bluuebunny/crossref_metadata_2025 huggingface dataset:
Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor
Authors: Waters Emily K. , Genga Ryan M. , Schwartz Michael C. , Nelson Jennifer A. , Schaub Robert G. , Olson Karen A. , Kurz Jeffrey C. , McGinness Kathleen E.
Published: March 2011

Hemophilia A and B are caused by deficiencies in coagulation factor VIII (FVIII) and factor IX, respectively, resulting in deficient blood coagulation via the intrinsic pathway. The extrinsic coagulation pathway, mediated by factor VIIa and tissue factor (TF), remains intact but is negatively regulated by tissue factor pathway inhibitor (TFPI), which inhibits both factor VIIa and its product, factor Xa. This inhibition limits clot initiation via the extrinsic pathway, whereas factor deficiency in hemophilia limits clot propagation via the intrinsic pathway. ARC19499 is an aptamer that inhibits TFPI, thereby enabling clot initiation and propagation via the extrinsic pathway. The core aptamer binds tightly and specifically to TFPI. ARC19499 blocks TFPI inhibition of both factor Xa and the TF/factor VIIa complex. ARC19499 corrects thrombin generation in hemophilia A and B plasma and restores clotting in FVIII-neutralized whole blood. In the present study, using a monkey model of hemophilia, FVIII neutralization resulted in prolonged clotting times as measured by thromboelastography and prolonged saphenous-vein bleeding times, which are consistent with FVIII deficiency. ARC19499 restored thromboelastography clotting times to baseline levels and corrected bleeding times. These results demonstrate that ARC19499 inhibition of TFPI may be an effective alternative to current treatments of bleeding associated with hemophilia.
IMiD immunomodulatory compounds block C/EBPβ translation through eIF4E down-regulation resulting in inhibition of MM
Authors: Li Shirong , Pal Rekha , Monaghan Sara A. , Schafer Peter , Ouyang Hongjiao , Mapara Markus , Galson Deborah L. , Lentzsch Suzanne
Published: March 2011

Immunomodulatory derivatives of thalidomide (IMiD compounds), such as pomalidomide and lenalidomide, are highly active in multiple myeloma (MM) treatment. However, the precise mechanisms of action and resistance in MM are unresolved. Here we show that IMiD compounds down-regulate CCAAT/enhancer-binding protein-β (C/EBPβ) resulting in abrogation of cell proliferation. Overexpression of C/EBPβ rescued MM cells from IMiD-induced inhibition of proliferation, indicating that C/EBPβ is critical in mediating antiproliferative effects. IMiD-induced decrease of C/EBPβ protein led to impaired transcription of interferon regulatory factor 4 (IRF4). Down-regulation of IRF4 by lenalidomide was confirmed by longitudinal studies of bone marrow samples from 23 patients obtained before and during lenalidomide treatment using CD138+/IRF4+ double labeling. In contrast to down-regulation of C/EBPβ protein, IMiD compounds did not alter C/EBPβ mRNA levels or protein stability, suggesting translational regulation of C/EBPβ. We could demonstrate that C/EBPβ protein expression is under eIF4E-translational control in MM. Furthermore, inhibition of the eIF4E-C/EBPβ axis by IMiD compounds was not observed in IMiD-resistant MM cells. However, targeting translation at a different level by inhibiting eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation overcame resistance, suggesting that this pathway is critical and might be a target to overcome drug resistance.
Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy
Authors: Wang Hongjie , Madhusudhan Thati , He Tao , Hummel Björn , Schmidt Simone , Vinnikov Ilya A. , Shahzad Khurrum , Kashif Muhammed , Muller-Krebs Sandra , Schwenger Vedat , Bierhaus Angelika , Rudofsky Gottfried , Nawroth Peter P. , Isermann Berend
Published: March 2011

Whereas it is generally perceived to be harmful, enhanced coagulation activation can also convey salutary effects. The high prevalence of the prothrombotic factor V Leiden (FVL) mutation in whites has been attributed to a positive selection pressure (eg, resulting from reduced blood loss or improved survival in sepsis). The consequences of enhanced coagulation activation, as observed in FVL carriers, on microvascular diabetic complications remain unknown. We therefore investigated the role of FVL in diabetic nephropathy. In heterozygous or homozygous diabetic FVL mice, albuminuria and indices of diabetic nephropathy were reduced compared with diabetic wild-type mice. This was associated with reduced glomerular apoptosis and preservation of podocytes in diabetic FVL-positive mice. In vitro, low-dose thrombin (50pM) prevented, whereas high-dose thrombin (20nM) aggravated, glucose-induced apoptosis in podocytes. In diabetic patients, the FVL mutation, but not the plasminogen activator inhibitor-1 4G/5G polymorphism, is associated with reduced albuminuria, which is consistent with a nephroprotective role of low but sustained thrombin generation. Consistently, anticoagulation of diabetic FVL-positive mice with hirudin abolished the nephroprotective effect. These results identify a nephroprotective function of low but sustained thrombin levels in FVL carriers, supporting a dual, context-dependent function of thrombin in chronic diseases.
HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients
Authors: Zerr Danielle M. , Fann Jesse R. , Breiger David , Boeckh Michael , Adler Amanda L. , Xie Hu , Delaney Colleen , Huang Meei-Li , Corey Lawrence , Leisenring Wendy M.
Published: March 2011

Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.
Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis
Authors: Fos José , Pabst Thomas , Petkovic Vibor , Ratschiller Daniel , Mueller Beatrice U.
Published: March 2011

CCAAT/enhancer binding protein-α (CEBPA) mutations in acute myeloid leukemia (AML) patients with a normal karyotype (NK) confer favorable prognosis, whereas NK-AML patients per se are of intermediate risk. This suggests that blocked CEBPA function characterizes NK-AML with favorable outcome. We determined the prognostic significance of CEBPA DNA binding function by enzyme-linked immunosorbent assay in 105 NK-AML patients. Suppressed CEBPA DNA binding was defined by 21 good-risk AML patients with inv(16) or t(8;21) (both abnormalities targeting CEBPA) and 8 NK-AML patients with dominant-negative CEBPA mutations. NK-AML patients with suppressed CEBPA function showed a better overall survival (P = .0231) and disease-free survival (P = .0069) than patients with conserved CEBPA function. Suppressed CEBPA DNA binding was an independent marker for better overall survival and disease-free survival in a multivariable analysis that included FLT3-ITD, NPM1 and CEBPA mutation status, white blood cell count, age and lactate dehydrogenase. These data indicate that suppressed CEBPA function is associated with favorable prognosis in NK-AML patients.
Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia
Authors: Barsam Sarah J. , Psaila Bethan , Forestier Marc , Page Lemke K. , Sloane Peter A. , Geyer Julia T. , Villarica Glynis O. , Ruisi Mary M. , Gernsheimer Terry B. , Beer Juerg H. , Bussel James B.
Published: March 2011

This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 109/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P = .001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r2 = −0.578, P = .015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect.
Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia
Authors: Montes Rosa , Ayllón Verónica , Gutierrez-Aranda Ivan , Prat Isidro , Hernández-Lamas M. Carmen , Ponce Laura , Bresolin Silvia , te Kronnie Geertruy , Greaves Mel , Bueno Clara , Menendez Pablo
Published: March 2011

Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency. Our limited understanding of transformation by MLL-AF4 is reflected in murine models, which do not accurately recapitulate the human disease. Human models for MLL-AF4 disease do not exist. Hematopoietic stem or progenitor cells (HSPCs) represent probable targets for transformation. Here, we explored in vitro and in vivo the impact of the enforced expression of MLL-AF4 in human cord blood-derived CD34+ HSPCs. Intrabone marrow transplantation into NOD/SCID-IL2Rγ−/− mice revealed an enhanced multilineage hematopoietic engraftment, efficiency, and homing to other hematopoietic sites on enforced expression of MLL-AF4. Lentiviral transduction of MLL-AF4 into CD34+ HSPCs increased the in vitro clonogenic potential of CD34+ progenitors and promoted their proliferation. Consequently, cell cycle and apoptosis analyses suggest that MLL-AF4 conveys a selective proliferation coupled to a survival advantage, which correlates with changes in the expression of genes involved in apoptosis, sensing DNA damage and DNA repair. However, MLL-AF4 expression was insufficient to initiate leukemogenesis on its own, indicating that either additional hits (or reciprocal AF4-MLL product) may be required to initiate ALL or that cord blood-derived CD34+ HSPCs are not the appropriate cellular target for MLL-AF4-mediated ALL.
The impact of inflammatory licensing on heme oxygenase-1–mediated induction of regulatory T cells by human mesenchymal stem cells
Authors: Mougiakakos Dimitrios , Jitschin Regina , Johansson C. Christian , Okita Riki , Kiessling Rolf , Le Blanc Katarina
Published: March 2011

