bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Dimensionality on Growth and Differentiation of Neural Progenitors from Different Regions of Fetal Rat Brain in vitro: 3-Dimensional Spheroid versus 2-Dimensional Monolayer Culture
Authors: Lu Haixia , Searle Karren , Liu Yong , Parker Terry
Published: February 2012

Three-dimensional (3-D) spheroids are widely used for culturing cells. However, 2-dimensional (2-D) monolayer cultures have also been adopted for culture and used in a broad range of cell biology studies. To address the effect of dimensionality on the growth and differentiation of neuroprogenitor cells in 3-D spheroids and 2-D monolayer cultures, cells were isolated from cerebral cortex, cerebella and brainstem of fetal rat brain then cultured in serum-free DMEM/F12 medium or DMEM with 10% FBS. The growth and differentiation of neuroprogenitor cells from three brain regions in spheroids was compared with that in monolayer cultures, and the differentiation components of neuroprogenitor cells were compared with in vivo brain sections. Neuroprogenitor cells in spheroids proliferate actively over 10 days in culture as showed by Ki67 incorporation and increase in spheroid diameter. More neuroprogenitor cells underwent neuronal differentiation in spheroids than in monolayer cultures. In comparison with fixed rat brain sections, the neuron to astrocyte ratio, as shown by neurofilament to glial fibrillary acidic protein immunoreactivity, in spheroids is similar to that found in adult rat tissue sections. Our results suggest that the spheroid culture system mimics the in vivo cytoarchitecture to a greater extent and more closely reflects the cellular composition in adult brain tissue. This supports the notion that the intercellular niche in spheroids is more favorable for the survival and differentiation of neuronal precursors, while the cues in monolayer cultures may favor glial cell survival. It is therefore concluded that dimensionality plays a significant role in determining cellular behavior in vitro.
Periodontal Disease-Associated Compensatory Expression of Osteoprotegerin Is Lost in Type 1 Diabetes Mellitus and Correlates with Alveolar Bone Destruction by Regulating Osteoclastogenesis
Authors: Silva Juliete Aparecida F. , Lopes Ferrucci Danilo , Peroni Luis Antônio , de Paula Ishi Eduardo , Rossa-Junior Carlos , Carvalho Hernandes F. , Stach-Machado Dagmar Ruth
Published: February 2012

Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects of PD and DM1 enhance bone destruction, confirms the importance of the RANKL signaling pathway in bone destruction in DM1 in animal models and suggests the existence of alternative mechanisms potentiating bone degradation in PD.
Microglial Activation in Neuroinflammation: Implications for the Etiology of Neurodegeneration
Authors: Kaneko Yoko S. , Nakashima Akira , Mori Keiji , Nagatsu Toshiharu , Nagatsu Ikuko , Ota Akira
Published: February 2012

Background: Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear. Objective: Our aim was to examine the regulation of activated microglia through their cell death and survival pathways. Methods: We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS). Results: LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2-associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS.Conclusion:An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration.
Relationship between Memory Performance and β-Amyloid Deposition at Different Stages of Alzheimer’s Disease
Authors: Chételat Gaël , Villemagne Victor L. , Pike Kerryn E. , Ellis Kathryn A. , Ames David , Masters Colin L. , Rowe Christopher C. ,   and the Australian Imaging Biomarkers and Lifestyle Study of Ageing (AIBL) Research Group
Published: February 2012

Background: Postmortem studies have suggested that β-amyloid (Aβ) deposition was only weakly related to the degree of cognitive impairment in Alzheimer’s disease (AD). The development of Aβ ligands for in vivo PET imaging has greatly facilitated the assessment of this question. Objective: The objective of the present study was to provide an overview of our current knowledge regarding the relationship between Aβ deposition and episodic memory deficits in nondemented elderly and in patients with mild cognitive impairment or AD. Methods: Information was obtained both from studies comparing memory performance in individuals with high Pittsburgh compound B (PiB) and those with low PiB and from studies performing correlation analyses between memory performance and PiB retention considered as a continuous variable. Results: Previous studies assessing the relationship between memory and global neocortical PiB reported conflicting findings, and overall suggest that this link is weak, probably indirect, and detectable only in early stages. Assessing the relationship with regional instead of global neocortical PiB, we found a specific relationship between episodic memory deficits and neocortical temporal PiB, independent from hippocampal atrophy, in the predementia stage of the disease. Conclusion: There is a relationship between regional Aβ deposition and episodic memory deficits in the presymptomatic stage of AD.
Evaluation of the Performance of Novel Aβ Isoforms as Theragnostic Markers in Alzheimer’s Disease: From the Cell to the Patient
Authors: Portelius Erik , Gustavsson Mikael K. , Zetterberg Henrik , Andreasson Ulf , Blennow Kaj
Published: February 2012

