bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiscale Simulations of Heat Transfer and Fluid Flow Problems
Authors: Tao Wen-Quan , He Ya-Ling
Published: March 2011

Multiscale simulation is a rapidly evolving area of research that will have a great impact on computational mathematics and numerical modeling in engineering. In this keynote lecture following parts are included. First, what is multiscale problem. In the thermal and fluid science multiscale problems may be classified into two categories: multiscale process and multiscale system. By multiscale process we mean that the overall behavior is governed by processes occur at different length scales. By multiscale system we refer to a system that is characterized by a large variation in length scales. The cooling of an electronic system is such a typical multiscale system. Existing numerical methods for three geometric scales (macro, meso and micro) are briefly mentioned. In the second part the necessity of multiscale simulation is discussed. Examples are provided for multiscale process and multiscale system. In this lecture focus is put on the simulation of multiscale process. In the third section numerical approaches developed for the simulation of multiscale processes are presented. There are two types of simulation approaches. One is the usage of a general governing equation and solving the entire flow field involving a variation of several orders in characteristic geometric scale. The other is the so-called “solving regionally and coupling at the interfaces”. In this approach the processes at different length level is simulated by different numerical methods and then information is exchanged at the interfaces between different regions. The exchange of information should be conducted in a way that is physically meaningful, mathematically stable, and computationally efficient. The key point is the establishment of the reconstruction operator, which transforms the data of few variables of macroscopic computation to large amount of variables of microscale or mesoscale simulation. For different coupling cases the existing methods for such operators are briefly reviewed. In the fourth part, four numerical examples of multiscale simulation are presented: liquid flow in nanochannels with roughness by using MDS and FVM, flow and heat transfer in a micro nozzle by using DSMC in fluid and FVM in solid, flow past a cylinder and natural convection heat transfer in a square cavity by using coupled FVM and LBM. Finally, it is pointed out that we have a long way to go in order to have a successful full multiscale simulation for the complicated engineering problems as transport process in PEMFC and refrigerant condensation process on a enhanced surface. Further researches are highly required to establish robust and quick-convergent numerical solution approaches. Some further research needs are proposed.
Pressureless nanoimprinting of anatase TiO2 precursor films
Authors: Richmond Dustin A. , Zhang Qifeng , Cao Guozhong , Weiss Dirk N.
Published: March 2011

A soft-imprint method for obtaining anatase TiO2 nanostructures is reported. The method is de facto pressureless and is performed without the need for dedicated imprint equipment. A titanium butoxide-based sol precursor is prepared with a heavy alcohol, methoxy ethanol, as a solvent. The use of an incompletely cross-linked very soft polydimethylsiloxane mold is found to be crucial for obtaining large-area high-quality imprints. The authors discuss quantitatively the observed substrate-constrained shrinkage of pillars and lines (ridges) during annealing.
Measuring the molecular polarizability of air
Authors: Madsen M. J. , Brown D. R. , Krutz S. R. , Milliman M. J.
Published: March 2011

We present an update of the “refractive index of air” experiment, which is commonly used in undergraduate advanced laboratories. The refractive index of air depends on the average molecular polarizability, which can be determined from the period of the phase shift in a Michelson interferometer as a function of air pressure. The measured average molecular polarizability of air is γmol=(2.118±0.091)×10−29 m3 (95% CI). The corresponding refractive index of air at atmospheric pressure is n=1.000265(11), which agrees with the accepted value of n=1.000271375(6).
In-plane sensitive electronic speckle pattern interferometer using a diffractive holographic optical element
Authors: Jallapuram Raghavendra , Healy Con , Mihaylova Emilia , Toal Vincent
Published: March 2011

We describe a student project in electronic speckle pattern interferometry. The project includes holographic recording of diffraction gratings in thick self-processing photopolymer layers made from off-the-shelf chemicals. The gratings are employed in a simple electronic speckle pattern interferometer to measure in-plane rotation.
Why do forces add vectorially? A forgotten controversy in the foundations of classical mechanics
Authors: Lange Marc
Published: March 2011

Despite the routine treatment it receives today, the parallelogram of forces was the subject of controversy, especially during the 19th century. The controversy concerned the reason why forces compose vectorially. If the parallelogram law is explained statically, then the parallelogram law transcends the laws of dynamics. Alternatively, if the parallelogram law is explained dynamically, then it becomes merely a corollary to Newton’s second law. I examine the three most important rival approaches to explaining the parallelogram law and identify their principal strengths, weaknesses, and consequences. The dispute among these approaches ultimately turns on whether the parallelogram law would still have held, if forces had not been governed by Newton’s second law.
Science Signaling
Podcast: 15 March 2011
Authors: Montell Craig , VanHook Annalisa M.
Published: March 2011

A protein required for light sensation also plays a role in thermosensing in the fruit fly.
Forcefully Translated
Authors: Wong Wei
Published: March 2011

