bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy and left ventricular non‐compaction
Authors: Siehr Stephanie L. , Bernstein Daniel , Yeh Justin , Berry Gerald J. , Rosenthal David N. , Hollander Seth A.
Published: October 2015

HC is a rare cause of congestive heart failure that typically presents with malignant ventricular arrhythmias in infants, often requiring urgent intervention. Successful heart transplantation in a patient with HC has only been reported once (J Heart Lung Transplant 2004: 23: 902). The combination of HC with concurrent LVNC has only been described three times (Int J Legal Med 2009: 123: 47; Hum Pathol 2005: 36: 403; Pediatr Dev Pathol 2012: 15: 397). We report two rare cases of HC with LVNC in two infants presenting with cardiogenic shock, one requiring ECMO support who was successfully bridged to orthotopic heart transplantation with a Berlin Heart LVAD.
Paraphrase Strategies in Metaphysics
Authors: von Solodkoff Tatjana
Published: October 2015

Philosophers often aim to demonstrate that the things we ordinarily think and say can be reconciled with our considered beliefs about the world. To this end, many philosophers try to paraphrase ordinary language claims by finding equivalent sentences that are less misleading. For instance, though we know that there is no British family that is the average one, we want to say that the average British family has 1.8 children, and we might do that by paraphrasing this claim as: there are nearly twice as many British children as British families. This article aims to introduce and distinguish different paraphrase strategies, sketch their role in metaphysical debates and highlight some crucial questions that proponents of such strategies face.
Suppression of net transpiration by multiple mechanisms conserves water resources during pupal diapause in the corn earworm Helicoverpa zea
Authors: Benoit Joshua B. , Zhang Qirui , Jennings Emily C. , Rosendale Andrew J. , Denlinger David L.
Published: October 2015

One critical aspect of an insect's ability to overwinter successfully is the effective management of its water resources. Maintenance of adequate water levels during winter is challenging because of the prevailing low relative humidity at that time of year and the short supply of environmental water that is not in the form of ice. These issues are further exacerbated for insects overwintering as pupae, comprising an immobile stage that is unable to move to new microhabitats if conditions deteriorate. The present study compares the water balance attributes of diapausing and nondiapausing pupae of the corn earworm Helicoverpa zea Boddie, aiming to identify the mechanisms used by diapausing pupae to maintain water balance during winter. Diapausing pupae are 10% larger than nondiapausing individuals. Water loss rates for nondiapausing pupae are low (0.21 mg h−1) and are suppressed (0.01 mg h−1) in diapausing pupae. Cuticular lipids, which serve to waterproof the cuticle and thus suppress cuticular water loss, are more than two‐fold more abundant on the surface of diapausing pupae, and oxygen consumption rates during diapause drop to almost one‐third the rate observed in nondiapausing pupae. Water gain can be accomplished only when atmospheric water content is near saturation or during contact with free water. At moderate relative humidities (20–40%), water loss rates are very low for diapausing pupae, suggesting that these moth pupae have robust mechanisms for combating water loss. The exceptional ability of H. zea to suppress water loss during diapause is probably a result of the combined effects of increased size, more abundant cuticular lipids and decreased metabolic rates.
Which Mental States Are Rationally Evaluable, And Why?
Authors: Nolfi Kate
Published: October 2015

What makes certain mental states subject to evaluation with respect to norms of rationality and justification, and others arational? In this paper, I develop and defend an account that explains why belief is governed by, and so appropriately subject to, evaluation with respect to norms of rationality and justification, one that does justice to the complexity of our evaluative practice in this domain. Then, I sketch out a way of extending the account to explain when and why other kinds of mental states are rationally evaluable. I argue that the cognitive or psychological mechanisms that give rise to and sustain our mental states help to render our mental states appropriate targets for evaluation with respect to norms of rationality and justification when the operation of these mechanisms is responsive, in a specific way, to our judgments about which kinds of considerations constitute rationalizing and justifying reasons for being in states of the relevant sort.
Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte‐derived dendritic cells
Authors: Rehman Z. U. , Knight J. S. , Koolaard J. , Simpson H. V. , Pernthaner A.
Published: October 2015

The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte‐derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co‐stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong TH1/TH2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS‐stimulated mdDCs and a trend (although not significant at P < 0·05) for reduced expression levels of CD40, CD80 and HLA‐DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy.
Histamine receptors expressed in circulating progenitor cells have reciprocal actions in ligation‐induced arteriosclerosis
Authors: Yamada Sohsuke , Wang Ke‐Yong , Tanimoto Akihide , Guo Xin , Nabeshima Atsunori , Watanabe Takeshi , Sasaguri Yasuyuki
Published: October 2015

