bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis C virus infection and risk of coronary artery disease: a systematic review of the literature
Authors: Roed Torsten , Lebech Anne‐Mette , Kjaer Andreas , Weis Nina
Published: July 2012

Background

Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery disease (CAD).

Methods

Studies were identified using several databases. Only studies on CAD in patients with HCV infection were included. A set of criteria for evaluating potential biases was made, based on known confounders and biases in observational research. Data were not synthesized because of the large heterogeneity in the included studies.

Results

Twelve eligible references were identified. Nine did not comply with our criteria of minimizing bias, and six studies were evaluated as potentially heavily biased. The studies of the highest quality showed a trend towards association of HCV with CAD. Five studies showed this association (three studies significantly), while one showed that HCV was a protective factor against CAD.

Conclusion

Our findings suggest an increased risk of CAD in HCV‐infected individuals. Further studies are needed to confirm this and to evaluate the magnitude of the association. Clinicians should be aware of this and strive to reduce CAD risk factors in patients with chronic HCV infection.
Fatigue and rapid hamstring/quadriceps force capacity in professional soccer players
Authors: Greco Camila C. , da Silva Wendell L. , Camarda Sérgio R. A. , Denadai Benedito S.
Published: July 2012

The aim of this study was to investigate the effect of fatigue induced by an exhaustive laboratory‐based soccer‐specific exercise on different hamstrings/quadriceps (H:Q) ratios of soccer players. Twenty‐two male professional soccer players (23·1 ± 3·4 year) performed maximal eccentric (ecc) and concentric (con) contractions for knee extensors (KE) and flexors (KF) at 60° s−1 and 180° s−1 to assess conventional (Hcon:Qcon) and functional (Hecc:Qcon) ratios. Additionally, they performed maximal voluntary isometric contraction for KE and KF, from which the maximal muscle strength, rate of force development (RFD) and RFD H:Q strength ratio (RFDH:Q) were extracted. Thereafter, subjects were performed an exhaustive laboratory‐based soccer‐specific exercise and a posttest similar to the pretest. There was significant reduction in Hcon:Qcon (0·60 ± 0·06 versus 0·58 ± 0·06, P<0·05) and in Hecc:Qcon (1·29 ± 0·2 versus 1·16 ± 0·2, P<0·01) after the soccer‐specific exercise. However, no significant difference between Pre and Post exercise conditions was found for RFDH:Q at 0–50 (0·53 ± 0·23 versus 0·57 ± 0·24, P>0·05) and 0–100 ms (0·53 ± 0·17 versus 0·55 ± 0·17, P>0·05). In conclusion, H:Q strength ratios based on peak force values are more affected by fatigue than RFDH:Q obtained during early contraction phase. Thus, fatigue induced by soccer‐specific intermittent protocol seems not reduce the potential for knee joint stabilization during the initial phase of voluntary muscle contraction.
Light History Influences the Response of Fluvial Biofilms to Zn Exposure
Authors: Corcoll Natàlia , Bonet Berta , Leira Manel , Montuelle Bernard , Tlili Ahmed , Guasch Helena
Published: July 2012

Fluvial biofilms are subject to multistress situations in natural ecosystems, such as the co‐occurrence of light intensity changes and metal toxicity. However, studies simultaneously addressing both factors are rare. This study evaluated in microcosm conditions the relationship between short‐term light intensity changes and Zn toxicity on fluvial biofilms with long‐term photoacclimation to different light conditions. Biofilms that had long‐term photoacclimation to 25 μmol photons · m−2 · s−1 (low light [LL] biofilms), 100 μmol photons · m−2 · s−1 (medium light [ML] biofilms), and 500 μmol photons · m−2 · s−1 (high light [HL] biofilms) were characterized by different structural (Chlorophyll‐a [Chl‐a], total biomass‐AFDW, EPS, algal groups, and diatom taxonomy) and physiological attributes (ETR‐I curves and photosynthetic pigments). HL biofilms showed higher light saturation intensity and a higher production of xanthophylls than LL biofilms. In contrast, LL biofilms had many structural differences; a higher proportion of diatoms and lower AFDW and EPS contents than ML and HL biofilms. A clear effect of light intensity changes on Zn toxicity was also demonstrated. Zn toxicity was enhanced when a sudden increase in light intensity also occurred, mainly with LL biofilms, causing higher inhibition of both the Φ′PSII and the ΦPSII. A decoupling of NPQ from de‐epoxidation reaction (DR) processes was also observed, indicating substantial damage to photoprotective mechanisms functioning in biofilms (i.e., xanthophyll cycle of diatoms) due to Zn toxicity. This study highlights the need to take into account environmental stress (e.g., light intensity changes) to better assess the environmental risks of chemicals (e.g., metals).
Ethical issues in umbilical cord blood banking: a comparative analysis of documents from national and international institutions
Authors: Petrini Carlo
Published: July 2012

