bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of the Variation of Strain Rates During a Rolling Pass in Compression Tests
Authors: Wang F. , Hwu Y. , Lenard J. G.
Published: September 2009

A Nb-V steel’s response to constant true strain rate compression was compared to its behavior when the strain rate varied as during a rolling pass. The constitutive behavior during the two types of tests was found not to differ in a significant manner.
The Influence of Test Temperature on the Ratchetting Behavior of Type 304 Stainless Steel
Authors: Ruggles M. B. , Krempl E.
Published: September 2009

The zero-to-tension ratchetting behavior was investigated under uniaxial loading at room temperature and at 550, 600, and 650°C. In History I the maximum stress level of ratchetting was equal to the stress reached in a tensile test at one percent strain. For History II the maximum stress level was established as the stress reached after a 2100 s relaxation at one percent strain. Significant ratchetting was observed for History I at room temperature but not at the elevated temperatures. The accumulated ratchet strain increases with decreasing stress rate. Independent of the stress rates used insignificant ratchet strain was observed at room temperature for History II. This observation is explained in the context of the viscoplasticity theory based on overstress by the exhaustion of the viscous contribution to the stress during relaxation. The viscous part of the stress is the driving force for the ratchetting in History I. Strain aging is presumably responsible for the lack of short-time inelastic deformation resulting in a nearly rate-independent behavior at the elevated temperatures.
Constitutive Modeling of Ratchetting Effects—Part I: Experimental Facts and Properties of the Classical Models
Authors: Chaboche J. L. , Nouailhas D.
Published: September 2009

The constitutive modeling of cyclic plasticity has made great progress during the past twenty years. One of the incompletely solved problems concerns ratchetting, that is the progressive strain accumulation, cycle-by-cycle, induced by the superposition of a cyclic secondary load to a constant primary load. The paper discusses the main experimental facts and identifies the main inadequacies of the classical cyclic constitutive equations when they are used to predict ratchetting effects.
Subcritical Crack Growth Characteristics on Compact Type Specimens and Indentation Cracks in Glass
Authors: Yoda M.
Published: September 2009

For the purpose of comparing crack growth characteristics on small indentation cracks with those for long cracks, subcritical crack growth data on soda-lime glass were obtained using the compact type (CT) specimens with long cracks and the indentation cracks. It was found that there is apparently a small crack effect in the as-indented cracks which increases crack growth. However, the annealed indentation crack shows the same trend of crack growth as that for the CT specimens. A residual stress effect can be used to explain this anomalous growth behavior of the as-indented cracks.
Stress-Strain Relations of SUS304 Stainless Steel After Cyclic Preloading
Authors: Ishikawa H. , Sasaki K.
Published: September 2009

To formulate the constitutive equation for nonproportional cyclic loading, the influence of preloading on subsequent loading should be investigated experimentally. In this paper, both the stress-strain relation and the equi-plastic strain surface of subsequent loading after cyclic preloading have been examined carefully from combined tension-compression and torsion test with SUS304 stainless steel. The equiplastic strain surface could be represented by the quadratic form of stress when it was probed from the current center of the yield surface after cyclic preloading. Then, all the stress-strain curves of subsequent radial loading from the center were confirmed to be represented by the modified Ramberg-Osgood law. As a result, the modified Ramberg-Osgood law obtained shows availability to derive the constitutive equations of cyclic plasticity.
A Unified Constitutive Model for Cyclic Viscoplasticity and Its Applications to Various Stainless Steels
Authors: Chaboche J. L. , Nouailhas D.
Published: September 2009

This paper deals with the monotonic and cyclic behavior of austenitic stainless steels and the way to model it. Developments made on constitutive equations led to elaborate sophisticated models justified by the complexity of the real behavior of these materials, especially at high temperature. In the first part, a survey of the various components introduced in the ONERA model is made in terms of a hierarchical presentation. The second part is devoted to several applications on different types of stainless steels in order to illustrate the capabilities of the model for various loading situations.
Effects of Sub-Freezing Temperatures on Graphite/Epoxy Composite Materials
Authors: Tsotsis T. K.
Published: September 2009

Moisture in composite materials has been the subject of considerable interest in the past decade. Many studies have shown that moisture directly causes damage in graphite/epoxy composite materials. With the increasing use of such composites in various environments, an assessment of the effects of sub-freezing and/or cryogenic temperatures on composites containing moisture is needed. This article presents a summary of these effects and demonstrates that reductions in strength at low temperatures are not due to the formation of ice crystals, but instead are due to changes in the residual stresses caused by absorbed moisture.
Calculation of electron emission from a gated single nanowire
Authors: Lei Da , Wang Weibiao , Zeng Leyong , Liang Jingqiu
Published: September 2009