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the aging population and is characterized by extracellular plaques in the brain. The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ) metabolism and aggregation in the pathogenesis of AD which has been translated into novel promising therapies with putative disease-modifying effects. Objective: The aim is to investigate the performance of truncated Aβ isoforms as theragnostic markers in clinical trials. Methods: Aβ isoforms were immunoprecipitated from human, mouse and dog cerebrospinal fluid (CSF) or cell media and analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: Aβ1–14, Aβ1–15, and Aβ1–16 are elevated in cell media and in CSF in response to γ-secretase inhibitor treatment. In a clinical trial including AD patients, Aβ1–14, Aβ1–15, and Aβ1–16 increased dose-dependently in response to treatment with the γ-secretase inhibitor LY450139. In dogs, Aβ1–37 was significantly increased in response to treatment with the γ-secretase modulator E2012. Conclusions: The results presented add to the current knowledge on APP processing and that Aβ isoforms can be used as novel biomarkers to monitor anti-Aβ treatments in clinical trials and may be valuable for making a go/no go decision for large and expensive phase 2 or 3 clinical trials.
Uveal Melanoma: The Inflammatory Microenvironment
Authors: Bronkhorst Inge H.G. , Jager Martine J.
Published: February 2012

Uveal melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of infiltrating macrophages and T cells is associated with a poor prognosis rather than a good one. The clear link between inflammation and cancer in this malignancy provides a paradigm for macrophage plasticity and function. Macrophages in uveal melanoma have an M2-like phenotype and are associated with the loss of one specific chromosome – monosomy 3. The central players involved in this process and discussed in this review include macrophages, T lymphocytes, chemokines and cytokines, including the macrophage-attraction molecules. When a tumor acquires the ability to release significant amounts of macrophage-attraction molecules it causes the expansion of a population of myeloid immature cells that may not only help the tumor to suppress immune reactions but also aid in the construction of new blood vessels for tumor growth. A better understanding of the molecular basis of a local myelomonocytic cell population will bring a better understanding of the immunopathology of this disease and will lead to therapeutic interventions in uveal melanoma. This review focuses on the roles of the local inflammatory microenvironment in the development and progression of uveal melanoma.
Functional Mannose-Binding Lectin Levels in Patients with End-Stage Renal Disease on Maintenance Hemodialysis
Authors: Satomura Atsushi , Fujita Takayuki , Yanai Mitsuru , Kumasaka Kazunari , Uehara Yuki , Okada Kazuyoshi , Fuke Yoshinobu , Nakayama Tomohiro
Published: February 2012

Background: Innate immunity is generally impaired in chronic renal failure (CRF). Mannose-binding lectin (MBL) has an important role in first-line host defense against pathogens via the lectin pathway. We recently reported that functional MBL was significantly lower in CRF patients than in healthy subjects. In this study, we aimed to determine whether functional MBL would be improved following hemodialysis (HD) therapy. Methods: This study included 22 patients with end-stage renal disease (ESRD) on maintenance HD. Functional MBL was measured every 6 months for 1 year after HD using an enzyme-linked immunosorbent assay. Results: Median serum functional MBL levels of ESRD patients were significantly higher after 6 and 12 months than at the start of HD therapy (p < 0.05 and p < 0.01, respectively). Furthermore, median functional MBL levels at 12 months were significantly higher than those at 6 months (p < 0.05). Conclusions: We found significant increases in serum functional MBL levels in patients on HD. Our results indicated that HD tailored to remove uremic toxins could improve functional MBL levels in these patients.
Cognitive Function in Health and Disease: The Role of Epigenetic Mechanisms
Authors: Mungenast Alison E. , Tsai Li-Huei
Published: February 2012

Epigenetic mechanisms regulate the interaction between the genome and the environment and have been implicated in the etiology of various brain diseases. One type of epigenetic modification, histone acetylation, is dynamically altered during memory formation. Histone acetylation is regulated by the activities of histone deacetylase (HDAC) and histone acetyltransferase enzymes. The use of HDAC inhibitors has emerged as a promising new strategy for the therapeutic intervention of neurodegenerative disease. We used a combination of pharmacological and mouse genetic approaches that allowed us to identify HDAC2 as a specific negative regulator of synaptic plasticity and memory formation. Our results suggest that HDAC inhibitors enhance cognitive function by inhibiting HDAC2, which renders HDAC2 target genes more accessible to transcriptional activators and coactivators recruited by neuronal activity stimulation. The data presented at the 2011 Barcelona ADPD Conference delineate a novel and important role for HDAC2 activity in the cognitive impairments associated with neurodegenerative disease.
The Effects of Apolipoproteins E3 and E4 on the Transforming Growth Factor-β System in Targeted Replacement Mice
Authors: Haas Adi , Liraz Ori , Michaelson Daniel M.
Published: February 2012