The issues of collection, storage, and use of cord blood (CB) stem cells have been addressed extensively in national and international guidelines, policies, and regulations. Many of these documents are not binding, but are nonetheless accorded considerable respect on account of the authority of the issuing organizations. Most discussion has to date focused on two topics: informed consent for collection, banking, and use and the debate between those who favor public storage for altruistic purposes and those who advocate private storage for autologous use. There is generally agreement or consensus in the guidelines that public storage for allogeneic transplants is preferable and that private storage should be discouraged. Given the consensus in national and international guidance on these two issues, it is time for other ethical issues to be examined in greater detail. These include additional uses of CB samples, for example, for research or for the production of blood‐derived drugs, and the economic implications arising from the extensive international network for the exchange of CB for transplantation.
Prospective Evaluation of a Clinical Practice Guideline for Diagnosis of Appendicitis in Children
Authors: Santillanes Genevieve , Simms Sonia , Gausche‐Hill Marianne , Diament Michael , Putnam Brant , Renslo Richard , Lee Jumie , Tinger Elga , Lewis Roger J.
Published: July 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:886–893 © 2012 by the Society for Academic Emergency Medicine

Objectives:  The objective was to assess the performance of a clinical practice guideline for evaluation of possible appendicitis in children. The guideline incorporated risk stratification, staged imaging, and early surgical involvement in high‐risk cases.

Methods:  The authors prospectively evaluated the clinical guideline in one pediatric emergency department (ED) in a general teaching hospital. Patients were risk‐stratified based on history, physical examination findings, and laboratory results. Imaging was ordered selectively based on risk category, with ultrasound (US) as the initial imaging modality. Computed tomography (CT) was ordered if the US was negative or indeterminate. Surgery was consulted before imaging in high‐risk patients.

Results:  A total of 475 patients were enrolled. Of those, 193 (41%) had appendicitis. No low‐risk patient had appendicitis. Medium‐risk patients had a 19% rate of appendicitis, and 83% of high‐risk patients had appendicitis. Factors associated with an increased likelihood of appendicitis included decreased bowel sounds; rebound tenderness; and presence of psoas, obturator, or Rovsing’s signs. Of the 475 patients, 276 (58%) were managed without a CT scan. Seventy‐one of the 193 (37%) patients with appendicitis went to the operating room without any imaging. The rate of missed appendicitis was 2%, and the rate of negative appendectomy was 1%.

Conclusions:  The clinical practice guideline performed well in a general teaching hospital. Rates of negative appendectomy and missed appendicitis were low and 58% of patients were managed without a CT scan.
Altered passive eruption diagnosis and treatment: a cone beam computed tomography‐based reappraisal of the condition
Authors: Batista Eraldo L. , Moreira Carla C. , Batista Felipe C. , de Oliveira Rafael R. , Pereira Karina K. Y.
Published: July 2012

Aim

To characterize anatomical features of altered passive eruption (APE)‐affected teeth using cone beam computed tomography (CBCT) and to present a novel combined surgical approach to its correction.

Clinical Innovation Report

Eighty‐four teeth from 14 subjects affected by APE were subjected to CBCT. Periodontal variables were recorded before surgery, and anatomical variables were measured on CBCTs. Clinical crown length was measured on study casts. Surgical treatment was carried out based on the lengths of the anatomical crowns transferred to a surgical guide that served as a reference for the incisions. The mean distance between the CEJ and the bone crest was on average <1 mm, facial bone thickness was ≥1 mm and soft tissue thickness was >1 mm for every tooth analysed; no association between the soft and the hard tissue thicknesses was observed.

Conclusion

The CBCT can be used in the diagnosis and treatment planning of APE cases. Anatomically, the APE cases described often presented a thick facial bone plate.
Skin‐to‐skin care in neonatal intensive care units in the Nordic countries: a survey of attitudes and practices
Authors: Olsson Emma , Andersen Randi D. , Axelin Anna , Jonsdottir Rakel B. , Maastrup Ragnhild , Eriksson Mats
Published: July 2012

Aim:  To investigate the application of skin‐to‐skin care (SSC) in the Nordic countries, the existence of guidelines for SSC and the attitudes of neonatal staff towards SSC.

Methods:  One questionnaire was distributed at unit level and one at staff level in all Nordic neonatal intensive care units (n = 109).

Results:  The unit questionnaire was answered by 95 (87%) units and the staff questionnaire by 1446 staff members (72%). All units offered SSC to various degrees, but guidelines only existed at 47% of them. Units in Denmark, Norway and Sweden seemed to use SSC earlier, longer and in more medically complicated situations than units in Finland and Iceland. Seventy‐seven per cent of the units had private rooms where parents and infants could stay together, still the physical environment of the units limited the use of SSC. Medical risks were considered the main barrier for further implementation of SSC, while general development and early interaction were the most frequently mentioned benefits.

Conclusion:  Skin‐to‐skin care is implemented in all Nordic neonatal units, but offered to various degrees, to various populations and to varying extents. Danish, Norwegian and Swedish units are offering SSC more extensively than units in Finland and Iceland.
Clinical outcomes of brain metastases treated with Gamma Knife radiosurgery with 3.0 T versus 1.5 T MRI‐based treatment planning: Have we finally optimised detection of occult brain metastases?
Authors: Loganathan Amritraj G , Chan Michael D , Alphonse Natalie , Peiffer Ann M , Johnson Annette J , McMullen Kevin P , Urbanic James J , Saconn Paul A , Bourland J Daniel , Munley Michael T , Shaw Edward G , Tatter Stephen B , Ellis Thomas L
Published: July 2012

Introduction

The goal of this study was to determine if clinically relevant endpoints were changed by improved MRI resolution during radiosurgical treatment planning.

