bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Susceptibility of Cryptococcus neoformans to Amphotericin B with Clinical Outcome
Authors: Larsen R. A. , Bauer M. , Pitisuttithum P. , Sanchez A. , Tansuphaswadikul S. , Wuthiekanun V. , Peacock S. J. , Simpson A. J. H. , Fothergill A. W. , Rinaldi M. G. , Bustamante B. , Thomas A. M. , Altomstone R. , Day N. P. J. , White N. J.
Published: September 2011

Testing of
Cryptococcus neoformans
for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. This report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (CSF) and the survival of 85 patients treated with amphotericin B (AMB). The Spearman rank correlation between the quantitative
in vitro
measure of susceptibility and the quantitative measure of the number of organisms in the patient's CSF was 0.37 (
P
< 0.01; 95% confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test replicate and 0.46 (
P
< 0.001; 95% CI, 0.21, 0.62) for the second susceptibility test replicate. The median
in vitro
estimated response (defined as the fungal burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was 5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died before day 14. These exploratory results suggest that patients whose isolates show a quantitative
in vitro
susceptibility response below 10 CFU/ml were more likely to survive beyond day 14.
Differential Association of Plasmodium falciparum Na
+
/H
+
Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum
Authors: Pelleau Stéphane , Bertaux Lionel , Briolant Sébastien , Ferdig Michael T. , Sinou Véronique , Pradines Bruno , Parzy Daniel , Jambou Ronan
Published: September 2011

Plasmodium falciparum
isolates with decreased susceptibility to quinine are increasingly being found in malaria patients. Mechanisms involved in this resistance are not yet understood. Several studies claim that alongside mutations in the Pf
crt
and Pf
mdr1
genes, the Pf
nhe-1
Na
+
/H
+
exchanger polymorphism plays a role in decreasing susceptibility. However, conflicting results on the link between the Pf
nhe-1
gene and quinine resistance arise from field- and culture-adapted isolates. We tested the association between Pf
nhe-1
, Pf
crt
, and Pf
mdr1
polymorphisms in field- and culture-adapted isolates from various countries with their
in vitro
susceptibility to quinine. Field isolates presented a higher diversity of the Pf
nhe-1
microsatellite sequence than culture-adapted isolates. In culture-adapted isolates but not in field isolates, mutations in the Pf
crt
and Pf
mdr1
genes, as well as a higher number of DNNND repeats in the Pf
nhe-1
gene, were associated with a higher 50% inhibitory concentration (IC
50
) of quinine. Furthermore, most of the culture-adapted isolates with more than one DNNND repeat in the Pf
nhe-1
gene also harbored mutated Pf
crt
and Pf
mdr1
genes with an apparent cumulative effect on quinine susceptibility. This study supports the involvement of the Pf
nhe-1
gene in the modulation of the
in vitro
quinine response when associated with mutated Pf
crt
and Pf
mdr1
genes. Culture adaptation could be responsible for selection of specific haplotypes of these three genes. Methods used for drug testing might thus influence the association between Pf
nhe-1
polymorphism and quinine susceptibility. However, we do not exclude the possibility that in particular settings, Pf
nhe-1
polymorphism can be used as a molecular marker for surveillance of quinine resistance.
Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins
Authors: Reeder Nancy L. , Kaplan Jerry , Xu Jun , Youngquist R. Scott , Wallace Jared , Hu Ping , Juhlin Kenton D. , Schwartz James R. , Grant Raymond A. , Fieno Angela , Nemeth Suzanne , Reichling Tim , Tiesman Jay P. , Mills Tim , Steinke Mark , Wang Shuo L. , Saunders Charles W.
Published: September 2011

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast,
Saccharomyces cerevisiae
. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus
Malassezia globosa
. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.
Interaction between Artemether-Lumefantrine and Nevirapine-Based Antiretroviral Therapy in HIV-1-Infected Patients
Authors: Kredo T. , Mauff K. , Van der Walt J. S. , Wiesner L. , Maartens G. , Cohen K. , Smith P. , Barnes K. I.
Published: September 2011

Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients and those stable on nevirapine-based therapy. Both groups received the recommended artemether-lumefantrine dose. Patients were admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient sampling until 21 days. Concentrations of lumefantrine, artemether, dihydroartemisinin, and nevirapine were determined by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome was observed day 7 lumefantrine concentrations, as these are associated with therapeutic response in malaria. We enrolled 36 patients (32 females). Median (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and 336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naïve groups, respectively (
P
= 0.0002). The median artemether area under the plasma concentration-time curve from 0 to 8 h [AUC
(0-8 h)
] (
P
< 0.0001) and dihydroartemisinin AUC
(60-68 h)
(
P
= 0.01) were lower in the nevirapine group. Combined artemether and dihydroartemisinin exposure decreased over time only in the nevirapine group (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90];
P
< 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95% CI, 1.31 to 3.45];
P
= 0.002). Adverse events were similar between groups, with no difference in electrocardiographic Fridericia corrected QT and P-R intervals at the expected time of maximum lumefantrine concentration (
T
max
). Nevirapine-based ART decreased artemether and dihydroartemisinin AUCs but unexpectedly increased lumefantrine exposure. The mechanism of the lumefantrine interaction remains to be elucidated. Studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.
Dynamic Virulence: Real-Time Assessment of Intracellular Pathogenesis Links Cryptococcus neoformans Phenotype with Clinical Outcome
Authors: Mansour Michael K. , Vyas Jatin M. , Levitz Stuart M.
Published: September 2011