Background: This study examined the possibility that apolipoprotein E4 (apoE4), the most prevalent genetic risk factor of Alzheimer’s disease, interacts isoform specifically with the transforming growth factor (TGF)-β system. Methods: This was pursued by measurements of the effects of apoE3 and apoE4 on the levels of TGF-β ligands and on activation of the Smad system in brains of human apoE targeted replacement mice, utilizing Western blot. Results: The study revealed that apoE4 reduces, isoform specifically, the levels of TGF-β1, TGF-β2 and TGF-β3 in the septum and of TGF-β3 in the hippocampus. In contrast, the levels and extent of phosphorylation of Smad1, 5 and 8 as well as of Smad2 and Smad3 in these brain areas were not affected by apoE4, suggesting that the apoE4-driven effects on the TGF-β system may be mediated via the Smad-independent non-canonical pathway. Conclusion: The possible role of the TGF-β system in mediating the pathological effects of apoE4 is discussed.
Coriandrum sativum L. Protects Human Keratinocytes from Oxidative Stress by Regulating Oxidative Defense Systems
Authors: Park G. , Kim H.G. , Kim Y.O. , Park S.H. , Kim S.Y. , Oh M.S.
Published: February 2012

Background: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. Methods and Results: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. Conclusion: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects.
Association between Nerve Growth Factor Gene Polymorphism and Executive Dysfunction in Japanese Patients with Early-Stage Alzheimer’s Disease and Amnestic Mild Cognitive Impairment
Authors: Nagata Tomoyuki , Shinagawa Shunichiro , Nukariya Kazutaka , Nakayama Ritsuko , Nakayama Kazuhiko , Yamada Hisashi
Published: February 2012

Background/Aims: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer’s disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. Methods: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. Results: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. Conclusion: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI.
Absolute Oral Bioavailability of Almorexant, a Dual Orexin Receptor Antagonist, in Healthy Human Subjects
Authors: Hoch Matthias , Hoever Petra , Zisowsky Jochen , Priestley Anthony , Fleet David , Dingemanse Jasper
Published: February 2012

Background/Aims: The aim of this single-center, open-label study was to assess the absolute bioavailability of an oral (tablet) versus intravenous formulation of almorexant in healthy subjects. Methods: A pilot phase in 3 healthy male subjects, which preceded the main study, consisted of a single 30-min intravenous infusion of 10 mg almorexant. Its objectives were to ensure the tolerability of the intravenous formulation and to select the intravenous dose for the main study. The main study was a randomized, two-way crossover study in 20 healthy subjects (10 males and 10 females). Subjects received a single oral dose of 200 mg almorexant and a single 30-min intravenous infusion of 20 mg almorexant. Results: All 23 subjects completed the study as planned. Almorexant was well tolerated; the main observed adverse events were somnolence and fatigue. A geometric mean total body clearance of 43 l/h (95% CI 39–47) and a volume of distribution of 683 liters (95% CI 552–845) were determined. The absolute oral bioavailability of almorexant was 11.2% (90% CI 9.6–13.1). Conclusion: Almorexant seems to possess a pronounced first-pass effect and metabolism.
Camptothecin Fails to Induce Apoptosis in Tumor Necrosis Factor-Alpha-Treated HaCaT Cells
Authors: Sun Jun , Han Jinzhao , Zhu Quangang , Li Zhen , Hu Jinhong
Published: February 2012