Methods and Materials

Between 2003 and 2008, 200 consecutive patients with brain metastases treated with Gamma Knife radiosurgery (GKRS) using either 1.5 T or 3.0 T MRI for radiosurgical treatment planning were retrospectively analysed. The number of previously undetected metastases at time of radiosurgery, distant brain failures, time delay to whole brain radiotherapy (WBRT), overall survival and likelihood of neurological death were determined.

Results

Additional metastases were detected in 31.3% and 24.5% of patients at time of radiosurgery with 3.0 T and 1.5 T MRI, respectively (P = 0.27). Patients with multiple metastases at diagnostic scan were more likely to have additional metastases detected by 3.0 T MRI (P < 0.1). Median time to distant brain failure was 4.87 months and 5.43 months for the 3.0 T and 1.5 T cohorts, respectively (P = 0.44). Median time to WBRT was 5.8 months and 5.3 months for the 3.0 T and 1.5 T cohorts, respectively (P = 0.87). Median survival was 6.4 months for the 3.0 T cohort, and 6.1 months for the 1.5 T cohort (P = 0.71). Likelihood of neurological death was 25.3% and 16.7% for the 3.0 and 1.5 T populations, respectively (P = 0.26).

Conclusions

The 3.0 T MRI‐based treatment planning for GKRS did not appear to affect the likelihood of distant brain failure, the need for WBRT or the likelihood of neurological death in this series.
Nervilia pangteyana sp. nov., a terrestrial orchid from western Himalaya, India
Authors: Jalal Jeewan Singh , Kumar Pankaj , Rawat Gopal S.
Published: July 2012

Nervilia pangteyana J. S. Jalal, Kumar & G. S. Rawat (Orchidaceae), a new species from western Himalaya (Uttarakhand), India is described, illustrated and compared with its closest relative. In addition, a key is given to distinguish between species of Nervilia in the western Himalayas.
Reproduction of beetle‐pollinated Anaxagorea dolichocarpa (Annonaceae) is resilient to habitat disturbance in rainforest fragments
Authors: Braun Marcus , Gottsberger Gerhard
Published: July 2012

Strong evidence exists that fragmentation negatively affects pollination and plant reproduction, but little research has been conducted with regards to tropical trees. Specifically, effects of forest fragmentation on reproduction of plants with beetle‐pollinated flowers are poorly understood, and there are no data on the impact of fragmentation on reproduction in the structurally important tropical family Annonaceae. We examined the relationship between fragment size, pollinator abundance and seed set of beetle‐pollinated Anaxagorea dolichocarpa (Annonaceae) in a disturbed Brazilian Atlantic rainforest. Flower and fruit production and abundance of pollinators were quantified over ten months in three large (306–388 ha) and three small (6–14 ha) forest fragments. We recorded per flower pollinator abundance, resulting fruit set (fruits per flower) and seed set (monocarps per fruit) for a total of 209 individually marked flowers, and compared pollinator abundance in 186 flowers across all fragments. Flower and fruit production differed among fragments, but were similar for the combined large and small fragments. Between 64.8% (large fragments) and 66.3% (small fragments) of flowers received at least one pollinator. We found no significant difference in pollinator numbers between large and small fragments, and no correlation between pollinator abundance and fruit and seed set. A single visitor had a high probability of pollinating a flower. We conclude that 1) fragment size had no influence on pollinator number and plant reproductive success, and 2) generalist behavior of the pollinating beetles mitigate the risk of pollination failure for the reproductively specialized plant. However, further research may yet reveal genetic impoverishment of populations in small fragments due to restricted pollinator movements.
Glutamine‐fueled mitochondrial metabolism is decoupled from glycolysis in melanoma
Authors: Filipp Fabian V. , Ratnikov Boris , De Ingeniis Jessica , Smith Jeffrey W. , Osterman Andrei L. , Scott David A.
Published: July 2012

In this perspective, we revise the historic notion that cancer is a disease of mitochondria. We summarize recent findings on the function and rewiring of central carbon metabolism in melanoma. Metabolic profiling studies using stable isotope tracers show that glycolysis is decoupled from the tricarboxylic acid (TCA) cycle. This decoupling is not ‘dysfunction’ but rather an alternate wiring required by tumor cells to remain metabolically versatile. In large part, this requirement is met by glutamine feeding the TCA cycle as an alternative source of carbon. Glutamine is also used in non‐conventional ways, like traveling in reverse through the TCA flux to feed fatty acid biosynthesis. Biosynthetic networks linked with non‐essential amino acids alanine, serine, arginine, and proline are also significantly impacted by the use of glutamine as an alternate carbon source.
Regulation of the sodium pump during cardiomyocyte adaptation to pregnancy
Authors: Elzwiei F. , Bassien‐Capsa V. , St‐Louis J. , Chorvatova A.
Published: July 2012

New findings

What is the central question of this study?

Pregnancy leads to sustained increases in cardiac output and stroke volume. The cellular mechanisms underlying the associated changes in myocardial function are poorly understood. We investigated the role of the sodium pump in the functional adaptations of cardiomyocytes to normal pregnancy.

What is the main finding and its importance?

We found that in normal pregnancy the expression of the α1 Na+–K+‐ATPase isoform is reduced in cardiomyocytes, and there is decreased sodium pump membrane current and elevated steady‐state intracellular sodium. Our findings suggest an important role for reduced expression and activity of the myocardial membrane sodium pump in the cardiac adaptations to pregnancy.

