bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vldlr overexpression causes hyperactivity in rats
Authors: Iwata Keiko , Izumo Nobuo , Matsuzaki Hideo , Manabe Takayuki , Ishibashi Yukiko , Ichitani Yukio , Yamada Kazuo , Thanseem Ismail , Anitha Ayyappan , Vasu Mahesh Mundalil , Shimmura Chie , Wakuda Tomoyasu , Kameno Yosuke , Takahashi Taro , Iwata Yasuhide , Suzuki Katsuaki , Nakamura Kazuhiko , Mori Norio 
Published: October 2012

Abstract

Background
Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.

Methods
We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.

Results
Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.

Conclusions
Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.
Aldosterone and the mineralocorticoid receptor in the cerebral circulation and stroke
Authors: Dinh Quynh N , Arumugam Thiruma V , Young Morag J , Drummond Grant R , Sobey Christopher G , Chrissobolis Sophocles 
Published: October 2012

Abstract
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Elevated plasma aldosterone levels are an independent cardiovascular risk factor and are thought to contribute to hypertension, a major risk factor for stroke. Evidence from both experimental and human studies supports a role for aldosterone and/or the mineralocorticoid receptor (MR) in contributing to detrimental effects in the cerebral vasculature and to the incidence and outcome of ischemic stroke. This article reviews the evidence, including the protective effects of MR antagonism. Specifically, the effects of aldosterone and/or MR activation on cerebral vascular structure and on immune cells will be reviewed. The existing evidence suggests that aldosterone and the MR contribute to cerebral vascular pathology and to the incidence and outcome of stroke. We suggest that further research into the signaling mechanisms underlying the effects of aldosterone and MR activation in the brain and its vasculature, especially with regard to cell-specific actions, will provide important insight into causes and potential treatments for cerebrovascular disease and stroke.
A revision of Artemia biodiversity in Macaronesia
Authors: Hontoria Francisco , Redón Stela , Maccari Marta , Varó Inmaculada , Navarro Juan Carlos , Ballell Lluis , Amat Francisco 
Published: October 2012

AbstractIn a biogeographical context, the term Macaronesia broadly embraces the North Atlantic archipelagos of the Azores, Madeira, Selvagens, the Canary Islands, and Cape Verde. The peculiar arid climatic conditions in some of these places have led to the development of marine salt exploitations, which can be counted among the hypersaline habitats of the brine shrimpArtemia(Branchiopoda, Anostraca). Parthenogenetic populations of this anostracan were described in the Canary Islands during the last decades of the 20th century, while the AmericanArtemia franciscanaspecies was recently found in the Cape Verde archipelago. Following an invasive pattern, this exotic species has recently reached the Canary Islands, too. This paper reports information dealing with biotope loss (solar saltworks) in this biogeographical region, together with possible consequences concerning the arrival of invasive species, two factors that frequently promote dramatic biodiversity losses. The discussion of this threat focuses mainly on the Canary Islands archipelago where native species ofArtemiastill exist.
Identification of an intestine-specific promoter and inducible expression of bacterial α-galactosidase in mammalian cells by a lac operon system
Authors: Zhai Yafeng , Shu Gang , Zhu Xiaotong , Zhang Zhiqi , Lin Xiajing , Wang Songbo , Wang Lina , Zhang Yongliang , Jiang Qingyan 
Published: October 2012

Abstract

Background
α-galactosidase has been widely used in animal husbandry to reduce anti-nutritional factors (such as α-galactoside) in feed. Intestine-specific and substrate inducible expression of α-galactosidase would be highly beneficial for transgenic animal production.

Methods
To achieve the intestine-specific and substrate inducible expression of α-galactosidase, we first identified intestine-specific promoters by comparing the transcriptional activity and tissue specificity of four intestine-specific promoters from human intestinal fatty acid binding protein, rat intestinal fatty acid binding protein, human mucin-2 and human lysozyme. We made two chimeric constructs combining the promoter and enhancer of human mucin-2, rat intestinal trefoil factor and human sucrase-isomaltase. Then a modified lac operon system was constructed to investigate the induction of α-galactosidase expression and enzyme activity by isopropyl β-D-1-thiogalactopyranoside (IPTG) and an α-galactosidase substrate, α-lactose.
We declared that the research carried out on human (Zhai Yafeng) was in compliance with the Helsinki Declaration, and experimental research on animals also followed internationally recognized guidelines.

