix , Hougaard David M , Nørgaard-Pedersen Bent , Nerup Jørn , Lernmark Åke , Pociot Flemming
Published: November 2010

Objective

A large, population-based case–control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes.

Design and methods

The design was an individually matched case–control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981–2002 birth cohorts and stored at −25 °C were identified from 2023 patients and from two matched controls (n=4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence.

Results

GAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P<0.0001). The HR decreased to 4.55 but remained significant (P<0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P<0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P<0.001) after controlling for parental diabetes and HLA-DQB1 alleles.

Conclusion

These data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004.
VEGFR1 expression is related to lymph node metastasis and serum VEGF may be a marker of progression in the follow-up of patients with differentiated thyroid carcinoma
Authors: Karaca Z , Tanriverdi F , Unluhizarci K , Ozturk F , Gokahmetoglu S , Elbuken G , Cakir I , Bayram F , Kelestimur F
Published: November 2010

Objective

Vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR1) are known to be related to thyroid tumorigenesis. The aim of the study was to examine the expressions and serum levels of VEGF, VEGFR1, IGF1, and IGF1 receptor (IGF1R) in patients with differentiated thyroid carcinoma (DTC) compared with patients with nodular goiter (NG).

Methods

We examined 39 patients with DTC who had a clinical history of at least 2 years and compared them with 25 patients who had a pathological diagnosis of NG after thyroidectomy. Serum VEGF, VEGFR1, and IGF1 levels were measured in both patient groups. The expressions of VEGF, VEGFR1, IGF1, and IGF1R were analyzed by the immunohistochemical method in the paraffin blocks of patients' thyroidectomy samples of the patients.

Results

The immunostainings scores for VEGF, VEGFR1, IGF1, and IGF1R were found to be higher in patients with DTC than in those with NG. Only VEGFR1 expression was related to lymph node metastasis at the time of surgery. None of the expressions were related to the long-term prognosis of the patients. Serum VEGF was found to be higher in patients with progressive DTC than in patients in clinical remission.

Conclusion

The expressions of VEGF and VEGFR1 were shown to be correlated with the expression of IGF1 and IGF1R. VEGFR1 expression may be an important index for the presence of lymph node metastasis at the time of thyroidectomy. Increased serum levels of VEGF may reflect disease recurrence in DTC.
Quasi-static and dynamic deformation behaviors of in situ Zr-based bulk-metallic-glass-matrix composites
Authors: Qiao J.W. , Feng P. , Zhang Y. , Zhang Q.M. , Liaw P.K. , Chen G.L.
Published: November 2010

Quasi-static and dynamic deformation behaviors of Zr-based bulk-metallic-glass-matrix composites, fabricated by Bridgman solidification, were investigated in this study. Upon quasi-static compressive loading, the composites exhibit ultrahigh strength, accompanied by considerable plasticity. The multiplication of shear bands on the lateral surface of deformed samples, and the highly-dense liquid drops on the fracture surface, are in agreement with the improved plasticity. However, upon dynamic loading, the mechanical properties of the composites deteriorate considerably, due to insufficient time to form profuse shear bands. The strain-rate responses of the mechanical properties of the crystalline alloys and the in situ and ex situ bulk metallic glass composites are compared, and the different deformation mechanisms of the in situ composites upon quasi-static and dynamic loading are explained.
Structural stability and Raman scattering of InN nanowires under high pressure
Authors: Yao L.D. , Luo S.D. , Shen X. , You S.J. , Yang L.X. , Zhang S.J. , Jiang S. , Li Y.C. , Liu J. , Zhu K. , Liu Y.L. , Zhou W.Y. , Chen L.C. , Jin C.Q. , Yu R.C. , Xie S.S.
Published: November 2010