Camptothecin (CPT), a DNA topoisomerase I inhibitor, was originally isolated from the fruits of the Chinese Camptotheca acuminata tree. CPT and its derivatives have been used in the treatment of psoriasis and cancer in China for decades. It is well known that tumor necrosis factor-α (TNF-α) is a key proinflammatory cytokine in the pathogenesis of psoriasis. In this study, we investigated the effect of CPT on TNF-α-treated HaCaT cells. The results indicated that CPT in the concentration range of 0.5–2.0 µg·ml–1 failed to show any proapoptotic effect in HaCaT cells. It was found that both CPT and TNF-α up-regulated the expression of TRAIL receptor 1/2 but not TRAIL in HaCaT cells. Furthermore, the expression of antiapoptotic proteins (IAP1, IAP2, and Bcl-XL) was up-regulated by TNF-α and suppressed by CPT in HaCaT cells. Because these gene products are known to be regulated by nuclear factor-kappa B (NF-ĸB), we examined the role of CPT on NF-ĸB activation. It was found that CPT not only failed to inhibit TNF-α-induced NF-ĸB activation but also contributed to NF-ĸB activation. In addition to these effects, CPT also promoted the production of interleukin-6, similar to TNF-α, in HaCaT cells. In conclusion, despite ample evidence supporting CPT-induced carcinoma cell apoptosis, our study clearly shows that CPT fails to show any proapoptotic effects in HaCaT cells, even though it enhanced TRAIL receptor 1/2 expression and inhibited the expression of TNF-α-induced antiapoptotic proteins. Taken together, this study demonstrates that CPT fails to block the activity of TNF-α. With respect to the NF-ĸB-activating role of CPT, we suggest that the benefit of CPT in the treatment of psoriasis should be reevaluated.
Comparison of the Antiseptic Efficacy of Tissue-Tolerable Plasma and an Octenidine Hydrochloride-Based Wound Antiseptic on Human Skin
Authors: Lademann J. , Richter H. , Schanzer S. , Patzelt A. , Thiede G. , Kramer A. , Weltmann K.-D. , Hartmann B. , Lange-Asschenfeldt B.
Published: February 2012

Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area.
In vitro Activities of Nisin Alone or in Combination with Vancomycin and Ciprofloxacin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains
Authors: Dosler Sibel , Gerceker A. Alev
Published: February 2012

Background: We investigated the in vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus (MSSA) strains. Methods: The minimum inhibitory concentrations were determined by microbroth dilution technique. Antibiotic combinations were assessed using the checkerboard technique. The time-kill curve method was used for determining the bactericidal activity of nisin alone and in combination. Results: For both MSSA and MRSA strains, the minimum inhibitory concentrations of nisin ranged between 4 and 16 mg/l. With a fractional inhibitory concentration of ≧0.5 as borderline, synergistic interactions were seen in three of five isolates with nisin-ciprofloxacin compared to two of five isolates with nisin-vancomycin combinations against both MSSA and MRSA. No antagonism was observed. The results of time-kill curve analysis demonstrated concentration-dependent rapid bactericidal activity of nisin and synergism almost in all strains when nisin was used in combination with ciprofloxacin, and early synergistic interactions in some of the strains when it was used in combination with vancomycin. Conclusion: Nisin seems to be a good candidate for further investigations in the treatment of Gram-positive bacteria, alone or in combination with antibiotics.
Drug-Refractory Ventricular Tachycardias After Myocarditis
Authors: Russo Antonio Dello , Casella Michela , Pieroni Maurizio , Pelargonio Gemma , Bartoletti Stefano , Santangeli Pasquale , Zucchetti Martina , Innocenti Ester , Di Biase Luigi , Carbucicchio Corrado , Bellocci Fulvio , Fiorentini Cesare , Natale Andrea , Tondo Claudio
Published: February 2012

Background—

Ventricular tachycardia (VT) is a significant therapeutic challenge in patients with myocarditis. This study aimed to assess the efficacy and safety of radiofrequency catheter ablation (RFCA) of VT in patients with myocarditis.

Methods and Results—

We enrolled 20 patients (15 men; age, 42 [28–52] years) with a history of biopsy-proven viral myocarditis and drug-refractory VT; 5 patients presented with electrical storm. The median left ventricular ejection fraction was 55% (45–60%). All patients underwent endocardial RFCA with an irrigated catheter, using contact electroanatomic mapping. Recurrence of sustained VT after endocardial RFCA was treated with additional epicardial RFCA. Endocardial RFCA was acutely successful in 14 patients (70%) while in the remaining 6 (30%) clinical VT was successfully ablated by epicardial RFCA. In 1 patient, hemodynamic instability required an intra-aortic balloon pump to complete RFCA. No major complication occurred during or after RFCA. Over a median follow-up time of 28 (11–48) months, 18 patients (90%) remained free of sustained VT; 2 patients (10%, both with baseline left ventricular ejection fraction ≤35%) died of acute heart failure unrelated to ventricular arrhythmias.

Conclusions—

In patients with myocarditis, RFCA of drug-refractory VT is feasible, safe, and effective. Epicardial RFCA should be considered as an important therapeutic option to increase success rate.
Serial Assessment of Coronary Artery Response to Paclitaxel-Eluting Stents Using Optical Coherence Tomography
Authors: Guagliumi Giulio , Bezerra Hiram G. , Sirbu Vasile , Ikejima Hideyuki , Musumeci Giuseppe , Biondi-Zoccai Giuseppe , Lortkipanidze Nikoloz , Fiocca Luigi , Capodanno Davide , Wang Wei , Tahara Satoko , Vassileva Angelina , Matiashvili Aleksandre , Valsecchi Orazio , Costa Marco A.
Published: February 2012

Background—

The paucity of longitudinal, serial high-resolution imaging studies has limited our understanding of in vivo arterial response to drug-eluting stents. We sought to investigate the human coronary response to paclitaxel-eluting stent implantation, using serial optical coherence tomography assessments.