While a myriad of studies have examined host factors that predispose persons to infection with the opportunistic fungal pathogen
Cryptococcus neoformans
, comparatively little has been done to examine how virulence factor differences among cryptococcal isolates may impact outcome. In the recent report by Alanio et al. (A. Alanio, M. Desnos-Ollivier, and F. Dromer, mBio 2:e00158-11, 2011), novel flow cytometry-based techniques were employed to demonstrate an association between the phenotype of
C. neoformans
-macrophage interactions, as measured by phagocytosis and intracellular replication, and patient outcomes, as determined by positive cultures on therapy and survival. These experiments establish that the prognosis of patients with cryptococcosis is influenced by the phenotypic properties of the infecting fungal isolate.
Unexpected lactonization accompanying addition of ethyl acetoacetate to chalcones derived from 3-acetylthiophene
Authors: Budak Yakup , Findik Esra
Published: September 2011

Chalcone derivatives containing thiophene ring were prepared by the condensation of 3-acetylthiophene with aromatic aldehydes in excellent yields. The addition of ethyl acetoacetate to chalcone derivatives3a–3hin the presence of solid NaOH in CH2Cl2resulted in the formation of the mixture of bicyclic lactone derivatives5a–5hand 6-(ethoxycarbonyl)cyclohexenone derivatives6a–6h.
Responsibility of sport and exercise medicine in preventing and managing chronic disease: applying our knowledge and skill is overdue: Figure 1
Authors: Matheson Gordon O , Klügl Martin , Dvorak Jiri , Engebretsen Lars , Meeuwisse Willem H , Schwellnus Martin , Blair Steven N , van Mechelen Willem , Derman Wayne , Börjesson Mats , Bendiksen Fredrik , Weiler Richard
Published: September 2011

Background

The rapidly increasing burden of chronic disease is difficult to reconcile with the large, compelling body of literature that demonstrates the substantial preventive and therapeutic benefits of comprehensive lifestyle intervention, including physical activity, smoking cessation and healthy diet. Physical inactivity is now the fourth leading independent risk factor for death caused by non-communicable chronic disease. Although there have been efforts directed towards research, education and legislation, preventive efforts have been meager relative to the magnitude of the problem. The disparity between our scientific knowledge about chronic disease and practical implementation of preventive approaches now is one of the most urgent concerns in healthcare worldwide and threatens the collapse of our health systems unless extraordinary change takes place.

Findings

The authors believe that there are several key factors contributing to the disparity. Reductionism has become the default approach for healthcare delivery, resulting in fragmentation rather than integration of services. This, in turn, has fostered a disease-based rather than a health-based model of care and has produced medical school curricula that no longer accurately reflect the actual burden of disease. Trying to ‘fit’ prevention into a disease-based approach has been largely unsuccessful because the fundamental tenets of preventive medicine are diametrically opposed to those of disease-based healthcare.

Recommendation

A clinical discipline within medicine is needed to adopt disease prevention as its own reason for existence. Sport and exercise medicine is well positioned to champion the cause of prevention by promoting physical activity.

Conclusion

This article puts forward a strong case for the immediate, increased involvement of clinical sport and exercise medicine in the prevention and treatment of chronic disease and offers specific recommendations for how this may begin.
Exercise-associated collapse: an evidence-based review and primer for clinicians
Authors: Asplund Chad A , O'Connor Francis G , Noakes Timothy D
Published: September 2011

Exercise-associated collapse (EAC) commonly occurs after the completion of endurance running events. EAC is a collapse in conscious athletes who are unable to stand or walk unaided as a result of light headedness, faintness and dizziness or syncope causing a collapse that occurs after completion of an exertional event. Although EAC is perhaps the most common aetiology confronted by the medical provider attending to collapsed athletes in a finish-line tent, providers must first maintain vigilance for other potential life-threatening aetiologies that cause collapse, such as cardiac arrest, exertional heat stroke or exercise-associated hyponatraemia. Previously, it has been believed that dehydration and hyperthermia were primary causes of EAC. On review of the evidence, EAC is now believed to be principally the result of transient postural hypotension caused by lower extremity pooling of blood once the athlete stops running and the resultant impairment of cardiac baroreflexes. Once life-threatening aetiologies are ruled out, treatment of EAC is symptomatic and involves oral hydration and a Trendelenburg position – total body cooling, intravenous hydration or advanced therapies is generally not needed.
Challenges of genetic testing in adolescents with cardiac arrhythmia syndromes
Authors: Cohen Lilian Liou , Stolerman Marina , Walsh Christine , Wasserman David , Dolan Siobhan M
Published: September 2011