The field-enhancement factor β on an individual nanowire with flattop was calculated analytically by the electrostatic method in a gated structure. To evaluate the influences of the geometrical parameters—including the gate-hole radius R, nanowire radius r0, nanowire length L, and gate-anode distance d2 for β—the authors proposed an ideal model of the gated single nanowire (L<d1), where d1 is the gate-cathode space. The calculation results showed that β decreases rapidly with both R and r0 and eventually saturates to a fixed value if R tends to infinity. It increases almost linearly with an increase in the nanowire height. When d2 is not much larger than d1 and R, β decreases slightly as d2 increases, but the effect of the gate-anode distance on β can be ignored if d2 is infinite. These results provide useful information on fabricating and designing gated nanowire cold cathodes for field-emission display panels and other nanoscale triodes.
Methicillin-Resistant
Staphylococcus aureus
Screening by Online Immunometric Monitoring of Bacterial Growth under Selective Pressure
Authors: Stenholm Teppo , Hakanen Antti J. , Vaarno Jonne , Pihlasalo Sari , Terho Perttu , Hänninen Pekka E. , Vuopio-Varkila Jaana , Huovinen Pentti , Kotilainen Pirkko
Published: September 2009

Rapid, high-throughput screening tools are needed to contain the spread of hospital-acquired methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) strains. Most techniques used in current clinical practice still require time-consuming culture for primary isolation of the microbe. We present a new phenotypic assay for MRSA screening. The technique employs a two-photon excited fluorescence (TPX) detection technology with
S. aureus
-specific antibodies that allows the online monitoring of bacterial growth in a single separation-free process. Different progressions of fluorescence signals are recorded for methicillin-susceptible and -resistant strains when the growth of
S. aureus
is monitored in the presence of cefoxitin. The performance of the new technique was evaluated with 20 MRSA strains, 6 methicillin-susceptible
S. aureus
strains, and 7 coagulase-negative staphylococcal strains and two different monoclonal
S. aureus
-specific antibodies. When either of these antibodies was used, the sensitivity and the specificity of the TPX assay were 100%. All strains were correctly classified within 8 to 12 h, and up to 70 samples were simultaneously analyzed on a single 96-well microtiter plate. As a phenotypic method, the TPX assay is suited for screening purposes. The final definition of methicillin resistance in any
S. aureus
strain should be based on the presence of the
mecA
gene. The main benefit afforded by the initial use of the TPX methodology lies in its low cost and applicability to high-throughput analysis.
Tn
6060
, a Transposon from a Genomic Island in a
Pseudomonas aeruginosa
Clinical Isolate That Includes Two Class 1 Integrons
Authors: Chowdhury Piklu Roy , Merlino John , Labbate Maurizio , Cheong Elaine Y.-L. , Gottlieb Thomas , Stokes H. W.
Published: September 2009

A 25,441-bp transposon was recovered from a
Pseudomonas aeruginosa
clinical isolate. While the transposition module was >99% identical to sequence of Tn
1403
, the element had been subject to rearrangements, with two In70.2-like class 1 integrons inserted into it in an unusual “tail-to-tail” configuration. One cassette array was the same as that in In70.2; however, the second was different, generating a transposon that collectively includes six resistance cassettes.
Phase I Evaluation of the Safety and Pharmacokinetics of a Single-Dose Intravenous Injection of a Murine Monoclonal Antibody against Hantaan Virus in Healthy Volunteers
Authors: Xu Rong , Yang Xiao Yan , Yang Dao Feng , Zou Chang Yong , Gong Pei Li , Zeng Fan Dian
Published: September 2009

Anti-Hantaan virus monoclonal antibody (AHM) is a murine monoclonal antibody against Hantaan virus being developed for the treatment of hemorrhagic fever with renal syndrome. The purpose of the present study was to describe the tolerance and pharmacokinetics of an intravenously administered single ascending dose of AHM in Chinese healthy volunteers. Four cohorts of 22 healthy subjects received AHM at 2.5 to 20 mg, and the results indicated that AHM was well tolerated. We established a highly sensitive, rapid, and accurate immunoassay for the kinetic analysis of AHM in serum. Serial blood samples were obtained after intravenous administration for up to 17 days. A one-compartment model was determined to best describe the disposition of AHM. The maximal level in serum and the area under the serum concentration-time curve were proportional to the doses. The mean clearance, the half-life, and the volume of distribution were constant, irrespective of the dose. AHM was slowly cleared and had a half-life of approximately 110 h. These data support the use of a treatment regimen in which AHM is given only once intravenously.
Nonclonal Emergence of Colistin-Resistant
Klebsiella pneumoniae
Isolates from Blood Samples in South Korea
Authors: Suh Ji-Yoeun , Son Jun Seong , Chung Doo Ryeon , Peck Kyong Ran , Ko Kwan Soo , Song Jae-Hoon
Published: September 2009