Methods and Results—

Thirty patients with at least 2 significant coronary lesions in different vessels were treated with a paclitaxel-eluting stent. The most severe stenosis (lesion A) was treated at the initial procedure, and the second target vessel (lesion B) was stented 3 months later. Optical coherence tomography was performed at baseline, 3-, and 9-month follow-up for lesions A and baseline and 6 months for lesions B. Prespecified end points were percent of uncovered and malapposed struts over time. In lesions A, uncovered struts were 3.77±4.94% and 3.02±4.35% at 3 versus 9 months (
P
=NS). Malapposed struts were 3.55±5.16% at post-procedure, 1.51±3.52% at 3 months, and 0.60±1.82% at 9 months (
P
<0.05, at 3 versus 9 months). Strut-level neointimal thickness was 0.19±0.09 mm and 0.20±0.11 mm (
P
=NS) over time. Newly acquired malapposition was detected in 10.4% and 3.3% of 2.5-mm segments at 3- and 9-month follow-up. In lesions B, uncovered struts were 2.91±5.47% at 6-months. Malapposed struts were 4.94±6.70% post-procedure and 1.01±3.11% at 6 months (
P
<0.01), with 0.19±0.09-mm neointimal thickness at follow-up.

Conclusions—

Optical coherence tomography imaging suggested the first 3 months to be the period with most biological activity after paclitaxel-eluting stent implantation, when the proliferative reaction mainly occurs and malapposition resolves. A less active, yet continuous, dynamic arterial response, with resolution and development of malapposition, occurs through 9 months post-treatment.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00704145.
Coronary Microcirculatory Resistance Is Independent of Epicardial Stenosis
Authors: Yong Andy S.C. , Ho Michael , Shah Maulik G. , Ng Martin K.C. , Fearon William F.
Published: February 2012

Background—

Recent studies show that coronary microcirculatory impairment is an independent predictor of poor outcomes in patients with cardiovascular disease. However, controversy exists over whether microcirculatory resistance, a measure of coronary microcirculatory status, is dependent on epicardial stenosis severity. Previous studies demonstrating that microcirculatory resistance is dependent on epicardial stenosis severity have not accounted for collateral flow in their measurement of microcirculatory resistance. We investigated whether the index of microcirculatory resistance is independent of epicardial stenosis by comparing the index of microcirculatory resistance (IMR) levels in patients before and after percutaneous coronary intervention (PCI).

Methods and Results—

Consecutive patients undergoing elective PCI of the left anterior descending artery were recruited. Patients who developed periprocedural myocardial infarction were excluded. A pressure-temperature sensor wire was used to measure the apparent IMR (IMR
app
), which does not adjust for collateral flow, and the true IMR (IMR
true
), which incorporates wedge pressure measurement to account for collateral flow, before and after PCI. In 43 patients, there was no difference between pre- and post-PCI IMR
true
(mean difference=0.8±11.7,
P
=0.675). IMR
app
was higher pre-PCI compared with post-PCI (mean difference=10.0±14.5,
P
<0.001). IMR
app
was higher than IMR
true
(mean difference=9.3±14.2,
P
<0.001), and the difference between the IMR
app
and IMR
true
became greater with decreasing fractional flow reserve and increasing coronary wedge pressure. Pre-PCI fractional flow reserve correlated modestly with IMR
app
(
r
=−0.33,
P
=0.03), but not IMR
true
(
r
=0.26,
P
=0.10).

Conclusions—

Coronary microcirculatory resistance is independent of functional epicardial stenosis severity when collateral flow is taken into account.
Viral Gene Transfer Rescues Arrhythmogenic Phenotype and Ultrastructural Abnormalities in Adult Calsequestrin-Null Mice With Inherited Arrhythmias
Authors: Denegri Marco , Avelino-Cruz José Everardo , Boncompagni Simona , De Simone Stefano Andrea , Auricchio Alberto , Villani Laura , Volpe Pompeo , Protasi Feliciano , Napolitano Carlo , Priori Silvia Giuliana
Published: February 2012

Rationale:

Catecholaminergic polymorphic ventricular tachycardia is an inherited disease that predisposes to cardiac arrest and sudden death. The disease is associated with mutations in the genes encoding for the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2). CASQ2 mutations lead to a major loss of CASQ2 monomers, possibly because of enhanced degradation of the mutant protein. The decrease of CASQ2 is associated with a reduction in the levels of Triadin (TrD) and Junctin (JnC), two proteins that form, with CASQ2 and RyR2, a macromolecular complex devoted to control of calcium release from the sarcoplasmic reticulum.

