bluuebunny/crossref_metadata_2025 huggingface dataset:
Comment on “The Incidence of Fire in Amazonian Forests with Implications for REDD”
Authors: Balch Jennifer K. , Nepstad Daniel C. , Brando Paulo M. , Alencar Ane
Published: December 2010

Aragão and Shimabukuro (Reports, 4 June 2010, p. 1275) reported that fires increase in agricultural frontiers even as deforestation decreases and concluded that these fires lead to unaccounted carbon emissions under the United Nations climate treaty's tropical deforestation and forest degradation component. Emissions from post-deforestation management activities are, in fact, included in these estimates—but burning of standing forests is not.
Electronic Spin Storage in an Electrically Readable Nuclear Spin Memory with a Lifetime >100 Seconds
Authors: McCamey D. R. , Van Tol J. , Morley G. W. , Boehme C.
Published: December 2010

Spin Control

Controlling and manipulating the spin of an electron is a central requirement for applications in spintronics. Some of the challenges researchers are facing include efficient creation of spin currents, minimization of Joule heating, and extending the lifetime of electronic spins, which is especially important for quantum information applications.
Costache and Valenzuela
(p.
1645
) address the first challenge by designing and fabricating an efficient and simple superconducting-based single-electron transistor that can produce spin current with controlled flow. Key to the design is asymmetric tunneling, which leads to a ratchet effect (or diode-like behavior), allowing the separation of up and down spins.

Jonietz
et al.

(p.
1648
) use electric currents five orders of magnitude smaller than those used previously in nanostructures to manipulate magnetization in a bulk material, MnSi, pointing the way toward decreased Joule heating in spintronic devices. This so-called spin-torque effect causes the rotation of the skyrmion lattice of spins, characteristic of MnSi, which is detected by neutron scattering. Finally,

McCamey
et al.

(p.
1652
) extend the short lifetime of an electronic spin of a phosphorous dopant by mapping it onto the much longer lived nuclear spin of the atom. Mapping the nuclear spin back onto the electronic spin allows production of a spin memory with a storage time exceeding 100s, which should prove useful for future practical applications.
Catalyzing NO to N
2
O in the Nitrogen Cycle
Authors: Moënne-Loccoz Pierre , Fee James A.
Published: December 2010

A structure for the bacterial enzyme cNOR reveals a biochemical mechanism driving nitrous oxide emissions.
Have You Seen Your Mother, Baby…
Authors: Betz Alexander G.
Published: December 2010

T cell development occurs in waves, involving distinct stem cell populations, throughout human fetal development.
Is the Frontier Really Endless?
Authors: Alberts Bruce
Published: December 2010

In this issue, the news team at
Science
names its annual breakthrough of the year (see p. 1604). This year the honor goes to the first quantum machine—a microscopic cantilever ingeniously lowered to its lowest possible energy, the quantum ground state. The result may lead to ultrasensitive force detectors and to ways of controlling an object's mechanical vibrations as deftly as we now control electricity and light. It also heralds further investigations of one of the great mysteries of physics: the chasm separating the world of familiar objects from the bizarre realm of quantum mechanics.
Genetic Analysis Points the Way to Individualized PSA Tests
Authors: Couzin-Frankel Jennifer
Published: December 2010

Some men with high levels of prostate-specific antigen don't have prostate cancer, leading to unnecessary biopsies, and some with low PSA levels do. This week, a group in Iceland suggests individualizing healthy and high levels for each man tested by focusing on genetic variants that affect PSA levels.
Diving Into the Oil Spill
Authors: Stokstad Erik
Published: December 2010

Through improved communication, researchers ultimately helped devise ways to deal with the leaking oil well in the Gulf of Mexico this year and assessed the scale of the spill.
The Year in News
Authors: Mervis Jeffrey
Published: December 2010

2010 was a busy year for science and science policy.
Science
lists some developments that tested the limits of our knowledge and influenced thinking about the global research enterprise.
Body's Hardworking Microbes Get Some Overdue Respect
Authors: Pennisi Elizabeth
Published: December 2010

This past decade has seen a shift in how we see the microbes and viruses in and on our bodies, most of which are commensal and just call the human body home; collectively, they have come to be called the human microbiome.
Inflammation Bares a Dark Side
Authors: Couzin-Frankel Jennifer
Published: December 2010