Activation of integrins on oligodendrocytes promotes translation of the mRNA encoding a myelin sheath component.
CMX001 (1-
O
-Hexadecyloxypropyl-Cidofovir) Inhibits Polyomavirus JC Replication in Human Brain Progenitor-Derived Astrocytes
Authors: Gosert Rainer , Rinaldo Christine Hanssen , Wernli Marion , Major Eugene O. , Hirsch Hans H.
Published: March 2011

Polyomavirus JC (JCV) replication causes progressive multifocal leukoencephalopathy (PML), a frequently fatal brain disease in immunodeficient patients, yet antiviral drugs are lacking. We characterized the lipid conjugate 1-
O
-hexadecyloxypropyl-cidofovir (CMX001) regarding JCV (Mad-4) replication in human brain progenitor-derived astrocytes (PDA) and the simian virus 40 (SV40) large-T-antigen-expressing COS-7 cells up to 7 days postinfection (dpi). We examined JCV loads by PCR, the infection rate by immunofluorescence, and host cell toxicity by WST-1 and BrdU incorporation assays. Supernatants from CMX001-treated PDA demonstrated a drug concentration-dependent decrease in JCV loads and infectivity. CMX001 had only a modest effect on host cell metabolism but reduced overall BrdU incorporation. In PDA at 7 dpi, the CMX001 50% effective concentration (EC
50
) was 5.55 nM, the 50% cytotoxic concentration (CC
50
) was 184.6 nM, and the 50% selectivity index (SI
50
) was 33.3. The EC
90
was 19.7 nM, the CC
90
was 5,054 nM, and the SI
90
was 256.1. In COS-7 cells, JCV replication was faster and the EC
50
and EC
90
were 18- and 37-fold higher than those in PDA, i.e., 0.1 μM and 0.74 μM (CC
50
, 0.67 μM; SI
50
, 6.7; CC
90
, 12.2 μM; SI
90
, 16.5) at 5 dpi. We conclude that CMX001 inhibits JCV replication at concentrations
in vitro
that can be attained by oral administration without significant side effects in clinical studies.
Changes in Antibiotic Distribution Due to Pancreatitis
Authors: Fanning Kent J. , Robertson Thomas A. , Prins Johannes B. , Roberts Michael S.
Published: March 2011

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution.
Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers
Authors: Bulitta J. B. , Kinzig M. , Landersdorfer C. B. , Holzgrabe U. , Stephan U. , Sörgel F.
Published: March 2011

Cystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (
P
≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.
Trypanocidal Furamidine Analogues: Influence of Pyridine Nitrogens on Trypanocidal Activity, Transport Kinetics, and Resistance Patterns
Authors: Ward Christopher P. , Wong Pui Ee , Burchmore Richard J. , de Koning Harry P. , Barrett Michael P.
Published: March 2011

Current therapies for human African trypanosomiasis (HAT) are unsatisfactory and under threat from emerging drug resistance linked to the loss of transporters, e.g., the P2 aminopurine transporter (TbAT1). Here we compare the uptake and trypanocidal properties of furamidine (DB75), recently evaluated in clinical trials against stage 1 (haemolymphatic) HAT, and two aza analogues, DB820 and CPD0801 (DB829), which are candidate compounds for treatment of stage 2 (neurological) disease. Values of 50% inhibitory concentrations (IC50s) determinedin vitroagainst both wild-type and transporter mutant parasites were submicromolar, with DB75 trypanotoxicity shown to be better than and DB820 trypanotoxicity similar to that of the widely used veterinary trypanocide diminazene, while CPD0801 was less active. Activity correlated with uptake and with the minimum drug exposure time necessary to kill trypanosomes: DB75 accumulated at double and 10-fold the rates of DB820 and CPD0801, respectively. All three compounds inhibited P2-mediated adenosine transport with similarKivalues, indicating affinity values for this permease in the low to submicromolar range. Uptake of DB75, DB820, and CPD0801 was significantly reduced intbat1−/−parasites and was sensitive to inhibition by adenine, showing that all three compounds are substrates for the P2 transporter. Uptakein vitrowas significantly less than that seen with parasites freshly isolated from infected rats, correlating with a downregulation of P2 activityin vitro. We conclude that DB75, DB820, and CPD0801 are actively accumulated byTrypanosoma brucei brucei, with P2 as the main transport route. The aza analogues of DB75 accumulate more slowly than furamidine itself and reveal less trypanocidal activity in standardin vitrodrug sensitivity assays.
Insertion Sequence IS
Aba11
Is Involved in Colistin Resistance and Loss of Lipopolysaccharide in Acinetobacter baumannii
Authors: Moffatt Jennifer H. , Harper Marina , Adler Ben , Nation Roger L. , Li Jian , Boyce John D.
Published: March 2011