Histamine is synthesized as a low‐molecular‐weight amine from L‐histidine by histidine decarboxylase (HDC). Recently, we demonstrated that carotid artery‐ligated HDC gene‐deficient mice (HDC–/–) showed less neointimal formation than wild‐type (WT) mice, indicating that histamine participates in the process of arteriosclerosis. However, little is known about the roles of histamine‐specific receptors (HHRs) in arteriosclerosis. To define the roles of HHRs in arteriosclerosis, we investigated intimal remodeling in ligated carotid arteries of HHR‐deficient mice (H1R–/– or H2R–/–). Quantitative analysis showed that H1R–/– mice had significantly less arteriosclerogenesis, whereas H2R–/– mice had more, as compared with WT mice. Bone marrow transplantation from H1R–/– or H2R–/– to WT mice confirmed the above observation. Furthermore, the increased expression of monocyte chemoattractant protein (MCP‐1), platelet‐derived growth factor (PDGF), adhesion molecules and liver X receptor (LXR)‐related inflammatory signaling factors, including Toll‐like receptor (TLR3), interleukin‐1 receptor (IL‐1R) and tumor necrosis factor receptor (TNF‐R), was consistent with the arteriosclerotic phenotype of H2R–/– mice. Peripheral progenitor cells in H2R–/– mice accelerate ligation‐induced arteriosclerosis through their regulation of MCP‐1, PDGF, adhesion molecules and LXR‐related inflammatory signaling factors. In contrast, peripheral progenitor cells act to suppress arteriosclerosis in H1R–/– mice, indicating that HHRs reciprocally regulate inflammation in the ligation‐induced arteriosclerosis.
Methotrexate‐associated lymphoproliferative disorder presenting as extranodal NK/T‐cell lymphoma arising in the lungs
Authors: Tajima Shogo , Takanashi Yusuke , Koda Kenji , Fukayama Masashi
Published: October 2015

Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstein–Barr virus (EBV) sometimes contributes to the development of MTX‐associated LPD. Herein, we report the case of a 64‐year‐old Japanese woman with RA who showed complications of EBV‐positive MTX‐associated LPD. This case is exceedingly rare in that the LPD was confined to the lungs and its subclassification was extranodal NK/T‐cell lymphoma. Only four cases of extranodal NK/T‐cell lymphoma in the setting of MTX‐associated LPD have ever been reported in the English language literature, only one of which was an extranasal NK/T‐cell lymphoma, similar to our case. Extranasal NK/T‐cell lymphomas show more aggressive behavior than nasal NK/T‐cell lymphomas, possibly reflected by the considerable re‐exacerbation of the lesions in only two months after the cessation of MTX in our case. However, the SMILE regimen (steroid, methotrexate, ifosfamide, l‐asparaginase, and etoposide) was able to suppress tumor growth in this case.
“It Wasn't Written for Me”: Law, Debt, and Therapeutic Contracts in Greek Psychiatry
Authors: Anne Davis Elizabeth
Published: October 2015

Since the international movement for patients’ rights began, law has played an ambiguous role in mediating conflicts over responsibility for the mentally ill. In Greece, this contention has been shaped by reforms designed to shift psychiatric treatment from custodial hospitals to outpatient settings, challenging patients to help care for themselves. This article addresses one of the normative techniques deployed by Greek therapists to foster patients’ responsibility in treatment: the therapeutic contract. By formalizing patients’ and therapists’ responsibilities to one other, contracts attach legalistic determinants to treatment that are said to have their own therapeutic efficacy. I examine the experiences of two patients in northeastern Greece who entered therapeutic contracts at moments of crisis in their treatment. Failures in these cases expose a conflict between the ethics of contract and the ethics of care. I argue that this conflict is intrinsic to the transactional model of public service relationships in liberal states.
Land and Law in Marijuana Country: Clean Capital, Dirty Money, and the Drug War's Rentier Nexus
Authors: Polson Michael
Published: October 2015

Despite its ongoing federal illegality, marijuana production has become a licit, or socially accepted, feature of northern California's real estate market. As such, marijuana is a key component of land values and the laundering of “illegal” wealth into legitimate circulation. By following land transaction practices, relations, and instruments, this article shows how formally equal property transactions become substantively unequal in light of the “il/legal” dynamics of marijuana land use. As marijuana becomes licit, prohibitionist policies have enabled the capture of ground rent by landed interests from the marijuana industry at a time when the price of marijuana is declining (in part due to its increasing licitness). The resulting “drug war rentier nexus,” a state–land–finance complex, is becoming a key, if obscured, component within marijuana's contemporary political economy.
A Case for Supreme Court Term Limits? The Changing Ideological Relationship between Appointing Presidents and Supreme Court Justices
Authors: Sharma Hemant , Glennon Colin
Published: October 2015

The desirability of complete judicial independence has been debated in several recent works. At issue is whether democratic theory is compatible with policy making by the unelected U.S. Supreme Court justices, particularly as their service becomes further removed from the time when elected officials played a role in their appointment. We examine the relationship between appointing presidents and Supreme Court justices. Relying on ideal points that place all actors in the same scale, our regression models show that a justice will drift from the ideology of an appointing president with each additional term served, even after controlling for ideological shifts in political climate. The beginning of the eleventh term is when ideological drift becomes significant. The connection between justices and democratically elected officials begins to wane after this point in a justice's tenure—a finding that is likely to be germane for proponents of term limits for Supreme Court justices.

