bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic and Pharmacodynamic Modeling To Determine the Dose of ST-246 To Protect against Smallpox in Humans
Authors: Leeds Janet M. , Fenneteau Frederique , Gosselin Nathalie H. , Mouksassi Mohamad-Samer , Kassir Nastya , Marier J. F. , Chen Yali , Grosenbach Doug , Frimm Annie E. , Honeychurch Kady M. , Chinsangaram Jarasvech , Tyavanagimatt Shanthakumar R. , Hruby Dennis E. , Jordan Robert
Published: December 2012

Although smallpox has been eradicated, the United States government considers it a “material threat” and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
A Trial of Discontinuation of Empiric Vancomycin Therapy in Patients with Suspected Methicillin-Resistant Staphylococcus aureus Health Care-Associated Pneumonia
Authors: Boyce John M. , Pop Olivia-Fabiola , Abreu-Lanfranco Odaliz , Hung Whitney Y. , Fisher Ann , Karjoo Afshin , Thompson Benjamin , Protopapas Zenon
Published: December 2012

Healthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results from lower-respiratory-tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empirical vancomycin, which is given for suspected methicillin-resistant
Staphylococcus aureus
(MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower-respiratory-tract cultures were not available. An antimicrobial stewardship team identified patients receiving empirical vancomycin for suspected or proven HCAP but for whom adequate lower-respiratory-tract cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empirical vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review. A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empirical vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) patients had a CPIS of ≤6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to that of a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures. In the absence of adequate lower-respiratory-tract cultures, it is reasonable to discontinue empirical vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and a CPIS of <6.
Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction
Authors: Chen Wei-Chun , Wang Sheng-Yang , Chiu Chien-Chih , Tseng Chin-Kai , Lin Chun-Kuang , Wang Hui-Chun , Lee Jin-Ching
Published: December 2012

Upon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of
Lindera erythrocarpa
Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.
The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response
Authors: Maue Alexander C. , Mohawk Krystle L. , Giles David K. , Poly Frédéric , Ewing Cheryl P. , Jiao Yuening , Lee Ginyoung , Ma Zuchao , Monteiro Mario A. , Hill Christina L. , Ferderber Jason S. , Porter Chad K. , Trent M. Stephen , Guerry Patricia
Published: December 2012

Campylobacter jejuni
is a major cause of bacterial diarrheal disease worldwide. The organism is characterized by a diversity of polysaccharide structures, including a polysaccharide capsule. Most
C. jejuni
capsules are known to be decorated nonstoichiometrically with methyl phosphoramidate (MeOPN). The capsule of
C. jejuni
81-176 has been shown to be required for serum resistance, but here we show that an encapsulated mutant lacking the MeOPN modification, an
mpnC
mutant, was equally as sensitive to serum killing as the nonencapsulated mutant. A nonencapsulated mutant, a
kpsM
mutant, exhibited significantly reduced colonization compared to that of wild-type 81-176 in a mouse intestinal colonization model, and the
mpnC
mutant showed an intermediate level of colonization. Both mutants were associated with higher levels of interleukin 17 (IL-17) expression from lamina propria CD4
+
cells than from cells from animals infected with 81-176. In addition, reduced levels of Toll-like receptor 4 (TLR4) and TLR2 activation were observed following
in vitro
stimulation of human reporter cell lines with the
kpsM
and
mpnC
mutants compared to those with wild-type 81-176. The data suggest that the capsule polysaccharide of
C. jejuni
and the MeOPN modification modulate the host immune response.
Pleiotropic actions of estrogen: a mitochondrial matter
Authors: Velarde Michael C.
Published: December 2012

Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While estrogen replacement therapy (ERT) in women was expected to reduce the health risks associated with the age-related decline in estrogen levels during menopause, ERT also resulted in increased progression to other types of diseases. Hence, distinguishing the signaling pathways that regulate the beneficial and detrimental effects of estrogen is important for developing interventions that selectively harness the hormone's beneficial effects, while minimizing its side effects. Estrogen can minimize mitochondrial dysfunction, which is thought to contribute to aging phenotypes. Decline in estrogen levels during menopause may lead to progressive mitochondrial dysfunction and may permanently alter cellular response, including that of estrogen (i.e., ERT). This review discusses the interplay between estrogen and mitochondrial function during the aging process and suggests a potential role of mitochondria in influencing the pleiotropic action of estrogen.
Acute Right Ventricular Failure in a Patient with Hepatic Cirrhosis
Authors: Soto Soto Jose , Geiger Xochiquetzal , Johnson Margaret M.
Published: December 2012