In vitro activities of colistin and other drugs were tested against 221
Klebsiella pneumoniae
isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant
K. pneumoniae
(CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in
K. pneumoniae
occurring independently and not by clonal spreading.
Novel Ribosomal Mutations in
Staphylococcus aureus
Strains Identified through Selection with the Oxazolidinones Linezolid and Torezolid (TR-700)
Authors: Locke Jeffrey B. , Hilgers Mark , Shaw Karen Joy
Published: September 2009

TR-700 (torezolid), the active moiety of the novel oxazolidinone phosphate prodrug TR-701, is highly potent against gram-positive pathogens, including strains resistant to linezolid (LZD). Here we investigated the potential of
Staphylococcus aureus
strains ATCC 29213 (methicillin-susceptible
S. aureus
[MSSA]) and ATCC 33591 (methicillin-resistant
S. aureus
[MRSA]) to develop resistance to TR-700. The spontaneous frequencies of mutation of MSSA 29213 and MRSA 33591 resulting in reduced susceptibility to TR-700 at 2× the MIC were 1.1 × 10
−10
and 1.9 × 10
−10
, respectively. These values are ∼16-fold lower than the corresponding LZD spontaneous mutation frequencies of both strains. Following 30 serial passages in the presence of TR-700, the MIC for MSSA 29213 remained constant (0.5 μg/ml) while increasing eightfold (0.25 to 2.0 μg/ml) for MRSA 33591. Serial passage of MSSA 29213 and MRSA 33591 in LZD resulted in 64- and 32-fold increases in LZD resistance (2 to 128 μg/ml and 1 to 32 μg/ml, respectively). Domain V 23S rRNA gene mutations (
Escherichia coli
numbering) found in TR-700-selected mutants included T2500A and a novel coupled T2571C/G2576T mutation, while LZD-selected mutants included G2447T, T2500A, and G2576T. We also identified mutations correlating with decreased susceptibility to TR-700 and LZD in the
rplC
and
rplD
genes, encoding the 50S ribosomal proteins L3 and L4, respectively. L3 mutations included Gly152Asp, Gly155Arg, Gly155Arg/Met169Leu, and ΔPhe127-His146. The only L4 mutation detected was Lys68Gln. TR-700 maintained a fourfold or greater potency advantage over LZD against all strains with ribosomal mutations. These data bring to light a variety of novel and less-characterized mutations associated with
S. aureus
resistance to oxazolidinones and demonstrate the low resistance potential of torezolid.
Role of
Plasmodium falciparum
Digestive Vacuole Plasmepsins in the Specificity and Antimalarial Mode of Action of Cysteine and Aspartic Protease Inhibitors
Authors: Moura Pedro A. , Dame John B. , Fidock David A.
Published: September 2009

Hemoglobin (Hb) degradation is essential for the growth of the intraerythrocytic stages of malarial parasites. This process, which occurs inside an acidic digestive vacuole (DV), is thought to involve the action of four aspartic proteases, termed plasmepsins (PMs). These enzymes have received considerable attention as potential antimalarial drug targets. Leveraging the availability of a set of PM-knockout lines generated in
Plasmodium falciparum
, we report here that a wide range of previously characterized or novel aspartic protease inhibitors exert their antimalarial activities independently of their effect on the DV PMs. We also assayed compounds previously shown to inhibit cysteine proteases residing in the DV. The most striking observation was a ninefold increase in the potency of the calpain inhibitor
N
-acetyl-leucinyl-leucinyl-norleucinal (ALLN) against parasites lacking all four DV PMs. Genetic ablation of PM III or PM IV also decreased the level of parasite resistance to the β-hematin binding antimalarial chloroquine. On the basis of the findings of drug susceptibility and isobologram assays, as well as the findings of studies of the inhibition of Hb degradation, morphological analyses, and stage specificity, we conclude that the DV PMs and falcipain cysteine proteases act cooperatively in Hb hydrolysis. We also identify several aspartic protease inhibitors, designed to target DV PMs, which appear to act on alternative targets early in the intraerythrocytic life cycle. These include the potent diphenylurea compound GB-III-32, which was found to be fourfold less potent against a
P. falciparum
line overexpressing plasmepsin X than against the parental nontransformed parasite line. The identification of the mode of action of these inhibitors will be important for future antimalarial drug discovery efforts focusing on aspartic proteases.
Pyruvate Formate Lyase Is Required for Pneumococcal Fermentative Metabolism and Virulence
Authors: Yesilkaya Hasan , Spissu Francesca , Carvalho Sandra M. , Terra Vanessa S. , Homer Karen A. , Benisty Rachel , Porat Nurith , Neves Ana R. , Andrew Peter W.
Published: September 2009