Mesenchymal stem cells (MSCs) are characterized by their manifold immunomodulatory and regenerative properties. The stress-responsive, cytoprotective, and immunoregulatory molecule heme oxygenase-1 (HO-1) was recently identified as a key contributor for MSC-mediated suppression of alloactivated T cells. As HO-1 has also been implicated in the induction of regulatory T cells (Tregs), we sought to examine its impact on MSC-driven promotion of Tregs. Human MSCs were shown to induce, in a HO-1–dependent fashion, IL-10+ Tr1 and transforming growth factor-β+ Th3 Treg-subsets in allo- and T-cell receptor-activated lymphocytes. Because inflammatory stimuli modulate (“license”) human MSCs, we were interested in whether an in vitro alloreactive micro-milieu within mixed lymphocyte reactions (MLRs) alters the HO-1 expression. We observed a substantial down-regulation of HO-1 facilitated by yet unidentified soluble factor(s) produced in an MLR, and most probably occurring at the level of its major transcription-factor NF-E2–related factor 2. Interestingly, HO-1 lost its impact regarding suppressiveness, Treg induction, and promotion of IL-10 production for MSCs, which were prelicensed in an MLR environment. Taken together, we show that HO-1 produced by human MSCs beyond its direct suppressive function promotes formation of Tr1 and Th3 Tregs and IL-10 production, functions, which are taken over by other molecules, among them COX-2, after an alloreactive priming.
Clonal immunoglobulin DNA in the plasma of patients with AIDS lymphoma
Authors: Wagner-Johnston Nina D. , Gellert Lan , Gocke Christopher D. , Lemas Victor M. , Lee Jeannette , Martínez-Maza Otoniel , Ambinder Richard F.
Published: March 2011

Immunoglobulin (Ig) gene rearrangements are used to define clonality of suspected B-lineage malignancy in tissue samples. To determine whether such rearrangements could be identified in plasma, we screened plasma from 14 consecutive patients with AIDS-related lymphoma with multiplex Ig primers. Clonally rearranged Ig DNA was detected in plasma from 7 of 14 patients. Patients in whom clonal Ig DNA remained detectable after combination chemotherapy died with lymphoma. Tumor was available from 1 patient, and the IgH amplification products from plasma and tumor were sequenced and confirmed to be identical. Ig DNA rearrangements in plasma may be useful as a lymphoma-specific tumor marker, and failure to clear clonal Ig DNA may identify patients at high risk for failure of standard therapy.
Observation of strong anisotropic forbidden transitions in (001) InGaAs/GaAs single-quantum well by reflectance-difference spectroscopy and its behavior under uniaxial strain
Authors: Yu Jin-Ling , Chen Yong-Hai , Tang Chen-Guang , Jiang ChongYun , Ye Xiao-Ling
Published: March 2011

The strong anisotropic forbidden transition has been observed in a series of InGaAs/GaAs single-quantum well with well width ranging between 3 nm and 7 nm at 80 K. Numerical calculations within the envelope function framework have been performed to analyze the origin of the optical anisotropic forbidden transition. It is found that the optical anisotropy of this transition can be mainly attributed to indium segregation effect. The effect of uniaxial strain on in-plane optical anisotropy (IPOA) is also investigated. The IPOA of the forbidden transition changes little with strain, while that of the allowed transition shows a linear dependence on strain.

PACS 78.66.Fd, 78.20.Bh, 78.20.Fm
An aeroponic culture system for the study of root herbivory on Arabidopsis thaliana
Authors: Vaughan Martha M , Tholl Dorothea , Tokuhisa James G
Published: March 2011

Background

Plant defense against herbivory has been studied primarily in aerial tissues. However, complex defense mechanisms have evolved in all parts of the plant to combat herbivore attack and these mechanisms are likely to differ in the aerial and subterranean environment. Research investigating defense responses belowground has been hindered by experimental difficulties associated with the accessibility and quality of root tissue and the lack of bioassays using model plants with altered defense profiles.

Results

We have developed an aeroponic culture system based on a calcined clay substrate that allows insect herbivores to feed on plant roots while providing easy recovery of the root tissue. The culture method was validated by a root-herbivore system developed for Arabidopsis thaliana and the herbivore Bradysia spp. (fungus gnat). Arabidopsis root mass obtained from aeroponically grown plants was comparable to that from other culture systems, and the plants were morphologically normal. Bradysia larvae caused considerable root damage resulting in reduced root biomass and water absorption. After feeding on the aeroponically grown root tissue, the larvae pupated and emerged as adults. Root damage of mature plants cultivated in aeroponic substrate was compared to that of Arabidopsis seedlings grown in potting mix. Seedlings were notably more susceptible to Bradysia feeding than mature plants and showed decreased overall growth and survival rates.