Pulmonary embolic disease is most commonly a manifestation of venous thromboembolism (VTE). However, fat, tumor, and air may all embolize to the pulmonary vasculature and lymphatics resulting in various clinical manifestations. Tumor emboli to small pulmonary vessels and lymphatics can lead to hypoxemic respiratory failure and shock. We present a 62-year-old male with history of mild COPD and end-stage liver disease secondary to hepatitis C admitted due to progressive shortness of breath and hypoxemia who developed shock and right ventricular failure. After a negative evaluation for venous thromboembolic disease, he had progressive respiratory and hemodynamic deterioration despite mechanical ventilation, renal replacement therapy, and vasopressive/inotropic support. Postmortem examination revealed diffuse micronodular moderately differentiated hepatocellular carcinoma (HCC) without a discrete mass, as well as numerous HCC tumor emboli to the lung and focally to the heart, consistent with disseminated hepatocellular tumor microembolism.
Progressive Epidural Hematoma in Patients with Head Trauma: Incidence, Outcome, and Risk Factors
Authors: Chen Hao , Guo Yan , Chen Shi-Wen , Wang Gan , Cao He-Li , Chen Jiong , Gu Yi , Tian Heng-Li
Published: December 2012

Progressive epidural hematoma (PEDH) after head injury is often observed on serial computerized tomography (CT) scans. Recent advances in imaging modalities and treatment might affect its incidence and outcome. In this study, PEDH was observed in 9.2% of 412 head trauma patients in whom two CT scans were obtained within 24 hours of injury, and in a majority of cases, it developed within 3 days after injury. In multivariate logistic regression, patient gender, age, Glasgow Coma Scale (GCS) score at admission, and skull fracture were not associated with PEDH, whereas hypotension (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.17–0.84), time interval of the first CT scanning (OR 0.42, 95% CI 0.19–0.83), coagulopathy (OR 0.36, 95% CI 0.15–0.85), or decompressive craniectomy (DC) (OR 0.46, 95% CI 0.21–0.97) was independently associated with an increased risk of PEDH. The 3-month postinjury outcome was similar in patients with PEDH and patients without PEDH (χ2=0.07,P=0.86). In conclusion, epidural hematoma has a greater tendency to progress early after injury, often in dramatic and rapid fashion. Recognition of this important treatable cause of secondary brain injury and the associated risk factors may help identify the group at risk and tailor management of patients with TBI.
Circulating Cytokines and Growth Factors in Pediatric Pulmonary Hypertension
Authors: Duncan Mark , Wagner Brandie D. , Murray Keri , Allen Jenna , Colvin Kelley , Accurso Frank J. , Ivy D. Dunbar
Published: December 2012

Background. Management of pediatric pulmonary hypertension (PH) remains challenging. We have assessed a panel of circulating proteins in children with PH to investigate their value as predictive and/or prognostic biomarkers. From these determinations, we aim to develop a practical, noninvasive tool to aid in the management of pediatric PH.Methods. Twelve cytokines and growth factors putatively associated with lung or vascular disease were examined in plasma specimens from 70 children with PH using multiplex protein array technology. Associations between hemodynamics, adverse events, and protein markers were evaluated.Results. Epidermal growth factor (EGF) and IL-6 were associated with important hemodynamics. Of the twelve proteins, VEGF and IL-6 were significantly, univariately associated with the occurrence of an adverse event, with odds ratios (95% confidence intervals) of 0.56 (0.33–0.98) and 1.69 (1.03–2.77), respectively. When hemodynamic predictors were combined with protein markers, the ability to predict adverse outcomes within the following year significantly increased.Conclusions. Specific circulating proteins are associated with hemodynamic variables in pediatric PH. If confirmed in additional cohorts, measurement of these proteins could aid patient care and design of clinical trials by identifying patients at risk for adverse events. These findings also further support a role for inflammation in pediatric PH.
Geometric Lattice Structure of Covering‐Based Rough Sets through Matroids
Authors: Huang Aiping , Zhu William
Published: December 2012

Covering‐based rough set theory is a useful tool to deal with inexact, uncertain, or vague knowledge in information systems. Geometric lattice has been widely used in diverse fields, especially search algorithm design, which plays an important role in covering reductions. In this paper, we construct three geometric lattice structures of covering‐based rough sets through matroids and study the
relationship among them. First, a geometric lattice structure of covering‐based rough sets is established through the transversal matroid induced by a covering. Then its characteristics, such as atoms, modular elements, and modular pairs, are studied. We also construct a one‐to‐one correspondence between this type of geometric lattices and transversal matroids in the context of covering‐based rough sets. Second, we present three sufficient and necessary conditions for two types of covering upper approximation operators to be closure operators of matroids. We also represent two types of matroids through closure axioms and then obtain two geometric lattice structures of covering‐based rough sets. Third, we study the relationship among these three geometric lattice structures. Some core concepts such as reducible elements in covering‐based rough sets are investigated with geometric lattices. In a word, this work points out an interesting view, namely, geometric lattice, to study covering‐based rough sets.
Grain Sorghum Response to Row Spacing and Plant Populations in the Texas Coastal Bend Region
Authors: Fernandez Carlos J. , Fromme Dan D. , Grichar W. James
Published: December 2012