Regulation of the sodium pump during normal pregnancy and its effect on the function of cardiomyocytes is poorly understood. Our objective was to evaluate the possible implication of the Na+–K+‐ATPase, the sodium pump which controls cellular ionic and metabolic homeostasis, in the adaptations of cardiomyocytes to normal pregnancy. We have used Western blots and patch‐clamp measurements to identify changes in the sodium pump proteins. Confocal microscopy was applied to estimate intracellular sodium concentration. Time‐resolved spectroscopy was employed to measure mitochondrial NAD(P)H fluorescence and estimate oxidative metabolic state. Optical microscopy was adopted to study the contractility responses of cardiomyocytes. Cells from non‐pregnant and pregnant rats (1 day prior parturition) were studied. Our results showed lower protein expression of the α1 Na+–K+‐ATPase isoform in cardiomyocytes in pregnant rats, decreased sodium pump membrane current and elevated steady‐state sodium concentration. In addition, ouabain, the inhibitor of the sodium pump capable of increasing cardiomyocyte contractility in non‐pregnant rats in a concentration‐dependent manner, failed to affect cell contractions in pregnant rats. We also noted modified responsiveness of the mitochondrial metabolic state to ouabain in cardiac cells. The gathered data confirmed that in pregnant rats, the sodium pump protein content and transmembrane flux are decreased, while the sensitivity of cardiomyocyte contractility and the sensitivity of mitochondrial metabolic redox state to ouabain are modified, pointing to regulation of the Na+–K+‐ATPase during cardiac cell adaptations to normal pregnancy.
Sustained postexercise vasodilatation and histamine receptor activation following small muscle‐mass exercise in humans
Authors: Barrett‐O'Keefe Zachary , Kaplon Rachelle E. , Halliwill John R.
Published: July 2012

New findings

What is the central question of this study?

The role of histamine‐mediated vasodilatation has been studied in the context of whole‐body cycling but not small muscle‐mass exercise.

What is the main finding and its importance?

These data indicate that histamine receptors are activated following dynamic, but not resistance, exercise. Furthermore, these data suggest that local factors associated with aerobic exercise, and not systemic factors, are responsible for activation of histamine receptors in the previously exercised muscle.

A sustained postexercise vasodilatation, which is histamine receptor mediated, has been observed following single bouts of whole‐body exercise, but the mechanisms that regulate activation of histamine receptors following exercise are undefined. Exploration of vasodilatation after small muscle‐mass dynamic or resistance exercise could provide novel insight into the pathways responsible for histamine receptor activation. We hypothesized that there would be a vasodilatation of the previously exercised limb following small muscle‐mass dynamic and resistance exercise, which would be mediated by histamine receptors. We studied men and women before and after single‐leg dynamic (n= 9) or resistance knee‐extension exercise (n= 12) on control and blockade days (combined oral H1 and H2 receptor antagonism with fexofenadine and ranitidine). We measured arterial blood pressure (automated brachial oscillometry) and femoral artery blood flow (Doppler ultrasound). Dynamic exercise elevated leg vascular conductance in the active leg by 27.2 ± 8.4% at 60 min postexercise (P < 0.05 versus pre‐exercise), but did not alter conductance in the rested leg (change, 4.6 ± 3.5%; P= 0.8 versus pre‐exercise). The rise in conductance was abolished on the blockade day (change, 3.7 ± 5.1%; P= 0.8 versus pre‐exercise, P= 0.2 versus control). Resistance exercise did not produce a sustained vasodilatation (change, –4.3 ± 4.7% at 60 min postexercise; P= 0.7 versus pre‐exercise). These data indicate that histamine receptors are activated following dynamic, but not resistance, exercise. Furthermore, these data suggest that local factors associated with aerobic exercise, and not systemic factors or factors associated with high muscle force, are responsible for activation of histamine receptors in the previously exercised muscle.
Postnatal development of electrophysiological properties of principal neurons in the rat basolateral amygdala
Authors: Ehrlich D. E. , Ryan S. J. , Rainnie D. G.
Published: July 2012

Key points

The amygdala mediates emotional processing, in particular fear learning, and disruption of its function is thought to contribute to the developmental origins of psychiatric disorders like depression, anxiety and autism spectrum disorders.

It is difficult to identify the causes of these disorders or provide effective intervention because most of what is known of amygdala physiology is based on the adult.

Using the whole‐cell patch clamp technique, we show that neurons in the developing rat amygdala undergo drastic changes to their electrophysiology, including passive membrane properties, intrinsic currents and resonance.

This provides the first evidence that amygdala neuron physiology is dynamic before adulthood, and likely to contribute to emotional development.

The results help us better understand the normative development of emotional processing and identify critical periods of maturation that may be sensitive to insult.