Infections caused by
Acinetobacter baumannii
are of increasing concern, largely due to the multidrug resistance of many strains. Here we show that insertion sequence IS
Aba11
movement can result in inactivation of the
A. baumannii
lipid A biosynthesis genes
lpxA
and
lpxC
, resulting in the complete loss of lipopolysaccharide production and high-level colistin resistance.
In Vitro Activity of Ceftaroline against Gram-Positive and Gram-Negative Pathogens Isolated from Patients in Canadian Hospitals in 2009
Authors: Karlowsky James A. , Adam Heather J. , DeCorby Melanie R. , Lagacé-Wiens Philippe R. S. , Hoban Daryl J. , Zhanel George G.
Published: March 2011

The
in vitro
activities of ceftaroline and comparative agents were determined for a collection of the most frequently isolated bacterial pathogens from hospital-associated patients across Canada in 2009 as part of the ongoing CANWARD surveillance study. In total, 4,546 isolates from 15 sentinel Canadian hospital laboratories were tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Compared with other cephalosporins, including ceftobiprole, cefepime, and ceftriaxone, ceftaroline exhibited the greatest potency against methicillin-susceptible
Staphylococcus aureus
(MSSA), with a MIC
90
of 0.25 μg/ml. Ceftaroline also demonstrated greater potency than ceftobiprole against community-associated methicillin-resistant
S. aureus
(MRSA) (MIC
90
, 0.5 μg/ml) and health care-associated MRSA (MIC
90
, 1 μg/ml) and was at least 4-fold more active than other cephalosporins against
Staphylococcus epidermidis
; all isolates of MSSA and MRSA tested were susceptible to ceftaroline (MIC, ≤1 μg/ml). Against streptococci, including
Streptococcus pneumoniae
, ceftaroline MICs (MIC
90
, ≤0.03 μg/ml) were comparable to those of ceftobiprole; however, against penicillin-nonsusceptible, macrolide-nonsusceptible, and multidrug-nonsusceptible isolates of
S. pneumoniae
, ceftaroline demonstrated 2- to 4-fold and 4- to 16-fold more potent activities than those of ceftobiprole and ceftriaxone, respectively. All isolates of
S. pneumoniae
tested were susceptible to ceftaroline (MIC, ≤0.25 μg/ml). Among Gram-negative isolates, ceftaroline demonstrated potent activity (MIC
90
, ≤0.5 μg/ml) against
Escherichia coli
(92.2% of isolates were susceptible),
Klebsiella pneumoniae
(94.1% of isolates were susceptible),
Proteus mirabilis
(97.7% of isolates were susceptible), and
Haemophilus influenzae
(100% of isolates were susceptible). Ceftaroline demonstrated less potent activity (MIC
90
, ≥4 μg/ml) against
Enterobacter
spp.,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
,
Klebsiella oxytoca
,
Serratia marcescens
, and
Stenotrophomonas maltophilia
. Overall, ceftaroline demonstrated potent
in vitro
activity against a recent collection of the most frequently encountered Gram-positive and Gram-negative isolates from patients attending hospitals across Canada in 2009.
In Vitro and In Vivo Intracellular Killing Effects of Tigecycline against Clinical Nontyphoid Salmonella Isolates Using Ceftriaxone as a Comparator
Authors: Tang Hung-Jen , Ko Wen-Chien , Chen Chi-Chung , Chen Po-Lin , Toh Han Siong , Weng Tzu Chieh , Yu Wen-Liang , Chiang Shyh-Ren , Chuang Yin-Ching
Published: March 2011

Salmonella
is an important, worldwide food-borne pathogen. Resistance to fluoroquinolones and cephalosporins has been increasingly reported, and new therapeutic agents are desperately needed. In this study, we evaluated the
in vitro
antimicrobial susceptibility of clinical nontyphoidal
Salmonella
isolates to tigecycline. Antibacterial activity of tigecycline, ceftriaxone, and ciprofloxacin were investigated by time-kill studies and the murine peritonitis model. The MIC
50
/MIC
90
values of tigecycline, ceftriaxone, and ciprofloxacin against 76
Salmonella
isolates were 0.25/0.5, 1/8, and 0.125/0.5 μg/ml, respectively. The intracellular inhibitory activity of tigecycline at 0.5 μg/ml (1× MIC) against
Salmonella
isolates in human peripheral blood mononuclear cells was sustained for 24 h. In a mouse peritonitis model, tigecycline reduced the extracellular and intracellular bacterial counts from 10
7
CFU/ml and 10
5
CFU/ml, respectively, to an undetectable level within 96 h. The results were similar to those obtained with ceftriaxone. The survival rate of mice exposed to tigecycline after being infected by an inoculum of 1 × 10
5
CFU was 80%, and that of mice exposed to ceftriaxone was 100%. When the inoculum was increased to 1.3 × 10
6
CFU, the survival rate of mice treated by tigecycline was 20%, and that of mice exposed to ceftriaxone was 0% (
P
= 0.2). When a ceftriaxone- and ciprofloxacin-resistant but tigecycline-susceptible isolate was tested, mice treated by tigecycline had a higher survival rate than those treated by ceftriaxone (15/20 [75%] versus 6/20 [30%];
P
= 0.011). Our results suggest that tigecycline is at least as effective as ceftriaxone for murine
Salmonella
infections and warrants further clinical investigations to delineate its potential against human
Salmonella
infections.
PION CORRELATIONS IN NUCLEAR MATTER
Authors: PANDA P. K. , DA PROVIDÊNCIA J. , SARANGI S.
Published: March 2011