Related Articles

Sharma, Hemant, and John M. Scheb II. 2011. “.” Politics & Policy 39 (): 1077‐1105. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2011.00325.x/abstract

Basabe‐Serrano, Santiago. 2012. “.” Politics & Policy 40 (): 339‐361. http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2012.00348.x/abstract

McCall, Madhavi. 2003. “.” Politics & Policy 31 (): 314‐343, http://onlinelibrary.wiley.com/doi/10.1111/j.1747‐1346.2003.tb00151.x/abstract

Related Media

The Judicial Common Space: http://epstein.usc.edu/research/JCS.html

The American Presidency Project. 2013. http://www.presidency.ucsb.edu/

Greene, Jamal. 2012. “.” . July 8. http://www.nytimes.com/roomfordebate/2012/07/08/another‐stab‐at‐the‐us‐constitution/revisiting‐the‐constitution‐we‐need‐term‐limits‐for‐federal‐judges
The Current Status and Future Direction of Nanotechnology Regulations: A View from Nano‐scientists
Authors: Corley Elizabeth A. , Kim Youngjae , Scheufele Dietram A.
Published: October 2015

This article presents an up‐to‐date view of leading U.S. nanoscientists' perceptions about the regulation of nanotechnology. Our analysis draws from the results of a 2011 mail survey with 444 of the most prolific nanoscientists in the United States to explore their perceptions about existing nanotech policies, the development of new nanotech policies, and mandatory policies about the implementation of safe lab practices for federally funded nanoresearch. In addition to exploring the scientists' perceptions about these pressing policy issues, we also test relationships between their perceptions about regulation and control variables such as gender, disciplinary affiliation, and political ideology. Last, the results of the 2011 data collection are compared with a similar mail survey that was conducted in 2007 with leading U.S. nanoscientists to explore any changes over the four‐year time period in scientists' perceptions about nanotechnology policy making, and governmental involvement in nanotechnology research.
Hidden Second‐order Stationary Spatial Point Processes
Authors: Hahn Ute , Vedel Jensen Eva B.
Published: October 2015

In the existing statistical literature, the almost default choice for inference on inhomogeneous point processes is the most well‐known model class for inhomogeneous point processes: reweighted second‐order stationary processes. In particular, theK‐function related to this type of inhomogeneity is presented astheinhomogeneousK‐function. In the present paper, we put a number of inhomogeneous model classes (including the class of reweighted second‐order stationary processes) into the common general framework of hidden second‐order stationary processes, allowing for a transfer of statistical inference procedures for second‐order stationary processes based on summary statistics to each of these model classes for inhomogeneous point processes. In particular, a general method to test the hypothesis that a given point pattern can be ascribed to a specific inhomogeneous model class is developed. Using the new theoretical framework, we reanalyse three inhomogeneous point patterns that have earlier been analysed in the statistical literature and show that the conclusions concerning an appropriate model class must be revised for some of the point patterns.
A review of the impacts of degradation threats on soil properties in theUK
Authors: Gregory A. S. , Ritz K. , McGrath S. P. , Quinton J. N. , Goulding K. W. T. , Jones R. J. A. , Harris J. A. , Bol R. , Wallace P. , Pilgrim E. S. , Whitmore A. P.
Published: October 2015

National governments are becoming increasingly aware of the importance of their soil resources and are shaping strategies accordingly. Implicit in any such strategy is that degradation threats and their potential effect on important soil properties and functions are defined and understood. In this paper, we aimed to review the principal degradation threats on important soil properties in theUK, seeking quantitative data where possible. Soil erosion results in the removal of important topsoil and, with it, nutrients, C and porosity. A decline in soil organic matter principally affects soil biological and microbiological properties, but also impacts on soil physical properties because of the link with soil structure. Soil contamination affects soil chemical properties, affecting nutrient availability and degrading microbial properties, whilst soil compaction degrades the soil pore network. Soil sealing removes the link between the soil and most of the ‘spheres’, significantly affecting hydrological and microbial functions, and soils on re‐developed brownfield sites are typically degraded in most soil properties. Having synthesized the literature on the impact on soil properties, we discuss potential subsequent impacts on the important soil functions, including food and fibre production, storage of water and C, support for biodiversity, and protection of cultural and archaeological heritage. Looking forward, we suggest a twin approach of field‐based monitoring supported by controlled laboratory experimentation to improve our mechanistic understanding of soils. This would enable us to better predict future impacts of degradation processes, including climate change, on soil properties and functions so that we may manage soil resources sustainably.
Ceppellini Lecture 2012: Collateral damage from HLA mismatching in kidney transplantation
Authors: Opelz G. , Döhler B.
Published: October 2015