Objective:

We intended to evaluate whether viral gene transfer of wild-type CASQ2 may rescue the broad spectrum of abnormalities caused by mutant CASQ2.

Methods and Results:

We used an adeno-associated serotype 9 viral vector to express a green fluorescent protein-tagged CASQ2 construct. Twenty weeks after intraperitoneal injection of the vector in neonate CASQ2 KO mice, we observed normalization of the levels of calsequestrin, triadin, and junctin, rescue of electrophysiological and ultrastructural abnormalities caused by CASQ2 ablation, and lack of life-threatening arrhythmias.

Conclusions:

We have proven the concept that induction of CASQ2 expression in knockout mice reverts the molecular, structural, and electric abnormalities and prevents life-threatening arrhythmias in CASQ2-defective catecholaminergic polymorphic ventricular tachycardia mice. These data support the view that development of CASQ2 viral gene transfer could have clinical application.
Generalization and Multirate Models of Motor Adaptation
Authors: Tanaka Hirokazu , Krakauer John W. , Sejnowski Terrence J.
Published: February 2012

When subjects adapt their reaching movements in the setting of a systematic force or visual perturbation, generalization of adaptation can be assessed psychophysically in two ways: by testing untrained locations in the work space at the end of adaptation (slow postadaptation generalization) or by determining the influence of an error on the next trial during adaptation (fast trial-by-trial generalization). These two measures of generalization have been widely used in psychophysical studies, but the reason that they might differ has not been addressed explicitly. Our goal was to develop a computational framework for determining when a two-state model is justified by the data and to explore the implications of these two types of generalization for neural representations of movements. We first investigated, for single-target learning, how well standard statistical model selection procedures can discriminate two-process models from single-process models when learning and retention coefficients were systematically varied. We then built a two-state model for multitarget learning and showed that if an adaptation process is indeed two-rate, then the postadaptation generalization approach primarily probes the slow process, whereas the trial-by-trial generalization approach is most informative about the fast process. The fast process, due to its strong sensitivity to trial error, contributes predominantly to trial-by-trial generalization, whereas the strong retention of the slow system contributes predominantly to postadaptation generalization. Thus, when adaptation can be shown to be two-rate, the two measures of generalization may probe different brain representations of movement direction.
Entropy Estimation in Turing's Perspective
Authors: Zhang Zhiyi
Published: February 2012

A new nonparametric estimator of Shannon's entropy on a countable alphabet is proposed and analyzed against the well-known plug-in estimator. The proposed estimator is developed based on Turing's formula, which recovers distributional characteristics on the subset of the alphabet not covered by a size-n sample. The fundamental switch in perspective brings about substantial gain in estimation accuracy for every distribution with finite entropy. In general, a uniform variance upper bound is established for the entire class of distributions with finite entropy that decays at a rate of O(ln(n)/n) compared to O([ln(n)]2/n) for the plug-in. In a wide range of subclasses, the variance of the proposed estimator converges at a rate of O(1/n), and this rate of convergence carries over to the convergence rates in mean squared errors in many subclasses. Specifically, for any finite alphabet, the proposed estimator has a bias decaying exponentially in n. Several new bias-adjusted estimators are also discussed.
Learning Coefficient of Generalization Error in Bayesian Estimation and Vandermonde Matrix-Type Singularity
Authors: Aoyagi Miki , Nagata Kenji
Published: February 2012

The term algebraic statistics arises from the study of probabilistic models and techniques for statistical inference using methods from algebra and geometry (Sturmfels, 2009 ). The purpose of our study is to consider the generalization error and stochastic complexity in learning theory by using the log-canonical threshold in algebraic geometry. Such thresholds correspond to the main term of the generalization error in Bayesian estimation, which is called a learning coefficient (Watanabe, 2001a , 2001b ). The learning coefficient serves to measure the learning efficiencies in hierarchical learning models. In this letter, we consider learning coefficients for Vandermonde matrix-type singularities, by using a new approach: focusing on the generators of the ideal, which defines singularities. We give tight new bound values of learning coefficients for the Vandermonde matrix-type singularities and the explicit values with certain conditions. By applying our results, we can show the learning coefficients of three-layered neural networks and normal mixture models.
A Multiscale Analysis of the Extreme Weather Events over Western Russia and Northern Pakistan during July 2010
Authors: Galarneau Thomas J. , Hamill Thomas M. , Dole Randall M. , Perlwitz Judith
Published: February 2012

This manuscript presents a detailed multiscale analysis—using observations, model analyses, and ensemble forecasts—of the extreme heat wave over Russia and historic floods over Pakistan during late July 2010, with an emphasis on the floods over northern Pakistan. The results show that recirculation of air and dynamically driven subsidence occurring with the intensification of the blocking anticyclone in late July 2010 were key factors for producing the exceptionally warm temperatures over western Russia. Downstream energy dispersion from the blocking region led to trough deepening northwest of Pakistan and ridge building over the Tibetan Plateau, thereby providing the linkage between the Russian heat wave and Pakistan flood events on the large scale, in agreement with previous studies.