Knowledge of the in vivo physiology and metabolism of
Streptococcus pneumoniae
is limited, even though pneumococci rely on efficient acquisition and metabolism of the host nutrients for growth and survival. Because the nutrient-limited, hypoxic host tissues favor mixed-acid fermentation, we studied the role of the pneumococcal pyruvate formate lyase (PFL), a key enzyme in mixed-acid fermentation, which is activated posttranslationally by PFL-activating enzyme (PFL-AE). Mutations were introduced to two putative
pfl
genes, SPD0235 and SPD0420, and two putative
pfl
A
genes, SPD0229 and SPD1774. End-product analysis showed that there was no formate, the main end product of the reaction catalyzed by PFL, produced by mutants defective in SPD0420 and SPD1774, indicating that SPD0420 codes for PFL and SPD1774 for putative PFL-AE. Expression of SPD0420 was elevated in galactose-containing medium in anaerobiosis compared to growth in glucose, and the mutation of SPD0420 resulted in the upregulation of
fba
and
pyk
, encoding, respectively, fructose 1,6-bisphosphate aldolase and pyruvate kinase, under the same conditions. In addition, an altered fatty acid composition was detected in SPD0420 and SPD1774 mutants. Mice infected intranasally with the SPD0420 and SPD1774 mutants survived significantly longer than the wild type-infected cohort, and bacteremia developed later in the mutant cohort than in the wild type-infected group. Furthermore, the numbers of CFU of the SPD0420 mutant were lower in the nasopharynx and the lungs after intranasal infection, and fewer numbers of mutant CFU than of wild-type CFU were recovered from blood specimens after intravenous infection. The results demonstrate that there is a direct link between pneumococcal fermentative metabolism and virulence.
Th2 but Not Th1 Immune Bias Results in Altered Lung Functions in a Murine Model of PulmonaryCryptococcus neoformansInfection
Authors: Jain Aditya V. , Zhang Yanmei , Fields W. Bradley , McNamara David A. , Choe Mun Y. , Chen Gwo-hsiao , Erb-Downward John , Osterholzer John J. , Toews Galen B. , Huffnagle Gary B. , Olszewski Michal A.
Published: September 2009

Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known ifCryptococcusneoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulentC. neoformansstrain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show thatC. neoformanscan significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.
Frequencies of Region of Difference 1 Antigen-Specific but Not Purified Protein Derivative-Specific Gamma Interferon-Secreting T Cells Correlate with the Presence of Tuberculosis Disease but Do Not Distinguish Recent from Remote Latent Infections
Authors: Hinks Timothy S. C. , Dosanjh Davinder P. S. , Innes John A. , Pasvol Geoffrey , Hackforth Sarah , Varia Hansa , Millington Kerry A. , Liu Xiao-Qing , Bakir Mustafa , Soysal Ahmet , Davidson Robert N. , Gunatheesan Rubamalar , Lalvani Ajit
Published: September 2009

The majority of individuals infected withMycobacterium tuberculosisachieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-γ)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n= 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n= 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection. When subjects with an IFN-γ enzyme-linked immunospot (ELISpot) assay response to one or more RD1-encoded antigens were analyzed, T cells from subjects with active disease recognized more pools of peptides from these antigens than T cells from subjects with nonrecent latent infection (P= 0.002). The T-cell frequencies for peptide pools were greater for subjects with active infection than for subjects with nonrecent latent infection for summed RD1 peptide pools (P≤ 0.006) and culture filtrate protein 10 (CFP-10) antigen (P= 0.029). Individuals with recently acquired (<6 months) versus remotely acquired (>6 months) latent infection did not differ in numbers of peptide pools recognized, proportions recognizing any individual antigen or peptide pool, or antigen-specific T-cell frequencies (P≥ 0.11). The hierarchy of immunodominance for different antigens was purified protein derivative (PPD) > CFP-10 > early secretory antigenic target 6 > Rv3879c > Rv3878 > Rv3873 > Acr1, and the hierarchies were very similar for active and remotely acquired latent infections. Responses to the DosR antigen α-crystallin were not associated with latency (P= 0.373). In contrast to the RD1-specific responses, the responses to PPD were not associated with clinical status (P> 0.17) but were strongly associated with positive tuberculin skin test results (≥15-mm induration;P≤ 0.01). Our results suggest that RD1-specific IFN-γ-secreting T-cell frequencies correlate with the presence of disease rather than with protective immunity inM. tuberculosis-infected individuals and do not distinguish recently acquired asymptomatic infection from remotely acquired latent infection.
Does exercise training during pregnancy influence fetal cardiovascular responses to an exercise stimulus? Insights from a randomised, controlled trial
Authors: Barakat R , Ruiz J R , Rodríguez-Romo G , Montejo-Rodríguez R , Lucia A
Published: September 2009