The ability to sequence individual genomes is leading to the identification of an increasing number of genetic risk factors for serious diseases. Knowledge of these risk factors can often provide significant medical and psychological benefit, but also raises complex ethical and social issues. This paper focuses on one area of rapid progress: the identification of mutations causing long QT syndrome and other cardiac channel disorders, which can explain some previously unexplained deaths in infants (SIDS) and children and adults (SUDS) and prevent others from occurring. This genetic knowledge, discovered posthumously in many cases, has implications for clinical care for surviving family members who might carry the same mutations. The information obtained from genetic testing, in the context of personal and family history, can guide individually tailored interventions that reduce risk and save lives. At the same time, obtaining and disclosing genetic information raises difficult issues about confidentiality and decision making within families. We draw on the experience of the Montefiore-Einstein Center for Cardiogenetics, which has played a leading role in the genetic diagnosis and clinical management of cardiac channel diseases, to explore some of the challenging ethical questions arising in affected families with adolescent children. We focus on the related issues of (1) family confidentiality, privacy and disclosure and (2) adolescent decision making about genetic risk, and argue for the value of interdisciplinary dialogue with affected families in resolving these issues.
Low-energy electron-induced decarbonylation of Fe(CO)5 films adsorbed on Au(111) surfaces
Authors: Hauchard Christelle , Rowntree Paul A.
Published: September 2011

The decarbonylation of Fe(CO)5 adsorbed in monolayer and multilayer films on Au(111)/mica substrates has been induced by 0–20 eV electrons and studied by grazing incidence IR spectroscopy. Our results show that the cross sections for the initial stages of this process in as-deposited films range from 60–300 Å2 and show considerable variations with the incident electron energy. The high sensitivity to low-energy electrons is believed to be the result of secondary reactions of anion fragments in the film with the neighbouring Fe(CO)5 moieties, leading to increasingly massive heteronuclear Fen(CO)m species and progressive CO elimination. Continued exposure to the electron beam leads to the slower degradation of these newly created species into an Fe-rich deposit containing traces of CO. These traces are removed by subsequent heating to ~300 K. Fe(CO)5 films that have been subjected to temperatures exceeding 125 K have no measurable sensitivity to the electron beam in the 0–20 eV regime; this is believed to be due to the structural transformation of the as-deposited thin film structure into 3D aggregates. This structural motif presents a very limited quantity of the adsorbed Fe(CO)5 to the incident beam, and may also form a protective layer of the robust Fen(CO)m species during the initial stages of exposure to the electrons.
Theoretical investigation of some N-nitrosodiphenylamine biological molecules — A natural bond orbital (NBO) study
Authors: Li Xiao-Hong , Zhang Rui-Zhou , Zhang Xian-Zhou
Published: September 2011

Theoretical study of several N-nitrosodiphenylamine biological molecules has been performed using quantum computational ab initio RHF and density functional B3LYP and B3PW91 methods with 6–311G++(d,p) basis set. Geometries obtained from density functional theory (DFT) calculations were used to perform Natural bond orbital (NBO) analysis. The p characters of two nitrogen natural hybrid orbitals (NHOs) σN3−N2 increase with increasing σp values of the substituents on the benzene, which results in a lengthening of the N3–N2 bond. The p characters of oxygen NHO σO1−N2 and nitrogen NHO σO1−N2 bond orbitals decrease with increasing σp values of the substituents on the benzene, which results in a shortening of the N2=O1 bond. It is also noted that decreased occupancy of the localized σN3−N2 orbital in the idealized Lewis structure, or increased occupancy of [Formula: see text]of the non-Lewis orbital, and their subsequent impact on molecular stability and geometry (bond lengths) are also related to the resulting p character of the corresponding nitrogen NHO of σN3−N2 bond orbital.
ENTROPY FOR PERICLASE AT HIGH COMPRESSIONS AND AT HIGH TEMPERATURES
Authors: SHARMA S. K. , SHARMA B. K. , KUMAR R. , SHARMA B. S.
Published: September 2011

We derive a relation for computing volume dependence of entropy at selected isotherms. This formula is based on the Al'tshuler et al. model (J. Appl. Mech. Tech. Phys.28 (1987) 129) for volume dependence of Grüneisen parameter. The formula for entropy obtained in the present study has been used to determine the results for MgO down to a volume ratio 0.50 at selected isotherms. The obtained results for entropy present a general agreement with those calculated by Cynn et al. (J. Phys. Chem.99(9) (1995) 7813). We also formulate a relationship between Debye temperature and entropy. And it is found that Debye temperature increases exponentially as entropy decreases.
BUCKLING INSTABILITY FOR A CHARGED AND SEMIFLEXIBLE POLYMER
Authors: GHAMARI KHABAT , NAJAFI ALI
Published: September 2011

