bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Modified Extragradient Methods for Solving Split Feasibility and Fixed Point Problems
Authors: Kong Zhao-Rong , Ceng Lu-Chuan , Wen Ching-Feng
Published: December 2012

We consider and study the modified extragradient methods for finding a common element of the solution set Γ of a split feasibility problem (SFP) and the fixed point set Fix(S) of a strictly pseudocontractive mapping S in the setting of infinite‐dimensional Hilbert spaces. We propose an extragradient algorithm for finding an element of Fix(S)∩Γ where S is strictly pseudocontractive. It is proven that the sequences generated by the proposed algorithm converge weakly to an element of Fix(S)∩Γ. We also propose another extragradient‐like algorithm for finding an element of Fix(S)∩Γ where S : C → C is nonexpansive. It is shown that the sequences generated by the proposed algorithm converge strongly to an element of Fix(S)∩Γ.
Limit‐Point/Limit‐Circle Results for Equations with Damping
Authors: Bartušek M. , Graef John R.
Published: December 2012

The authors study the nonlinear limit‐point and limit‐circle properties for the second order nonlinear damped differential equation (a(t) | y′|p−1y′)′ + b(t) | y′|q−1y′ + r(t) | y|λ−1y = 0, where 0 < λ ≤ p ≤ q, a(t) > 0, and r(t) > 0. Some examples are given to illustrate the main results.
Development and Remodeling of the Vertebrate Blood-Gas Barrier
Authors: Makanya Andrew , Anagnostopoulou Aikaterini , Djonov Valentin
Published: December 2012

During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB. In the noncompliant avian lung, attenuation proceeds through cell-cutting processes that result in remarkable thinning of the epithelial layer. A host of morphoregulatory molecules, including transcription factors such as Nkx2.1, GATA, HNF-3, and WNT5a; signaling molecules including FGF, BMP-4, Shh, and TFG-βand extracellular proteins and their receptors have been implicated. During normal physiological function, the BGB may be remodeled in response to alterations in transmural pressures in both blood capillaries and airspaces. Such changes are mitigated through rapid expression of the relevant genes for extracellular matrix proteins and growth factors. While an appreciable amount of information regarding molecular control has been documented in the mammalian lung, very little is available on the avian lung.
Effective Combination of Photodynamic Therapy and Imiquimod 5% Cream in the Treatment of Actinic Keratoses: Three Cases
Authors: Held Laura , Eigentler Thomas Kurt , Leiter Ulrike , Garbe Claus , Berneburg Mark-Jürgen
Published: December 2012

Background. The therapy for actinic keratoses includes photodynamic therapy (PDT) and imiquimod 5% cream. The sequential use of both could result in better clinical outcomes.Objectives. To enhance efficacy of therapies while improving tolerability, convenience, and patient adherence with a scheme combining two concomitant or sequential AK treatments.Methods. All patients underwent one session of conventional PDT. Two weeks after, the PDT imiquimod 5% cream was applied to the treatment area once daily for three days per week. One course continued for four weeks followed by a clinical evaluation and decision about further treatment. Patients who had not cleared all of their AK lesions in the treatment area in course 1 participated in a second 4-week course of treatment.Limitations. Small size of population.Results. Three participants were enrolled. Two patients showed complete clinical clearance of AKs. The effect was also noted after long-term followup, at months seven and eleven. No subject discontinued for an adverse event. There were severe local skin reactions in two participants which were severe erythema, scaling, and crusting. One patient showed no response to the therapy.Conclusions. Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses. This initial proof-of-concept should be studied in larger clinical trials.
Cancer Vaccines: State of the Art of the Computational Modeling Approaches
Authors: Pappalardo Francesco , Chiacchio Ferdinando , Motta Santo
Published: December 2012