Results
The activity of the human mucin-2 promoter was about 2 to 3 times higher than that of other intestine-specific promoters. In the lac operon system, the repressor significantly decreased (P < 0.05) luciferase activity by approximately 6.5-fold and reduced the percentage of cells expressing green fluorescent protein (GFP) by approximately 2-fold. In addition, the expression level of α-galactosidase mRNA was decreased by 6-fold and α-galactosidase activity was reduced by 8-fold. In line with our expectations, IPTG and α-lactose supplementation reversed (P < 0.05) the inhibition and produced a 5-fold increase of luciferase activity, an 11-fold enhancement in the percentage of cells with GFP expression and an increase in α-galactosidase mRNA abundance (by about 5-fold) and α-galactosidase activity (by about 7-fold).

Conclusions
We have successfully constructed a high specificity inducible lac operon system in an intestine-derived cell line, which could be of great value for gene therapy applications and transgenic animal production.
Cerebral venous outflow resistance and interpretation of cervical plethysmography data with respect to the diagnosis of chronic cerebrospinal venous insufficiency
Authors: Beggs C , Shepherd S , Zamboni P 
Published: October 2012

Objective: While chronic cerebrospinal venous insufficiency (CCSVI) can be characterized using cervical plethysmography, much remains unknown about the haemodynamics associated with this procedure. The aim of the study was therefore to gain a deeper understanding of the observed haemodynamics. Method: Forty healthy controls and 44 CCSVI patients underwent cervical plethysmography, which involved placing a strain-gauge collar around their necks and tipping them from the upright (90°) to supine position (0°) in a chair. Once stabilized, they were returned to the upright position, allowing blood to drain from the neck. A mathematical model was used to calculate the hydraulic resistance of the extracranial venous system for each subject in the study. Results: The mean hydraulic resistance of the extracranial venous system was 10.28 (standard deviation [SD] 5.14) mmHg.s/mL in the healthy controls and 16.81 (SD 9.22) in the CCSVI patients ( P < 0.001). Conclusions: The haemodynamics of the extracranial venous system are greatly altered in CCSVI patients.
The new Roche Vitamin D Total assay: fit for its purpose?
Authors: Emmen Judith M.A. , Wielders Jos P.M. , Boer Arjen-Kars , van den Ouweland Johannes M.W. , Vader Huib L. 
Published: October 2012

Abstract

Background: Measurement of serum 25-hydroxyvitamin D [25(OH)D] is used to assess vitamin D status. We evaluated the analytical performance of a new automated assay, Elecsys Vitamin D Total (Roche Diagnostics, Mannheim, Germany), based on competitive protein binding.

Methods: The Elecsys assay was tested for imprecision, linearity and functional sensitivity at three test-sites and compared to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, a high-performance liquid chromatography (HPLC) method and the Liaison 25(OH) Vitamin D Total immunoassay (Diasorin).

Results: Imprecision testing with human serum specimens showed within-run CVs of ≤6% and between-run CVs of ≤8%. The assay was linear from 33 up to at least 111 nmol/L and showed equivalent 25(OH)D levels for matched serum and heparinized plasma samples. The assay correlated reasonable to well with LC-MS/MS (r=0.93; y=1.07x–5.04 nmol/L), HPLC (r=0.91, y=0.90x+3.03 nmol/L) and the Liaison assay (r=0.86, y=1.19x+2.80 nmol/L). Some of the samples showed large between-method differences.

Conclusions: The new Elecsys assay fulfilled present analytical performance requirements and showed close agreement to other well-established methods for 25(OH)D analysis, making it fit for routine assessment of vitamin D status.
25-Hydroxyvitamin D testing: challenging the performance of current automated immunoassays
Authors: Farrell Chris , Soldo Joshua , Williams Paul , Herrmann Markus 
Published: October 2012

Abstract

Background: Clinical laboratories require accurate and precise 25-hydroxyvitamin D (25-OHD) immunoassays to allow comparison of patient results with published decision limits. However, some variation in performance has been found with the previous generation of automated 25-OHD immunoassays. This study assessed the performance of four recently released automated 25-OHD immunoassays against a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.

Methods: A total of 983 samples from apparently healthy adults, plus 253 samples chosen to challenge the performance of the assays, were analyzed by the latest generation of immunoassays from Abbott, DiaSorin, Roche and Siemens. LC-MS/MS analysis was performed on a random subset of 264 samples. The precision of the immunoassays was assessed over 5 days with samples ranging between 3.0 and 370 nmol/L in concentration.