Conclusions

A root-herbivore system consisting of Arabidopsis thaliana and larvae of the opportunistic herbivore Bradysia spp. has been established that mimics herbivory in the rhizosphere. Bradysia infestation of Arabidopsis grown in this culture system significantly affects plant performance. The culture method will allow simple profiling and in vivo functional analysis of root defenses such as chemical defense metabolites that are released in response to belowground insect attack.
3D angle gathers from reverse time migration
Authors: Xu Sheng , Zhang Yu , Tang Bing
Published: March 2011

Common-image gathers are an important output of prestack depth migration. They provide information needed for velocity model building and amplitude and phase information for subsurface attribute interpretation. Conventionally, common-image gathers are computed using Kirchhoff migration on common-offset/azimuth data volumes. When geologic structures are complex and strong contrasts exist in the velocity model, the complicated wave behaviors will create migration artifacts in the image gathers. As long as the gather output traces are indexed by any surface attribute, such as source location, receiver location, or surface plane-wave direction, they suffer from the migration artifacts caused by multiple raypaths. These problems have been addressed in a significant amount of work, resulting in common-image gathers computed in the reflection angle domain, whose traces are indexed by the subsurface reflection angle and/or the subsurface azimuth angle. Most of these efforts have concentrated on Kirchhoff and one-way wave-equation migration methods. For reverse time migration, subsurface angle gathers can be produced using the same approach as that used for one-way wave-equation migration. However, these approaches need to be revisited when producing high-quality subsurface angle gathers in three dimensions (reflection angle/azimuth angle), especially for wide-azimuth data. We have developed a method for obtaining 3D subsurface reflection angle/azimuth angle common-image gathers specifically for the amplitude-preserved reverse time migration. The method builds image gathers with a high-dimensional convolution of wavefields in the wavenumber domain. We have found a windowed antileakage Fourier transform method that leads to an efficient and practical implementation. This approach has generated high-resolution angle-domain gathers on synthetic 2.5D data and 3D wide-azimuth real data.
Shot-gather time migration of planar reflectors without velocity model
Authors: Bóna Andrej
Published: March 2011

Standard migration techniques require a velocity model. A new and fast prestack time migration method is presented that does not require a velocity model as an input. The only input is a shot gather, unlike other velocity-independent migrations that also require input of data in other gathers. The output of the presented migration is a time-migrated image and the migration velocity model. The method uses the first and second derivatives of the traveltimes with respect to the location of the receiver. These attributes are estimated by computing the gradient of the amplitude in a shot gather. The assumptions of the approach are a laterally slowly changing velocity and reflectors with small curvatures; the dip of the reflector can be arbitrary. The migration velocity corresponds to the root mean square (rms) velocity for laterally homogeneous media for near offsets. The migration expressions for 2D and 3D cases are derived from a simple geometrical construction considering the image of the source. The strengths and weaknesses of the methods are demonstrated on synthetic data. At last, the applicability of the method is discussed by interpreting the migration velocity in terms of the Taylor expansion of the traveltime around the zero offset.
Evaluation of variable gas saturation on acoustic log data from the Haynesville Shale gas play, NW Louisiana, USA
Authors: Lucier Amie M. , Hofmann Ronny , Bryndzia L. Taras
Published: March 2011

Many technical challenges must be overcome to ensure the economic development of a shale gas resource including: (1) making an accurate assessment of gas distribution and saturation, (2) identifying target zones that optimize the impact of hydraulic fracture stimulation and completion, and (3) drilling safe and cost-effective wells. In order to meet these challenges, it is necessary to characterize the physical and mechanical properties of the shales. Sonic logs provide important data about the rock and fluid properties that can be used for this characterization. One motivation for this work was to determine how sonic logs in gas-bearing shales can be used to characterize rock properties, derive mechanical properties, and estimate in-situ stresses.
Interaction between alk1 and blood flow in the development of arteriovenous malformations
Authors: Corti Paola , Young Sarah , Chen Chia-Yuan , Patrick Michael J. , Rochon Elizabeth R. , Pekkan Kerem , Roman Beth L.
Published: March 2011

Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.
MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action
Authors: Wen Jiayu , Parker Brian J. , Jacobsen Anders , Krogh Anders
Published: March 2011

Microarray expression analyses following miRNA transfection/inhibition and, more recently, Argonaute cross-linked immunoprecipitation (CLIP)-seq assays have been used to detect miRNA target sites. CLIP and expression approaches measure differing stages of miRNA functioning—initial binding of the miRNP complex and subsequent message repression. We use nonparametric predictive models to characterize a large number of known target and flanking features, utilizing miRNA transfection, HITS-CLIP, and PAR-CLIP data. In particular, we utilize the precise spatial information provided by CLIP-seq to analyze the predictive effect of target flanking features. We observe distinct target determinants between expression-based and CLIP-based data. Target flanking features such as flanking region conservation are an important AGO-binding determinant—we hypothesize that CLIP experiments have a preference for strongly bound miRNP–target interactions involving adjacent RNA-binding proteins that increase the strength of cross-linking. In contrast, seed-related features are major determinants in expression-based studies, but less so for CLIP-seq studies, and increased miRNA concentrations typical of transfection studies contribute to this difference. While there is a good overlap between miRNA targets detected by miRNA transfection and CLIP-seq, the detection of CLIP-seq targets is largely independent of the level of subsequent mRNA degradation. Also, models built using CLIP-seq data show strong predictive power between independent CLIP-seq data sets, but are not strongly predictive for expression change. Similarly, models built from expression data are not strongly predictive for CLIP-seq data sets, supporting the finding that the determinants of miRNA binding and mRNA degradation differ. Predictive models and results are available at http://servers.binf.ku.dk/antar/.
Mechanism of escape from nonsense-mediated mRNA decay of human β-globin transcripts with nonsense mutations in the first exon
Authors: Neu-Yilik Gabriele , Amthor Beate , Gehring Niels H. , Bahri Sharif , Paidassi Helena , Hentze Matthias W. , Kulozik Andreas E.
Published: March 2011