The extratropical downstream energy dispersion and enhanced convective outflow on the large scale associated with the active phase of the Madden–Julian oscillation facilitated the formation of an intense upper-level jet northwest of Pakistan. During this same period an intense southeasterly, low-level, barrier jet–like feature formed over northern Pakistan in conjunction with a westward-moving monsoon depression. This low-level jet and deep easterly flow on the equatorward flank of an anomalous anticyclone over the Tibetan Plateau further enhanced the transport of deep tropical moisture into Pakistan and produced a sustained upslope flow and an extended period of active convection, thereby providing an important contribution leading to the exceptional rainfall amounts. The deep easterly flow and intense low-level jet were features that were absent during previous convective episodes over northern Pakistan in 2010, and hence, were likely key factors in the increased severity of the late July event.
Culture, Visual Perspective, and the Effect of Material Success on Perceived Life Quality
Authors: Wirtz Derrick , Scollon Christie Napa
Published: February 2012

Is a life characterized by material success one that will be seen favorably by others? In two studies, we explored the effect of a target person’s material success on perceptions of the target’s life quality. Participants viewed a survey ostensibly completed by another person—which experimentally varied the target’s material success in the form of income—before globally rating the target’s life. Study 1 provided a cross-cultural comparison, finding that Singaporeans, but not Americans, rated a target high in material success as having a life of greater quality than a target low in material success. Study 2 investigated the moderating effect of visual perspective among Singaporeans, hypothesizing that adopting another’s perspective emphasizes the shared belief that material success is an indicator of life quality. Consistent with this reasoning, participants who adopted a third-person visual perspective rated a target high in material success as having a life of greater quality than a target low in material success, but those who adopted a first-person visual perspective did not rate targets differently based on material success.
The publics’ concern for global warming: A cross-national study of 47 countries
Authors: Kvaløy Berit , Finseraas Henning , Listhaug Ola
Published: February 2012

This article relies on data from the 2005–09 World Values Survey to examine individual and cross-national variation in perception of the seriousness of global warming. The data show that a large majority of the public in all countries are concerned about the problem of global warming and that this assessment is part of a broader concern for global environmental issues. The widespread concern implies that global warming has the potential to generate mass political participation and demand for political action. Motivated by a value-based approach to the study of public opinion, the article shows that perception of the seriousness of the problem is positively correlated with high education, post-materialism, and a leftist position on the left–right scale. In addition, religious beliefs are important, suggesting that there is some diversity in the value basis for the issue and that it is not only linked to the ‘new-politics’ perspective. Variation across nations in wealth and CO2 emissions is not significantly related to the publics’ assessments of the problem, and, somewhat counterintuitively, people from countries relatively more exposed to climate-related natural disasters are less concerned about global warming. We suggest possible explanations for the latter finding and discuss our results in relation to the broader literature on environmental change, insecurity, and the potential for conflict.
Climate variability, economic growth, and civil conflict
Authors: Koubi Vally , Bernauer Thomas , Kalbhenn Anna , Spilker Gabriele
Published: February 2012

Despite many claims by high-ranking policymakers and some scientists that climate change breeds violent conflict, the existing empirical literature has so far not been able to identify a systematic, causal relationship of this kind. This may either reflect de facto absence of such a relationship, or it may be the consequence of theoretical and methodological limitations of existing work. In this article we revisit the climate–conflict hypothesis along two lines. First, we concentrate on indirect effects of climatic conditions on conflict, whereas most of the existing literature focuses on direct effects. Specifically, we examine the causal pathway linking climatic conditions to economic growth and to armed conflict, and argue that the growth–conflict part of this pathway is contingent on the political system. Second, we employ a measure of climatic variability that has advantages over those used in the existing literature because it can presumably take into account the adaptation of production to persistent climatic changes. For the empirical analysis we use a global dataset for 1980–2004 and design the testing strategy tightly in line with our theory. Our empirical analysis does not produce evidence for the claim that climate variability affects economic growth. However, we find some, albeit weak, support for the hypothesis that non-democratic countries are more likely to experience civil conflict when economic conditions deteriorate.
Could climate change precipitate peace?
Authors: Gartzke Erik
Published: February 2012