Abstract  The basolateral amygdala (BLA) is critically involved in the pathophysiology of psychiatric disorders, which often emerge during brain development. Several studies have characterized postnatal changes to the morphology and biochemistry of BLA neurons, and many more have identified sensitive periods of emotional maturation. However, it is impossible to determine how BLA development contributes to emotional development or the aetiology of psychiatric disorders because no study has characterized the physiological maturation of BLA neurons. We addressed this critical knowledge gap for the first time using whole‐cell patch clamp recording in rat BLA principal neurons to measure electrophysiological properties at postnatal day (P)7, P10, P14, P21, P28 and after P35. We show that intrinsic properties of these neurons undergo significant transitions before P21 and reach maturity around P28. Specifically, we observed significant reductions in input resistance and membrane time constant of nearly 10‐ and 4‐fold, respectively, from P7 to P28. The frequency selectivity of these neurons to input also changed significantly, with peak resonance frequency increasing from 1.0 Hz at P7 to 5.7 Hz at P28. In the same period, maximal firing frequency significantly increased and doublets and triplets of action potentials emerged. Concomitantly, individual action potentials became significantly faster, firing threshold hyperpolarized 6.7 mV, the medium AHP became faster and shallower, and a fast AHP emerged. These results demonstrate neurons of the BLA undergo vast change throughout postnatal development, and studies of emotional development and treatments for juvenile psychiatric disorders should consider the dynamic physiology of the immature BLA.
Simplified Fluid-Structure Model for Duckbill Valve Flow
Authors: Wang J. , Weaver D. S. , Tullis S.
Published: July 2012

Duckbill valves (DBVs), made of a fabric reinforced layered rubber composite, are extensively used for nonreturn axial water flows with low back pressures. Fluid–structure interaction (FSI) is directly involved in the opening process of the DBV, with the opening depending on the pressure differential across the valve. In this paper, a simplified FSI model of the DBV is presented using a finite element method (FEM). The valve is modeled as a laminated thick shell structure with some simplifications to the boundary conditions. The pressure load acting on the shell surface of the DBV is a function of the variable valve cross-sectional area and determined, for preliminary analysis purposes, by using a simple potential flow model for the fluid mechanics. The hyperelasticity of the rubber and orthotropy of the fiber reinforcement, as well as large deflections of the DBV, are considered in the simulation. The valve is modeled as being closed when the upstream pressure is applied, and the transient opening process is tracked until a steady state opening is achieved. Several static cases of viscous flow passing through the deformed valve structure have also been carried out to compare the pressure and velocity fields of fluid flow with the corresponding pressure and velocity distribution predicted by the simplified model and to compare the hydraulic performance of the DBV predicted by both models.
Chemical Inhibitors of the Type Three Secretion System: Disarming Bacterial Pathogens
Authors: Duncan Miles C. , Linington Roger G. , Auerbuch Victoria
Published: July 2012

The recent and dramatic rise of antibiotic resistance among bacterial pathogens underlies the fear that standard treatments for infectious disease will soon be largely ineffective. Resistance has evolved against nearly every clinically used antibiotic, and in the near future, we may be hard-pressed to treat bacterial infections previously conquered by “magic bullet” drugs. While traditional antibiotics kill or slow bacterial growth, an important emerging strategy to combat pathogens seeks to block the ability of bacteria to harm the host by inhibiting bacterial virulence factors. One such virulence factor, the type three secretion system (T3SS), is found in over two dozen Gram-negative pathogens and functions by injecting effector proteins directly into the cytosol of host cells. Without T3SSs, many pathogenic bacteria are unable to cause disease, making the T3SS an attractive target for novel antimicrobial drugs. Interdisciplinary efforts between chemists and microbiologists have yielded several T3SS inhibitors, including the relatively well-studied salicylidene acylhydrazides. This review highlights the discovery and characterization of T3SS inhibitors in the primary literature over the past 10 years and discusses the future of these drugs as both research tools and a new class of therapeutic agents.
Cobicistat Boosts the Intestinal Absorption of Transport Substrates, Including HIV Protease Inhibitors and GS-7340,
In Vitro
Authors: Lepist Eve-Irene , Phan Truc K. , Roy Anupma , Tong Leah , MacLennan Kelly , Murray Bernard , Ray Adrian S.
Published: July 2012

The experimental pharmacoenhancer cobicistat (COBI), a potent mechanism-based inhibitor of cytochrome P450 3A enzymes, was found to inhibit the intestinal efflux transporters P-glycoprotein and breast cancer resistance protein. Consistent with its transporter inhibition, COBI significantly increased the absorptive flux of potential candidates for clinical coadministration, including the HIV protease inhibitors atazanavir and darunavir and the lymphoid cell- and tissue-targeted prodrug of the nucleotide analog tenofovir, GS-7340, through monolayers of Caco-2 cells
in vitro
.
Effect on Hepatitis C Virus Replication of Combinations of Direct-Acting Antivirals, Including NS5A Inhibitor Daclatasvir
Authors: Pelosi Lenore A. , Voss Stacey , Liu Mengping , Gao Min , Lemm Julie A.
Published: July 2012

Three hepatitis C virus (HCV) inhibitors, asunaprevir (ASV; BMS-650032), daclatasvir (DCV; BMS-790052), and BMS-791325, each targeting a different nonstructural protein of the virus (NS3, NS5A, and NS5B, respectively), have independently demonstrated encouraging preclinical profiles and are currently undergoing clinical evaluation. Since drug-resistant variants have rapidly developed in response to monotherapy with almost all direct-acting antiviral agents (DAAs) for HCV, the need for combination therapies to effectively eradicate the virus from infected patients is clear. These studies demonstrated the additive-synergistic effects on replicon inhibition and clearance of combining NS3 protease or NS5B RNA polymerase inhibitors with the first-in-class, NS5A replication complex inhibitor daclatasvir (DCV) and reveal new resistance pathways for combinations of two small-molecule inhibitors that differ from those that develop during monotherapy. The results suggest that under a specific selective pressure, a balance must be reached in the fitness costs of substitutions in one target gene when substitutions are also present in another target gene. Further synergies and additional novel resistance substitutions were observed during triple-combination treatment relative to dual-drug therapy, indicating that, in combination, HCV inhibitors can exert cross-target influences on resistance development. Enhanced synergies in replicon inhibition and a reduced frequency of resistance together lend strong support to the utility of combinations of DAAs for the treatment of HCV, and the identification of altered resistance profiles during combination treatment provides useful information for monitoring resistance in the clinic.
Infection with Toxoplasma gondii Alters Lymphotoxin Expression Associated with Changes in Splenic Architecture
Authors: Glatman Zaretsky Arielle , Silver Jonathan S. , Siwicki Marie , Durham Amy , Ware Carl F. , Hunter Christopher A.
Published: July 2012