Two grain sorghum (Sorghum bicolor L. Moench) studies were conducted in the Coastal Bend Region of Texas over a two-year period. In one study, sorghum growth and yield were compared when planted in a single row on beds or planted in twin rows on beds with different plant populations under dryland or irrigation. Above average rainfall occurred in May 2000 which resulted in twin rows at any plant population producing higher yields than the single row at lower plant population. In 2001, single-row plantings with either plant population (124,000–160,000 or 161,000–198,000 plants/ha) produced higher yield than twin rows planted at 161,000–198,000 plants/ha. Under irrigation, twin rows planted at 161,000–198,000 plants/ha produced higher yields than single row at the same population; however, no other yield differences were noted when row systems or plant populations were compared. In another study, 38 cm row spacings were compared with 76 cm row spacings under two plant populations. In 2000, when rains fell at an opportune time, no yield differences were noted; however, in 2001 with below average rainfall, the 76 cm plantings at 170,000–200,000 and 210,000–240,000 plants/ha produced higher yield than the 38 cm plantings at those same plant populations.
Intestinal, Airway, and Cardiovascular Relaxant Activities of Thymoquinone
Authors: Ghayur Muhammad Nabeel , Gilani Anwarul Hassan , Janssen Luke Jeffrey
Published: December 2012

Thymoquinone (TQ) is a bioactive component found in many medicinal herbs. In this study, we report the smooth and cardiac muscle relaxant activities of this compound. TQ concentration dependently suppressed spontaneously contracting rabbit jejunum while also relaxed high K+-(80 mM) induced contractions in jejunum and guinea-pig ileum, indicating activity at voltage-operated Ca++channels (VOCC). Further, TQ displaced Ca++concentration-response curves, obtained in a Ca++-free environment, to the right, showing blockade of VOCC. Similar activity was observed with verapamil, a standard VOCC blocker. TQ also exhibited nonadrenergic relaxation of agonist-induced contractions in guinea-pig trachea. When tested in fluo-4-loaded mouse lung slices, TQ inhibited ACh-induced airway narrowing and Ca++signalling in airway smooth muscle cells. In endothelium-intact and endothelium-denuded rat aorta, TQ inhibited high K+-induced contractions at significantly lower concentrations than phenylephrine-(PE-) (1 microM) induced contractions. Relaxation of PE-induced contractions was resistant to blockade by L-NAME and atropine. In guinea-pig atria, TQ showed noncholinergic relaxation of atrial force and rate of contractions. These data suggest smooth and cardiac muscle relaxant activity of TQ possibly mediated, in part, via blockade of VOCC. The results also justify the use of TQ containing plants in related health disorders like colic, diarrhoea, cough, and asthma.
Parallel Mesh Adaptive Techniques Illustrated with Complex Compressible Flow Simulations
Authors: Leyland Pénélope , Casagrande Angelo , Savoy Yannick
Published: December 2012

The aim of this paper is to discuss efficient adaptive parallel solution techniques on unstructured 2D and 3D meshes. We concentrate on the aspect of parallel a posteriori mesh adaptation. One of the main advantages of unstructured grids is their capability to adapt dynamically by localised refinement and derefinement during the calculation to enhance the solution accuracy and to optimise the computational time. Grid adaption also involves optimisation of the grid quality, which will be described here for both structural and geometrical optimisation.
Password Authentication Based on Fractal Coding Scheme
Authors: Al-Saidi Nadia M. G. , Said Mohamad Rushdan Md. , Othman Wan Ainun M.
Published: December 2012

Password authentication is a mechanism used to authenticate user identity over insecure communication channel. In this paper, a new method to improve the security of password authentication is proposed. It is based on the compression capability of the fractal image coding to provide an authorized user a secure access to registration and login process. In the proposed scheme, a hashed password string is generated and encrypted to be captured together with the user identity using text to image mechanisms. The advantage of fractal image coding is to be used to securely send the compressed image data through a nonsecured communication channel to the server. The verification of client information with the database system is achieved in the server to authenticate the legal user. The encrypted hashed password in the decoded fractal image is recognized using optical character recognition. The authentication process is performed after a successful verification of the client identity by comparing the decrypted hashed password with those which was stored in the database system. The system is analyzed and discussed from the attacker’s viewpoint. A security comparison is performed to show that the proposed scheme provides an essential security requirement, while their efficiency makes it easier to be applied alone or in hybrid with other security methods. Computer simulation and statistical analysis are presented.
Methanolic Root Extract ofRauwolfia serpentinaBenth Improves the Glycemic, Antiatherogenic, and Cardioprotective Indices in Alloxan-Induced Diabetic Mice
Authors: Azmi Muhammad Bilal , Qureshi Shamim A.
Published: December 2012