Growing interest in the social consequences of climate change has fueled speculation that global warming could lead to an increase in various forms of political violence. This article examines the effects of climate change on international conflict subsequent to the onset of European industrialization. Surprisingly, analysis at the system level suggests that global warming is associated with a reduction in interstate conflict. This naive relationship is suspect, however, as the increased consumption of carbon-based fuels is itself associated with changing patterns of politics and prosperity. In particular, economic development has been viewed as a cause of both climate change and interstate peace. Incorporating measures of development, democracy, cross-border trade, and international institutions reveals that systemic trends toward peace are actually best accounted for by the increase in average international income. The results imply that climate change, which poses a number of critical challenges for citizens and policymakers, need not be characterized as fundamentally a security issue, though climate change may have important security implications on the periphery of world politics. The analysis here also suggests that efforts to curb climate change should pay particular attention to encouraging clean development among middle-income states, as these countries are the most conflict prone. Ironically, stagnating economic development in middle-income states caused by efforts to combat climate change could actually realize fears of climate-induced warfare.
Civil war, climate change, and development: A scenario study for sub-Saharan Africa
Authors: Devitt Conor , Tol Richard SJ
Published: February 2012

This article presents a model of development, civil war and climate change. There are multiple interactions. Economic growth reduces the probability of civil war and the vulnerability to climate change. Climate change increases the probability of civil war. The impacts of climate change, civil war and civil war in the neighbouring countries reduce economic growth. The model has two potential poverty traps – one is climate-change-induced and one is civil-war-induced – and the two poverty traps may reinforce one another. The model is calibrated to sub-Saharan Africa and a double Monte Carlo analysis is conducted in order to account for both parameter uncertainty and stochasticity. Although the IPCC Special Report on Emission Scenarios (SRES) is used as the baseline, thus assuming rapid economic growth in Africa and convergence of African living standards to the rest of the world, the impacts of civil war and climate change (ignored in SRES) are sufficiently strong to keep a number of countries in Africa in deep poverty with a high probability.
Come rain or shine: An analysis of conflict and climate variability in East Africa
Authors: Raleigh Clionadh , Kniveton Dominic
Published: February 2012

Previous research on environment and security has contested the existence, nature and significance of a climate driver of conflict. In this study, we have focused on small-scale conflict over East Africa where the link between resource availability and conflict is assumed to be more immediate and direct. Using the parameter of rainfall variability to explore the marginal influence of the climate on conflict, the article shows that in locations that experience rebel or communal conflict events, the frequency of these events increases in periods of extreme rainfall variation, irrespective of the sign of the rainfall change. Further, these results lend support to both a ‘zero-sum’ narrative, where conflicting groups use force and violence to compete for ever-scarcer resources, and an ‘abundance’ narrative, where resources spur rent-seeking/wealth-seeking and recruitment of people to participate in violence. Within the context of current uncertainty regarding the future direction of rainfall change over much of Africa, these results imply that small-scale conflict is likely to be exacerbated with increases in rainfall variability if the mean climate remains largely unchanged; preferentially higher rates of rebel conflict will be exhibited in anomalously dry conditions, while higher rates of communal conflict are expected in increasingly anomalous wet conditions.
Emotion-Related Self-Regulation in Children
Authors: Eisenberg Nancy , Sulik Michael J.
Published: February 2012

In this article, the authors review basic conceptual issues in research on children’s emotion-related self-regulation, including the differentiation between self-regulation that is effortful and voluntary and control-related processes that are less amenable to effortful control. In addition, the authors summarize what researchers know about developmental changes in self-regulatory capacities, give examples of various methods used to assess these abilities, and summarize findings on the relations between self-regulation or effortful control and positive adjustment and maladjustment. Finally, the authors discuss some strategies for effectively teaching students about emotion regulation.
Continuous Assessment Improved Academic Achievement and Satisfaction of Psychology Students in Spain
Authors: Carrillo-de-la-Peña María T. , Pérez Jorge
Published: February 2012

The authors present the experience of a continuous assessment procedure carried out in the second term of a physiological psychology course during 3 consecutive academic years at a Spanish university. Each year, the academic outcomes of students under continuous assessment (the experimental group) were compared with those of students under traditional assessment (the control group), with 903 total students. To control for possible differences in prior academic achievement, grades in the first term of the same subject were used as a covariate, and progress was assessed from the first-term to the second-term evaluations in the experimental and control groups. The results provided robust evidence of the positive impact of continuous assessment on all indices of academic outcomes considered. In addition, responses to a self-report questionnaire revealed that continuous assessment improved students’ satisfaction and was perceived by students as a procedure that promotes deeper learning.