In this article, we address the problem of Euler's buckling instability in a charged semi-flexible polymer that is under the action of a compressive force. We consider this instability as a phase transition and investigate the role of thermal fluctuations in the buckling critical force. By performing molecular dynamic simulations, we show that the critical force decreases when the temperature increases. Repulsive electrostatic interaction in the finite temperature is in competition with thermal fluctuations to increase the buckling threshold.
NONLINEAR WIND-RESISTANT DESIGN METHOD FOR CABLE NET FAÇADES
Authors: FENG RUO-QIANG , YE JIHONG , WU YUE , SHEN SHI-ZHAO
Published: September 2011

Cable net façades are sensitive to the fluctuating wind loads due to their high flexibility, light weight, and small damping. Since the cable net façade is a new kind of structure with obvious geometrically nonlinear behavior, there is no proper corresponding wind-resistant design method. In this paper, first, the nonlinear random vibration theory is used to determine the wind-induced nonlinear response formulation of the cable net façade. Then, a nonlinear wind-resistant design method for the cable net façade is developed based on the structural response. Finally, the accuracy of this wind-resistant method is verified, and the scope of the application is discussed.
CORRELATION BETWEEN MICROSTRUCTURE AND YIELD STRESS IN MAGNETICALLY STABILIZED FLUIDIZED BEDS
Authors: VALVERDE J. M. , ESPIN M. J. , QUINTANILLA M. A. S. , CASTELLANOS A.
Published: September 2011

A magnetofluidized bed consists of a bed of magnetizable particles subjected to a gas flow in the presence of an externally applied magnetic field. In the absence of magnetic field, there is a given gas velocity at which naturally cohesive fine particles can form a network of permanent interparticle contacts capable of sustaining small stresses. This gas velocity marks the jamming transition of the fluidized bed. For gas velocities above the jamming transition, the bed resembles a liquid. Below the jamming transition, the bed behaves as a weak solid and it has a nonvanishing tensile strength. In the absence of magnetic field, the tensile strength of the solidlike stabilized bed has its only origin in nonmagnetic attractive forces acting between particles. In the presence of a magnetic field, the gas velocity at the jamming transition and the tensile strength of the bed depend on the field strength as a consequence of the magnetostatic attraction induced between the magnetized particles. In this work we present experimental measurements on the jamming transition and tensile strength of magnetofluidized beds of linearly magnetizable fine powders. It is shown that powders with similar magnetic susceptibility but different strength of the nonmagnetic forces show a different response to the magnetic field. This finding can be explained by the influence of the nonmagnetic natural forces on the network of contacts. Thus, our experimental results reported in this paper reinforce the role of short-ranged interparticle contact forces on the behavior of the system, which contrasts with the usual modeling approach in which the magnetofluidized bed is viewed as a continuum medium and a fundamental assumption is that the fields can be averaged over large distances as compared with particle size.
Geometric clustering
Authors: Cabello Sergio , Giannopoulos Panos , Knauer Christian , Marx Dániel , Rote Günter
Published: September 2011

We study the parameterized complexity of the
k
-center problem on a given
n
-point set
P
in ℝ

d

, with the dimension
d
as the parameter. We show that the rectilinear 3-center problem is fixed-parameter tractable, by giving an algorithm that runs in
O
(
n
log
n
) time for any fixed dimension
d
. On the other hand, we show that this is unlikely to be the case with both the Euclidean and rectilinear
k
-center problems for any
k
≥ 2 and
k
≥ 4 respectively. In particular, we prove that deciding whether
P
can be covered by the union of 2 balls of given radius or by the union of 4 cubes of given side length is W[1]-hard with respect to
d
, and thus not fixed-parameter tractable unless FPT=W[1]. For the Euclidean case, we also show that even an
n

o
(
d
)

-time algorithm does not exist, unless there is a 2

o
(
n
)

-time algorithm for
n
-variable 3SAT, that is, the Exponential Time Hypothesis fails.
Memoryless facility location in one pass
Authors: Fotakis Dimitris
Published: September 2011

We present the first one-pass memoryless algorithm for metric Facility Location that maintains a set of facilities approximating the optimal facility configuration within a constant factor. The algorithm is randomized and very simple to state and implement. It processes the demand points one-by-one as they arrive, and keeps in memory only the facility locations currently open. We prove that its competitive ratio is less than 14 in the special case of uniform facility costs, and less than 49 in the general case of nonuniform facility costs.
Succinct indexes for strings, binary relations and multilabeled trees
Authors: Barbay Jérémy , He Meng , Munro J. Ian , Satti Srinivasa Rao
Published: September 2011

We define and design succinct indexes for several abstract data types (ADTs). The concept is to design auxiliary data structures that ideally occupy asymptotically less space than the information-theoretic lower bound on the space required to encode the given data, and support an extended set of operations using the basic operators defined in the ADT. The main advantage of succinct indexes as opposed to succinct (integrated data/index) encodings is that we make assumptions only on the ADT through which the main data is accessed, rather than the way in which the data is encoded. This allows more freedom in the encoding of the main data. In this article, we present succinct indexes for various data types, namely strings, binary relations and multilabeled trees. Given the support for the interface of the ADTs of these data types, we can support various useful operations efficiently by constructing succinct indexes for them. When the operators in the ADTs are supported in constant time, our results are comparable to previous results, while allowing more flexibility in the encoding of the given data.