In this study, the effects of maternal physical activity level on several fetal haemodynamic parameters such as pulsatility index of the fetal middle cerebral and umbilical arteries and cerebral-to-fetal ratio, as well as on fetal heart rate responses to one bout of moderate exercise (20 min cycle-ergometry at ∼60% of age-predicted maximum heart rate) during the third pregnancy trimester were assessed. 26 Sedentary and 26 physically active gravidae aged 29 (3) and 30 (2) years, respectively, were studied. Maternal exercise did not have a deleterious effect on fetal haemodynamics (particularly, cerebral-to-fetal ratio remained within normal limits with exercise). Overall, maternal training status did not influence the fetal cardiovascular variables studied.
Electromyographic analysis of knee push up plus variations: what is the influence of the kinetic chain on scapular muscle activity?
Authors: Maenhout A , Van Praet K , Pizzi L , Van Herzeele M , Cools A
Published: September 2009

Objective

First, to look for appropriate closed kinetic chain exercises to restore intramuscular imbalance between upper trapezius (UT) and serratus anterior (SA) in overhead athletes. Second, to determine the influence of using diagonal pattern muscle recruitment during knee push up plus (KPP) exercises on scapular electromyographic activity.

Design

Single group repeated-measures design.

Setting

Controlled laboratory study.

Participants

Thirty-two physically active individuals in good general health who did not have a history of neck and/or shoulder injury or surgery nor participated in high-level overhead sports or performed upper limb strength training for more than 5 h/week.

Interventions

Subjects performed the standard KPP and six variations.

Main outcome measurements

Electromyographic activity of the three trapezius parts and the SA.

Results

Four exercises with a low UT/SA can be selected for rehabilitation of intramuscular balance: standard KPP, KPP with homolateral leg extension, KPP with a wobble board and homolateral leg extension and one-handed KPP. The use of a wobble board during KPP exercises and performance on one hand has no influence on SA electromyographic activity.

Heterolateral leg extension during KPP stimulates lower trapezius activity, whereas homolateral leg extension stimulates SA activity.

Conclusions

In case of intramuscular scapular imbalance, some exercises are preferable over others because of their low UT/SA ratio. The use of a kinetic chain approach during KPP exercises influences scapular muscle activity.
THE OPTIMAL INVENTORY CONTROL OF A SYSTEM WITH RANDOM LEAD TIME WHERE RANDOM SUPPLY INTERRUPTIONS AFFECT THE REPLENISHMENT
Authors: HOU YUMEI , ZHANG QIANG
Published: September 2009

This paper analyzes a continuous-review inventory system with random supply interruptions and stochastic lead time. In such a system, a monopolistic supplier alternates between random ON and OFF periods. The variable (r,q)-policy is used. With a constant demand rate, the leadtime may be interrupted by a random number of OFF periods of the supplier. Using the regenerative cycle analysis, a long-run average cost function is obtained and shown to have some important properties. Accordingly, an effective search algorithm is proposed to find the sub-optimal inventory policy. In the end, we also investigate the effects on the average cost of the uncertain order delay which attribute to both the supply interruptions and the random leadtime. Numerical examples are presented to demonstrate the effectiveness of the search algorithm.
Malaria Management: Past, Present, and Future
Authors: Enayati A. , Hemingway J.
Published: September 2009

The prospect of malaria eradication has been raised recently by the Bill and Melinda Gates Foundation with support from the international community. There are significant lessons to be learned from the major successes and failures of the eradication campaign of the 1960s, but cessation of transmission in the malaria heartlands of Africa will depend on a vaccine and better drugs and insecticides. Insect control is an essential part of reducing transmission. To date, two operational scale interventions, indoor residual spraying and deployment of long-lasting insecticide-treated nets (LLINs), are effective at reducing transmission. Our ability to monitor and evaluate these interventions needs to be improved so that scarce resources can be sensibly deployed, and new interventions that reduce transmission in a cost-effective and efficient manner need to be developed. New interventions could include using transgenic mosquitoes, larviciding in urban areas, or utilizing cost-effective consumer products. Alongside this innovative development agenda, the potential negative impact of insecticide resistance, particularly on LLINs, for which only pyrethroids are available, needs to be monitored.
Learning: From Association to Cognition
Authors: Shanks David R.
Published: September 2009

Since the very earliest experimental investigations of learning, tension has existed between association-based and cognitive theories. Associationism accounts for the phenomena of both conditioning and “higher” forms of learning via concepts such as excitation, inhibition, and reinforcement, whereas cognitive theories assume that learning depends on hypothesis testing, cognitive models, and propositional reasoning. Cognitive theories have received considerable impetus in regard to both human and animal learning from recent research suggesting that the key illustration of cue selection in learning, blocking, often arises from inferential reasoning. At the same time, a dichotomous view that separates noncognitive, unconscious (implicit) learning from cognitive, conscious (explicit) learning has gained favor. This review selectively describes key findings from this research, evaluates evidence for and against associative and cognitive explanatory constructs, and critically examines both the dichotomous view of learning as well as the claim that learning can occur unconsciously.
Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications
Authors: Rudin Charles M. , Avila-Tang Erika , Harris Curtis C. , Herman James G. , Hirsch Fred R. , Pao William , Schwartz Ann G. , Vahakangas Kirsi H. , Samet Jonathan M.
Published: September 2009