B cell responses are required for resistance toToxoplasma gondii; however, the events that lead to production of class-switched antibodies duringT. gondiiinfection have not been defined. Indeed, mice challenged with the parasite exhibited an expansion of T follicular helper cells and germinal center B cells in the spleen. Unexpectedly, this was not associated with germinal center formation and was instead accompanied by profound changes in splenic organization. This phenomenon was transient and was correlated with a decrease in expression of effector proteins that contribute to splenic organization, including lymphotoxins α and β. The importance of lymphotoxin was confirmed, as the use of a lymphotoxin β receptor agonist results in partial restoration of splenic structure. Splenectomized mice were used to test the splenic contribution to the antibody response duringT. gondiiinfection. Analysis of splenectomized mice revealed delayed kinetics in the production of parasite-specific antibody, but the mice did eventually develop normal levels of parasite-specific antibody. Together, these studies provide a better understanding of how infection withT. gondiiimpacts the customized structures required for the optimal humoral responses to the parasite and the role of lymphotoxin in these events.
Roles of Chaperone/Usher Pathways of Yersinia pestis in a Murine Model of Plague and Adhesion to Host Cells
Authors: Hatkoff Matthew , Runco Lisa M. , Pujol Celine , Jayatilaka Indralatha , Furie Martha B. , Bliska James B. , Thanassi David G.
Published: July 2012

Yersinia pestis
and many other Gram-negative pathogenic bacteria use the chaperone/usher (CU) pathway to assemble virulence-associated surface fibers termed pili or fimbriae.
Y. pestis
has two well-characterized CU pathways: the
caf
genes coding for the F1 capsule and the
psa
genes coding for the pH 6 antigen. The
Y. pestis
genome contains additional CU pathways that are capable of assembling pilus fibers, but the roles of these pathways in the pathogenesis of plague are not understood. We constructed deletion mutations in the usher genes for six of the additional
Y. pestis
CU pathways. The wild-type (WT) and usher deletion strains were compared in the murine bubonic (subcutaneous) and pneumonic (intranasal) plague infection models.
Y. pestis
strains containing deletions in CU pathways
y0348-0352
,
y1858-1862
, and
y1869-1873
were attenuated for virulence compared to the WT strain by the intranasal, but not subcutaneous, routes of infection, suggesting specific roles for these pathways during pneumonic plague. We examined binding of the
Y. pestis
WT and usher deletion strains to A549 human lung epithelial cells, HEp-2 human cervical epithelial cells, and primary human and murine macrophages.
Y. pestis
CU pathways
y0348-0352
and
y1858-1862
were found to contribute to adhesion to all host cells tested, whereas pathway
y1869-1873
was specific for binding to macrophages. The correlation between the virulence attenuation and host cell binding phenotypes of the usher deletion mutants identifies three of the additional CU pathways of
Y. pestis
as mediating interactions with host cells that are important for the pathogenesis of plague.
Type 2 Innate Immunity in Helminth Infection Is Induced Redundantly and Acts Autonomously following CD11c+Cell Depletion
Authors: Smith Katherine A. , Harcus Yvonne , Garbi Natalio , Hämmerling Günter J , MacDonald Andrew S. , Maizels Rick M.
Published: July 2012

Infection with gastrointestinal helminths generates a dominant type 2 response among both adaptive (Th2) and innate (macrophage, eosinophil, and innate lymphoid) immune cell types. Two additional innate cell types, CD11chighdendritic cells (DCs) and basophils, have been implicated in the genesis of type 2 immunity. Investigating the type 2 response to intestinal nematode parasites, includingHeligmosomoides polygyrusandNippostrongylus brasiliensis, we first confirmed the requirement for DCs in stimulating Th2 adaptive immunity against these helminths through depletion of CD11chighcells by administration of diphtheria toxin to CD11c.DOG mice. In contrast, responsiveness was intact in mice depleted of basophils by antibody treatment. Th2 responses can be induced by adoptive transfer of DCs, but not basophils, exposed to soluble excretory-secretory products from these helminths. However, innate type 2 responses arose equally strongly in the presence or absence of CD11chighcells or basophils; thus, in CD11c.DOG mice, the alternative activation of macrophages, as measured by expression of arginase-1, RELM-α, and Ym-1 (Chi3L3) in the intestine followingH. polygyrusinfection or in the lung followingN. brasiliensisinfection, was unaltered by depletion of CD11c-expressing DCs and alveolar macrophages or by antibody-mediated basophil depletion. Similarly, goblet cell-associated RELM-β in lung and intestinal tissues, lung eosinophilia, and expansion of innate lymphoid (“nuocyte”) populations all proceeded irrespective of depletion of CD11chighcells or basophils. Thus, while CD11chighDCs initiate helminth-specific adaptive immunity, innate type 2 cells are able to mount an autonomous response to the challenge of parasite infection.
THE MASS DIFFERENCE OF $F-\bar{F}$ WITH SO(3) FAMILY GAUGE SYMMETRY
Authors: LI HONG-LEI , BAO SHOU-SHAN , SI ZONG-GUO
Published: July 2012