Inclusion of human leukocyte antigen (HLA) matching in donor kidney allocation schemes has been based solely on its association with graft survival. Other long‐term effects associated with HLA incompatibility are largely unexplored. Data from deceased donor kidney transplants reported to the Collaborative Transplant Study have been analyzed to assess the relation between HLA mismatching and clinical events to 3 years post‐transplant, and an overview of these analyses is presented. A significant correlation was observed between the number of mismatches and the need for anti‐rejection therapy during the first year post‐transplant, which was maintained for HLA‐DR and HLA‐A + B mismatching separately and at years 2 and 3 post‐transplant. The number of HLA‐DR mismatches and the number of HLA‐A + B mismatches as well as rejection treatment showed significant associations with the dose of maintenance steroids. The cumulative incidences of death with a functioning graft from infection or cardiovascular causes, but not from cancer, were also significantly associated with HLA mismatching. The number of HLA‐DR mismatches showed a significant association with the incidence of non‐Hodgkin lymphoma and hip fractures. These findings show that the adverse consequences of HLA mismatching on kidney transplants extend beyond an effect on graft survival, and include an increased risk of death with a functioning graft, non‐Hodgkin lymphoma and hip fracture.
Extracting multiple interacting root systems using X‐ray microcomputed tomography
Authors: Mairhofer Stefan , Sturrock Craig J. , Bennett Malcolm J. , Mooney Sacha J. , Pridmore Tony P.
Published: October 2015

Root system interactions and competition for resources are active areas of research that contribute to our understanding of how roots perceive and react to environmental conditions. Recent research has shown this complex suite of processes can now be observed in a natural environment (i.e. soil) through the use of X‐ray microcomputed tomography (μCT), which allows non‐destructive analysis of plant root systems. Due to their similar X‐ray attenuation coefficients and densities, the roots of different plants appear as similar greyscale intensity values in μCT image data. Unless they are manually and carefully traced, it has not previously been possible to automatically label and separate different root systems grown in the same soil environment. We present a technique, based on a visual tracking approach, which exploits knowledge of the shape of root cross‐sections to automatically recover from X‐ray μCT data three‐dimensional descriptions of multiple, interacting root architectures growing in soil. The method was evaluated on both simulated root data and real images of two interacting winter wheat Cordiale (Triticumaestivum L.) plants grown in a single soil column, demonstrating that it is possible to automatically segment different root systems from within the same soil sample. This work supports the automatic exploration of supportive and competitive foraging behaviour of plant root systems in natural soil environments.
The aPKC/Par3/Par6 Polarity Complex and Membrane Order Are Functionally Interdependent in Epithelia During Vertebrate Organogenesis
Authors: Abu‐Siniyeh Ahmed , Owen Dylan M. , Benzing Carola , Rinkwitz Silke , Becker Thomas S. , Majumdar Arindam , Gaus Katharina
Published: October 2015

The differential distribution of lipids between apical and basolateral membranes is necessary for many epithelial cell functions, but how this characteristic membrane organization is integrated within the polarity network during ductal organ development is poorly understood. Here we quantified membrane order in the gut, kidney and liver ductal epithelia in zebrafish larvae at 3–11 days post fertilization (dpf) with Laurdan 2‐photon microscopy. We then applied a combination of Laurdan imaging, antisense knock‐down and analysis of polarity markers to understand the relationship between membrane order and apical‐basal polarity. We found a reciprocal relationship between membrane order and the cell polarity network. Reducing membrane condensation by exogenously added oxysterol or depletion of cholesterol reduced apical targeting of the polarity protein, aPKC. Conversely, using morpholino knock down in zebrafish, we found that membrane order was dependent upon the Crb3 and Par3 polarity protein expression in ductal epithelia. Hence our data suggest that the biophysical property of membrane lipid packing is a regulatory element in apical basal polarity.
Cheek Tooth Extraction Via a Minimally Invasive Transbuccal Approach and Intradental Screw Placement in 54 Equids
Authors: Langeneckert Frederik , Witte Thomas , Schellenberger Frank , Czech Christian , Aebischer David , Vidondo Beatriz , Koch Christoph
Published: October 2015

Objective

To describe (1) preoperative findings and surgical technique, (2) intraoperative difficulties, and (3) postoperative complications and long‐term outcome of equine cheek tooth extraction using a minimally invasive transbuccal screw extraction (MITSE) technique.

Study Design

Retrospective case series.

Animals

Fifty‐four equids; 50 horses, 3 ponies, and 1 mule.