The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years show that lung cancers in never smokers are much more likely to carry activating mutations of the epidermal growth factor receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anticancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never-smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers. (Clin Cancer Res 2009;15(18):5646–61)
Effects of Speaking Rate and Vowel Length on Formant Frequency Displacement in Japanese
Authors: Hirata Yukari , Tsukada Kimiko
Published: September 2009

This study examined effects of phonemic vowel length and speaking rate, two factors that affect vowel duration, on the first and second formants of all vowels in Japanese. The aim was to delineate the aspects of formant displacement that are governed by the physiological proclivity of vowel production shared across languages, and the aspects that reveal language-specific phenomena. Acoustic analysis revealed that the phonemic long vowels occupied a more peripheral portion of the F1 × F2 vowel space than the phonemic short vowels (effect of vowel length), but effects of speaking rate were less clear. This was because of the significant interactions of the two effects: the formants of phonemic short vowels were more affected by speaking rates than the phonemic long vowels. Regression analyses between F2 and duration revealed that formant displacement occurs when vowels are less than 200 ms. Similarities and differences found for Japanese and English are discussed in terms of physiological proclivity of vowel production versus language-specific phonological encoding.
Perceptual Assimilation and L2 Learning: Evidence from the Perception of Southern British English Vowels by Native Speakers of Greek and Japanese
Authors: Lengeris Angelos
Published: September 2009

This study examined the extent to which previous experience with duration in first language (L1) vowel distinctions affects the use of duration when perceiving vowels in a second language (L2). Native speakers of Greek (where duration is not used to differentiate vowels) and Japanese (where vowels are distinguished by duration) first identified and rated the eleven English monophthongs, embedded in /bVb/ and /bVp/ contexts, in terms of their L1 categories and then carried out discrimination tests on those English vowels. The results demonstrated that both L2 groups were sensitive to durational cues when perceiving the English vowels. However, listeners were found to temporally assimilate L2 vowels to L1 category/categories. Temporal information was available in discrimination only when the listeners’ L1 duration category/categories did not interfere with the target duration categories and hence the use of duration in such cases cannot be attributed to its perceptual salience as has been proposed.
Studies of the Extracellular ATP-Adenosine Pathway in Human Urinary Tract Epithelial Cells
Authors: Mohlin Camilla , Säve Susanne , Nilsson Mikael , Persson Katarina
Published: September 2009

Aims: Extracellular ATP may be metabolized to AMP and adenosine by the ectonucleotidases CD39 and CD73 and, in this study, we characterized the pathways for adenosine formation in human urinary tract epithelial cells. Methods: Bladder (RT4) and kidney (A498) epithelial cells were grown in cell culture and the expression of CD39 and CD73 was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. High-performance liquid chromatography was used to determine adenosine formation in cell medium. Results: RT-PCR and immunohistochemistry revealed a high CD73 and a low CD39 expression in human urinary tract epithelial cells, whereas neutrophils had a higher CD39 than CD73 expression. Adenosine was produced when the cells were exposed to 5′-AMP (substrate for CD73), but not when exposed to 5′-ATP (substrate for CD39). A pronounced inhibition of 5′-AMP-induced adenosine formation by the CD73 inhibitor AMP-CP confirmed the involvement of CD73. Adenosine production from 5′-ATP was slightly increased (p < 0.05) when epithelial cells were cocultured with neutrophils. Conclusions: The data demonstrate that adenosine formation from extracellular ATP is negligible in urinary tract epithelial cells due to low CD39 expression in this cell type. However, the epithelial cells express CD73 and are able to convert extracellular AMP to adenosine.
Comparative in vitro Study of Different Peritoneal Dialysis Solutions on Cytokine Production by Peripheral Blood Mononuclear Cells
Authors: Bacharaki Dimitra , Thodis Elias , Passadakis Ploumis , Kantartzi Konstantia , Kriki Pelagia , Vargemezis Vassilis
Published: September 2009