The aim of the study was to evaluate the phytochemistry and the effect of methanolic root extract (MREt) ofRauwolfia serpentinaon alloxan-induced diabeticWistermale mice. Mice were divided in control (distilled water at 1 mL/kg) and alloxan-induced diabetic mice which subdivided into diabetic (distilled water at 1 mL/kg), negative (0.05% dimethyl sulfoxide at 1 mL/kg), positive (glibenclamide at 5 mg/kg) controls, and three test groups (MREt at 10, 30, and 60 mg/kg). All treatments were given orally for 14 days. Qualitatively MREt showed the presence of alkaloids, carbohydrates, flavonoids, glycosides, cardiac glycosides, phlobatannins, resins, saponins, steroids, tannins, and triterpenoids, while quantitatively extract was rich in total phenols. The flavonoids, saponins and alkaloids were also determined in root powder. MREt found effective in improving the body weights, glucose and insulin levels, insulin/glucose ratio, glycosylated and total hemoglobin in test groups as compared to diabetic control. Similarly, significantly decreased levels of total cholesterol, triglycerides, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c) cholesterols were found in test groups. Significant lipolysis with improved glycogenesis was also found in liver tissues of all test groups. ALT levels were found normal in all groups. Thus, MREt improves the glycemic, antiatherogenic, coronary risk, and cardioprotective indices in alloxan-induced diabetic mice.
Late Onset Neurodegeneration with Brain-Iron Accumulation Presenting as Parkinsonism
Authors: Fekete Robert
Published: December 2012

Neurodegeneration with brain-iron accumulation (NBIA) encompasses a family of neurodegenerative disorders connected by evidence of abnormal brain iron deposition. Advances in imaging and genetic testing expanded the clinical spectrum of these disorders. Here, a case of parkinsonism and dystonia with orofacial stereotypies is presented. While the patient was initially diagnosed with Parkinson’s disease and placed on levodopa therapy, dopamine transporter imaging via (123)I-FP-CIT SPECT (DaTSCAN) was normal. MRI brain showed “eye of the tiger” sign on T2 weighted imaging. NBIA should be considered in the differential diagnosis of atypical parkinsonism.
Changes in Protein, Nonnutritional Factors, and Antioxidant Capacity during Germination ofL. campestrisSeeds
Authors: Jiménez Martínez C. , Cardador Martínez A. , Martinez Ayala A. L. , Muzquiz M. , Martin Pedrosa M. , Dávila-Ortiz G.
Published: December 2012

The changes in SDS-PAGE proteins patterns, oligosaccharides and phenolic compounds ofL. campestrisseeds, were evaluated during nine germination days. SDS-PAGE pattern showed 12 bands in the original protein seeds, while in the samples after 1–9 germination days, the proteins located in the range of 28–49 and 49–80 kDa indicated an important reduction, and there was an increase in bands about 27 kDa. On the other hand, oligosaccharides showed more than 50% of decrease in its total concentration after 4 germination days; nevertheless after the fifth day, the oligosaccharides concentration increases and rises more than 30% of the original concentration. Phenolic compounds increased their concentration since the first germination day reaching until 450% more than the original seed level. The obtained results are related with liberation or increase of phenolic compounds with antioxidant properties, allowing us to suggest that the germination would be used to produce legume foods for human consumption with better nutraceutical properties.
Mixed Convection Flow along a Stretching Cylinder in a Thermally Stratified Medium
Authors: Mukhopadhyay Swati , Ishak Anuar
Published: December 2012

An analysis for the axisymmetric laminar boundary layer mixed convection flow of a viscous and incompressible fluid towards a stretching cylinder immersed in a thermally stratified medium is presented in this paper. Similarity transformation is employed to convert the governing partial differential equations into highly nonlinear ordinary differential equations. Numerical solutions of these equations are obtained by a shooting method. It is found that the heat transfer rate at the surface is lower for flow in a thermally stratified medium compared to that of an unstratified medium. Moreover, both the skin friction coefficient and the heat transfer rate at the surface are larger for a cylinder compared to that for a flat plate.
Effects of Auraptene on IGF-1 Stimulated Cell Cycle Progression in the Human Breast Cancer Cell Line, MCF-7
Authors: Krishnan Prasad , Kleiner-Hancock Heather
Published: December 2012