As a simple extension, a non-Abelian family gauge symmetry SO(3), as well as three family Majorana neutrinos, was introduced to explain the tri-bimaximal mixing matrix of neutrinos. We discuss the effect of the possible SO(3) family gauge interaction to the mass differences of [Formula: see text] and [Formula: see text], and get the constrains to the new gauge bosons.
CONTINUOUS MULTIPLE OLAP QUERIES FOR DATA STREAMS
Authors: PARIMALA N. , BHAWNA S.
Published: July 2012

Querying data stream data continuously has been addressed mostly as transactional queries with some attempts at analytical processing. But, in most of the proposals a single query is executed for a given window of data. In this paper, we propose to continuously execute multiple related OLAP queries (CMOLAP) for the data chosen from a data stream. The chosen data defines the context. The context data is temporarily stored in the form of a multidimensional cube to perform OLAP operations. Three sets of operations are defined. The first converts the data in a stream to a context, the second allows altering the context and the third set is analytical which operates on the context and produces an output stream. More than one related analytic operation can be performed for the data in a context. The sequence of operations, referred to as context queries, is continuously executed for a time-based window. As a result it is possible to do enhanced related analysis of data. We have also developed a GUI interface where the queries can be expressed in a user friendly manner.
POSTURE AND GROUND REACTION FORCE RELATED INFLUENCES ON TAI CHI PUSHING MOVEMENT
Authors: WANG LIN-HWA , LO KUO-CHENG , SU FONG-CHIN
Published: July 2012

The goal of this study was to investigate the differences in ground reaction force during a Tai Chi Chuan (TCC) pushing movement between those with and without TCC experience through a detailed 3D dynamic analysis of the lower extremities. Seven TCC practitioners who had practiced the TCC push-hands movement for 6.0 ± 4.8 years and eight males without any TCC experience were recruited in this study. An eight-camera Expert Vision Eagle motion analysis system and two Kistler force plates were used to collect kinematic data (100 Hz) and the ground reaction force (1000 Hz). About 34 retro-reflective markers were placed on anatomical significant locations that determine embedded axes for segments. Results showed that the angular motions of the knee joint were different between the two groups, both in pattern and magnitude. Compared with the TCC group, the non-TCC group had significantly smaller peak abduction angles at the ankle joint (p < 0.05). The magnitude of the vertical force of the TCC group was greater, whereas the medial and posterior shear forces were smaller. The significant difference in vertical force (p < 0.05) and fraction opponent force of vertical force were found significantly different (p < 0.05) between the two groups. The patterns of the anteroposterior component of the ground reaction force during pushing were different, but those for the other two components were similar. Different lower-limb kinematics and kinetics were found between those with and those without TCC experience during TCC pushing movement and it was also found that the TCC practitioners could generate more effective force transfer than the group with no prior TCC experience. It was further concluded that vertical force plays an important role in a pushing movement, and posterior force exerted from the opponent was absorbed and transformed into anterior force to help the TCC practitioners remain stable.
Carbon nanotubes and metalloporphyrins and metallophthalocyanines-based materials for electroanalysis
Authors: Zagal José H. , Griveau Sophie , Santander-Nelli Mireya , Granados Silvia Gutierrez , Bedioui Fethi
Published: July 2012

We discuss here the state of the art on hybrid materials made from single (SWCNT) or multi (MWCNT) walled carbon nanotubes and MN4complexes such as metalloporphyrins and metallophthalocyanines. The hybrid materials have been characterized by several methods such as cyclic voltammetry (CV), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and scanning electrochemical microscropy (SECM). The materials are employed for electrocatalysis of reactions such as oxygen and hydrogen peroxide reduction, nitric oxide oxidation, oxidation of thiols and other pollutants.
Phthalocyanines in batteries and supercapacitors
Authors: Oni Joshua , Ozoemena Kenneth I.
Published: July 2012

Numerous are the ways through which phthalocyanines have been put into very good use. The on-going search for new energy storage and conversion systems has made phthalocyanines even prettier as alternatives to metal and metal oxide catalysts because of their lower cost. This review article looks through a very narrow window of the applications of phthalocyanines in batteries and supercapacitors as a means of improving the qualities such as cycle property, energy density, capacity, open circuit voltage, etc, of these devices.
Nanostructured metallophthalocyanine complexes: synthesis and electrocatalysis
Authors: Pillay Jeseelan , Vilakazi Sibulelo
Published: July 2012

In this review, we have attempted to summarize the synthesis and catalytic applications of the nanophthalocyanine complexes. In cases where possible, we have compared the catalytic activity of the nanophthalocyanines to the bulk material. Catalytic detection of dopamine, epinephrine, glucose and some pollutants using nanostructured metallophthalocyanine have been covered.
Microelectrodes based on porphyrins for the determination of ascorbic acid in pharmaceutical samples and beverages
Authors: Stefan-van Staden Raluca-Ioana , Balasoiu Simona Cornelia , van Staden Jacobus Frederick , Radu Gabriel-Lucian
Published: July 2012