Methods

Fifty‐eight MITSE procedures were performed to extract cheek teeth in 54 equids. Peri‐ and intraoperative difficulties, as well as short‐ (<1 month) and long‐term (>6 months) postoperative complications were recorded. Followup information was obtained through telephone interviews, making specific inquiries about nasal discharge, facial asymmetry, and findings consistent with surgical site infection.

Results

Preoperative findings that prompted exodontia included 50 cheek teeth with apical infections, 48 fractures, 4 neoplasia, 2 displacements, and 1 supernumerary tooth. Previous oral extraction was attempted but had failed in 55/58 (95%) animals because of cheek tooth fracture in 28, or insufficient clinical crown for extraction with forceps in 27. MITSE was successful in removing the entire targeted dental structure in 47/58 (81%) procedures. However, MITSE failed to remove the entire targeted dental structure in 11/58 (19%) procedures and was followed by repulsion in 10/11 (91%). Short‐term postoperative complications included bleeding (4/58 procedures, 7%) and transient facial nerve paralysis (4/58 procedures, 7%). Owners were satisfied with the functional and cosmetic outcome for 40/41 (98%) animals with followup.

Conclusion

MITSE offers an alternate for cheek tooth extraction in equids, where conventional oral extraction is not possible or has failed. Overall, there was low morbidity, which compares favorably with invasive buccotomy or repulsion techniques.
Screening pigs for xenotransplantation: prevalence and expression of porcine endogenous retroviruses in Göttingen minipigs
Authors: Semaan Marwan , Rotem Avi , Barkai Uriel , Bornstein Stefan , Denner Joachim
Published: October 2015

Background

To establish the safety of xenotransplantation when cells, tissues, or organs of pigs are used, an effective screening for potential zoonotic microorganisms has to be performed. In doing so, special attendance has to be paid to porcine endogenous retroviruses (PERVs) that are widely distributed as proviruses in the genome of pigs. PERV‐A and PERV‐B are present in all pigs, they infect human cells in vitro and therefore represent a direct risk. PERV‐C infects only pig cells; however, recombinant PERV‐A/C infecting human cells and replicating at a higher rate were found in pigs indicating an indirect risk. To prevent the transmission of PERV, it was suggested to use animals characterized by a low expression of PERV‐A and PERV‐B that are free of PERV‐C and cannot generate recombinants. Göttingen minipigs are used for numerous biomedical investigations and they are well characterized; however, the prevalence and the expression of PERV in these animals were not yet investigated.

Methods

The presence and expression of all PERVs including a new variant (nv) of PERV‐C and PERV‐A/C were analyzed using PCR and real‐time PCR methods. Altogether, 15 animals belonging to different families were analyzed. To make a low expression better measurable, peripheral blood mononuclear cells (PBMCs) of the animals were stimulated with phytohaemagglutinin generally increasing the expression of PERV and allowing a better classification into animals with high and low expression. As a major end point, the release of virus particles able to infect susceptible human 293 cells was investigated.

Results

PERV‐A, PERV‐B, PERV‐C, and PERV‐Cnv were found in the genome of all investigated Göttingen minipigs, but recombinant PERV‐A/Cs were not found. When the expression of PERV was compared with that in previously analyzed pig strains, it was higher than in German landrace and some other pigs, but lower than in Yucatan miniature pigs. Virus particles able to infected human 293 cells were not detected even after mitogen treatment of the PBMCs.

Conclusion

The Göttingen minipigs are well defined concerning their physiologic parameters, their health status, and their genetics, and therefore, they may be considered as donor animals for at least cell xenotransplantation. When the prevalence and the expression of PERVs were analyzed in these animals, it was demonstrated that although PERV‐A, ‐B, and ‐C proviruses were found in all animals, their expression was low. Additional investigations are required to assess the suitability of Göttingen minipigs and other animals for xenotransplantation in terms of microbiological safety.
Technical Note: Clinical translation of the Rapid‐Steady‐State‐T1 MRI method for direct cerebral blood volume quantification
Authors: Perles‐Barbacaru Teodora‐Adriana , Tropres Irene , Sarraf Michel G. , Chechin David , Zaccaria Affif , Grand Sylvie , Le Bas Jean‐François , Berger François , Lahrech Hana
Published: October 2015

Purpose:

In preclinical studies, the Rapid‐Steady‐State‐T1 (RSST1) MRI method has advantages over conventional MRI methods for blood volume fraction (BVf) mapping, since after contrast agent administration, the BVf is directly quantifiable from the signal amplitude corresponding to the vascular equilibrium magnetization. This study focuses on its clinical implementation and feasibility.

Methods:

Following sequence implementation on clinical Philips Achieva scanners, the RSST1‐method is assessed at 1.5 and 3 T in the follow‐up examination of neurooncological patients receiving 0.1–0.2 mmol/kg Gd‐DOTA to determine the threshold dose needed for cerebral BVf quantification. Confounding effects on BVf quantification such as transendothelial water exchange, transverse relaxation, and contrast agent extravasation are evaluated.