Over the past decade, it has become widely accepted that inflammation is a driving force behind chronic diseases that will kill nearly all of us: cancer, diabetes and obesity, Alzheimer's disease, and atherosclerosis.
Climatologists Feel the Heat As Science Meets Politics
Authors: Kerr Richard A. , Kintisch Eli
Published: December 2010

In the past few years, climate scientists finally agreed that the world is indeed warming, humans are behind it, and natural processes are unlikely to rein it in—just as they had suspected.
Toll-Like Receptor 4 Gene (
TLR4
), but Not
TLR2
, Polymorphisms Modify the Risk of Tonsillar Disease Due to
Streptococcus pyogenes
and
Haemophilus influenzae
Authors: Liadaki Kyriaki , Petinaki Efthimia , Skoulakis Charalampos , Tsirevelou Paraskeui , Klapsa Dimitra , Germenis Anastasios E. , Speletas Matthaios
Published: December 2010

Tonsillar disease (recurrent tonsillitis and/or tonsillar hypertrophy) is one of the most common human disorders, with
Streptococcus pyogenes
(group A beta-hemolytic streptococcus [GAS]) and
Haemophilus influenzae
representing the most common pathogens. Until now, no study has investigated why some individuals are more susceptible to tonsillar infections caused by specific bacteria than others. The aim of this study was to uncover possible associations between common Toll-like receptor gene (
TLR
) polymorphisms and tonsillar disease. The
TLR2
-R753Q,
TLR4
-D299G, and
TLR4
-T399I polymorphisms were determined in a cohort of 327 patients subjected to tonsillectomy due to recurrent tonsillitis (
n
= 245) and tonsillar hypertrophy (
n
= 82) and 245 healthy bone marrow donors. Associations of the aforementioned polymorphisms with the isolated bacterial strains after tonsillectomy were also investigated. Interestingly, carriers of the
TLR4
polymorphisms displayed an approximately 3-fold increased risk for GAS infections (for
TLR4
-D299G, odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.16 to 6.79,
P
= 0.038; for
TLR4
-T399I, OR = 3.01, 95% CI = 1.29 to 7.02,
P
= 0.023), and this association was more profound in patients with recurrent tonsillitis. On the contrary, the presence of the
TLR4
-T399I polymorphism was associated with a 2-fold decreased risk of
Haemophilus influenzae
carriage (OR = 0.38, 95% CI = 0.15 to 0.96,
P
= 0.038). In the end, no significant differences were observed, considering the genotype and allele frequencies of the above-mentioned polymorphisms, between patients and controls. Our findings indicate that, regarding tonsillar infections,
TLR4
polymorphisms predispose individuals to GAS infection, while they are protective against
Haemophilus influenzae
infection. This result further elucidates the role that host immune genetic variations might play in the susceptibility to common infections and tonsillar disease.
Persistence of
Leishmania donovani
Antibodies in Past Visceral Leishmaniasis Cases in India
Authors: Gidwani Kamlesh , Picado Albert , Ostyn Bart , Singh Shri Prakash , Kumar Rajiv , Khanal Basudha , Lejon Veerle , Chappuis François , Boelaert Marleen , Sundar Shyam
Published: December 2010

The persistence of anti-
Leishmania donovani
antibodies in past visceral leishmaniasis (VL) cases was retrospectively assessed by means of the direct agglutination test (DAT) and the rK39 enzyme-linked immunosorbent assay (ELISA). Antibody titers remained high for an extended period of time in past cases of VL. These results highlight the need to carefully elicit the history of patients with VL symptoms.
Molecular Determination of H Antigens of Salmonella by Use of a Microsphere-Based Liquid Array
Authors: McQuiston John R. , Waters R. Jordan , Dinsmore Blake A. , Mikoleit Matthew L. , Fields Patricia I.
Published: December 2010