Cancer vaccines are a real application of the extensive knowledge of immunology to the field of oncology. Tumors are dynamic complex systems in which several entities, events, and conditions interact among them resulting in growth, invasion, and metastases. The immune system includes many cells and molecules that cooperatively act to protect the host organism from foreign agents. Interactions between the immune system and the tumor mass include a huge number of biological factors. Testing of some cancer vaccine features, such as the best conditions for vaccine administration or the identification of candidate antigenic stimuli, can be very difficult or even impossible only through experiments with biological models simply because a high number of variables need to be considered at the same time. This is where computational models, and, to this extent, immunoinformatics, can prove handy as they have shown to be able to reproduce enough biological complexity to be of use in suggesting new experiments. Indeed, computational models can be used in addition to biological models. We now experience that biologists and medical doctors are progressively convinced that modeling can be of great help in understanding experimental results and planning new experiments. This will boost this research in the future.
Glutamine and Alanyl-Glutamine Increase RhoA Expression and ReduceClostridium difficileToxin-A-Induced Intestinal Epithelial Cell Damage
Authors: Santos Ana A. Q. A. , Braga-Neto Manuel B. , Oliveira Marcelo R. , Freire Rosemeire S. , Barros Eduardo B. , Santiago Thiago M. , Rebelo Luciana M. , Mermelstein Claudia , Warren Cirle A. , Guerrant Richard L. , Brito Gerly A. C.
Published: December 2012

Clostridium difficileis a major cause of antibiotic-associated colitis and is associated with significant morbidity and mortality. Glutamine (Gln) is a major fuel for the intestinal cell population. Alanyl-glutamine (Ala-Gln) is a dipeptide that is highly soluble and well tolerated. IEC-6 cells were used in thein vitroexperiments. Cell morphology was evaluated by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Cell proliferation was assessed by WST-1 and Ki-67 and apoptosis was assessed by TUNEL. Cytoskeleton was evaluated by immunofluorescence for RhoA and F-actin. RhoA was quantified by immunoblotting. TcdA induced cell shrinkage as observed by AFM, SEM, and fluorescent microscopy. Additionally, collapse of the F-actin cytoskeleton was demonstrated by immunofluorescence. TcdA decreased cell volume and area and increased cell height by 79%, 66.2%, and 58.9%, respectively. Following TcdA treatment, Ala-Gln and Gln supplementation, significantly increased RhoA by 65.5% and 89.7%, respectively at 24 h. Ala-Gln supplementation increased cell proliferation by 137.5% at 24 h and decreased cell apoptosis by 61.4% at 24 h following TcdA treatment. In conclusion, TcdA altered intestinal cell morphology and cytoskeleton organization, decreased cell proliferation, and increased cell apoptosis. Ala-Gln and Gln supplementation reduced intestinal epithelial cell damage and increased RhoA expression.
Roles of Organic Acid Anion Secretion in Aluminium Tolerance of Higher Plants
Authors: Yang Lin-Tong , Qi Yi-Ping , Jiang Huan-Xin , Chen Li-Song
Published: December 2012

Approximately 30% of the world’s total land area and over 50% of the world’s potential arable lands are acidic. Furthermore, the acidity of the soils is gradually increasing as a result of the environmental problems including some farming practices and acid rain. At mildly acidic or neutral soils, aluminium(Al) occurs primarily as insoluble deposits and is essentially biologically inactive. However, in many acidic soils throughout the tropics and subtropics, Al toxicity is a major factor limiting crop productivity. The Al-induced secretion of organic acid (OA) anions, mainly citrate, oxalate, and malate, from roots is the best documented mechanism of Al tolerance in higher plants. Increasing evidence shows that the Al-induced secretion of OA anions may be related to the following several factors, including (a) anion channels or transporters, (b) internal concentrations of OA anions in plant tissues, (d) temperature, (e) root plasma membrane (PM) H+-ATPase, (f) magnesium (Mg), and (e) phosphorus (P). Genetically modified plants and cells with higher Al tolerance by overexpressing genes for the secretion and the biosynthesis of OA anions have been obtained. In addition, some aspects needed to be further studied are also discussed.
Characterization of Sera with Discordant Results from Reverse Sequence Screening for Syphilis
Authors: Lee Kyunghoon , Park Hyewon , Roh Eun Youn , Shin Sue , Park Kyoung Un , Park Myoung Hee , Song Eun Young
Published: December 2012