The saturation properties of the nuclear matter taking pion correlations into account are studied. We construct a Bogoliubov transformation for the pion pair operators and calculate the energy associated with the pion pairs. The pion dispersion relation is investigated. The correlation energy due to one-pion exchange in nuclear matter and neutron matter at random phase approximation using the generator coordinate method is also studied. The techniques of the charged pion correlations are discussed in the neutron matter calculations. We observe that there is no sign of the pion condensation in this model.
Report of the 4th international symposium on empirical software engineering and measurement ESEM 2010
Authors: Lutteri Emiliano , Russo Barbara , Succi Giancarlo
Published: March 2011

This report summarizes the research works, in particular the full and short papers, presented at the 4th International Symposium on Empirical Software Engineering and Measurement (ESEM 2010), held the 16th and 17th of September in Bolzano-Bozen, Italy. The program provided thirty full papers, twenty six short papers and three invited talks held by Bertrand Meyer, Steve Fraser and Carlo Ghezzi.
Guest column: testing linear properties
Authors: Sudan Madhu
Published: March 2011

The last two decades have seen enormous progress in the development of sublinear-time algorithms -- i.e., algorithms that examine/reveal properties of "data" in less time than it would take to read all of the data. A large, and important, subclass of such properties turn out to be "linear". In particular, these developments have contributed to the rich theory of probabilistically checkable proofs (PCPs) and locally testable codes (LTCs). In this survey, we focus on some of the general technical themes at work behind the many results in this area.
Nanoparticle Facilitated Charge Transfer and Voltage of a High Capacity VB2 Anode
Authors: Licht Stuart , Ghosh Susanta , Wang Baohui , Jiang Dianlu , Asercion Joseph , Bergmann Harry
Published: March 2011

The storage of multiple electrons per molecule provides opportunities to greatly enhance electrochemical energy capacity. VB2 releases, via electrochemical oxidation, 11 electrons per molecule at a favorable, electrochemical potential. Coupled with an air cathode, this 4060 mAh/g intrinsic capacity anode, has energy capacity greater than that of gasoline. Nanochemical improvements of VB2 are probed to facilitate charge transfer and discharge voltage. Nanoparticle formation is accomplished with a planetary ball mill media (tungsten carbide) with hardness comparable to that of VB2 (8–9 Mohs2). Mechanochemical synthesized, VB2 nanorods, exhibit higher voltage, sustain higher rate, and depth of discharge than macroscopic VB2.
The Effects of Ultraviolet Exposure on the Device Characteristics of Atomic Layer Deposited-ZnO:N Thin Film Transistors
Authors: Kim Jae-Min , Lim S. J. , Nam Taewook , Kim Doyoung , Kim Hyungjun
Published: March 2011

We investigated the effects of ultraviolet (UV) light illumination on nitrogen-doped atomic layer deposited (ALD)-ZnO:N thin film transistors (TFTs). ALD ZnO:N thin films grown at 125°C were used as active layers for back-gate TFT devices. As-fabricated ALD ZnO:N TFTs showed proper drain current modulation response to a gate voltage sweep with a 5.4 V threshold voltage and a clear pinch-off. However, the threshold voltage was significantly shifted in the negative direction by UV exposure due to an associated increase in carrier concentration, resulting in the loss of current modulation by gate voltage sweep. In addition, we observed a resistivity change in ALD ZnO:N thin films with time after UV exposure. The resistivity decreased by several orders of magnitude upon UV light exposure and recovered toward its original value after switching off the UV light. Accordingly, the transfer curves of TFT devices using a ZnO:N active layer also exhibited recovery characteristics. We formed a thin Al2O3 passivation layer on top of the TFT surface in order to suppress the recovery effect.
Typologies of Extreme Longevity Myths
Authors: Young Robert D. , Desjardins Bertrand , McLaughlin Kirsten , Poulain Michel , Perls Thomas T.
Published: March 2011

Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity.Design and Methods. American Social Security Death Index files for the period 1980–2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims.Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance), Shangri-La Myth (geographic), Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud.Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism.
Copy Number Alterations and Methylation in Ewing's Sarcoma
Authors: Jahromi Mona S. , Jones Kevin B. , Schiffman Joshua D.
Published: March 2011

Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs) and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.
A Weak Convergence Theorem for Total Asymptotically Pseudocontractive Mappings in Hilbert Spaces
Authors: Qin Xiaolong , Cho SunYoung , Kang ShinMin
Published: March 2011

The modified Ishikawa iterative process is investigated for the class of total asymptotically pseudocontractive mappings. A weak convergence theorem of fixed points is established in the framework of Hilbert spaces.
About Robust Stability of Caputo Linear Fractional Dynamic Systems with Time Delays through Fixed Point Theory
Authors: De la Sen M
Published: March 2011

This paper investigates the global stability and the global asymptotic stability independent of the sizes of the delays of linear time-varying Caputo fractional dynamic systems of real fractional order possessing internal point delays. The investigation is performed via fixed point theory in a complete metric space by defining appropriate nonexpansive or contractive self-mappings from initial conditions to points of the state-trajectory solution. The existence of a unique fixed point leading to a globally asymptotically stable equilibrium point is investigated, in particular, under easily testable sufficiency-type stability conditions. The study is performed for both the uncontrolled case and the controlled case under a wide class of state feedback laws.
A Decade of Experience Using mTor Inhibitors in Liver Transplantation
Authors: Campsen Jeffrey , Zimmerman Michael A. , Mandell Susan , Kaplan Maria , Kam Igal
Published: March 2011

Some studies suggest that Sirolimus (SRL) is associated with an increased risk of death in liver transplant recipients compared to treatment with calcineurin inhibitors (CNIs). We compared patients who received SRL or CNI in the first year after liver transplant. Our database included 688 patients who received a liver transplant. The patients were divided into groups. (1) CNI + MPS (mycophenolate sodium) at time of discharge. (2) CNI + MPS at time of discharge; SRL was added within the first 6 months and continued through the first year. (3) CNI + MPS at time of discharge; SRL was added within the first 6 months and discontinued before the first year. (4) SRL as primary immunosuppression. (5) SRL as primary immunosuppression and discontinued before the first year. We used mortality and graft loss as the primary measures of outcome. We also quantified renal function using the change in glomerular filtration rate (GFR), the presence of biopsy proven acute cellular reject (ACR), and steroid-resistant rejection (SRR). There were no significant differences in mortality or graft loss. There was no difference in patient or graft survival. Patients that received SRL as primary immunosuppression had 50% less rejection compared to controls.
Implementing Estimation of Capacity for Freeway Sections
Authors: Shao Chang-qiao
Published: March 2011

Based on the stochastic concept for freeway capacity, the procedure of capacity estimation is developed. Due to the fact that it is impossible to observe the value of the capacity and to obtain the probability distribution of the capacity, the product‐limit method is used in this paper to estimate the capacity. In order to implement estimation of capacity using this technology, the lifetime table based on statistical methods for lifetime data analysis is introduced and the corresponding procedure is developed. Simulated data based on freeway sections in Beijing, China, were analyzed and the results indicate that the methodology and procedure are applicable and validated.
Adjuvant Combination and Antigen Targeting as a Strategy to Induce Polyfunctional and High-Avidity T-Cell Responses against Poorly Immunogenic Tumors
Authors: Aranda Fernando , Llopiz Diana , Díaz-Valdés Nancy , Riezu-Boj José Ignacio , Bezunartea Jaione , Ruiz Marta , Martínez Marta , Durantez Maika , Mansilla Cristina , Prieto Jesús , Lasarte Juan José , Borrás-Cuesta Francisco , Sarobe Pablo
Published: March 2011

Low antigen expression and an absence of coimmunostimulatory signals may be partly responsible for the low immunogenicity of many tumors. It may be possible to overcome this situation by defining a combination of adjuvants and antigens that can activate a high-avidity antitumor response. Using the poorly immunogenic B16-OVA melanoma cells as tumor model, we tested different combinations of adjuvants and antigens to treat established tumors. In the absence of exogenous antigens, repeated administration of the TLR7 ligand Imiquimod together with anti-CD40 agonistic antibodies activated only innate immunity, which was insufficient to reject intradermal tumors. Administering this adjuvant combination together with OVA as a tumor antigen induced T-cell responses that delayed tumor growth. However, administering a combination of anti-CD40 plus TLR3 and TLR7 ligands, together with antigen targeting to dendritic cells through TLR4, was sufficient to induce tumor rejection in 50% of mice. This response was associated with a greater activation of innate immunity and induction of high-avidity polyfunctional CD8+ T-cell responses, which each contributed to tumor rejection. This therapy activated T-cell responses not only against OVA, which conferred protection against a rechallenge with B16-OVA cells, but also activated T-cell responses against other melanoma-associated antigens. Our findings support the concept that multiple adjuvant combination and antigen targeting may be a useful immunotherapeutic strategy against poorly immunogenic tumors. Cancer Res; 71(9); 3214–24. ©2011 AACR.
Calcineurin Signaling as a Negative Determinant of Keratinocyte Cancer Stem Cell Potential and Carcinogenesis
Authors: Dotto G. Paolo
Published: March 2011