Serotyping of
Salmonella
has been an invaluable subtyping method for epidemiologic studies for more than 70 years. The technical difficulties of serotyping, primarily in antiserum production and quality control, can be overcome with modern molecular methods. We developed a DNA-based assay targeting the genes encoding the flagellar antigens (
fliC
and
fljB
) of the Kauffmann-White serotyping scheme. Fifteen H antigens (H:a, -b, -c, -d, -d/j, -e,h, -i, -k, -r, -y, -z, -z
10
, -z
29
, -z
35
, and -z
6
), 5 complex major antigens (H:G, -EN, -Z4, -1, and -L) and 16 complex secondary antigens (H:2, -5, -6, -7, -f, -m/g,m, -m/m,t, -p, -s, -t/m,t, -v, -x, -z
15
, -z
24
, -z
28
, and -z
51
) were targeted in the assay. DNA probes targeting these antigens were designed and evaluated on 500 isolates tested in parallel with traditional serotyping methods. The assay correctly identified 461 (92.2%) isolates based on the 36 antigens detected in the assay. Among the isolates considered correctly identified, 47 (9.4%) were partially serotyped because probes corresponding to some antigens in the strains were not in the assay, and 13 (2.6%) were monophasic or nonmotile strains that possessed flagellar antigen genes that were not expressed but were detected in the assay. The 39 (7.8%) strains that were not correctly identified possessed an antigen that should have been detected by the assay but was not. Apparent false-negative results may be attributed to allelic divergence. The molecular assay provided results that paralleled traditional methods with a much greater throughput, while maintaining the integrity of the Kauffmann-White serotyping scheme, thus providing backwards-compatible epidemiologic data. This assay should greatly enhance the ability of clinical and public health laboratories to serotype
Salmonella
.
Clinically Healthy Skin of Dogs Is a Potential Reservoir for Canine Papillomaviruses
Authors: Lange Christian E. , Zollinger Sabrina , Tobler Kurt , Ackermann Mathias , Favrot Claude
Published: December 2010

Papillomaviruses have been linked to several skin disorders in the dog. In order to have a suitable diagnostic tool for canine papillomavirus detection, eight PCRs with published primer combinations were evaluated. The most sensitive PCR was used to demonstrate that papillomavirus DNA can be detected on nonlesional skin of dogs.
Beyond the Consensus: Dissecting Within-Host Viral Population Diversity of Foot-and-Mouth Disease Virus by Using Next-Generation Genome Sequencing
Authors: Wright Caroline F. , Morelli Marco J. , Thébaud Gaël , Knowles Nick J. , Herzyk Pawel , Paton David J. , Haydon Daniel T. , King Donald P.
Published: December 2010

The diverse sequences of viral populations within individual hosts are the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence of the inoculum determined by NGS was identical to that previously determined using the Sanger method. However, NGS revealed the fine polymorphic substructure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher-frequency polymorphisms identified encoded changes within codons associated with heparan sulfate binding and were present in both foot lesions, revealing intermediate stages in the evolution of a tissue culture-adapted virus replicating within a mammalian host. We identified 2,622, 1,434, and 1,703 polymorphisms in the inoculum and in the two foot lesions, respectively: most of the substitutions occurred in only a small fraction of the population and represented the progeny from recent cellular replication prior to onset of any selective pressures. We estimated the upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 × 10
−4
per nucleotide. The greater depth of detection achieved by NGS demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within hosts.
Serotype-Specific Inactivation of the Cellular DNA Damage Response during Adenovirus Infection
Authors: Forrester Natalie A. , Sedgwick Garry G. , Thomas Anoushka , Blackford Andrew N. , Speiseder Thomas , Dobner Thomas , Byrd Philip J. , Stewart Grant S. , Turnell Andrew S. , Grand Roger J. A.
Published: December 2010

Adenovirus type 5 (Ad5) inactivates the host cell DNA damage response by facilitating the degradation of Mre11, DNA ligase IV, and p53. In the case of p53, this is achieved through polyubiquitylation by Ad5E1B55K and Ad5E4orf6, which recruit a Cul5-based E3 ubiquitin ligase. Recent evidence indicates that this paradigm does not apply to other adenovirus serotypes, since Ad12, but not Ad5, causes the degradation of TOPBP1 through the action of E4orf6 alone and a Cul2-based E3 ubiquitin ligase. We now have extended these studies to adenovirus groups A to E. While infection by Ad4, Ad5, and Ad12 (groups E, C, and A, respectively) cause the degradation of Mre11, DNA ligase IV, and p53, infection with Ad3, Ad7, Ad9, and Ad11 (groups B1, B1, D, and B2, respectively) only affects DNA ligase IV levels. Indeed, Ad3, Ad7, and Ad11 cause the marked accumulation of p53. Despite this, MDM2 levels were very low following infection with all of the viruses examined here, regardless of whether they increase p53 expression. In addition, we found that only Ad12 causes the degradation of TOPBP1, and, like Ad5, Ad4 recruits a Cul5-based E3 ubiquitin ligase to degrade p53. Surprisingly, Mre11 and DNA ligase IV degradation do not appear to be significantly affected in Ad4-, Ad5-, or Ad12-infected cells depleted of Cul2 or Cul5, indicating that E1B55K and E4orf6 recruit multiple ubiquitin ligases to target cellular proteins. Finally, although Mre11 is not degraded by Ad3, Ad7, Ad9, and Ad11, no viral DNA concatemers could be detected. We suggest that group B and D adenoviruses have evolved mechanisms based on the loss of DNA ligase IV and perhaps other unknown molecules to disable the host cell DNA damage response to promote viral replication.
Deerpox Virus Encodes an Inhibitor of Apoptosis That Regulates Bak and Bax
Authors: Banadyga Logan , Lam Sing-Chi , Okamoto Toru , Kvansakul Marc , Huang David C. , Barry Michele
Published: December 2010