Reverse sequence screening for syphilis (RSSS) (screening with treponemal tests, followed by confirmation with nontreponemal tests) has been increasingly adopted. CDC recommends confirmation of discordant results (reactive EIA/CIA and nonreactive nontreponemal test) withTreponema pallidumparticle agglutination assay (TP-PA). We characterized sera with discordant results from RSSS with Architect Syphilis TP CIA. Among 15,713 screening tests using Architect Syphilis TP at Seoul National University Gangnam Center between October 2010 and May 2011, 260 (1.7%) showed reactive results. Rapid plasma reagin (RPR) and TP-PA were performed on 153 available sera among them. On sera with discordant results between Architect Syphilis TP and TP-PA, INNO-LIA Syphilis Score and FTA-ABS were performed. Among 153 sera, RPR was nonreactive in 126 (82.4%). Among them, TP-PA was positive in 103 (81.7%), indeterminate (±) in 7 (5.6%), and negative in 16 (12.7%). Out of 16 CIA(+)/RPR(−)/TP-PA(−) sera, INNO-LIA Syphilis Score and/or FTA-ABS were negative on 14 sera. Out of 7 CIA(+)/RPR(−)/TP-PA(±) sera, INNO-LIA Syphilis Score and FTA-ABS were positive/reactive in 6 sera. RSSS with confirmation by TP-PA on sera with discordant results between Architect Syphilis TP and RPR effectively delineated those discordant results and could be successfully adopted for routine checkup for syphilis.
Optimisation of the Enzymatic Hydrolysis of Blood Cells with a Neutral Protease
Authors: Zheng Yanbin , Chen Qiushi , Shan Anshan , Zhang Hao
Published: December 2012

For utilizing the blood cells (BCs) effectively, enzymatic hydrolysis was applied to produce the enzymatically hydrolyzed blood cells (EHBCs) by using a neutral protease as a catalyst. The results of the single-factor experiments showed optimal substrate concentration, enzyme to substrate ratio (E/S), pH, temperature, and incubation period were 1.00%, 0.10, 7.00, 50.00°C, and 12.00 h, respectively. The optimized hydrolysis conditions from response surface methodology (RSM) were pH 6.50, E/S 0.11, temperature 45.00°C, and incubation period 12.00 h. Under these conditions (substrate concentration 1.00%), the degree of hydrolysis (DH) was 35.06%. The free amino acids (FAAs) content of the EHBCs (35.24%) was 40.46 times higher than BCs while the total amino acids (TAAs) content was lower than BCs. The scores of lysine (human 0.87; pig 0.97), valine (human 1.42; pig 1.38), leucine (human 1.50; pig 1.90), tyrosine (human 0.84; pig 1.09), and histidine (human 2.17; pig 2.50) indicated that the EHBCs basically fulfilled the adult human and pig nutritional requirements. The calculated protein efficiency ratios (C-PERs) of the EHBCs were 3.94, 6.19, 21.73, and 2.04. In summary, the EHBCs were produced successfully with optimized conditions and could be a novel protein source for humans and pigs.
A Retrospective Longitudinal Cohort Study of Antihypertensive Drug Use and New-Onset Diabetes in Taiwanese Patients
Authors: Huang Ching-Ya , Ma Tsochiang , Tien Liyun , Hsieh Yow-Wen , Lee Shwu-Yi , Chen Hung-Yi , Jong Gwo-Ping
Published: December 2012

Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined in a clinical setting. The aim was to investigate the association between antihypertensive drugs and NOD in Taiwan. We conducted a retrospective study of hypertensive Taiwanese patients receiving antihypertensive drugs treatment between January 2006 and December 2011. Clinical information and laboratory parameters were collected by reviewing the medical records. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 120 NOD cases were identified in 1001 hypertensive patients during the study period. The risk of NOD after adjusting sex, age, baseline characteristics, and lipid profiles was higher among users of thiazide diuretics (OR, 1.65; 95% confidence interval (CI), 1.12–2.45) and nondihydropyridine (non-DHP) calcium channel blockers (CCBs) (OR, 1.96; 95% CI, 1.01–3.75) than among nonusers. Other antihypertensive drug classes were not associated with risk of NOD. Our results show that patients with hypertension who take thiazide diuretics and non-DHP CCBs are at higher risk of developing NOD than those who take other classes of antihypertensive drugs in Taiwan.
Vitamin D and Bone Disease
Authors: Christodoulou S. , Goula T. , Ververidis A. , Drosos G.
Published: December 2012

Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.
Using Nanoinformatics Methods for Automatically Identifying Relevant Nanotoxicology Entities from the Literature
Authors: García-Remesal Miguel , García-Ruiz Alejandro , Pérez-Rey David , de la Iglesia Diana , Maojo Víctor
Published: December 2012

Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a “proof of concept” that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine.
Predictors of Developing Hepatocellular Carcinoma in Treated HCV-Carriers in Morocco according to University Hospital Experience
Authors: Cherradi Younès , Afifi Rajaa , Benbrahim Hanaa , Essamri Wafaa , Benelbarhdadi Imane , Ajana Fatima Zahra , El Malki Hadj Omar , Benazzouz Mustapha , Essaid Abdellah
Published: December 2012