The degradation of nonsense-mutated β-globin mRNA by nonsense-mediated mRNA decay (NMD) limits the synthesis of C-terminally truncated dominant negative β-globin chains and thus protects the majority of heterozygotes from symptomatic β-thalassemia. β-globin mRNAs with nonsense mutations in the first exon are known to bypass NMD, although current mechanistic models predict that such mutations should activate NMD. A systematic analysis of this enigma reveals that (1) β-globin exon 1 is bisected by a sharp border that separates NMD-activating from NMD-bypassing nonsense mutations and (2) the ability to bypass NMD depends on the ability to reinitiate translation at a downstream start codon. The data presented here thus reconcile the current mechanistic understanding of NMD with the observed failure of a class of nonsense mutations to activate this important mRNA quality-control pathway. Furthermore, our data uncover a reason why the position of a nonsense mutation alone does not suffice to predict the fate of the affected mRNA and its effect on protein expression.
On duality and endomorphisms of lattices of closed convex sets
Authors: Slomka Boaz A.
Published: March 2011

The class of closed convex sets in is a lattice with respect to the operations of intersections and closed convex hulls of unions. We completely classify the endomorphisms of this lattice and its sublattice consisting of sets containing the origin 0. We show that they consist of constant maps and maps induced by the affine group. As a consequence, we obtain a characterization of the duality mapping for the class of closed convex sets containing 0. Moreover, by modifying a proof of Böröczky and Schneider we obtain the same result for the sublattice consisting of compact bodies containing 0.
On the complexity group of stable curves
Authors: Busonero Simone , Melo Margarida , Stoppino Lidia
Published: March 2011

In this paper, we study combinatorial properties of stable curves. To the dual graph of any nodal curve, there is naturally associated a group, which is the group of components of the Néron model of the generalized Jacobian of the curve. We study the order of this group, called the complexity. In particular, we provide a partial characterization of the stable curves having maximal complexity, and we provide an upper bound, depending only on the genus g of the curve, on the maximal complexity of stable curves; this bound is asymptotically sharp for g ≫ 0. Eventually, we state some conjectures on the behavior of stable curves with maximal complexity, and prove partial results in this direction.
Isoperimetric inequalities for wave fronts and a generalization of Menzin's conjecture for bicycle monodromy on surfaces of constant curvature
Authors: Howe Sean , Pancia Matthew , Zakharevich Valentin
Published: March 2011

The classical isoperimetric inequality relates the lengths of curves to the areas that they bound. More specifically, we have that for a smooth, simple closed curve of length L bounding area A on a surface of constant curvature c,

L
2 ≥ 4πA – cA
2

with equality holding only if the curve is a geodesic circle. We prove generalizations of the isoperimetric inequality for both spherical and hyperbolic wave fronts (i.e. piecewise smooth curves which may have cusps). We then discuss “bicycle curves” using the generalized isoperimetric inequalities. The euclidean model of a bicycle is a unit segment AB that can move so that it remains tangent to the trajectory of point A (the rear wheel is fixed on the bicycle frame), as discussed in [Finn, The College Mathematics Journal, 33, 2002], [Tabachnikov, Israel J. Math. 151: 1–28, 2006], and [Levi, Tabachnikov, Experiment. Math. 18: 173–186, 2009]. We extend this definition to a general Riemannian manifold, and concern ourselves in particular with bicycle curves in the hyperbolic plane H
2 and on the sphere S
2. We prove results along the lines of those in [Levi, Tabachnikov, Experiment. Math. 18: 173–186, 2009] and resolve both spherical and hyperbolic versions of Menzin's conjecture, which relates the area bounded by a curve to its associated monodromy map.
The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease
Authors: Leoni Valerio
Published: March 2011