Results: Immunoassays showed significant differences in precision at 25-OHD concentrations of 3.0–86.5 nmol/L but all showed acceptable precision at higher concentrations. The DiaSorin assay agreed with LC-MS/MS across the measuring range of samples tested (7.7–425 nmol/L). The other assays showed generally good performance, but had some limitations when their performance was challenged with samples with low and high 25-OHD concentrations, heterophilic antibodies or high 25-OHD2 concentrations. The C3-epimer of 25-OHD was identified in 40.4% of healthy adults tested and was a source of analytical variance in immunoassays.

Conclusions: The latest generation of 25-OHD immunoassays has improved performance compared to previous assays. However, some immunoassays can still give discrepant results and this is most apparent when immunoassays are evaluated with a range of samples that challenge their analytical performance.
The completeness of Kant’s metaphysical exposition of space
Authors: Blomme Henny 
Published: October 2012

Abstract
In the first edition of his book on the completeness of Kant’s table of judgments, Klaus Reich shortly indicates that the B-version of the metaphysical exposition of space in the Critique of pure reason is structured following the inverse order of the table of categories. In this paper, I develop Reich’s claim and provide further evidence for it. My argumentation is as follows: Through analysis of our actually given representation of space as some kind of object (the formal intuition of space in general), the metaphysical exposition will show that this representation is secondary to space considered as an original, undetermined and as such unrepresentable intuitive manifold. Now, following Kant, the representation of any kind of object involves diversity, synthesis and unity. In the case of our representation of space as formal intuition, this involves, firstly, a manifold a priori, i.e. space as pure form, delivered by the transcendental Aesthetic, secondly, a figurative, productive synthesis of that manifold, and, thirdly, the unity provided by the categories. Analysing our given representation of space – the task of the metaphysical exposition – amounts to dismantling its unity and determine its characteristics with respect to the categories.
Difficulty Still Awaits: Kant, Spinoza, and the Threat of Theological Determinism
Authors: Brewer Kimberly , Watkins Eric 
Published: October 2012

Abstract
In a short and much-neglected passage in the second Critique, Kant discusses the threat posed to human freedom by theological determinism. In this paper we present an interpretation of Kant’s conception of and response to this threat. Regarding his conception, we argue that he addresses two versions of the threat: either God causes appearances (and hence our spatio-temporal actions) directly or he does so indirectly by causing things in themselves which in turn cause appearances. Kant’s response to the first version is that God cannot cause appearances directly because they depend essentially on the passive sensibility of finite beings. Kant’s response to the second version is that human beings are endowed with transcendental freedom, which blocks the causal transitivity that is presupposed by this version. We also contrast his position on this topic with Leibniz’s and Spinoza’s.
Logica naturalis, Healthy Understanding and the Reflecting Power of Judgment in Kant’s Philosophy
Authors: Rodríguez Manuel Sánchez 
Published: October 2012

Abstract
The aim of this article is to explore the origin of the difficulty of founding the reflecting power of judgment as Kant outlines it in the Preface of the third Critique. Although a foundation for this faculty was only established in 1790, we must interpret it as a critical solution to an old problem, which Kant had already recognized around 1770. Through his comprehension of the meaning of healthy understanding and native wit he already confirms the impossibility of determining the correctness of our judging activity from the use of rules. This approach of the problem must be understood in the context of the controversy about the concept ‘logica naturalis’ in the Leibniz-Wolffian aesthetics and logic. In close conjunction with this tradition, Kant already tries to offer an elucidation of the question of judging through the aesthetics.
Beauty, Disinterested Pleasure, and Universal Communicability: Kant’s Response to Burke
Authors: Vandenabeele Bart 
Published: October 2012

Abstract
Although Kant (wrongly) holds that the universal communicability of aesthetic judgments logically follows from the disinterested character of the pleasure upon which they are based, Kant’s emphasis on the a priori validity of judgments of beauty can be viewed as a rebuttal of the kind of empiricist arguments that Burke offers to justify the social nature of the experience of beauty. I argue that the requirement of universal communicability is not a mere addition to the requirement of universal validity and is far more relevant to an adequate characterisation of the beautiful than has customarily been assumed. I further argue that the ‘exemplary necessity’ of pure judgments of taste, if understood correctly, reveals beauty’s primordial social significance, enabling us to become alive to a profound universal solidarity among aesthetic subjects.
Remarque philologique sur le terme «Classe» dans le § 11 de la Critique de la raison pure
Authors: Bitran Maurice 
Published: October 2012