Results:

For a dose ≥0.13 mmol/kg at 1.5 T and ≥0.16 mmol/kg at 3 T, the RSST1‐signal time course in macrovessels and brain tissue with Gd‐DOTA impermeable vasculature reaches a steady state at maximum amplitude for about 8 s. In macrovessels, a BVf of 100% was obtained validating cerebral microvascular BVf quantification (3.5%–4.5% in gray matter and 1.5%–2.0% in white matter). In tumor tissue, a continuously increasing signal is detected, necessitating signal modeling for tumor BVf calculation.

Conclusions:

Using approved doses of Gd‐DOTA, the steady state RSST1‐signal in brain tissue is reached during the first pass and corresponds to the BVf. The first‐pass duration is sufficient to allow accurate BVf quantification. The RSST1‐method is appropriate for serial clinical studies since it allows fast and straightforward BVf quantification without arterial input function determination. This quantitative MRI method is particularly useful to assess the efficacy of antiangiogenic agents.
Benzo[
b
]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase
Authors: Jortzik Esther , Zocher Kathleen , Isernhagen Antje , Mailu Boniface M. , Rahlfs Stefan , Viola Giampietro , Wittlin Sergio , Hunt Nicholas H. , Ihmels Heiko , Becker Katja
Published: October 2015

The heme-containing enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and IDO-2 catalyze the conversion of the essential amino acid tryptophan into kynurenine. Metabolites of the kynurenine pathway and IDO itself are involved in immunity and the pathology of several diseases, having either immunoregulatory or antimicrobial effects. IDO-1 plays a central role in the pathogenesis of cerebral malaria, which is the most severe and often fatal neurological complication of infection with
Plasmodium falciparum
. Mouse models are usually used to study the underlying pathophysiology. In this study, we screened a natural compound library against mouse IDO-1 and identified 8-aminobenzo[
b
]quinolizinium (compound 2c) to be an inhibitor of IDO-1 with potency at nanomolar concentrations (50% inhibitory concentration, 164 nM). Twenty-one structurally modified derivatives of compound 2c were synthesized for structure-activity relationship analyses. The compounds were found to be selective for IDO-1 over IDO-2. We therefore compared the roles of prominent amino acids in the catalytic mechanisms of the two isoenzymes via homology modeling, site-directed mutagenesis, and kinetic analyses. Notably, methionine 385 of IDO-2 was identified to interfere with the entrance of
l
-tryptophan to the active site of the enzyme, which explains the selectivity of the inhibitors. Most interestingly, several benzo[
b
]quinolizinium derivatives (6 compounds with 50% effective concentration values between 2.1 and 6.7 nM) were found to be highly effective against
P. falciparum
3D7 blood stages in cell culture with a mechanism independent of IDO-1 inhibition. We believe that the class of compounds presented here has unique characteristics; it combines the inhibition of mammalian IDO-1 with strong antiparasitic activity, two features that offer potential for drug development.
Parasite-Specific CD4
+
IFN-γ
+
IL-10
+
T Cells Distribute within Both Lymphoid and Nonlymphoid Compartments and Are Controlled Systemically by Interleukin-27 and ICOS during Blood-Stage Malaria Infection
Authors: Villegas-Mendez Ana , Shaw Tovah N. , Inkson Colette A. , Strangward Patrick , de Souza J. Brian , Couper Kevin N.
Published: October 2015

Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)–yellow fluorescent protein (YFP) and IL-10–green fluorescent protein (GFP) reporter mice, we show that CD4
+
YFP
+
T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stage
Plasmodium yoelii
infection. Mature splenic CD4
+
YFP
+
GFP
+
T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4
+
YFP
+
GFP
+
T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4
+
YFP
+
GFP
+
T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4
+
YFP
+
T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4
+
T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs.
Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose
Authors: McDonald Erin M. , Pilonieta M. Carolina , Nick Heidi J. , Detweiler Corrella S.
Published: October 2015

During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype.Salmonella entericaserovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-γ) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-γ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killedSalmonella enterica, the Gram-positive bacteriumBacillus subtilis, orMycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-γ-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-γ-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented bothSalmonella- and LPS-stimulated hemophagocytosis. Inhibition of NF-κB also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response.
Transport of hexavalent chromium in the vadose zone by capillary and evaporative transport from chromium ore processing residue
Authors: Rhoades Katrina , Eun Jongwan , Tinjum James M.
Published: October 2015