Introduction. Hepatitis C is the first major cause for HCC in Morocco. Antiviral treatment reduces the risk of developing HCC but few cases of HCC in HCV-treated patients were reported. We aimed to define this population’s features and to identify predictive factors of developing HCC. Patients and Methods. We included all HCV carriers who developed HCC after antiviral treatment from January 2002 to April 2010. We compare HCV-treated patients with no developed HCC to HCC population using khi-2 and Fisher Exact analysis. Results. 369 HVC-treated patients were considered, and 20 HCC were reported. The risk of HCC was not significant according to gender and genotypes (resp., P=0.63 and P=0.87). Advanced age and severe fibrosis were significant risk factors (resp., P=0.003 and P=0.0001). HCC was reported in 2.6% of sustained virological responders versus 12.5% of nonresponders (P=0.004). Conclusion. In our series, 5% of previously treated patients developed an HCC. Advanced age and severe fibrosis at HCV diagnosis are predictive factors of HCC occurrence. Sustained virological response reduces considerably the risk of HCC occurrence but screening is indicated even after SVR.
Hyperglycemia Increases Susceptibility to Ischemic Necrosis
Authors: Lévigne D. , Tobalem M. , Modarressi A. , Pittet-Cuénod B.
Published: December 2012

Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemiaper seon the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemiaper seincreases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.
Immunoregulation byTaenia crassicepsand Its Antigens
Authors: Peón Alberto N. , Espinoza-Jiménez Arlett , Terrazas Luis I.
Published: December 2012

Taenia crassicepsis a cestode parasite of rodents (in its larval stage) and canids (in its adult stage) that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced byT. crassicepsand its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.
Photosensitizer Adhered to Cell Culture Microplates Induces Phototoxicity in Carcinoma Cells
Authors: Ziegler Verena , Kiesslich Tobias , Krammer Barbara , Plaetzer Kristjan
Published: December 2012

In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings.
The AC-OK Cooccurring Screen: Reliability, Convergent Validity, Sensitivity, and Specificity
Authors: Cherry Andrew L. , Dillon Mary E.
Published: December 2012

The principal barriers to universal screening for the cooccurring disorders of mental illness and substance abuse are training, time, cost, and a reliable and valid screen. Although many of the barriers to universal screening still remain intact, the lack of a cooccurring screen that is effective and can be administered in a cost efficient way is no longer an obstacle. This study examined the reliability, factor structure, and convergent validity of the 15-item AC-OK Cooccurring Screen. A total of 2,968 AC-OK Cooccurring Screens administrated to individuals who called or went to one of the nine participating mental health and substance abuse treatment facilities were administrated and analyzed. Principal axis factor (PAF) analysis was used in the confirmatory factor analysis to identify the common variance among the items in the scales while excluding unique variance. Cronbach's Alpha was used to establish internal consistency (reliability) of each subscale. Finally, the findings from the AC-OK Cooccurring Screen were compared to individual scores on two standardized reference measures, the addiction severity index and the Client assessment record (a measure of mental health status) to determine sensitivity and specificity. This analysis of the AC-OK Cooccurring Screen found the subscales to have excellent reliability, very good convergent validity, excellent sensitivity, and sufficient specificity to be highly useful in screening for cooccurring disorders in behavioral health settings. In this study, the AC-OK Cooccurring Screen had a Cronbach's Alpha of .92 on the substance abuse subscale and a Cronbach's Alpha of .80 on the mental health subscale.
The Interactive Effects of Affect Lability, Negative Urgency, and Sensation Seeking on Young Adult Problematic Drinking
Authors: Karyadi Kenny , Coskunpinar Ayca , Dir Allyson L. , Cyders Melissa A.
Published: December 2012