Poxviruses encode numerous proteins that inhibit apoptosis, a form of cell death critical to the elimination of virally infected cells. Sequencing of the deerpox virus genome revealed DPV022, a protein that lacks obvious homology to cellular members of the Bcl-2 family but shares limited regions of amino acid identity with two unique poxviral inhibitors of apoptosis, M11L and F1L. Given the limited homology, we sought to determine whether DPV022 could inhibit apoptosis. Here we show that DPV022 localized to the mitochondria, where it inhibited apoptosis. We used a
Saccharomyces cerevisiae
model system to demonstrate that in the absence of all other Bcl-2 family proteins, DPV022 interacted directly with Bak and Bax. We confirmed the ability of DPV022 to interact with Bak and Bax by immunoprecipitation and showed that DPV022 prevented apoptosis induced by Bak and Bax overexpression. Moreover, we showed that DPV022 blocked apoptosis even when all the endogenous mammalian antiapoptotic proteins were neutralized by a combination of selective BH3 ligands. During virus infection, DPV022 interacted with endogenous Bak and Bax and prevented the conformational activation of both of them. Thus, we have characterized a novel poxviral inhibitor of apoptosis with intriguing amino acid differences from the well-studied proteins M11L and F1L.
Palmitoylation of MIR2 Is Required for Its Function
Authors: Anania Veronica G. , Coscoy Laurent
Published: December 2010

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two RING finger E3 ubiquitin ligases (MIR1 and MIR2) that mediate ubiquitination and degradation of cellular proteins important for the establishment of an efficient antiviral immune response. MIR1 and MIR2 share 30% sequence identity; however, their substrate preferences are varied. MIR1 has been shown to primarily downregulate major histocompatibility complex class I (MHC-I), whereas MIR2 can downregulate a wide range of cell surface proteins. Many of the MIR substrates are thought to be present in lipid raft microdomains, a subregion of the plasma membrane known to be important for a wide range of signal transduction events. Palmitoylation is a posttranslational modification that increases recruitment of transmembrane proteins to lipid rafts. In this study, we investigated the importance of palmitoylation for MIR function. We present evidence that MIR2-mediated downregulation of MHC-I and platelet endothelial cell adhesion molecule 1 (PECAM-1) but not other substrates is inhibited in the presence of the drug 2-bromohexadecanoic acid (2-Br), a chemical inhibitor of palmitoylation. Biochemical analysis indicates that MIR2 is directly palmitoylated on cysteine 146. Mutation of this cysteine to a phenylalanine prevents MIR2 palmitoylation and blocks the ability of MIR2 to downregulate MHC-I and PECAM-I but not B7.2 and intercellular adhesion molecule 1 (ICAM-I), consistent with the phenotype observed after 2-Br treatment. Unpalmitoylated MIR2 does not interact with MHC-I and is thus unable to ubiquitinate and downregulate MHC-I from the cell surface. Furthermore, we observed that MIR2 is palmitoylated
in vivo
during lytic infection. Palmitoylation may act to regulate MIR2 function and localization during viral infection by allowing MIR2 to properly interact with and downregulate multiple substrates known to play an important role in the host immune response.
A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop To Prime Low CD4 Use and Macrophage Infection
Authors: Musich Thomas , Peters Paul J. , Duenas-Decamp Maria José , Gonzalez-Perez Maria Paz , Robinson James , Zolla-Pazner Susan , Ball Jonathan K. , Luzuriaga Katherine , Clapham Paul R.
Published: December 2010