Calcineurin is the only known serine-threonine phosphatase under calcium–calmodulin control and key regulator of the immune system. Treatment of patients with calcineurin-inhibitory drugs like cyclosporin A and FK506 to prevent graft rejection dramatically increases the risk of cutaneous squamous cell carcinoma, which is a major cause of death after organ transplants. Recent evidence indicates that suppression of calcineurin signaling, together with its impact on the immune system, exerts direct tumor-promoting effects in keratinocytes, enhancing cancer stem cell potential. The underlying mechanism involves interruption of a double negative regulatory axis, whereby calcineurin and nuclear factors of activated T-cell signaling inhibits expression of ATF3, a negative regulator of p53. The resulting suppression of keratinocyte cancer cell senescence is of likely clinical significance for the many patients under treatment with calcineurin inhibitors and may be of relevance for other cancer types in which altered calcium–calcineurin signaling plays a role. Cancer Res; 71(6); 2029–33. ©2011 AACR.
Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Amrein Philip C. , Attar Eyal C. , Takvorian Tak , Hochberg Ephraim P. , Ballen Karen K. , Leahy Kathleen M. , Fisher David C. , LaCasce Ann S. , Jacobsen Eric D. , Armand Philippe , Hasserjian Robert P. , Werner Lillian , Neuberg Donna , Brown Jennifer R.
Published: March 2011

Purpose: Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we tested the activity of dasatinib in patients with relapsed CLL.

Experimental Design: Patients were eligible for this phase II trial if they had documented CLL/SLL and had failed at least 1 prior therapy with a fludarabine-containing regimen and if they required therapy according to NCI-WG criteria. The starting dose of dasatinib was 140 mg daily.

Results: Fifteen patients were enrolled, with a median age of 59 and a median of 3 prior regimens. All patients had received fludarabine, and 5 were fludarabine-refractory. Eleven of the 15 (73%) had high risk del(11q) or del(17p) cytogenetics. The primary toxicity was myelosuppression, with grade 3 or 4 neutropenia and thrombocytopenia in 10 and 6 patients, respectively. Partial responses by NCI-WG criteria were achieved in 3 of the 15 patients (20%; 90% CI: 6–44). Among the remaining 12 patients, 5 had nodal responses by physical exam, and 1 patient had a nodal and lymphocyte response but with severe myelosuppression. Pharmacodynamic studies indicated apoptosis in peripheral blood CLL cells within 3 to 6 hours after dasatinib administration, associated with downregulation of Syk (spleen tyrosine kinase) mRNA.

Conclusions: Dasatinib as a single agent has activity in relapsed and refractory CLL. Clin Cancer Res; 17(9); 2977–86. ©2011 AACR.
JAG2 Induction in Hypoxic Tumor Cells Alters Notch Signaling and Enhances Endothelial Cell Tube Formation
Authors: Pietras Alexander , von Stedingk Kristoffer , Lindgren David , Påhlman Sven , Axelson Håkan
Published: March 2011

Several studies have revealed links between hypoxia and activation of Notch in solid tumors. While most reports have focused on intracellular domain of the Notch1 receptor (icN1) stabilization by direct interaction with HIF proteins, little attention has been given to Notch ligand regulation during hypoxia. Here we show that the Notch ligand JAG2 is transcriptionally activated by hypoxia in a HIF-1α dependent manner. Hypoxic JAG2 induction resulted in elevated Notch activity in tumor cells, as was measured by increased icN1 levels and induction of the Notch target gene HEY1. In primary tumor material, JAG2 expression correlated with vascular development and angiogenesis gene signatures. In line with this, coculture experiments of endothelial cells with hypoxic breast cancer cells displayed a reduction in number of capillary-like tubes formed upon JAG2 siRNA treatment of the breast cancer cells. Together these results suggest that a hypoxic induction of JAG2 in tumor cells mediates a hypoxia-regulated cross-talk between tumor and endothelial cells. Mol Cancer Res; 9(5); 626–36. ©2011 AACR.
Platelet Protease Nexin-1, a Serpin That Strongly Influences Fibrinolysis and Thrombolysis
Authors: Boulaftali Yacine , Ho-Tin-Noe Benoit , Pena Ana , Loyau Stéphane , Venisse Laurence , François Déborah , Richard Benjamin , Arocas Véronique , Collet Jean-Philippe , Jandrot-Perrus Martine , Bouton Marie-Christine
Published: March 2011

Background—

Protease nexin-1 (PN-1) is a serpin that inhibits plasminogen activators, plasmin, and thrombin. PN-1 is barely detectable in plasma, but we have shown recently that PN-1 is present within the α-granules of platelets.