Abstract
§ 11 of the Critique of Pure Reason, intended to strengthen the explanation of the categories in the second edition, introduces in its two first remarks the important distinction between the mathematical and the dynamical that will occur also in other later works.
In these remarks Kant creates a two-fold grouping within the categories, which seems to be spoilt by a lexical weakness concerning the terms «Classe» and «Abtheilung».
As this textual anomaly does not rest on any philosophical foundation we propose a correction aiming at expressing the original Kantian thought.
Are We Ready To Stratify Treatment for Diffuse Large B-Cell Lymphoma Using Molecular Hallmarks?
Authors: Barton Sarah , Hawkes Eliza A. , Wotherspoon Andrew , Cunningham David 
Published: October 2012

abstractLearning Objectives:After completing this course, the reader will be able to: Describe the oncogenic drivers in DLBCL, especially those that have recently been identified, and how they relate to the oncogenic DLBCL subtypes.Describe the prognostic and potentially predictive implications of DLBCL COO subtype for chemotherapy and rituximab.Outline the evidence for novel targeted therapies and therapeutic strategies in DLBCL, how they may be stratified by DLBCL subtype or to specific tumor molecular features, and how these strategies can be incorporated into current treatment paradigms and prospective clinical trial design.CME This article is available for continuing medical education credit at CME.TheOncologist.comThe division of the heterogeneous entity of diffuse large B-cell lymphoma (DLBCL) into the ontogenic phenotypes of germinal center B-cell-like (GCB) and activated B-cell-like (ABC) is optimally determined by gene expression profiling (GEP), although simpler immunohistochemistry (IHC) algorithms are alternatively being used. The cell-of-origin (COO) classification assists in prognostication and may be predictive of response to therapy. Mounting data suggests that IHC methods of classifying COO may be inaccurate. GEP categorization of COO is superior in defining prognostically and biologically distinct DLBCL subtypes, but current barriers to its widescale use include inaccessibility, cost, and lack of methodological standardization and prospective validation. The poorer prognosis of ABC-DLBCL is frequently associated with constitutive activity in the NF-κB pathway and aberrations in upstream or downstream regulators of this pathway. The molecular mechanisms underlying lymphomagenesis in GCB-DLBCL are arguably less well defined, but C-REL amplification and mutations in BCL-2 and EZH2 are common. New technologies, such as next-generation sequencing, are rapidly revealing novel pathogenic genetic aberrations, and DLBCL treatment strategies are increasingly being designed focusing on distinctive pathogenic drivers within ontogenic phenotypes. This review examines emerging molecular targets and novel therapeutic agents in DLBCL, and discusses whether stratifying therapy for DLBCL using molecular features is merited by current preclinical and clinical evidence.
Integration of Microseismic Data, Fracture and Reservoir Simulation into the Development of Fractured Horizontal Wells in the Cardium Formation - A Tight Oil Case Study
Authors: Quirk David , Ziarani Ali S. , Mills Scott , Wagner Kevin , Chen Cheney 
Published: October 2012

Abstract
Multi-fractured horizontal wells have been used successfully to exploit tight gas and shale gas reservoirs in North America over the last decade. This technology has also been successfully implemented in tight oil reservoirs in recent years. Some of the prominent tight oil plays in Canada are the Cardium, Bakken and Viking formations. Higher oil prices and depleting conventional resources have challenged operators to exploit these tight oil resources. Some of the primary reservoir engineering challenges are the optimization of the fracture spacing along the length of a horizontal wellbore, and the spacing between the horizontal wells in a resource play.
Three-dimensional reservoir simulation is the most reliable technique for reservoir modeling from these complex completions in permeability-challenged reservoirs. For an accurate representation, reservoir simulation requires data input from different sources to be incorporated into the model. In this study, microseismic data was integrated with a fracture-pumping operation to create a calibrated fracture model in a pseudo-3D fracture simulator. This fracture simulation model was subsequently imported into a multi-layer numerical reservoir model developed for the Cardium formation. The reservoir model was production matched using the fracture conductivities from the calibrated fracture model.
The history-matched reservoir model was then used to understand production depletion in this tight oil reservoir. Sensitivity studies were conducted on the history-matched model for fracture and wellbore spacing optimization. An improvement in the recovery factor was shown when fracture spacing was reduced, and when wellbores were more closely spaced. The time to production interference between fractures and wellbores helps optimize the play. This paper presents the workflow (integrating microseismic and fracturing studies) and results of a 3D reservoir simulation study conducted on a fractured horizontal well in the Cardium tight oil formation.