Background/Aims: Peritoneal dialysis solutions (PDS), new and conventional, do not yet have a clinical biocompatibility profile. We aimed at a comparative laboratory profile based on the effect of PDS on peripheral blood mononuclear cell (PBMC) cytokine release. Method: PBMCs from 19 healthy volunteers were incubated at a concentration of 106/ml in fresh PDS and control medium (RPMI 1640), and stimulated or not with 10μg/ml Escherichia coli lipopolysaccharide. The tested PDS were glucose/lactate 1.5 and 4.25%, glucose/pyruvate 1.0 and 4.0%, icodextrin and amino acid solutions. The initial incubation in culture flasks for 15 min was followed by 1:1 dilution with RPMI and by additional incubation for 22 h as a ‘recovery period’. At the end, the supernatants were tested for cytokines IL-6 and TNFα by ELISA. Results: The hypertonic glucose solutions, irrespective of the buffer, had the most adverse effect on PBMC cytokine release. The icodextrin and amino acid solutions seemed close to the isotonic glucose PDS. The substitution of pyruvate for lactate buffer seemed to offer an advantage only for the hypertonic glucose-based solutions. Conclusions: Icodextrin and amino acid solutions seem to offer an advantage only compared to hypertonic glucose PDS.
Identifying Risk for Attrition during Treatment for Depression
Authors: Warden Diane , Trivedi Madhukar H. , Wisniewski Stephen R. , Lesser Ira M. , Mitchell Jeff , Balasubramani G.K. , Fava Maurizio , Shores-Wilson Kathy , Stegman Diane , Rush A. John
Published: September 2009

Background: Understanding patients’ ambivalence about treatment persistence may be useful in tailoring retention interventions for individual patients with major depressive disorder. Methods: Participants (n = 265) with major depressive disorder were enrolled into an 8-week trial with a selective serotonin reuptake inhibitor. At baseline and week 2, the participants were asked about their intent to return for the next visit, complete the study and continue in the study should they experience side effects or no improvement. Dropouts were defined as participants who discontinued attending clinic visits before completing the trial. Results: Participants who at baseline reported an uncertain/negative intent to continue if they experienced side effects or no improvement dropped out at a significantly higher rate by weeks 6 and 8. Uncertain/negative intent at week 2 predicted attrition at all following visits. Dropouts without side effects were more likely to have reported an uncertain/negative intent to attend at both baseline and week 2, while dropouts who experienced side effects were more likely to have reported an uncertain/negative intent to attend only at baseline. Positive intent to continue was associated with greater symptom improvement in both dropouts and completers despite the possibility of lack of efficacy. Conclusions: Participants’ pretreatment concerns about continuing antidepressant treatment in the presence of side effects signals challenges to the completion of a full 8-week acute phase treatment, even if the participant does not develop side effects. Individualized review of concerns and tailoring appropriate interventions may be necessary to reduce attrition.
Treatment of Progressive Stroke with Tirofiban – Experience in 35 Patients
Authors: Philipps Jörg , Thomalla Götz , Glahn Jörg , Schwarze Michael , Röther Joachim
Published: September 2009

Background: In an open pilot study, we studied the safety and efficacy of treatment with the nonpeptide glycoprotein IIb/IIIa antagonist tirofiban in patients with progressive ischemic stroke. The rationale for the use of tirofiban in progressive stroke is the effect on vessel patency and microcircu lation. Methods: Patients with acute ischemic stroke and progression of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) in the first 96 h after stroke onset were treated with intravenous tirofiban. Serial NIHSS measurements and intra- and extracerebral bleeding complications were recorded. Results: Progressive stroke was observed in 35 patients with a mean progression of 5.4 (SD 4.1) points on the NIHSS. No severe bleeding complications occurred during tirofiban treatment. Analysis of variance revealed a significant interaction between stroke etiology (small-vessel vs. large-vessel occlusion) and NIHSS during treatment with tirofiban: patients with small-vessel occlusion showed significant improvement, while patients with large-vessel occlusion did not. The mean NIHSS improvement after tirofiban infusion was 3.4 (SD 3.4) for small-vessel occlusion versus 0.8 (SD 4.2) for large-vessel occlusion (p = 0.048). Conclusion: Treatment with tirofiban was well tolerated in patients with progressive stroke. However, only patients with small-vessel occlusion recovered significantly during infusion of tirofiban. The effect of tirofiban in progressive stroke and different subgroups of stroke deserves to be studied in a randomized controlled trial.
Comparison of Bevacizumab and Triamcinolone for Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion – A Matched-Pairs Analysis
Authors: Guthoff Rainer , Meigen Thomas , Hennemann Kathrin , Schrader Wolfgang
Published: September 2009