Prior studies have suggested that affect lability might reduce the risk for problematic drinking among sensation seekers by compensating for their deficiencies in emotional reactivity and among individuals high on negative urgency by disrupting stable negative emotions. Due to the high prevalence of college drinking, this study examined whether affect lability interacted with sensation seeking and negative urgency to influence college student problematic drinking. 414 college drinkers (mean age: 20, 77% female, and 74% Caucasian) from a US Midwestern University completed self-administered questionnaires online. Consistent with our hypotheses, our results indicated that the effects of sensation seeking and negative urgency on problematic drinking weakened at higher levels of affect lability. These findings emphasize the importance of considering specific emotional contexts in understanding how negative urgency and sensation seeking create risk for problematic drinking among college students. These findings might also help us better understand how to reduce problematic drinking among sensation seekers and individuals high on negative urgency.
Modulation of the Antibiotic Activity by Extracts fromAmburana cearensisA. C. Smith andAnadenanthera macrocarpa(Benth.) Brenan
Authors: Figueredo Fernando G. , Ferreira Emerson O. , Lucena Bruno F. F. , Torres Cícero M. G. , Lucetti Daniel L. , Lucetti Elaine C. P. , Silva João Marcos F. L. , Santos Francisco A. V. , Medeiros Cássio R. , Oliveira Gardênia M. M. , Colares Aracélio V. , Costa José G. M. , Coutinho Henrique D. M. , Menezes Irwin R. A. , Silva Júlio C. F. , Kerntopf Marta R. , Figueiredo Patrícia R. L. , Matias Edinardo F. F.
Published: December 2012

The aim of this study was to verify the possible interactions between ethanol extracts ofAmburana cearensisA. C. Smith andAnadenanthera macrocarpa(Benth.) Brenan, combined with six antimicrobial drugs against multiresistant strains ofStaphylococcus aureusandEscherichia coliisolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC). The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract ofAnadenanthera macrocarpaagainst EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 μg/mL. Among theβ-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin againstS. aureus358.
High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis
Authors: Vukusic Kristina , Jonsson Marianne , Brantsing Camilla , Dellgren Göran , Jeppsson Anders , Lindahl Anders , Asp Julia
Published: December 2012

3D environment and high cell density play an important role in restoring and supporting the phenotypes of cells represented in cardiac tissues. The aim of this study was therefore to investigate the suitability of high density sphere (HDS) cultures for studies of cardiomyocyte-, endothelial-, and stem-cell biology. Primary adult cardiac cells from nine human biopsies were cultured using different media for up to 9 weeks. The possibilities to favor a certain cell phenotype and induce production of extra cellular matrix (ECM) were studied by histology, immunohistochemistry, and quantitative real-time PCR. Defined media gave significant increase in both cardiac- and progenitor-specific markers and also an intraluminal position of endothelial cells over time. Cardiac media showed indication of differentiation and maturity of HDS considering the ECM production and activities withinNOTCHregulation but no additional cardiac differentiation. Endothelial media gave no positive effects on endothelial phenotype but increased proliferation without fibroblast overgrowth. In addition, indications for early vasculogenesis were found. It was also possible to affect the Wnt signaling in HDS by addition of a glycogen synthase kinase 3 (GSK3) inhibitor. In conclusion, these findings show the suitability of HDS asin vitromodel for studies of cardiomyocyte-, endothelial-, and stem-cell biology.
Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction
Authors: Khan Muhammad , Li Ting , Ahmad Khan Muhammad Khalil , Rasul Azhar , Nawaz Faisal , Sun Meiyan , Zheng Yongchen , Ma Tonghui
Published: December 2012

Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines. In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation. However, the molecular mechanism of GSH depletion remained unexplored. The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner. This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells. Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.
Characterization of the Newly Developed Soybean Cultivar DT2008 in Relation to the Model Variety W82 Reveals a New Genetic Resource for Comparative and Functional Genomics for Improved Drought Tolerance
Authors: Ha Chien Van , Le Dung Tien , Nishiyama Rie , Watanabe Yasuko , Tran Uyen Thi , Dong Nguyen Van , Tran Lam-Son Phan
Published: December 2012

Soybean (Glycine max) productivity is adversely affected by drought stress worldwide, including Vietnam. In the last few years, we have made a great effort in the development of drought-tolerant soybean cultivars by breeding and/or radiation-induced mutagenesis. One of the newly developed cultivars, the DT2008, showed enhanced drought tolerance and stable yield in the field conditions. The purpose of this study was to compare the drought-tolerant phenotype of DT2008 and Williams 82 (W82) by assessing their water loss and growth rate under dehydration and/or drought stress conditions as a means to provide genetic resources for further comparative and functional genomics. We found that DT2008 had reduced water loss under both dehydration and drought stresses in comparison with W82. The examination of root and shoot growths of DT2008 and W82 under both normal and drought conditions indicated that DT2008 maintains a better shoot and root growth rates than W82 under both two growth conditions. These results together suggest that DT2008 has better drought tolerance degree than W82. Our results open the way for further comparison of DT2008 and W82 at molecular levels by advanced omic approaches to identify mutation(s) involved in the enhancement of drought tolerance of DT2008, contributing to our understanding of drought tolerance mechanisms in soybean. Mutation(s) identified are potential candidates for genetic engineering of elite soybean varieties to improve drought tolerance and biomass.
A Field Study on Simulation of CO2 Injection and ECBM Production and Prediction of CO2 Storage Capacity in Unmineable Coal Seam
Authors: He Qin , Mohaghegh Shahab D. , Gholami Vida
Published: December 2012