The CD4 binding site (CD4bs) on the HIV-1 envelope plays a major role in determining the capacity of R5 viruses to infect primary macrophages. Thus, envelope determinants within or proximal to the CD4bs have been shown to control the use of low CD4 levels on macrophages for infection. These residues affect the affinity for CD4 either directly or indirectly by altering the exposure of CD4 contact residues. Here, we describe a single amino acid determinant in the V1 loop that also modulates macrophage tropism. Thus, we identified an E153G substitution that conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop monoclonal antibody (MAb), 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12. These observations are consistent with an altered conformation or exposure of the V3 loop that enables the envelope to use low CD4 levels for infection. The modest shifts in b12 sensitivity suggest that residue 153 impacts on the exposure of the CD4bs. However, the more intense shifts in sCD4 sensitivity suggest additional mechanisms that likely include an increased ability of the envelope to undergo conformational changes following binding to suboptimal levels of cell surface CD4. In summary, we show that a conserved determinant in the V1 loop modulates the V3 loop to prime low CD4 use and macrophage infection.
Facebook activity of residents and fellows and its impact on the doctor–patient relationship
Authors: Moubarak Ghassan , Guiot Aurélie , Benhamou Ygal , Benhamou Alexandra , Hariri Sarah
Published: December 2010

Aim

Facebook is an increasingly popular online social networking site. The purpose of this study was to describe the Facebook activity of residents and fellows and their opinions regarding the impact of Facebook on the doctor–patient relationship.

Methods

An anonymous questionnaire was emailed to 405 residents and fellows at the Rouen University Hospital, France, in October 2009.

Results

Of the 202 participants who returned the questionnaire (50%), 147 (73%) had a Facebook profile. Among responders, 138 (99%) displayed their real name on their profile, 136 (97%) their birthdates, 128 (91%) a personal photograph, 83 (59%) their current university and 76 (55%) their current position. Default privacy settings were changed by 61% of users, more frequently if they were registered for >1 year (p=0.02). If a patient requested them as a ‘friend’, 152 (85%) participants would automatically decline the request, 26 (15%) would decide on an individual basis and none would automatically accept the request. Eighty-eight participants (48%) believed that the doctor–patient relationship would be altered if patients discovered that their doctor had a Facebook account, but 139 (76%) considered that it would change only if the patient had open access to their doctor's profile, independent of its content.

Conclusions

Residents and fellows frequently use Facebook and display personal information on their profiles. Insufficient privacy protection might have an impact the doctor–patient relationship.
Electrocardiography of the normal domestic pet rabbit
Authors: Lord B. , Boswood A. , Petrie A.
Published: December 2010

To establish a well‐tolerated technique for recording electrocardiograms (ECGs) and a reference range for the normal pet rabbit ECG, 46 healthy pet rabbits were studied. The following reference ranges were calculated. Heart rate was 198 to 330 bpm. P waves had a duration of 0.01 to 0.05 seconds and an amplitude of 0.04 to 0.12 mV. The P‐R interval was 0.04 to 0.08 seconds and the duration of the QRS complex was 0.02 to 0.06 seconds. The amplitude of the R wave was 0.03 to 0.39 mV. The Q‐T interval was 0.08 to 0.16 seconds. The amplitude of the T wave was 0.05 to 0.17 mV. Mean electrical axis was found to be −43° to +80°. Evidence of variation due to breed or bodyweight was not found to be significant, except for a quadratic relationship between R wave amplitude and bodyweight. The ECG recording technique used in this study for pet rabbits was well tolerated and shown to be both reliable and repeatable.
U–Pb Neoproterozoic–Ordovician protolith age constraints for high- to medium-pressure rocks thrust over low-grade metamorphic rocks in theIxcamilpa area, Acatlán Complex, southern Mexico
Authors: Ramos-Arias M. A. , Keppie J. D.
Published: December 2010