The presence of theɛ4allele in apolipoprotein E (ApoE) represents the most important genetic risk factor for late onset sporadic Alzheimer's disease (AD), together with age and mid-life hypercholesterolemia. ApoE4 is the most important lipid transporter between cells in the CNS and it was found that ApoE4 is involved in Amyloid β (Aβ) formation, fibrilisation, accumulation, in the aggregation and hyperphosphorylation of tau and in the metabolism of brain cholesterol and in neurodegeneration. Low cerebrospinal fluid (CSF) Aβ1-42 is a marker of Aβ plaque load in the brain. High CSF t-tau and p-tau concentrations reflect axonal and neuronal damage and injury, which correlates with a neurofibrillary tangle stage and load, also reflecting the intensity of the disease process. Magnetic resonance imaging (MRI) brain atrophy is a biomarker of neurodegeneration and is the result of loss of neurons, synapses and dendritic arborization. ApoE genotype interacts with the AD biomarkers:ɛ4carriers were found to present with lower concentrations of Aβ1-42, higher tau and p-tau, higher tau/Aβ ratio and a higher degree of brain atrophy at any disease stage, changing the test performances and the ability to distinguish between the different cognitive condition. The presence of theɛ4allele was also found to increase the power to predict further cognitive decline. Even if the presence of ApoE4 is not a deterministic factor for AD, it seems to shift the progression of the disease towards a younger age and faster progression. It is also likely that theɛ4allele increases the intensity of the pathological process in several ways. In the study of cognitive impaired patients and in their follow-up, biomarkers should be interpreted in consideration of the ApoE genotype in order to better predict the progression of the disease.
False positive troponin result caused by a true macrotroponin
Authors: Michielsen Etienne C.H.J. , Bisschops Pieter G.T. , Janssen Marcel J.W.
Published: March 2011

Background: A 35-year-old female presented with complaints of tiredness, shortness of breath and recent onset of chest pain. The cardiac troponin I (cTnI) concentration was elevated at 6.4 μg/L (Abbott Architect reference value: <0.03 μg/L) with a normal ECG. Physical examination, radiological imaging and routine laboratory investigations did not provide an explanation for the elevated cTnI concentration.

Methods: Use of different troponin assays, dilutions with assay diluent, addition of mouse serum, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) were used to investigate possible interference.

Results: Troponin concentrations were below the level of detection when measured using all other troponin immunoassays. Serial dilutions of sample and addition of mouse serum did not alter the results. However, PEG precipitation and GFC showed the presence of a high molecular weight immunoreactive protein. Using GFC and protein-A IgG precipitation, the interference could be identified as a macrocomplex containing IgG and (fragments of) cTnI.

Conclusions: We report a false positive cTnI result caused by a true macrotroponin, containing IgG and (fragments of) cTnI. This macrotroponin was only immunoreactive in the Abbott Architect cTnI immunoassay. Clinicians should be aware of analytical interference when troponin results are constantly elevated in the absence of (non)coronary causes of an increased troponin.
From Pathways to Genomes and Beyond: The Metabolic Engineering Toolbox and Its Place in Biofuels Production
Authors: Liu Leqian , Reed Ben , Alper Hal
Published: March 2011

Concerns about the availability of petroleum-derived fuels and chemicals have led to the exploration of metabolically engineered organisms as novel hosts for biofuels and chemicals production. However, the complexity inherent in metabolic and regulatory networks makes this undertaking a complex task. To address these limitations, metabolic engineering has adapted a wide-variety of tools for altering phenotypes. In this review, we will highlight traditional and recent metabolic engineering tools for optimizing cells including pathway-based, global, and genomics enabled approaches. Specifically, we describe these tools as well as provide demonstrations of their effectiveness in optimizing biofuels production. However, each of these tools provides stepping stones towards the grand goal of biofuels production. Thus, developing methods for largescale cellular optimization and integrative approaches are invaluable for further cell optimization. This review highlights the challenges that still must be met to accomplish this goal.
Nanostructured Inorganic Solar Cells
Authors: Musselman Kevin P. , Schmidt-Mende Lukas
Published: March 2011

Recent progress in the development of nanostructured inorganic solar cells is reviewed. Nanostructuring of inorganic solar cells offers the possibility of reducing the cost of photovoltaics by allowing smaller amounts of lower-grade photovoltaic semiconductors to be used. Various fabrication methods used to nanostructure traditional photovoltaic semiconductors are detailed and the performance of resulting devices is discussed. The synthesis of solar cells by solution-based methods using less traditional, abundant materials is identified as a promising route to widescale photovoltaic electricity generation, and nanostructured solar cell geometries are highlighted as essential in this approach. Templating and self-assembling methods used to produce appropriate low-cost nanostructures from solutions are detailed, and the performance of preliminary ultra-low-cost cells made with these structures is reviewed.
Efficient Anode and Cathode Materials for Amorphous Silicon Solar Cell Driven all Solar Electrolysis of Water
Authors: Khan Shahed U. M. , Frites Mourad , Ingler William B.
Published: March 2011