Using our techniques, we design a succinct encoding that represents a string of length
n
over an alphabet of size σ using
n
H

k

(
S
) + lg σ ·
o
(
n
) +
O
(
n
lg σ/lg lg lg σ) bits to support access/rank/select operations in
o
((lg lg σ)
1+ϵ
) time, for any fixed constant ϵ > 0. We also design a succinct text index using
n
H
0
(
S
) +
O
(
n
lg σ/lg lg σ) bits that supports finding all the occ occurrences of a given pattern of length
m
in
O
(
m
lg lg σ + occ lg
n
/lg
ϵ
σ) time, for any fixed constant 0 < ϵ < 1. Previous results on these two problems either have a lg σ factor instead of lg lg σ in the running time, or are not compressed. Finally, we present succinct encodings of binary relations and multi-labeled trees that are more compact than previous structures.
Self-organizing and self-reconfigurable event routing in ad hoc networks with causal dependency awareness
Authors: Pei Guanhong , Ravindran Binoy , Jensen E. Douglas
Published: September 2011

Publish/Subscribe (P/S) is a communication paradigm of growing popularity for information dissemination in large-scale distributed systems. The weak coupling between information producers and consumers in P/S systems is attractive for loosely coupled and dynamic network infrastructures such as ad hoc networks. However, achieving end-to-end timeliness and reliability properties when P/S events are causally dependent is an open problem in ad hoc networks.

In this article, we present, evaluate benefits of, and compare with past work an architecture design that can effectively support timely and reliable delivery of events and causally related events in ad hoc environments, and especially in mobile ad hoc networks (MANETs).

With observations from both realistic application model and simulation experiments, we reveal causal dependencies among events and their significance in a typical use notional system. We also examine and propose engineering methodologies to further tailor an event-based system to facilitate its self-reorganizing capability and self-reconfiguration. Our design features a two-layer structure, including novel distributed algorithms and mechanisms for P/S tree construction and maintenance. The trace-based experimental simulation studies illustrate our design's effectiveness in both cases with and without causal dependencies.
Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to ameliorate interleukin-18-induced cardiac hypertrophy
Authors: Majumdar Gipsy , Rooney Robert J. , Johnson I. Maria , Raghow Rajendra
Published: September 2011

We investigated the genome-wide consequences of pan-histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and m-carboxycinnamic acid bis-hydroxamide (CBHA) in the hearts of BALB/c mice eliciting hypertrophy in response to interleukin-18 (IL-18). Both TSA and CBHA profoundly altered cardiac chromatin structure that occurred concomitantly with normalization of IL-18-induced gene expression and amelioration of cardiac hypertrophy. The hearts of mice exposed to IL-18 +/− TSA or CBHA elicited distinct gene expression profiles. Of 184 genes that were differentially regulated by IL-18 and TSA, 33 were regulated in an opposite manner. The hearts of mice treated with IL-18 and/or CBHA elicited 147 differentially expressed genes (DEGs), a third of which were oppositely regulated by IL-18 and CBHA. Ingenuity Pathways and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs showed that IL-18 impinged on TNF-α- and IFNγ-specific gene networks relegated to controlling immunity and inflammation, cardiac metabolism and energetics, and cell proliferation and apoptosis. These TNF-α- and IFNγ-specific gene networks, extensively connected with PI3K, MAPK, and NF-κB signaling pathways, were oppositely regulated by IL-18 and pan-HDACIs. Evidently, both TSA and CBHA caused a two- to fourfold induction of phosphatase and tensin homolog expression to counteract IL-18-induced proinflammatory signaling and cardiac hypertrophy.
Engraftment of Insulin-Producing Cells from Porcine Islets in Non-Immune-Suppressed Rats or Nonhuman Primates Transplanted Previously with Embryonic Pig Pancreas
Authors: Hammerman Marc R.
Published: September 2011

Transplantation therapy for diabetes is limited by unavailability of donor organs and outcomes complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation (embryonic day 28 (E28)) engraft long-term in non-immune, suppressed diabetic rats or rhesus macaques. Morphologically, similar cells originating from adult porcine islets of Langerhans (islets) engraft in non-immune-suppressed rats or rhesus macaques previously transplanted with E28 pig pancreatic primordia. Our data are consistent with induction of tolerance to an endocrine cell component of porcine islets induced by previous transplantation of embryonic pig pancreas, a novel finding we designate organogenetic tolerance. The potential exists for its use to enable the use of pigs as islet cell donors for humans with no immune suppression requirement.
Tillage and Fertilizer Management Effects on Soil-Atmospheric Exchanges of Methane and Nitrous Oxide in a Corn Production System
Authors: Nyakatawa Ermson Z. , Mays David A. , Way Thomas R. , Watts Dexter B. , Torbert Henry A. , Smith Douglas R.
Published: September 2011