Purpose: Our aim was to evaluate differences in the outcome of bevacizumab or triamcinolone acetate (TA) treatment in patients with macular edema (ME) after central retinal vein occlusion (CRVO). Procedures: In a retrospective assessment 9 bevacizumab-treated patients and 9 TA-treated ones with ME after CRVO were pair-matched according to initial best-corrected visual acuity (BCVA) and central macular thickness (CMT) as measured by Stratus optical coherence tomography. BCVA and CMT were the main endpoints. Results: The initial BCVA of 0.15 ± 0.1 increased not significantly by 1.0 ± 3.1 lines in the bevacizumab-treated patients after a mean of 10 months. The initial BCVA of 0.17 ± 0.1 decreased by –1.0 ± 5.2 lines after a mean of 13 months following initial TA injection. The only significant decrease in mean CMT by 239 ± 209 µm occurred 8 weeks after initial bevacizumab injection. Conclusions: Both substances are able to stabilize CMT and BCVA in ME after CRVO, but only bevacizumab was devoid of unfavorable intraocular pressure elevation.
Oral Treatment with Probiotics Reduces Allergic Symptoms in Ovalbumin-Sensitized Mice: A Bacterial Strain Comparative Study
Authors: Hougee S. , Vriesema A.J.M. , Wijering S.C. , Knippels L.M.J. , Folkerts G. , Nijkamp F.P. , Knol J. , Garssen J.
Published: September 2009

Background/Aim: Evidence demonstrating an important role of the intestinal microbiota in the incidence of allergic disorders has led to the concept of using probiotics as possible antiallergic therapy. This study aimed to select a bacterial strain with the best antiallergic treatment effects from a panel of 6 bacterial strains in a mouse model of ovalbumin(OVA)-allergic asthma. Methods: OVA-sensitized BALB/c mice were orally administered the bacterial strains Bifidobacterium breve M-16V, B. infantis NumRes251, B. animalis NumRes252 and NumRes253, Lactobacillus plantarum NumRes8 and L. rhamnosus NumRes6. After challenge by OVA inhalation in the lungs, the response to methacholine was measured. Pulmonary inflammation was assessed by analyzing bronchoalveolar lavage fluid for the presence of eosinophils, neutrophils, macrophages and lymphocytes and for interleukin 4, interleukin 5, interleukin 10 and interferon-γ. OVA-specific IgE, IgG1 and IgG2a were measured in serum. Next, the effect on acute allergic skin reaction was measured after treatment with B. breve M-16V and L. plantarum NumRes8. Results: Of the panel of 6 strains, B. breve M-16V and L. plantarum NumRes8 inhibited (1) the response to methacholine, (2) reduced the number of eosinophils in the bronchoalveolar lavage fluid, (3) reduced both OVA-specific IgE and (4) OVA-specific IgG1, whereas the other strains did not affect all these parameters simultaneously. B. breve M-16V but not L. plantarum NumRes8 reduced interleukin 4, interleukin 5 and interleukin 10. Furthermore, B. breve M-16V but not L. plantarum NumRes8 reduced acute allergic skin reactions to OVA. Conclusion: B. breve M-16V was identified as the most potent antiallergic strain.
TLR3 in Human Eosinophils: Functional Effects and Decreased Expression during Allergic Rhinitis
Authors: Månsson Anne , Fransson Mattias , Adner Mikael , Benson Mikael , Uddman Rolf , Björnsson Sven , Cardell Lars-Olaf
Published: September 2009

Background/Aim: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. Methods: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. Results: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-ĸB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. Conclusions: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.
Nasal Lavage in Pregnant Women with Seasonal Allergic Rhinitis: A Randomized Study
Authors: Garavello Werner , Somigliana Edgardo , Acaia Barbara , Gaini Lorenzo , Pignataro Lorenzo , Gaini Renato Maria
Published: September 2009

Background: Nasal rinsing appears particularly suitable in the management of pregnant women with seasonal allergic rhinitis since no deleterious effects on the fetus are to be expected. However, to date, no studies have specifically investigated this option. Methods: Pregnant women with seasonal allergic rhinitis were randomized to intranasal lavage with hypertonic saline solution 3 times daily (n = 22) versus no local therapy (n = 23) during a 6-week period corresponding to the pollen season. Patients were invited to keep a daily record of rhinitis symptoms (rhinorrea, obstruction, nasal itching and sneezing), to record consumption of oral antihistamine and to undergo rhinomanometry. Results: The rhinitis score was similar at study entry but a statistically significant improvement in this score was observed in the study group during all subsequent weeks (p < 0.001 for weeks 2–6). The mean number of daily antihistamines use per patient per week was significantly reduced at weeks 2, 3 and 6 (p < 0.001, p < 0.001 and p = 0.001, respectively). Baseline rhinomanometry performed at week 1 showed similar nasal resistance in the study and control groups. In contrast, a statistically significant difference emerged in the 2 following evaluations. At week 3, nasal resistance in the study and control groups was 0.96 ± 0.44 and 1.38 ± 0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was 0.94 ± 0.38 and 1.35 ± 0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was reported in the active group. Conclusions: Nasal rinsing is a safe and effective treatment option in pregnant women with seasonal allergic rhinitis.