High-grade and high-pressure rocks in Acatlán Complex (southern Mexico) are inferred to have been emplaced either during the convergence and collision between Laurentia and Gondwana or during subduction on the western margin of Pangea. In the Ixcamilpa area, such rocks occur in a synformal nappe and are subdivided into (1) the Neoproterozoic–Ordovician Piaxtla Suite (metapsammite, meta-pelite, and amphibolite) that passes structurally upwards from blueschist through eclogite to amphibolite facies; intruded by (2) Cambro-Ordovician megacrystic granitoids; both of which were thrust westwards over (3) the Carboniferous Zumpango Unit consisting of clastic and meta-volcanic rocks. Laser ablation – inductively coupled plasma – mass spectrometry (LA–ICP–MS) U–Pb zircon geochronology yielded age population peaks at (i) 435–490 Ma, probably derived from Acatlán granitoids; (ii) 500–700 Ma, likely derived from the Yucatan Peninsula and Brasiliano orogens; (iii) 800–900 Ma, with provenance in the Goiás arc of eastern Amazonia; and (iv) 950–1300 Ma, sourced either from Oaxaquia, Amazonia, or Laurentia: the younger ca. 310–360 Ma ages are limited to the Zumpango Unit and likely have a local provenance. The overall similarity of the Piaxtla rocks in the Ixcamilpa area and those in the Piaxtla-Mimilulco median belt suggests that Ixcamilpa nappe roots in the median belt, which is interpreted as an extrusion zone within the Acatlán Complex. Since neither high-pressure belt represents a closed ocean, deposition of the Neoproterozoic–Ordovician rocks is inferred to have taken place on the southern margin of Rheic Ocean adjacent to Oaxaquia–Amazonia, whereas the Carboniferous rocks were deposited on the western margin of Pangea synchronous with extrusion of the high-pressure rocks.
Numerical modeling of underwater rockfalls
Authors: Turmel Dominique , Locat Jacques
Published: December 2010

A marine environment presents various settings where talus slopes are formed via gravity-driven rockfall processes similar to those existing on land. This is the case along fjords or submarine canyons, where submarine installations or natural sanctuaries, such as coral reefs, need to be protected. In submarine rockfall analysis, the effect of the ambient fluid, in addition to hydrodynamic constraints and water currents, must be considered. A finite volume model has been developed to model two-dimensional rockfall behaviour in a Newtonian fluid, such as water or air. Turbulent and incompressible flow around the moving rock is described with a pressure–velocity iterative method on a dynamic three-dimensional unstructured mesh of polyhedral cells. Pressure, shear, and turbulent forces are then applied to the moving rock. In this paper, we compare underwater rockfall behaviour with air rockfall behaviour in three different situations: free fall, bouncing on a horizontal plane, and bouncing on an inclined plane. A true-scale experiment has been conducted to validate the model. The results of various modeling suggest that, contrary to the air case, the speed of the blocks will be strongly influenced by the block density and volume.
Field investigation of a suction break designed to control slope-induced desaturation in an oxygen barrier
Authors: Maqsoud Abdelkabir , Bussière Bruno , Aubertin Michel , Chouteau Michel , Mbonimpa Mamert
Published: December 2010

Covers with capillary barrier effects (CCBEs) can be used as oxygen barriers to limit gas flux into waste disposal sites. Laboratory and field measurements show that the hydraulic behaviour of such a layered cover system is influenced by its slope geometry and gravity drainage, which can result in local desaturation that may be detrimental to cover performance. Such desaturation can be minimized by placing a suction break in the moisture-retaining layer of the inclined cover. This novel approach was applied in the field to an existing inclined CCBE. The three-layer cover was then subjected to different boundary conditions to evaluate the influence of the suction break on hydraulic behaviour. Volumetric water content and suction measurements demonstrated that a zone of water saturation and low suction was created upslope of the suction break under natural climatic conditions. The hydrological behaviour close to the suction break was not significantly affected by a forced drought of 78 days (without water infiltration). The results also reveal that the suction break had a relatively limited upslope zone of influence (typically less than 10 m). The monitoring results are confirmed by geophysical measurements used to characterize water distribution in the inclined CCBE.
EXTENSION OF THE POINCARÉ GROUP AND NON-ABELIAN TENSOR GAUGE FIELDS
Authors: SAVVIDY GEORGE
Published: December 2010

In the recently proposed generalization of the Yang–Mills theory, the group of gauge transformation gets essentially enlarged. This enlargement involves a mixture of the internal and space–time symmetries. The resulting group is an extension of the Poincaré group with infinitely many generators which carry internal and space–time indices.