Land application of poultry litter (PL) presents an opportunity to improve soil productivity and disposal of poultry waste. We investigated methane (CH4) and nitrous oxide (N2O) emissions from agricultural soil receiving PL and ammonium nitrate (AN) fertilizers using surface (SA), soil incorporation (SI), and subsurface band (BA) application methods in conventional (CT) and no-tillage (NT) systems on a Decatur silt loam soil in North Alabama. Plots under CT and NT were sinks of CH4in spring, summer, and fall. In winter, the plots had net emissions of 3.32 and 4.24 g CH4ha-1day-1in CT and NT systems, respectively. Plots which received AN were net emitters of CH4and N2O, whereas plots which received PL were net sinks of CH4. Plots which received PL using SA or SI methods were net emitters of N2O, whereas under PL using BA application, the plots were net sinks of N2O. Our study indicates that using subsurface band application of PL was the most promising environmentally sustainable poultry waste application method for reducing CH4and N2O emissions from agricultural soil in NT and CT corn production systems on the Decatur soil in north Alabama.
Probiotics for the Control of Parasites: An Overview
Authors: Travers Marie-Agnès , Florent Isabelle , Kohl Linda , Grellier Philippe
Published: September 2011

Probiotics are defined as live organisms, which confer benefits to the host. Their efficiency was demonstrated for the treatment of gastrointestinal disorders, respiratory infections, and allergic symptoms, but their use is mostly limited to bacterial and viral diseases. During the last decade, probiotics as means for the control of parasite infections were reported covering mainly intestinal diseases but also some nongut infections, that are all of human and veterinary importance. In most cases, evidence for a beneficial effect was obtained by studies using animal models. In a few cases, cellular interactions between probiotics and pathogens or relevant host cells were also investigated using in vitro culture systems. However, molecular mechanisms mediating the beneficial effects are as yet poorly understood. These studies indicate that probiotics might indeed provide a strain-specific protection against parasites, probably through multiple mechanisms. But more unravelling studies are needed to justify probiotic utilisation in therapeutics.
On the Use of EEG or MEG Brain Imaging Tools in Neuromarketing Research
Authors: Vecchiato Giovanni , Astolfi Laura , De Vico Fallani Fabrizio , Toppi Jlenia , Aloise Fabio , Bez Francesco , Wei Daming , Kong Wanzeng , Dai Jounging , Cincotti Febo , Mattia Donatella , Babiloni Fabio
Published: September 2011

Here we present an overview of some published papers of interest for the marketing research employing electroencephalogram (EEG) and magnetoencephalogram (MEG) methods. The interest for these methodologies relies in their high-temporal resolution as opposed to the investigation of such problem with the functional Magnetic Resonance Imaging (fMRI) methodology, also largely used in the marketing research. In addition, EEG and MEG technologies have greatly improved their spatial resolution in the last decades with the introduction of advanced signal processing methodologies. By presenting data gathered through MEG and high resolution EEG we will show which kind of information it is possible to gather with these methodologies while the persons are watching marketing relevant stimuli. Such information will be related to the memorization and pleasantness related to such stimuli. We noted that temporal and frequency patterns of brain signals are able to provide possible descriptors conveying information about the cognitive and emotional processes in subjects observing commercial advertisements. These information could be unobtainable through common tools used in standard marketing research. We also show an example of how an EEG methodology could be used to analyze cultural differences between fruition of video commercials of carbonated beverages in Western and Eastern countries.
Exact Solutions of Nonlinear Equation of Rod Deflections Involving the Lauricella Hypergeometric Functions
Authors: Scarpello Giovanni Mingari , Ritelli Daniele
Published: September 2011

The stress induced in a loaded beam will not exceed some threshold, but also its maximum deflection, as for all the elastic systems, will be controlled. Nevertheless, the linear beam theory fails to describe the large deflections; highly flexible linear elements, namely, rods, typically found in aerospace or oil applications, may experience large displacements—but small strains, for not leaving the field of linear elasticity—so that geometric nonlinearities become significant. In this article, we provide analytical solutions to large deflections problem of a straight, cantilevered rod under different coplanar loadings. Our researches are led by means of the elliptic integrals, but the main achievement concerns the Lauricella hypergeometric functions use for solving elasticity problems. Each of our analytic solutions has been individually validated by comparison with other tools, so that it can be used in turn as a benchmark, that is, for testing other methods based on the finite elements approximation.
Molecular Characterization and Expression of α‐Globin and β‐Globin Genes in the Euryhaline Flounder (Platichthys flesus)
Authors: Lu Weiqun , Mayolle Aurelie , Cui Guoqiang , Luo Lei , Balment Richard J.
Published: September 2011