Column tests were conducted to evaluate the transport of Cr from underlying chromium ore processing residue (COPR) through the vadose zone in capped and uncapped scenarios and to determine if an asphalt cover system is a viable containment strategy. Four large (140 mm diameter) columns and one small (50 mm diameter) column were filled with COPR underlying a silty sand. Wet–dry cycling (representing precipitation events) induced suction gradients in the uncapped columns. At termination, the uncapped columns contained 10–120 mg/kg Cr on the surface (background Cr level, 8.3 mg/kg), and the capped columns had Cr concentrations equal to background levels, indicating that the capped surface limited Cr migration to the surface. The smaller column was constructed to study the evaporative transport of Cr by simulating a heat source (i.e., sunshine) to increase suction. Soil specimens from the surface of the small-diameter, uncapped column were as high as 410 mg/kg Cr(VI) after 4 weeks. A series of numerical analyses was conducted to interpret and validate the experimental results and to quantify Cr(VI) transport through composite asphalt caps. Through column testing and numerical analysis, in a controlled condition, Cr was found to migrate from COPR in the vadose zone by evaporation and capillary rise, but a controlled, capped condition effectively limited Cr migration.
Are small fishes more sensitive to habitat loss? A generic size-based model
Authors: van der Lee Adam S. , Koops Marten A.
Published: October 2015

Habitat loss represents the greatest threat to freshwater biodiversity. The potential for life history attributes to correlate with the risks associated with habitat loss represents a possible mechanism for more effective and rapid assessments, especially in data-limited situations. Body size correlates with many other life history attributes and is a good starting point for investigating correlates with habitat loss. Here, we use a generic stage-based matrix population model, parameterized using length-based allometries, to investigate if such a mechanism exists. Our analysis revealed that small species (shorter maximum body length) were initially more sensitive to the loss of habitat. Moreover, distinct stage-based patterns exist showing an increased sensitivity of population growth rate for small species to both habitat loss and vital rate perturbations of pre-adult stages. This indicates that the pre-adult period represents a critical stage for the continued production of small species and increased importance of the conservation of habitat used by young-of-the-year and juvenile fishes.
Maximal isotropic subbundles of orthogonal bundles of odd rank over a curve
Authors: Choe Insong , Hitching George H.
Published: October 2015

An orthogonal bundle over a curve has an isotropic Segre invariant determined by the maximal degree of a maximal isotropic subbundle. This invariant and the induced stratifications on moduli spaces of orthogonal bundles were studied for bundles of even rank in [I. Choe and G. H. Hitching, A stratification on the moduli space of symplectic and orthogonal bundles over a curve, Internat. J. Math. 25(5) (2014), Article ID: 1450047, 27pp.]. In this paper, we obtain analogous results for bundles of odd rank. We compute the sharp upper bound on the isotropic Segre invariant. Also we show the irreducibility of the induced strata on the moduli spaces of orthogonal bundles of odd rank, and compute their dimensions.
Invariant trilinear forms for spherical degenerate principal series of complex symplectic groups
Authors: Clare Pierre
Published: October 2015

We compute generalized Bernstein–Reznikov integrals associated with standard complex symplectic forms by studying Knapp–Stein intertwining operators between spherical degenerate principal series of [Formula: see text].
Hybrid high algebraic order two-step method with vanished phase-lag and its first, second, third, fourth and fifth derivatives
Authors: Ma Junyan , Simos T. E.
Published: October 2015

A hybrid tenth algebraic order two-step method with vanished phase-lag and its first, second, third, fourth and fifth derivatives are obtained in this paper. We will investigate

• the construction of the method • the local truncation error (LTE) of the newly obtained method. We will also compare the lte of the newly developed method with other methods in the literature (this is called the comparative LTE analysis) • the stability (interval of periodicity) of the produced method using frequency for the scalar test equation different from the frequency used in the scalar test equation for phase-lag analysis (this is called stability analysis) • the application of the newly obtained method to the resonance problem of the Schrödinger equation. We will compare its effectiveness with the efficiency of other known methods in the literature.

It will be proved that the developed method is effective for the approximate solution of the Schrödinger equation and related periodical or oscillatory initial value or boundary value problems.
Efficient Evaluation of Physical Unclonable Functions Using Entropy Measures
Authors: Pehl Michael , Hiller Matthias , Graeb Helmut
Published: October 2015

Physical unclonable functions (PUFs) are security primitives which are based on uncontrollable variations in the manufacturing process and can be used as secure key storage and for identification and authentication. While some work has been done on global evaluation of PUFs with respect to predictability, there is no systematic evaluation strategy to give designers insights into design problems. However, flaws in the design can give an adversary an advantage to guess the response of a PUF. Therefore, this work focuses on a systematic scheme for designers to evaluate the predictability of PUF implementation. Also, the used entropy measures are compared to state-of-the-art metrics for PUFs, convergence properties are presented and the scheme is validated using simulation results for PUFs.
Digital Compensation Method for the Path Delay Mismatches in GRO-TDC
Authors: Park Pyoungwon , Nag Dipankar , Yan Dan Lei , Arasu Muthukumaraswamy Annamalai
Published: October 2015