Auraptene is being investigated for its chemopreventive effects in many models of cancer including skin, colon, prostate, and breast. Many mechanisms of action including anti-inflammatory, antiproliferative, and antiapoptotic effects are being suggested for the chemopreventive properties of auraptene. We have previously shown in theN-methylnitrosourea induced mammary carcinogenesis model that dietary auraptene (500 ppm) significantly delayed tumor latency. The delay in time to tumor corresponded with a significant reduction in cyclin D1 protein expression in the tumors. Since cyclin D1 is a major regulator of cell cycle, we further studied the effects of auraptene on cell cycle and the genes related to cell cycle in MCF-7 cells. Here we show that auraptene significantly inhibited IGF-1 stimulated S phase of cell cycle in MCF-7 cells and significantly changed the transcription of many genes involved in cell cycle.
Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology
Authors: Di Dalmazi Guido , Pagotto Uberto , Pasquali Renato , Vicennati Valentina
Published: December 2012

Type 2 diabetes mellitus is the result of interaction between genetic and environmental factors, leading to heterogeneous and progressive pancreaticβ-cell dysfunction. Overweight and obesity are major contributors to the development of insulin resistance and impaired glucose tolerance. The inability ofβcells to secrete enough insulin produces type 2 diabetes. Abnormalities in other hormones such as reduced secretion of the incretin glucagon-like peptide 1 (GLP-1), hyperglucagonemia, and raised concentrations of other counterregulatory hormones also contribute to insulin resistance, reduced insulin secretion, and hyperglycaemia in type 2 diabetes. Clinical-overt and experimental cortisol excess is associated with profound metabolic disturbances of intermediate metabolism resulting in abdominal obesity, insulin resistance, and low HDL-cholesterol levels, which can lead to diabetes. It was therefore suggested that subtle abnormalities in cortisol secretion and action are one of the missing links between insulin resistance and other features of the metabolic syndrome. The aim of this paper is to address the role of glucocorticoids on glucose homeostasis and to explain the relationship between hypercortisolism and type 2 diabetes.
Local and Global Dynamics in a Discrete Time Growth Model with Nonconcave Production Function
Authors: Brianzoni Serena , Mammana Cristiana , Michetti Elisabetta
Published: December 2012

We study the dynamics shown by the discrete time neoclassical one‐sector growth model with differential savings while assuming a nonconcave production function. We prove that complex features exhibited are related both to the structure of the coexixting attractors and to their basins. We also show that complexity emerges if the elasticity of substitution between production factors is low enough and shareholders save more than workers, confirming the results obtained while considering concave production functions.
Periodontal Health and Caries Prevalence Evaluation in Patients Affected by Parkinson's Disease
Authors: Cicciù Marco , Risitano Giacomo , Lo Giudice Giuseppe , Bramanti Ennio
Published: December 2012

Parkinson's disease (PD) is a progressive neurodegenerative disorder related to the loss or absence of dopaminergic neurons in the brain. These deficits result in slowness of movement, tremor, rigidity, and dysfunction of behaviour. These symptoms negatively influence the patient’s capability to carry out the daily oral hygiene manoeuvres. The aim of this work is to record the oral health condition of PD patients evaluated at the IRCSS Bonino-Puleio in Messina. The oral health of 45 consecutive PD patients (study group) with neurologic diagnosis based on United Kingdom Brain Bank Criteria has been compared with that of another 45 no PD patients of the same age (control group). The evaluation of the general oral condition was recorded underlining tooth loss, active periodontal disease, and presence of untreated caries. The frequency of untreated caries, periodontal diseases, and missing teeth of the study group was significantly higher than in control group. Based on the data results, clinicians should direct high attention to the oral hygiene of patients with PD, above all at the early stages of the caries or periodontal disease, in order to prevent serious evolution of those pathologic dental conditions that may finally result in the tooth extraction event.
Direct Adaptive Fuzzy Sliding Mode Control with Variable Universe Fuzzy Switching Term for a Class of MIMO Nonlinear Systems
Authors: Haigang Guo , Hongxing Li , Weijing Zhao , Zhankui Song
Published: December 2012

Combining adaptive fuzzy sliding mode control with fuzzy or variable universe fuzzy switching technique, this study develops two novel direct adaptive schemes for a class of MIMO nonlinear systems with uncertainties and external disturbances. The proposed control schemes consist of fuzzy equivalent control terms, fuzzy switching control terms (in scheme one) or variable universe fuzzy switching control terms (in scheme two), and compensation control terms. The compensation control terms are used to relax the assumption on fuzzy approximation error. Based on Lyapunov stability theory, the parameters update laws are adaptively tuned online and the global asymptotic stability of the closed‐loop system can be guaranteed. The major contribution of this study is to develop a novel framework for designing direct adaptive fuzzy sliding mode control scheme facing model uncertainties and external disturbances. The derived schemes can effectively solve the chattering problem and the equivalent control calculation in that environment. Simulation results performed on a two‐link robotic manipulator demonstrate the feasibility of the proposed control schemes.
Bridelia ferrugineaProduces Antineuroinflammatory Activity through Inhibition of Nuclear Factor-kappa B and p38 MAPK Signalling
Authors: Olajide Olumayokun A. , Aderogba Mutalib A. , Okorji Uchechukwu P. , Fiebich Bernd L.
Published: December 2012