Different porphyrins were used for the design of seven carbon paste and seven diamond paste based microelectrodes, which were employed for the determination of ascorbic acid in pharmaceutical and beverages samples using differential pulse voltammetry (DPV). The limits of detection lie between 1.1 × 10-14and 5.1 × 10-7M while the sensitivities were between 3.07 pA/M and 1285.18 A/M. Ascorbic acid was recovered reliable from pharmaceutical and beverages samples in percentages higher than 92.00% and 91.50%, respectively. The surface of the microelectrodes can easily be renewed by simple polishing, obtaining a fresh surface ready for use in a new assay.
Heavy metal effects on physicochemical properties of non-aggregated azaphthalocyanine derivatives
Authors: Tuhl Ahmad , Makhseed Saad , Zimcik Petr , Al-Awadi Nouria , Novakova Veronika , Samuel Jacob
Published: July 2012

Two series of peripherally substituted azaphthalocyanines (AzaPcs) containing different transition metals ( Al(III), Zn(II), Ga(III), In(III) and Fe(II) ) were synthesized and studied for their photophysical properties. As confirmed by UV-vis and1H NMR analyses, the non-aggregation behavior was effectively induced by the applied bulky peripheral substituents which had no effect on the photophysical properties. Tuning the Q-band position was clearly achievable by using different central heavy metals which have considerable effects on the fluorescence quantum yield and singlet oxygen generation efficiency. This comparative study showed an interesting linear relationship between the former and atomic number of the central metal. The indium containing complexes exhibited the best result due to the heavy metal effect and therefore could be promoted as a potential photosensitizer in photodynamic therapy (PDT) application.
Trends in the optical and redox properties of tetraphenyltetraphenanthroporphyrins
Authors: Mack John , Lobb Kevin , Nyokong Tebello , Shen Zhen , Kobayashi Nagao
Published: July 2012

The results of TD-DFT calculations for a series of tetraaryltetraphenanthroporphyrins containing para-substituents with differing electron donating and accepting properties are compared to the observed optical and redox properties and Michl's perimeter model is used as a conceptual framework for analyzing the results.
Electronic structures, spectroscopic properties, and reaction activities of porphyrins with alkali metal ions: density functional theory approach to the central metal effects
Authors: Zhao Luyang , Qi Dongdong , Zhang Lijuan , Bai Ming , Cai Xue
Published: July 2012

Density functional theory (DFT) calculation method was employed to investigate a series of nine alkali metal porphyrins (alk-Pors), namely HLiPor , HNaPor , HKPor , Li2Por , LiNaPor , LiKPor , Na2Por , NaKPor , and K2Por . These molecules show different configurations depending on different metal ions which locate over the central hole of the porphyrin ligand. Alk-Pors with larger-radius metal ion have smaller binding energy and thus is more difficult to keep stable. Further detailed molecular stability analysis was carried out by noncovalent interaction and electrostatic interaction via RDG and NBO charge distribution. UV-vis spectra of these nine compounds also show different spectral shapes depending on the central metals, and the dominant state transitions with high degeneracy are revealed to be influenced by high molecular symmetric order. Finally their difference in reactivity due to the electronegativity of central metals and the nature of porphyrin rings are predicted by electrostatic potential and Fukui functions.
Issues arising from refactoring studies
Authors: Counsell Steve , Swift Stephen
Published: July 2012

In theory, refactoring should reverse the trend in code decay and many studies have explored the different facets of refactoring (both its trends and characteristics). While much progress has been made in this area, a number of observations about refactoring studies have become evident to us over the past seven years in the time during which we have been undertaking empirical studies in this area. This paper outlines our experiences of the issues that arise with refactoring studies. We outline six of those issues, together forming the set of challenges that are still prevalent in this area. The purpose of the paper is thus to put under the spotlight the real potential benefits of refactoring, but more importantly the challenges that our experiences have raised
Method cohesion analysis through concept lattices
Authors: Tiwari Manisha , Joshi Padmaja
Published: July 2012

Cohesion in object oriented technology is usually associated with a class and hence majority of the available cohesion metrics capture cohesion of classes. Methods which are the main contributors to class cohesion are not analyzed for their internal cohesiveness. This concept paper proposes method cohesion analysis through concept lattices. The approach facilitates rapid identification of elements (statements or variables) in methods that are less cohesive with respect to the remaining part of the method. The paper discusses the analysis and interpretation of cohesion lattices. The approach is demonstrated through dummy examples
Precise static analysis for generic programs in object oriented languages
Authors: Kumar Surender , Kumar Rajeev
Published: July 2012

Genericity enriched with multiple data types and classes is becoming a common feature of object oriented languages. Therefore, static analysis of such generic programs is gaining importance. Unfortunately such work does not exist. In this work, we statically analyse such generic programs for approximating the possible dynamic (run-time) types of objects. We propose a single pass technique for analyzing the generic programs inter-procedurally statement-wise following the control flow of the execution. The technique is able to resolve the covariance, contravariance and invariance relationship existing amongst different instances with type parameters as arguments to a class. We assess the performance of the proposed technique by carrying out experiments on a set of standard benchmark programs