CO2 sequestration into a coal seam project was studied and a numerical model was developed in this paper to simulate the primary and secondary coal bed methane production (CBM/ECBM) and carbon dioxide (CO2) injection. The key geological and reservoir parameters, which are germane to driving enhanced coal bed methane (ECBM) and CO2 sequestration processes, including cleat permeability, cleat porosity, CH4 adsorption time, CO2 adsorption time, CH4 Langmuir isotherm, CO2 Langmuir isotherm, and Palmer and Mansoori parameters, have been analyzed within a reasonable range. The model simulation results showed good matches for both CBM/ECBM production and CO2 injection compared with the field data. The history-matched model was used to estimate the total CO2 sequestration capacity in the field. The model forecast showed that the total CO2 injection capacity in the coal seam could be 22,817 tons, which is in agreement with the initial estimations based on the Langmuir isotherm experiment. Total CO2 injected in the first three years was 2,600 tons, which according to the model has increased methane recovery (due to ECBM) by 6,700 scf/d.
PI Controller Design for Time Delay Systems Using an Extension of the Hermite-Biehler Theorem
Authors: Elmadssia Sami , Saadaoui Karim , Benrejeb Mohamed
Published: December 2012

We consider stabilizing first-order
systems with time delay. The set of all stabilizing proportional-integral
PI controllers are determined using an extension of the
Hermite-Biehler theorem. The time delay is approximated by a
second-order Padé approximation. For uncertain plants, with
interval type uncertainty, robust stabilizing PI controllers are
determined.
Numerical Modeling Chemical Vapor Infiltration of SiC Composites
Authors: Zhu Yaochan , Schnack Eckart
Published: December 2012

The multiphase field model for chemical vapor infiltration (CVI) of SiC/SiC composites is developed in this study, thereby to reproduce the microstructure evolution during CVI process and to achieve better understanding of the effect of process parameters (e.g., temperature, pressure, etc.) on the final product. In order to incorporate the thermodynamics of methyltrichlorosilane (MTS) pyrolysis into phase field model framework, the reduced chemical reaction mechanism is adopted. The model consists of a set of nonlinear partial differential equations by coupling Ginzburg‐Landau type phase field equations with mass balance equations (e.g., convection‐diffusion equation) and the modified Navier‐Stokes equations which accounts for the fluid motion. The microstructure of preferential codeposition of Si, SiC under high ratio of H2 to MTS is simulated and the potential risk of blockage of the premature pores during isothermal CVI process is predicted. The competitive growth mechanism of SiC grains is discussed and the formation process of potential premature pore blockage is reproduced.
Mathematical Development and Comparison of a Hybrid PBM-DEM Description of a Continuous Powder Mixing Process
Authors: Sen Maitraye , Dubey Atul , Singh Ravendra , Ramachandran Rohit
Published: December 2012

This paper describes the development of a multidimensional population balance model (PBM) which can account for the dynamics of a continuous powder mixing/blending process. The PBM can incorporate the important design and process conditions and determine their effects on the various critical quality attributes (CQAs) accordingly. The important parameters considered in this study are blender dimensions and presence of noise in the inlet streams. The blender dynamics have been captured in terms of composition of the ingredients, (relative standard deviation) RSD, and (residence time distribution) RTD. PBM interacts with discrete element modeling (DEM) via one-way coupling which forms a basic framework for hybrid modeling. The results thus obtained have been compared against a full DEM simulation which is a more fundamental particle-level model that elucidates the dynamics of the mixing process. Results show good qualitative agreement which lends credence to the use of coupled PBM as an effective tool in control and optimization of mixing process due to its relatively fewer computational requirements compared to DEM.
p55PIK Transcriptionally Activated by MZF1 Promotes Colorectal Cancer Cell Proliferation
Authors: Deng Yu , Wang Jing , Wang Guihua , Jin Yuan , Luo Xuelai , Xia Xianmin , Gong Jianping , Hu Junbo
Published: December 2012