Few non-noble metal based anode and cathode materials were investigated for all solar electrolysis of water to hydrogen and oxygen gases powered by double junction amorphous silicon (Dj-a-Si) solar cell under solar simulated light of 1 sun. The highest hydrogen generation current efficiency of 58.68% was obtained when Pt wire was used as a cathode with the non-noble metal based Ni-Co
Silencing of CDK5 as potential therapy for Alzheimer’s disease
Authors: López-Tobón Alejandro , Castro-Álvarez John Fredy , Piedrahita Diego , Boudreau Ryan L. , Gallego-Gómez Juan Carlos , Cardona-Gómez Gloria Patricia
Published: March 2011

Neurodegeneration is one of the greatest public health challenges for the 21st century. Among neurodegenerative diseases, Alzheimer’s disease (AD) is the most prevalent and best characterized. Nevertheless, despite the large investment in AD research, currently there is no effective therapeutic option. In the present review, we highlight a novel alternative, which takes advantage of the biotechnological outbreak deployed by the discovery of the RNA interference-based gene silencing mechanism, and its application as a tool for neurodegeneration treatment. Here, we highlight cyclin-dependent kinase 5 (CDK5) as a key candidate target for therapeutic gene silencing. Unlike other members of the cyclin-dependent kinase family, CDK5 does not seem to play a crucial role in cell cycle regulation. By contrast, CDK5 participates in multiple functions during nervous system development and has been established as a key mediator of Tau hyperphosphorylation and neurofibrillary pathology, thus serving as an optimal candidate for targeted therapy in the adult nervous system. We propose that the use of RNA interference for CDK5 silencing presents an attractive and specific therapeutic alternative for AD and perhaps against other tauopathies.
Imaging spatial learning in the brain using immediate early genes: insights, opportunities and limitations
Authors: Barry Daniel N. , Commins Sean
Published: March 2011

Immediate early gene (IEG) imaging offers a sophisticated approach to study the neural basis of learning in the brain. Demonstrating a high degree of spatial resolution, the activation of entire neuronal ensembles at multiple time-points can be observed. IEG imaging techniques have revealed a high level of responsiveness to spatial exploration within the hippocampus and other brain regions. The pattern of IEG activation is tightly linked with specific environments and appears to be involved in the subsequent consolidation of spatial information. This incidental learning is a potential confounding factor in studies investigating the neural correlates of spatial learning in both the radial arm maze and water maze. Although both these tasks increase hippocampal IEG expression from baseline levels, where control groups have fully explored the apparatus in the absence of task demands, or where animals are performing a non-spatial task, IEG expression in this region is comparable to spatially trained groups. However, the relationship between IEG expression and task performance, as well as the pattern of brain activation has been shown to differentiate between experimental and control groups. Inconsistencies between training protocols appear to contribute to the discrepancies between reported findings, and the role of IEG expression in the retention of spatial memory tasks remains unclear. Further investigation of the time course and dynamics of IEG expression during learning and retention is required to fully interpret observed results.
Correlation Between Chemical Composition of Steel, Optimal Hardened Layer, and Optimal Residual Stress Distribution
Authors: Kobasko Nikolai I.
Published: March 2011

A method for optimizing the chemical composition of steels to obtain optimal residual stress distribution throughout the section of a steel part is proposed, which is based on the analytical equation for the calculation of ideal critical diameter (DI). The advantage of this method consists of the opportunity to calculate the ideal critical size for a variety of geometries on the basis of their respective continuos-cooling transformation (CCT) diagrams. Detailed discussions are provided relating to the optimal depth of the hardened layer, which provides high surface compressive residual stresses and minimal tensile stresses in the core. It is also shown that the ratio of the DI to the diameter of the part with an optimal residual stress distribution should be the same, that is, DI/Dopt=const with steel parts of varying sizes. This relationship can be used for the development of new technologies for large-sized parts based on the results obtained for small parts. The service life of steel parts increases after intensive quenching due to the formation of high surface compressive residual stresses and improved mechanical properties. During intensive quenching, the effect of additional strengthening (super strengthening) of the material is observed, which is connected with the intensification of cooling process within the martensite range.
Emulsification Performance Used for NPE Replacement in Solvent-Based Formulations
Authors: Lowe Elizabeth H. , Milbradt Robert
Published: March 2011