In order to understand the possible role of globin genes in fish salinity adaptation, we report the molecular characterization and expression of all four subunits of haemoglobin, and their response to salinity challenge in flounder. The entire open reading frames of α1‐globin and α2‐globin genes were 432 and 435 bp long, respectively, whereas the β1‐globin and β2‐globin genes were both 447 bp. Although the head kidney (pronephros) is the predicted major site of haematopoiesis, real‐time PCR revealed that expression of α‐globin and β‐globin in kidney (mesonephros) was 1.5 times higher than in head kidney. Notably, the α1‐globin and β1‐globin mRNA expression was higher than α2‐globin and β2‐globin in kidney. Expression levels of all four globin subunits were higher in freshwater‐ (FW‐) than in seawater‐ (SW‐)adapted fish kidney. If globins do play a role in salinity adaptation, this is likely to be more important in combating the hemodilution faced by fish in FW than the dehydration and salt loading which occur in SW.
Energy Conversion in Protocells with Natural Nanoconductors
Authors: Xu Jian , Vanderlick T. Kyle , LaVan David A.
Published: September 2011

While much nanotechnology leverages solid-state devices, here we present the analysis of designs for hybrid organic-inorganic biomimetic devices, “protocells,” based on assemblies of natural ion channels and ion pumps, “nanoconductors,” incorporated into synthetic supported lipid bilayer membranes. These protocells mimic the energy conversion scheme of natural cells and are able to directly output electricity. The electrogenic mechanisms have been analyzed and designs were optimized using numerical models. The parameters that affect the energy conversion are quantified, and limits for device performance have been found using numerical optimization. The electrogenic performance is compared to conventional and emerging technologies and plotted on Ragone charts to allow direct comparisons. The protocell technologies summarized here may be of use for energy conversion where large-scale ion concentration gradients are available (such as the intersection of fresh and salt water sources) or small-scale devices where low power density would be acceptable.
A Review on Nanofluids: Preparation, Stability Mechanisms, and Applications
Authors: Yu Wei , Xie Huaqing
Published: September 2011

Nanofluids, the fluid suspensions of nanomaterials, have shown many interesting properties, and the distinctive features offer unprecedented potential for many applications. This paper summarizes the recent progress on the study of nanofluids, such as the preparation methods, the evaluation methods for the stability of nanofluids, and the ways to enhance the stability for nanofluids, the stability mechanisms of nanofluids, and presents the broad range of current and future applications in various fields including energy and mechanical and biomedical fields. At last, the paper identifies the opportunities for future research.
Diagnosis/Classification Criteria for Behcet's Disease
Authors: Davatchi Fereydoun
Published: September 2011

Historical Background. The ISG criteria for Behcet's, created in 1990, have excellent specificity, but lack sensitivity. The International Criteria for Behcet's Disease (ICBD) was created in 2006, as replacement to ISG. The aim of this study was to compare their performance. ISG and ICBD Criteria. For ISG oral aphthosis is mandatory. The presence of any two of the following (genital aphthosis, skin lesions, eye lesions, and positive pathergy test) will diagnose/classify the patient as BD. For ICBD, vascular lesions were added, while oral aphthosis is no more mandatory. Getting 3 or more points diagnose/classify the patient as BD (genital aphthosis 2 points, eye lesions 2 points, and the remaining each one point). Performance and Comparison of ISG and ICBD. Their sensitivity, specificity, and accuracy (percent agreement), were tested in three independent cohort of patients from Far-East (China), Middle-East (Iran), and Europe (Germany). The sensitivity for ISG was respectively 65.4%, 78.1%, 83.7% and for ICBD 87%, 98.2%, and 96.5%. The specificity for ISG was 99.2%, 98.8%, 89.5% and for ICBD 94.1%, 95.6%, and 73.7%. The accuracy for ISG was 74.2%, 85.5%, 85.5% and for ICBD 88.9%, 97.3%, and 89.5%. Conclusion. ICBD has better sensitivity, and accuracy than ISG.
Understanding Methods for Estimating HIV-Associated Maternal Mortality
Authors: Rosen James E. , de Zoysa Isabelle , Dehne Karl , Mangiaterra Viviana , Abdool-Karim Quarraisha
Published: September 2011

The impact of HIV on maternal mortality and more broadly on the health of women, remains poorly documented and understood. Two recent reports attempt to address the conceptual and methodological challenges that arise in estimating HIV-related maternal mortality and trends. This paper presents and compares the methods and discusses how they affect estimates at global and regional levels. Country examples of likely patterns of mortality among women of reproductive age are provided to illustrate the critical interactions between HIV and complications of pregnancy in high-HIV-burden countries. The implications for collaboration between HIV and reproductive health programmes are discussed, in support of accelerated action to reach the Millennium Development Goals and improve the health of women.
Young's Modulus of Single-Crystal Fullerene Nanotubes
Authors: Kizuka Tokushi , Miyazawa Kun'ichi , Tokumine Takayuki
Published: September 2011