Bridelia ferrugineais commonly used in traditional African medicine (TAM) for treating various inflammatory conditions. Extracts from the plant have been shown to exhibit anti-inflammatory property in a number ofin vivomodels. In this study the influence ofB. ferruginea(BFE) on the production of PGE2, nitrite, and proinflammatory cytokines from LPS-stimulated BV-2 microglia was investigated. The effects of BFE on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expressions were evaluated in LPS-activated rat primary microglia. The roles of NF-κB and MAPK signalling in the actions of BFE were also investigated. BFE (25–200 μg) inhibited the production of PGE2, nitrite, tumour necrosis factor-α(TNFα), and interleukin-6 (IL-6) as well as COX-2 and iNOS protein expressions in LPS-activated microglial cells. Further studies to elucidate the mechanism of anti-inflammatory action of BFE revealed interference with nuclear translocation of NF-κBp65 through mechanisms involving inhibition of IκB degradation. BFE prevented phosphorylation of p38, but not p42/44 or JNK MAPK. It is suggested thatBridelia ferrugineaproduces anti-inflammatory action through mechanisms involving p38 MAPK and NF-κB signalling.
A DFT and Semiempirical Model-Based Study of Opioid Receptor Affinity and Selectivity in a Group of Molecules with a Morphine Structural Core
Authors: Bruna-Larenas Tamara , Gómez-Jeria Juan S.
Published: December 2012

We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31 levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.
Secondary Structural Preferences of Some Antibacterial Cyclooctapeptides in the Presence of Calcium(II)
Authors: Stevens Tarshona , McNeil Nykia , Lin Xiuli , Ngu-Schwemlein Maria
Published: December 2012

The purpose of this study is to understand the interactions of some antibacterial cationic amphipathic cyclooctapeptides with calcium(II) and their secondary structural preferences. The thermodynamic parameters associated with calcium(II) interactions, between the antibacterial active cyclooctapeptides (COP 1–6) and those that did not exhibit significant activities (COP 7–9), were studied by isothermal titration calorimetry. Calcium(II) binding in the absence and presence of micellar dodecylphosphocholine (DPC), a membrane mimicking detergent, was conducted by circular dichroism (CD). Both groups of cyclopeptides showed weak binding affinities for calcium(II) (Kb ca. 10−3 M−1). However, CD data showed that the antimicrobial peptides COP 1–6 adopted a twisted beta-sheet structure (positive CD absorption band at ca. 203 nm) in the presence of calcium(II) in micellar DPC. In contrast, COP 7–9, which lacked antibacterial activity, adopted a different conformational structure (negative CD absorption band at ca. 203 nm). These results indicate that these cyclopeptides could adopt secondary structural preferences in the presence of calcium(II) amidst a hydrophobic environment to elicit their antibacterial activity. These findings could be useful in facilitating the design of cyclopeptide derivatives that can adopt this beta-sheet-like secondary structure and, thereby, provide a useful molecular template for crafting antibacterial compounds.
Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway
Authors: Peng Chih-Yu , Yang Hui-Wen , Chu Yin-Hung , Chang Yu-Chao , Hsieh Ming-Ju , Chou Ming-Yung , Yeh Kun-Tu , Lin Yueh-Min , Yang Shun-Fa , Lin Chiao-Wen
Published: December 2012

Caffeic acid phenethyl ester (CAPE), an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM). Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2) protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and potently decreased migration by reducing focal adhesion kinase (FAK) phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.
Roles of PI3K/AKT/GSK3/mTOR Pathway in Cell Signaling of Mental Illnesses
Authors: Kitagishi Yasuko , Kobayashi Mayumi , Kikuta Kanae , Matsuda Satoru
Published: December 2012

Several pharmacological agents acting on monoamine neurotransmission are used for the management of mental illnesses. Regulation of PI3K/AKT and GSK3 pathways may constitute an important signaling center in the subcellular integration of the synaptic neurotransmission. The pathways also modulate neuronal cell proliferation, migration, and plasticity. There are evidences to suggest that inflammation of neuron contributes to the pathology of depression. Inflammatory activation of neuron contributes to the loss of glial elements, which are consistent with pathological findings characterizing the depression. A mechanism of anti-inflammatory reactions from antidepressant medications has been found to be associated with an enhancement of heme oxygenase-1 expression. This induction in brain is also important in neuroprotection and neuroplasticity. As enzymes involved in cell survival and neuroplasticity are relevant to neurotrophic factor dysregulation, the PI3K/AKT/GSK3 may provide an important signaling for the neuroprotection in depression. In this paper, we summarize advances on the involvement of the PI3K/AKT/GSK3 pathways in cell signaling of neuronal cells in mental illnesses.
Investigation of High-Frequency Internal Wave Interactions with an Enveloped Inertia Wave
Authors: Casaday B. , Crockett J.
Published: December 2012