The digital compensation method for path delay mismatches in the time-to-digital converter (TDC) based on gated-ring oscillator (GRO) is proposed and demonstrated. The output of the GRO is digitized by the combination of a counter and a phase-to-digital converter (PDC) producing an integer and a fractional digital value, respectively. Due to the delay mismatches between two paths, the integer and fractional digital values are not synchronized thereby causing calculation errors. In order to reduce the errors, a correction bit (CB) is generated and then the erroneous output is fixed by the additional but simple digital circuits. Measurement results show that calculation errors due to the delay mismatches are corrected by the proposed compensation method and it reduces the quantization noise power by 10[Formula: see text]dB at high frequency offset.
Write Assist SRAM Cell with Asymmetrical Bitline Access Transistors for Enhanced Data Stability and Write Ability
Authors: Salahuddin Shairfe Muhammad , Kursun Volkan
Published: October 2015

A novel six-transistor static random-access memory (6T SRAM) cell is proposed in this paper for enhancing the data stability and write ability as compared to the conventional memory circuits. Asymmetrically gate overlapped / underlapped FinFETs are employed as bitline access transistors in the proposed SRAM cell. The strength of the asymmetrical bitline access transistors are weakened during read operations. Furthermore, voltage transfer characteristics (VTCs) of cross-coupled inverters have narrower transition regions in the new SRAM cell as compared to the conventional SRAM cells. The proposed SRAM cell thereby provides stronger read data stability as compared to the conventional symmetrical SRAM cells. The strength of bitline access transistors are enhanced during write operations as the direction of current flow is reversed in the new asymmetrical SRAM cell. The power supply voltage of a selected word floats during write operations. The write voltage margin is thereby significantly increased with the proposed SRAM cell as compared to the conventional SRAM cells. The read data stability and write ability are both enhanced by up to 51.7% and 65.5%, respectively, with the proposed SRAM cell as compared to the conventional symmetrical six-FinFET SRAM cells in a 15[Formula: see text]nm FinFET technology.
Elliptic equations with indefinite and unbounded potential and a nonlinear concave boundary condition
Authors: Hu Shouchuan , Papageorgiou Nikolaos S.
Published: October 2015

We consider an elliptic problem driven by the negative Laplacian plus an indefinite and unbounded potential and a superlinear reaction. The boundary condition is parametric, nonlinear and superlinear near zero. Thus, the problem is a new version of the classical “convex–concave” problem (problem with competing nonlinearities). First, we prove a bifurcation-type result describing the set of positive solutions as the parameter [Formula: see text] varies. We also show the existence of a smallest positive solution [Formula: see text] and investigate the properties of the map [Formula: see text]. Finally, by imposing bilateral conditions on the reaction we generate two more solutions, one of which is nodal.
COMPUTATIONAL MODEL OF PLATELET FLOW IN CAROTID ARTERY BIFURCATION
Authors: LI GUOJIE , CHEN BIN
Published: October 2015

Atherosclerotic plaque tends to occur and develop in carotid artery sinus, where stenoses and other lesions can cause cerebral disturbances. The hemodynamics and the platelet profiles in the carotid artery are simultaneously simulated in the present study to reveal the mechanism of the atherosclerotic plaque formation. Firstly, an unsteady PISO solver on unstructured tetrahedral grids is developed to simulate the hemodynamics of carotid artery bifurcation. And small platelets are treated as spherical solid particle described by Newtonian motion equation in the simulation, including inertial force, drag force, shear lift force, virtual mass force and pressure gradient force. Secondly, the visualization experiment for the platelet flow in the straight micro-channel is setup to validate the numerical model. Using the present method, the platelet flow in a carotid artery bifurcation is analyzed. The results show that the outer vascular wall near the bifurcation is more vulnerable in carotid artery sinus, which is mainly due to the lower wall shear stress (WSS) and platelets backflow in the region.
Weak Gabor bi-frames on periodic subsets of the real line
Authors: Li Yun-Zhang , Jia Hui-Fang
Published: October 2015

In this paper, we introduce the concept of weak Gabor bi-frame (WGBF) in a general closed subspace [Formula: see text] of [Formula: see text]. It is a generalization of Gabor bi-frame, and is new even if [Formula: see text]. A WGBF for [Formula: see text] contains all information of [Formula: see text] to some extent. Let [Formula: see text], [Formula: see text], and [Formula: see text] be an [Formula: see text]-periodic subset of [Formula: see text] with positive measure. This paper is devoted to characterizing WGBFs for [Formula: see text] of the form [Formula: see text] It is well-known that, if [Formula: see text], the projections of Gabor frames for [Formula: see text] onto [Formula: see text] cannot cover all Gabor frames for [Formula: see text]. This paper presents a Zak transform-domain and a time-domain characterization of WGBFs for [Formula: see text]. These characterizations are new even if [Formula: see text]. Some examples are also provided to illustrate the generality of our theory.