Methods and Results—

In this study, the role of platelet PN-1 in fibrinolysis was investigated with the use of human platelets incubated with a blocking antibody and platelets from PN-1–deficient mice. We showed by using fibrin-agar zymography and fibrin matrix that platelet PN-1 inhibited both the generation of plasmin by fibrin-bound tissue plasminogen activator and the activity of fibrin-bound plasmin itself. Rotational thromboelastometry and laser scanning confocal microscopy were used to demonstrate that PN-1 blockade or deficiency resulted in increased clot lysis and in an acceleration of the lysis front. Protease nexin-1 is thus a major determinant of the lysis resistance of platelet-rich clots. Moreover, in an original murine model in which thrombolysis induced by tissue plasminogen activator can be measured directly in situ, we observed that vascular recanalization was significantly increased in PN-1–deficient mice. Surprisingly, general physical health, after tissue plasminogen activator–induced thrombolysis, was much better in PN-1–deficient than in wild-type mice.

Conclusions—

Our results reveal that platelet PN-1 can be considered as a new important regulator of thrombolysis in vivo. Inhibition of PN-1 is thus predicted to promote endogenous and exogenous tissue plasminogen activator–mediated fibrinolysis and may enhance the therapeutic efficacy of thrombolytic agents.
Long-Term Cardiac pro-B-Type Natriuretic Peptide Gene Delivery Prevents the Development of Hypertensive Heart Disease in Spontaneously Hypertensive Rats
Authors: Cataliotti Alessandro , Tonne Jason M. , Bellavia Diego , Martin Fernando L. , Oehler Elise A. , Harders Gerald E. , Campbell Jarryd M. , Peng Kaw-Whye , Russell Stephen J. , Malatino Lorenzo S. , Burnett John C. , Ikeda Yasuhiro
Published: March 2011

Background—

Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR).

Methods and Results—

We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expression. In SHR, a single systemic administration of AAV9 vector allowed long-term cardiac BNP overexpression, resulting in reductions in systolic and diastolic BP for 9 months after injection. Left ventricular (LV) thickness, LV end-systolic dimensions, and LV mass were reduced, whereas ejection fraction was significantly increased, in BNP-treated compared with untreated SHR. Circumferential systolic strain and strain rate of the early phase of diastole were improved in BNP-treated compared with untreated SHR. Noncardiac overexpression of BNP via AAV2 vector was not associated with changes in BP and plasma BNP in SHR. Furthermore, normal Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart weights 4 weeks after injection without BP reduction.

Conclusions—

AAV9 vector facilitates sustained cardiac proBNP overexpression and improves LV function in hypertensive heart disease. Long-term proBNP delivery improved both systolic and diastolic function. The effects on cardiac structure and function occurred independently of BP-lowering effects in normal Wistar rats.
Parents as educators of sex and relationship education
Authors: Turnbull Triece , van Wersch Anna , van Schaik Paul
Published: March 2011

Objective: To identify how British families discuss sexual matters and to determine if the use of a multimedia computer program increases knowledge to promote communication about sexual topics.

Design: A mixed-method approach in which families were interviewed within the family environment.

Method: Twenty families from the north east of England were recruited through purposive sampling. The first element of the research involved semi-structured interviews to identify how sexual matters were discussed within families. Interviews were recorded, transcribed verbatim and analyzed using the modified grounded theory approach of Strauss and Corbin. 1 The second part of the research involved families exploring a sex and relationship education resource to determine if knowledge and confidence in knowledge enhanced communication about sexual matters within families.

Results: The majority of parents and their children were found to discuss sexual matters openly within families. The resource was found to affect communication of sexual topics and increased knowledge and confidence in knowledge of parents and their children.

Conclusion: The results highlight the feasibility of using multimedia computer programs to educate and increase communication about sexual matters within families. Future research needs to focus on more diverse populations to assess the accuracy of this research and the possibility of developing parent programmes with the aim of educating parents so they can provide effective sex education to their children.
The historical anatomy of a contact zone
Authors: Raj Kapil
Published: March 2011

Founded in 1690 as an entrepôt by the English East India Company, Calcutta has been at the intersection of a number of heterogeneous long- and short-range networks of trade, finance, diplomacy, law, crafts and learning. This article explores the history of the first century of its existence during which it grew from insignificance to become the second most important city of the British Empire. During this period Calcutta also emerged as a world-city of scientific knowledge making in botany, geology, geodesy, map-making, geography, history, linguistics and ethnology. Calcutta thus provides an excellent case study of the co-construction of knowledge and urbanity in the early modern context of globalisation. As a contact zone between different ethnic, professional and religious communities, each with their specific knowledge practices, this article shows that new forms of knowledge, many at the heart of the second scientific revolution, were produced in this city through attempts at recognising and managing difference in this cosmopolitan context.
Selling steel in the 1920s
Authors: Nomura Chikayoshi
Published: March 2011