Using ray theory, we explore the effect an envelope function has on high-frequency, small-scale internal wave propagation through a low-frequency, large-scale inertia wave. Two principal interactions, internal waves propagating through an infinite inertia wavetrain and through an enveloped inertia wave, are investigated. For the first interaction, the total frequency of the high-frequency wave is conserved but is not for the latter. This deviance is measured and results of waves propagating in the same direction show the interaction with an inertia wave envelope results in a higher probability of reaching that Jones' critical level and a reduced probability of turning points, which is a better approximation of outcomes experienced by expected real atmospheric interactions. In addition, an increase in wave action density and wave steepness is observed, relative to an interaction with an infinite wavetrain, possibly leading to enhanced wave breaking.
The Role of Deubiquitinating Enzymes in Synaptic Function and Nervous System Diseases
Authors: Kowalski Jennifer R. , Juo Peter
Published: December 2012

Posttranslational modification of proteins by ubiquitin has emerged as a critical regulator of synapse development and function. Ubiquitination is a reversible modification mediated by the concerted action of a large number of specific ubiquitin ligases and ubiquitin proteases, called deubiquitinating enzymes (DUBs). The balance of activity of these enzymes determines the localization, function, and stability of target proteins. While some DUBs counter the action of specific ubiquitin ligases by removing ubiquitin and editing ubiquitin chains, other DUBs function more generally to maintain the cellular pool of free ubiquitin monomers. The importance of DUB function at the synapse is underscored by the association of specific mutations in DUB genes with several neurological disorders. Over the last decade, although much research has led to the identification and characterization of many ubiquitin ligases at the synapse, our knowledge of the relevant DUBs that act at the synapse has lagged. This review is focused on highlighting our current understanding of DUBs that regulate synaptic function and the diseases that result from dysfunction of these DUBs.
A Wide-Beam Scanning Mode for Near-Space Passive SARs
Authors: Zhou Peng , Ren Peng , Dai Yongshou
Published: December 2012

A near-space passive SAR consists of a passive radar receiver placed on a near-space vehicle and another existing radar on a satellite serving as an illuminator. In this paper, we present a wide-beam scanning mode for near-space passive SARs for the purpose of increasing the azimuth scene extension. The receiving distance of a near-space SAR is much shorter than that of a satellite-based SAR, and the synthetic aperture time for a near-space passive SAR is not longer than the time interval during which a target transverses the azimuth beam of a transmitter. We design our novel mode by spreading the azimuth beam of a receiver to match the azimuth footprint of the transmitter. We also synchronize the azimuth beam of the receiver with that of the satellite within seconds during the beam scanning to further increase the scene extension. Furthermore, we formulate the azimuth scene extension and the footprint overlapping time for near-space passive SARs in terms of the possible locations of the involved satellites and receivers. Experimental simulations demonstrate the effectiveness of our proposed mode, especially revealing that the wide-beam scanning mode improves the azimuth scene extension and footprint overlapping time over the wide-beam mode, without decreasing azimuth resolution.
Identification of Prophages and Prophage Remnants within the Genome of Avibacterium paragallinarum Bacterium
Authors: Roodt Y. , Bragg R. R. , Albertyn J.
Published: December 2012

Bacterial whole genome sequencing has delivered an abundance of prophage sequences as a by-product and the analysis of these sequences revealed ways in which phages have affected the genome of their host bacteria in various bacterial species. The aim of this study was to identify the phage-related sequences in the draft assembly of the Avibacterium paragallinarum genome, the causative agent of infectious coryza in poultry. Whole genome assembly was not possible due to the presence of gaps and/or repeats existent on the ends of contigs. However, genome annotation revealed prophage and prophage remnant sequences present in this genome. From the results obtained, a complete Mu-like bacteriophage could be identified that was termed AvpmuC-2M. A complete sequence of HP2-like bacteriophage, named AvpC-2M-HP2, was also identified.
Association between Neurocognitive Impairment and the Short Allele of the 5-HTT Promoter Polymorphism in Depression: A Pilot Study
Authors: Kalska Hely , Pesonen Ullamari , Lehikoinen Sanna , Stenberg Jan-Henry , Lipsanen Jari , Niemi-Pynttäri Jussi , Tuunainen Arja
Published: December 2012