We performed bending tests on single-crystal nanotubes composed of fullerene C70molecules byin situtransmission electron microscopy with measurements of loading forces by an optical deflection method. The nanotubes with the outer diameters of 270–470 nm were bent using simple-beam and cantilever-beam loading by the piezomanipulation of silicon nanotips. Young's modulus of the nanotubes increased from 61 GPa to 110 GPa as the outer diameter decreased from 470 nm to 270 nm. Young's modulus was estimated to be 66% of that of single-crystal C60nanotubes of the same outer diameter.
MYB Is Essential for Mammary Tumorigenesis
Authors: Yu Miao Rebecca , Drabsch Yvette , Cross Ryan Stanley , Cheasley Dane , Carpinteri Sandra , Pereira Lloyd , Malaterre Jordane , Gonda Thomas J. , Anderson Robin L. , Ramsay Robert G.
Published: September 2011

MYB oncogene upregulation is associated with estrogen receptor (ER)-positive breast cancer, but disease requirements for MYB function in vivo have not been explored. In this study, we provide evidence of a critical requirement for MYB functions in models of human and murine breast cancer. In human breast cancer, we found that MYB expression was critical for tumor cell growth both in vitro and in vivo in xenograft settings. In transgenic knockout mice, tissue-specific deletion of the murine MYB gene caused a transient defect in mammary gland development that was reflected in delayed ductal branching and defective apical bud formation. In mouse mammary tumor virus (MMTV)-NEU mice where tumors are initiated by activation of HER2, MYB deletion was sufficient to abolish tumor formation. In the more aggressive MMTV-PyMT model system, MYB deletion delayed tumorigenesis significantly. Together, the findings in these transgenic knockout models implied that MYB was critical during an early window in mammary development when it was essential for tumor initiation, even though MYB loss did not exert a lasting impact upon normal mammary function. Two important MYB-target genes that promote cell survival, BCL2 and GRP78/BIP, were each elevated compared with nontransformed mammary epithelial cells, thereby promoting survival as confirmed in colony formation assays in vitro. Taken together, our findings establish a role for MYB at the hub of ER- and HER2-dependent pathways in mammary carcinogenesis. Cancer Res; 71(22); 7029–37. ©2011 AACR.
Chemotherapy Induces Intratumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T-cell Infiltration and Tumor Control
Authors: Hong Michelle , Puaux Anne-Laure , Huang Caleb , Loumagne Laure , Tow Charlene , Mackay Charles , Kato Masashi , Prévost-Blondel Armelle , Avril Marie-Françoise , Nardin Alessandra , Abastado Jean-Pierre
Published: September 2011

T-cell infiltration is known to impact tumor growth and is associated with cancer patient survival. However, the molecular cues that favor T-cell infiltration remain largely undefined. Here, using a genetically engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumor growth. Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression of these chemokines and favored T-cell infiltration into cutaneous tumors. In patients with melanoma, these chemokines were also upregulated in chemotherapy-sensitive lesions following chemotherapy, and correlated with T-cell infiltration, tumor control, and patient survival. We found that dacarbazine, temozolomide, and cisplatin induced expression of T-cell–attracting chemokines in several human melanoma cell lines in vitro. These data identify the induction of intratumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with antitumor activity. Therefore, identifying chemotherapeutic drugs able to induce the expression of T-cell–attracting chemokines in cancer cells may represent a novel strategy to improve the efficacy of cancer immunotherapy. Cancer Res; 71(22); 6997–7009. ©2011 AACR.
Molecular Imaging of TGFβ-Induced Smad2/3 Phosphorylation Reveals a Role for Receptor Tyrosine Kinases in Modulating TGFβ Signaling
Authors: Nyati Shyam , Schinske Katrina , Ray Dipankar , Nyati Mukesh , Ross Brian Dale , Rehemtulla Alnawaz
Published: September 2011

Purpose: The dual modality of TGFβ, both as a potent tumor suppressor and a stimulator of tumor progression, invasion, and metastasis, make it a critical target for therapeutic intervention in human cancers. The ability to carry out real-time, noninvasive imaging of TGFβ-activated Smad signaling in live cells and animal models would significantly improve our understanding of the regulation of this unique signaling cascade. To advance these efforts, we developed a highly sensitive molecular imaging tool that repetitively, noninvasively, and dynamically reports on TGFBR1 kinase activity.

Experimental Design: The bioluminescent TGFβR1 reporter construct was developed using a split firefly luciferase gene containing a functional sensor of Smad2 phosphorylation, wherein inhibition of TGFβ receptor1 kinase activity leads to an increase in reporter signaling. The reporter was stably transfected into mammalian cells and used to image in vivo and in vitro bioluminescent activity as a surrogate for monitoring TGFBR1 kinase activity.

Results: The reporter was successfully used to monitor direct and indirect inhibition of TGFβ-induced Smad2 and SMAD3 phosphorylation in live cells and tumor xenografts and adapted for high-throughput screening, to identify a role for receptor tyrosine kinase inhibitors as modulators of TGFβ signaling.

Conclusion: The reporter is a dynamic, noninvasive imaging modality for monitoring TGFβ-induced Smad2 signaling in live cells and tumor xenografts. It has immense potential for identifying novel effectors of R-Smad phosphorylation, for validating drug–target interaction, and for studying TGFβ signaling in different metastasis models. Clin Cancer Res; 17(23); 7424–39. ©2011 AACR.