p55PIK, regulatory subunit of class IA phosphatidylinositol 3-kinase (PI3K), plays a crucial role in cell cycle progression by interaction with tumor repressor retinoblastoma (Rb) protein. A recent study showed that Rb protein can localize to the mitochondria in proliferative cells. Aberrant p55PIK expression may contribute to mitochondrial dysfunction in cancer progression. To reveal the mechanisms of p55PIK transcriptional regulation, the p55PIK promoter characteristics were analyzed. The data show that myeloid zinc finger 1, MZF1, is necessary for p55PIK gene transcription activation. ChIP (Chromatin immuno-precipitation) assay shows that MZF1 binds to the cis-element “TGGGGA” in p55PIK promoter. In MZF1 overexpressed cells, the promoter activity, expression of p55PIK, and cell proliferation rate were observed to be significantly enhanced. Whereas in MZF1-silenced cells, the promoter activity and expression of p55PIK and cell proliferation level was statistically decreased. In CRC tissues, MZF1 and p55PIK mRNA expression were increased (P=0.046,P=0.047, resp.). A strong positive correlation (Rs=0.94) between MZF1 and p55PIK mRNA expression was observed. Taken together, we concluded that p55PIK is transcriptionally activated by MZF1, resulting in increased proliferation of colorectal cancer cells.
CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+T Cells
Authors: Cobb Dustin , Guo Siqi , Smeltz Ronald B.
Published: December 2012

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-γby CD8+T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-γproduction. The effect of CpG and IL-15 was also evident with CD8+T cells recovered from mice infected with the parasiteTrypanosoma cruzi(T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+T cells and CD4+CD25+regulatory T cells. Although IFN-γwas not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+T cells required expression of the IFN-γ-inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8+T-cell responses to infectious agents and tumors.
Photo-Induced Antitumor Effect of 3,6-Bis(1-methyl-4-vinylpyridinium) Carbazole Diiodide
Authors: Chou Ya-Shuan , Chang Cheng-Chung , Chang Ta-Chau , Yang Tsung-Lin , Young Tai-Horng , Lou Pei-Jen
Published: December 2012

We have applied a fluorescent molecule 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) for tumor targeting and treatment. In this study, we investigated the photo-induced antitumor effect of BMVC.In vitrocell line studies showed that BMVC significantly killed TC-1 tumor cells at light dose greater than 40 J/cm2. The fluorescence of BMVC in the tumor peaked at 3 hours and then gradually decreased to reach the control level after 24 hours.In vivotumor treatment studies showed BMVC plus light irradiation (iPDT) significantly inhibited the tumor growth. At day 24 after tumor implantation, tumor volume was measured to be225±79 mm3,2542±181 mm3,1533±766 mm3, and1317±108 mm3in the iPDT, control, light-only, and BMVC-only groups, respectively. Immunohistochemistry studies showed the microvascular density was significantly lower in the iPDT group. Taken together, our results demonstrated that BMVC may be a potent tumor-specific photosensitizer (PS) for PDT.
Enhanced Production of Cellulase from Pineapple Waste by Response Surface Methodology
Authors: Saravanan P. , Muthuvelayudham R. , Viruthagiri T.
Published: December 2012

Optimization of the media components for cellulase production usingTrichoderma reeseiwas carried out. The optimization of cellulase production using pineapple waste as substrate was performed with statistical methodology based on experimental designs. The screening of nutrients and their influence on the cellulase production was studied using a Plackett-Burman design. Avicel, soybean cake flour, KH2PO4, and yeast extract were found to have the positive influence for the production of cellulase. The selected components were optimized using response surface methodology. The optimum concentrations are avicel: 26.5 g/L, soybean cake flour: 22.5 g/L, KH2PO4: 4.5 g/L, and yeast extract: 12.3 g/L. A maximum cellulase activity of 8.61 IU/mL was obtained under the optimized medium in the validation experiment.
MYC Regulation of CHK1 and CHK2 Promotes Radioresistance in a Stem Cell-like Population of Nasopharyngeal Carcinoma Cells
Authors: Wang Wen-Jun , Wu Si-Pei , Liu Jia-Bin , Shi Yong-Sheng , Huang Xue , Zhang Qian-Bing , Yao Kai-Tai
Published: December 2012