High-pressure in situ angular dispersive x-ray diffraction study on the wurtzite-type InN nanowires has been carried out by means of the image-plate technique and diamond-anvil cell (DAC) up to about 31.8 GPa. The pressure-induced structural transition from the wurtzite to a rocksalt-type phase occurs at about 14.6 GPa, which is slightly higher than the transition pressure of InN bulk materials (∼12.1 GPa). The relative volume reduction at the transition point is close to 17.88%, and the bulk modulus B0 is determined through fitting the relative volume-pressure experimental data related to the wurtzite and rocksalt phases to the Birch–Murnaghan equation of states. Moreover, high-pressure Raman scattering for InN nanowires were also investigated in DAC at room temperature. The corresponding structural transition was confirmed by assignment of phonon modes. We calculated the mode Grüneisen parameters for the wurtzite and rocksalt phases of InN nanowires.
Fiber metallic glass laminates
Authors: Sun B.A. , Cheung K.P. , Fan J.T. , Lu J. , Wang W.H.
Published: November 2010

The fabrication and properties of fiber metallic glass laminates (FMGL) composite composed of Al-based metallic glasses ribbons and fiber/epoxy layers were reported. The metallic glass composite possesses structural features of low density and high specific strength compared to Al-based metallic glass and crystalline Al alloys. The material shows pronounced tensile ductility compared to monolithic bulk metallic glasses.
Irradiation-induced defect clustering and amorphization in silicon carbide
Authors: Weber William J. , Gao Fei
Published: November 2010

Previous computer simulations of multiple 10 keV Si cascades in 3C–SiC demonstrated that many damage-state properties exhibit relatively smooth, but noticeably different, dose dependencies. A more recent analysis of these damage-state properties, which includes additional data at low and intermediate doses, reveals more complex relationships between system energy, swelling, energy per defect, relative disorder, elastic modulus, and elastic constant, C11. These relationships provide evidence for the onset of both defect clustering and solid-state amorphization, which appear to be driven by local energy and elastic instabilities from the accumulation of defects. The results provide guidance on experimental approaches to reveal the onset of these processes.
First-principles study of the structural and elastic properties of Ti5Si3 with substitutions Zr, V, Nb, and Cr
Authors: Wang Hui-Yuan , Si Wen-Ping , Li Shi-Long , Zhang Nan , Jiang Qi-Chuan
Published: November 2010

The formation enthalpy, electronic structures, and elastic moduli of the intermetallic compound Ti5Si3 with substitutions Zr, V, Nb, and Cr are investigated by using first-principles methods based on the density-functional theory. Our calculation shows that the site occupancy behaviors of alloying elements in Ti5Si3, determined by their atom radius, are consistent with the available experimental observations. Furthermore, using the Voigt–Reuss–Hill (VRH) approximation method, we obtained the bulk modulus B, shear modulus G, and the Young’s modulus E. Among these four substitutions, the V, Nb, and Cr substitutions can improve the ductility of Ti5Si3 effectively, while Zr substitution has little effect on the elastic properties of Ti5Si3. The elastic property variations of Ti5Si3 due to different substitutions are found to be correlated with the Me4d–Me4d antibonding and the strengthened Me4d–Si bonding in the solids.
Error estimation of nanoindentation mechanical properties near a dissimilar interface via finite element analysis and analytical solution methods
Authors: Zhao Y. , Ovaert T.C.
Published: November 2010

Nanoindentation methods are well suited for probing the mechanical properties of a heterogeneous surface, since the probe size and contact volumes are small and localized. However, the nanoindentation method may introduce errors in the computed mechanical properties when indenting near the interface between two materials having significantly different mechanical properties. Here we examine the case where a soft material is loaded in close proximity to an interface of higher modulus, such as the case when indenting bone near a metallic implant. The results are derived from both an approximate analytical quarter space solution and a finite element model, and used to estimate the error in indentation-determined elastic modulus as a function of the distance from the apex of contact to the dissimilar interface, for both Berkovich and spherical indenter geometries. Sample data reveal the potential errors in mechanical property determination that can occur when indenting near an interface having higher stiffness, or when characterizing strongly heterogeneous materials. The results suggest that caution should be used when interpreting results in the near-interfacial region.