Depression has been shown to be associated with cognitive deficits in various cognitive domains. However, it is still unclear which factors contribute to cognitive impairment. The objective of this study was to find out whether a functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene is associated with the impairment of cognitive functioning among depressed patients. In a pilot study, a sample of 19 patients with major depressive disorder (MDD) and 19 healthy controls was investigated with an extensive psychiatric and neuropsychological examination. All participants were genotyped for 5-HTTLPR. Depressed patients with the short allele of the 5-HTT promoter region exhibited inferior cognitive performance compared to patients with the long allele polymorphism. In healthy controls, no association between genotype and cognitive performance was found. The result suggests that in MDD patients with the short allele of the 5-HTTLPR polymorphism the vulnerability to cognitive impairment is increased compared to MDD patients without the short allele inheritance. These preliminary findings need to be confirmed in a larger cohort of MDD patients.
Convenient Synthesis of a Novel Flavonoid with Extended π‐System: Active Agent for UVA Protection
Authors: Al-Busafi Saleh
Published: December 2012

Flavonoid derivative with extended cinnamic acid moiety was synthesized using Baker‐Venkataraman reaction. The compound shows interesting UV absorption properties which make it a good UVA absorber. A bathochromic shift of 18 nm was observed when the size of cinnamic acid segment was increased by one styrylogous extension.
PRSS3/Mesotrypsin Is a Therapeutic Target for Metastatic Prostate Cancer
Authors: Hockla Alexandra , Miller Erin , Salameh Moh'd A. , Copland John A. , Radisky Derek C. , Radisky Evette S.
Published: December 2012

PRSS3/mesotrypsin is an atypical isoform of trypsin that has been associated with breast, lung, and pancreatic cancer cell malignancy. In analyses of open source transcriptional microarray data, we find that PRSS3 expression is upregulated in metastatic prostate cancer tissue, and that expression of PRSS3 in primary prostate tumors is prognostic of systemic progression following prostatectomy. Using a mouse orthotopic model with bioluminescent imaging, we show that PRSS3/mesotrypsin is critical for prostate cancer metastasis. Silencing of PRSS3 inhibits anchorage-independent growth of prostate cancer cells in soft agar assays, and suppresses invasiveness in Matrigel transwell assays and three-dimensional (3D) cell culture models. We further show that treatment with recombinant mesotrypsin directly promotes an invasive cellular phenotype in prostate cancer cells and find that these effects are specific and require the proteolytic activity of mesotrypsin, because neither cationic trypsin nor a mesotrypsin mutant lacking activity can drive the invasive phenotype. Finally, we show that a newly developed, potent inhibitor of mesotrypsin activity can suppress prostate cancer cell invasion to a similar extent as PRSS3 gene silencing. This study defines mesotrypsin as an important mediator of prostate cancer progression and metastasis, and suggests that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment. Mol Cancer Res; 10(12); 1555–66. ©2012 AACR.
Comparative Study of the Effects of Recombinant Human Epidermal Growth Factor and Basic Fibroblast Growth Factor on Corneal Epithelial Wound Healing and Neovascularization in vivo and in vitro
Authors: Yan Limeng , Wu Wei , Wang Zhichong , Li Chaoyang , Lu Xiaohe , Duan Hucheng , Zhou Jin , Wang Xiaoran , Wan Pengxia , Song Yiyue , Tang Jing , Han Yu
Published: December 2012

Purpose: This study was undertaken to investigate the effects of recombinant human epidermal growth factor (rhEGF) and basic fibroblast growth factor (bFGF) on corneal wound healing and neovascularization (CNV). Methods: The positive effects of 10 ng/ml rhEGF and bFGF on the proliferation of corneal epithelial cells (SD-HCEC1s), rabbit keratocyte cells (RKCs) and human umbilical vein endothelial cells (HUVECs) as well as the effects on the migration capacity on HUVECs were observed. An animal central corneal wound and CNV model was established in rabbits. One eye of each group was chosen randomly for topical administration of rhEGF, bFGF or normal saline, and variability in the area of corneal epithelial wound healing and CNV was observed. Results: The optimal concentration of rhEGF and bFGF for the proliferation of corneal epithelial cells was 10 ng/ml. The promotive effect of 10 ng/ml rhEGF on the proliferation of RKCs and HUVECs was less than that of 10 ng/ml bFGF. In the animal experiment, the healing rate of the corneal epithelium in the rhEGF group was better than in the other groups on day 1. On day 3, the healing rates of the 3 groups were nearly equal. The CNV area in the rhEGF group was less than that of the bFGF group. Conclusions: rhEGF and bFGF both had promotive effects on corneal epithelial wound healing, but rhEGF had a weaker promotive effect on CNV than bFGF. With long-term application of growth factor drugs, rhEGF is suggested for lessening the growth of CNV.