Radiotherapy is the most successful nonsurgical treatment for nasopharyngeal carcinoma (NPC). Despite this, the prognosis remains poor. Although NPCs initially respond well to a full course of radiation, recurrence is frequent. The cancer stem cell (CSC) hypothesis provides a framework for explaining the discrepancy between the response of NPC to therapy and the poor survival rate. In this study, a stem cell-like subpopulation (PKH26+) was identified in NPC cell lines using a label-retention technique. PKH26+ cells were enriched for clonogenicity, sphere formation, side-population cells, and resistance to radiotherapy. Using genomic approaches, we show that the proto-oncogene c-MYC (MYC) regulates radiotolerance through transcriptional activation of CHK1 (CHEK1) and CHK2 (CHEK2) checkpoint kinases through direct binding to the CHK1 and CHK2 promoters. Overexpression of c-MYC in the PKH26+ subpopulation leads to increased expression of CHK1 and CHK2 and subsequent activation of the DNA-damage-checkpoint response, resulting in radioresistance. Furthermore, loss of CHK1 and CHK2 expression reverses radioresistance in PKH26+ (c-MYC high expression) cells in vitro and in vivo. This study elucidates the role of the c-MYC-CHK1/CHK2 axis in regulating DNA-damage-checkpoint responses and stem cell characteristics in the PKH26+ subpopulation. Furthermore, these data reveal a potential therapeutic application in reversal of radioresistance through inhibition of the c-MYC-CHK1/CHK2 pathway. Cancer Res; 73(3); 1219–31. ©2012 AACR.
Acute and Fractionated Irradiation Differentially Modulate Glioma Stem Cell Division Kinetics
Authors: Gao Xuefeng , McDonald J. Tyson , Hlatky Lynn , Enderling Heiko
Published: December 2012

Glioblastoma multiforme (GBM) is one of the most aggressive human malignancies with a poor patient prognosis. Ionizing radiation either alone or adjuvant after surgery is part of standard treatment for GBM but remains primarily noncurative. The mechanisms underlying tumor radioresistance are manifold and, in part, accredited to a special subpopulation of tumorigenic cells. The so-called glioma stem cells (GSC) are bestowed with the exclusive ability to self-renew and repopulate the tumor and have been reported to be less sensitive to radiation-induced damage through preferential activation of DNA damage checkpoint responses and increased capacity for DNA damage repair. During each fraction of radiation, non–stem cancer cells (CC) die and GSCs become enriched and potentially increase in number, which may lead to accelerated repopulation. We propose a cellular Potts model that simulates the kinetics of GSCs and CCs in glioblastoma growth and radiation response. We parameterize and validate this model with experimental data of the U87-MG human glioblastoma cell line. Simulations are conducted to estimate GSC symmetric and asymmetric division rates and explore potential mechanisms for increased GSC fractions after irradiation. Simulations reveal that in addition to their higher radioresistance, a shift from asymmetric to symmetric division or a fast cycle of GSCs following fractionated radiation treatment is required to yield results that match experimental observations. We hypothesize a constitutive activation of stem cell division kinetics signaling pathways during fractionated treatment, which contributes to the frequently observed accelerated repopulation after therapeutic irradiation. Cancer Res; 73(5); 1481–90. ©2012 AACR.
Molecular Pathways: Multimodal Cancer-Killing Mechanisms Employed by Oncolytic Vesiculoviruses
Authors: Mahoney Douglas J. , Stojdl David F.
Published: December 2012

Cancer is a heterogeneous disease that, for the most part, is not effectively managed with existing therapies. Oncolytic viruses are an attractive class of experimental cancer medicine because, unlike conventional chemotherapeutic and molecularly targeted drugs, they orchestrate tumor cell death in multiple ways simultaneously. In this review, we discuss the numerous cancer-killing “pathways” marshalled by oncolytic vesiculoviruses. From directly infecting and lysing malignant cells, to engaging the host's innate and adaptive anticancer immune responses, to inducing vascular collapse within a tumor, oncolytic vesiculovirus therapy commandeers a coordinated, multipronged assault on cancer that is curative in numerous preclinical models. And as our appreciation of these mechanisms has progressed, so has our capacity to engineer improved outcomes. Notably, efforts to polarize the host's immune system toward the tumor and away from the virus have been particularly effective in immunocompetent murine models, and hold tremendous therapeutic promise for human patients. With a first-in-man phase I trial recently initiated in the United States, the clinical significance of oncolytic vesiculorivus therapy, after nearly 15 years of development, may soon come into focus. Clin Cancer Res; 19(4); 758–63. ©2012 AACR.