The increase in the world’s population has led to an increased demand for agricultural products, which in turn calls for more intensive farming and higher crop yields. To minimize the impact on the environment, society demands more environmentally-friendly products to be used. Regulatory authorities have answered the public’s call for “greener” chemistries by applying pressure to not only replace the more harmful active ingredients, but also the formulation inerts. The Crop Protection Industry has used nonylphenol ethoxylates (NPEs) as inert ingredients in pesticides and spray adjuvants for decades. The implementation of European Directive 2003-53 EC, which bans the use of NPEs, has caused many American markets to look for alternatives for nonylphenol-based surfactants as well. Substitute chemistries typically are chosen based on hydrophile-lipophile balance (HLB) values and cloud points. This study uses an alternative method of selection by evaluating the emulsifier performance in commonly used solvents in emulsifiable concentrates (ECs), emulsion oil-in-water (EW), and oil dispersion (OD) formulations. A modified cylinder test is used for the evaluation of a wide range of surfactants. The emulsifier, solvent, and hard water are placed in a glass cylinder, inverted multiple times, and allowed to stand undisturbed for 24 h. The emulsification performance is then calculated based on the phase height of each emulsion, which is then compared to the performance of the systems, which includes NPEs. The solvents used in the study are not only the common naptha-based solvents as seen in many ECs, but also in the more environmentally-friendly formulation types such as EWs and ODs, which use mineral oils, seed oils, and seed oil methyl esters. This method offers an easy way to reformulate NPE-containing formulations with regard to sustainability and an emulsifier selection guide for environmentally-friendly formulations in general.
A Fluorescent Tracer Method for Evaluating Spray Transport and Fate of Field and Laboratory Spray Applications
Authors: Fritz Bradley K. , Hoffmann W. Clint , Jank Phil
Published: March 2011

Field and laboratory testing spray nozzles and application systems use spray collectors to assess where the spray deposits once it leaves the spray system. Tracer materials, such as oil and water soluble fluorescent dyes, can be mixed into spray solutions in small amounts with minimal impact on the solution physical properties and atomization characteristics of the nozzle or spray system. Depending on the dye and recovery methods used, detection levels may range from g/ha down to the parts per trillion making them practical for use in studies where these ranges may occur, such as drift studies that measure in-swath and downwind deposition. Exposed samples can be quickly processed, typically using non-toxic solvents such as purified water or ethyl alcohol. This quick, inexpensive processing allows users the flexibility to plan studies requiring large numbers of samples. Spray formulations using these dyes at specific rates are used as the basis for establishing a set of standard concentrations which are used to relate fluorescence to dye concentration. Laboratory evaluations of tracer deposition compare the fluorescence of processed samples with the fluorescence from a set of reference samples with known dye concentrations allowing users to calculate the actual amount of dye in the sample and thus concentration on the sample being processed. This work will present the step by step process of converting dye concentrations from known and unknown samples to deposition measurements. A downloadable Microsoft Excel® spreadsheet will be made available to allow users to replicate these techniques. This technique effectively allows these tracer materials to provide a direct measure of the amount of active ingredient and/or spray mixture that deposits on sampling surfaces of interest.
The Use of a VRS-Based Pioneer 3-AT Robot in Pavement Inspections
Authors: Chang Jia-Ruey , Yu Feng-Chi , Huang Tsun-Cheng , Kang Shih-Chung , Hsieh Shang-Hsien
Published: March 2011

This study proposed a framework of the Pioneer 3-AT (P3-AT) autonomous robot for pavement inspection that was integrated with a highly accurate virtual reference station (VRS) positioning technique. The two test sites were 60 km apart; one was rigid pavement and the other was flexible pavement. Two VRS systems were adopted: (1) A VRS system developed by Taiwan Control Signal Co., Limited and (2) Virtual Base Station Real-Time Kinematic (also called e-GPS system) from Taiwan National Land Surveying and Mapping Center. First, the tire pressure and horizontal movement of the P3-AT were calibrated on the two test sites. Then the accuracy of the positioning data provided by VRS to guide the P3-AT was investigated under both static and dynamic conditions at distances of movement from 0.25 to 20 m, to verify the stability and feasibility of this framework. We observed that standard deviations in positioning were less than 0.03 m and rms values were close to prescribed distances in static tests. The reproducible errors were less than 0.03 m in dynamic tests. The results showed that the two VRS systems were able to provide the P3-AT with accurate positioning data on the two test sites. This study also successfully demonstrated the use of the P3-AT in autonomously surveying surface distresses and manholes and its ability to accurately plot slabs on a rigid pavement. Since the P3-AT possesses the properties of low volume, slow speed, flexible modules, and low price, this study confirms that the P3-AT integrated with the VRS positioning technique has the potential to provide significant assistance in automatic pavement inspections of specific areas, such as airports, and for particular purposes, such as Quality Control/Quality Assurance testing.
Partnership for Research & Education in Plants (PREP): Involving High School Students in Authentic Research in Collaboration with Scientists
Authors: BROOKS ERIC , DOLAN ERIN , TAX FRANS
Published: March 2011

A partnership between scientists, high school teachers, and their students provides authentic research experiences to help students understand the nature and processes of science. The Partnership for Research and Education in Plants (PREP) engages students in a large-scale genomics research project using classroom-tested protocols that can help to find the function of a disabled gene in the widely studied plant Arabidopsis thaliana. Here, we describe the framework of PREP in the classroom within the context of the National Science Education Standards.