Through a case study on the Tata Iron and Steel Company, this article aims to clarify how a large-scale Indian industrial enterprise developed its business strategy in order to expand suitable sales networks in the 1920s, when the consumption pattern of steel changed drastically. In correspondence with the change, the company devised a business strategy to develop its sales network to minimise information asymmetries between the company, the end user and the intermediary merchant. The development of the sales network enabled the company to cultivate an emerging demand in domestic outlets, thereby helping the company survive after the 1920s. Besides, these successes could have prompted the House of Tata, the family owning the steel company, to initiate development in the domestic market to further its interest after the 1920s. Presumably, this resulted in the sharing of its views with some of the local merchants and entrepreneurs who had opposed the laissez-faire policy of the colonial government to preserve domestic outlets in their hands.
Globalization and the Legitimacy of Intergovernmental Organizations
Authors: Machida Satoshi
Published: March 2011

Focusing on ‘democratic deficit’, this article examines how globalization affects the legitimacy of intergovernmental organizations (IGOs). Two contextual factors are considered: (i) democracy at the domestic level and (ii) global inequality. Since these two factors determine the severity of democratic deficit in each country, the impact of globalization on citizens’ support for IGOs significantly varies across states. Globalization does not undermine the legitimacy of IGOs in democratically well-attuned rich states. The Pew Global Attitudes Project 2002 lends support to this primary argument.
Just War Tradition and Buddhism
Authors: Jayasuriya Laksiri
Published: March 2011

Just war, a concept stemming from Christian theological scholarship, has become part of the Western social and political lexicon. This article examines how Buddhism as a non-Abrahamic faith has dealt with just war thinking. To this end, it specifically analyzes some of the recent scholarly studies of just war ideology in relation to the civil war in Sri Lanka. It is argued that just war thinking is essentially a question of how issues of religion and politics are handled in Buddhist countries.
Robert W. Cox and Critical Theory of International Relations
Authors: Moolakkattu John S.
Published: March 2011

Robert W. Cox’s contribution to International Relations theory places the discipline in a transformational framework. Building on Gramsci’s ideas and a variety of other sources eclectically, his theory goes beyond the neorealist statecentric framework and brings out the connections between material conditions, ideas and institutions in what he terms the formation of ‘world orders’. How people organize themselves in the sphere of production not only determines their own life but also that of their states and the world order. In saying that change can come from any one of the spheres (material conditions, ideas and institutions), he denies and goes beyond the base–superstructure thesis of Marxism. Cox identifies creation of a vibrant civil society, emergence of organic intellectuals representing the marginalized, development of community-level solidarity, participatory democracy, non-violent methods of conflict resolution, pluralism and multilateralism as key elements of his transformational agenda. This essay explores Cox’s main ideas relating to transformational international relations and the strategies envisaged for transformation.
Studies on the composites produced from co-weaved poly ether ether ketone and glass fiber fabric
Authors: Indu Shekar R. , Satheesh Kumar M.N. , Damodhara Rao P.M. , Yaakob Z. , Kotresh T.M. , Siddaramaiah  , Chandrakala
Published: March 2011

The extruded poly ether ether ketone (PEEK) and glass fiber yarns were used to obtain the co-weaved hybrid fiber fabrics. Compression molding technique was employed to obtain the glass—PEEK composites from the hybrid fiber fabric. Composites having different thickness values of 3.3, 3.6, and 4.5 mm have been fabricated by varying the number of layers (15, 17, and 20 layers) of co-weaved fabrics. The mechanical properties such as flexural strength and inter laminar shear strength as a function of number of layers of fabric have been evaluated. Low-velocity (2.1 m/s) repeated drop weight impact tests were carried out on the fabricated composites at 5 and 10 J incident energy. The number of drops to failure was observed to be more in 5 J compared to 10 J incident energy. Effects of frequency on the viscoelastic behavior were investigated using dynamic mechanical analyzer by sweeping at different frequency and temperature ranges. Master curves were generated by time—temperature superposition of the experimental data at a reference temperature of 156°C. The dielectric properties such as relative permittivity and loss tangent of glass—PEEK composites was found to be less dependent on the frequency (8—13 GHz) and temperature (50—300° C), which is an indication for its use in typical aerospace applications such as radomes.
Feeling Like You Know Who You Are: Perceived True Self-Knowledge and Meaning in Life
Authors: Schlegel Rebecca J. , Hicks Joshua A. , King Laura A. , Arndt Jamie
Published: March 2011

The essence of who a person really is has been labeled the “true self,” and an emerging area of research suggests that this self-concept plays an important role in the creation of a fulfilling existence. Three studies investigate the role of the subjective feeling that one possesses knowledge of one’s true self in meaning in life judgments. Consistently, the perception of availability of true self-knowledge (operationalized as the metacognitive experience of ease in describing one’s true self) predicted meaning in life judgments over and above other potentially related constructs such as mood and self-esteem. Conversely, the subjective availability of knowledge of how one actually behaves (i.e., one’s actual self) was unrelated to meaning in life judgments. Implications and directions for future research are discussed.