The matrix representations of the extended Poincaré generators are expressible in terms of Pauli–Lubanski vector in one case and in terms of its invariant derivative in another. In the later case the generators of the gauge group are transversal to the momentum and are projecting the non-Abelian tensor gauge fields into the transversal plane, keeping only their positively definite spacelike components.
A SEASONALLY FORCED EPIDEMIC MODEL WITH TARGETED ANTIVIRAL PROPHYLAXIS
Authors: QIU ZHIPENG
Published: December 2010

In this paper, we propose a mathematical model to describe the transmission dynamics of infectious diseases with targeted antiviral prophylaxis strategy. Our model incorporates seasonal driving force since seasonal force has a great effect on the spread of infectious diseases. Based on the local stability of disease free equilibrium we derive the control reproduction number [Formula: see text]. Sufficient conditions for the global stability of the disease free equilibrium are obtained. Using the persistence theory for discrete dynamical system, we prove that the infectious disease will remain endemic if [Formula: see text]. Simulation results are also provided to study the effect of targeted antiviral prophylaxis on transmission dynamics of infectious disease and investigate the influence of seasonality on the efficiency of targeted antiviral prophylaxis strategy.
Phosphorylation of radixin regulates cell polarity and Mrp-2 distribution in hepatocytes
Authors: Suda Jo , Zhu Lixin , Karvar Serhan
Published: December 2010

Radixin, the dominant ezrin-radixin-moesin (ERM) protein in hepatocytes, has two important binding domains: an NH2-terminal region that binds to plasma membrane and a COOH-terminal region that binds to F-actin after a conformational activation by phosphorylation at Thr564. The present studies were undertaken to investigate the cellular changes in expression of radixin in WIF-B cells and to assess radixin distribution and its influence on cell polarity. We used a recombinant adenoviral expression system encoding radixin wild-type and Thr564 mutants fused to cyan fluorescent protein (CFP), as well as conventional immunostaining procedures. Functional analyses were characterized quantitatively. Similar to endogenous radixin, adenovirus-infected radixin-CFP-wild type and nonphosphorylatable radixin-CFP-T564A were found to be expressed heavily in the compartment of canalicular membrane vacuoles, typically colocalizing with multidrug resistance-associated protein 2 (Mrp-2). Expression of radixin-CFP-T564D, which mimics constant phosphorylation, was quite different, being rarely associated with canalicular membranes. The WIF-B cells were devoid of a secretory response, T567D radixin became predominantly redistributed to the basolateral membrane, usually in the form of dense, long spikes and fingerlike projections, and the altered cell polarity involved changes in apical membrane markers. Differences in polar distribution of radixin suggest a role for the linker protein in promoting formation and plasticity of membrane surface projections and also suggest that radixin might be an organizer and regulator of Mrp-2 and cell polarity in hepatocytes.
Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice
Authors: Becker Luis E. , Koleganova Nadezda , Piecha Grzegorz , Noronha Irene L. , Zeier Martin , Geldyyev Aman , Kökeny Gabor , Ritz Eberhard , Gross Marie-Luise
Published: December 2010

Despite an only minor reduction in the glomerular filtration rate, uninephrectomy (UNX) markedly accelerates the rate of growth of atherosclerotic plaques in ApoE−/− mice. It has been suggested that vitamin D receptor (VDR) activation exerts an antiproliferative effect on vascular smooth muscle cells, but the side effects may limit its use. To assess a potentially different spectrum of actions, we compared the effects of paricalcitol and calcitriol on remodeling and calcification of the aortic wall in sham-operated and UNX ApoE−/− mice on a diet with normal cholesterol content. Sham-operated and UNX mice were randomly allotted to treatment with solvent, calcitriol (0.03 μg/kg) or paricalcitol (0.1 μg/kg) 5 times/wk intraperitoneally for 10 wk. Semithin (0.6 μm) sections of the aorta were analyzed by 1) morphometry, 2) immunohistochemistry, and 3) Western blotting of key proteins involved in vascular calcification and growth. Compared with sham-operated animals (5.6 ± 0.24), the wall-to-lumen ratio (x100) of the aorta was significantly higher in solvent- and calcitriol-treated UNX animals (6.64 ± 0.27 and 7.17 ± 0.81, respectively, P < 0.05), but not in paricalcitol-treated UNX (6.1 5 ± 0.32). Similar differences were seen with respect to maximal plaque height. Expression of transforming growth factor (TGF)-β1 in aortic intima/plaque was also significantly higher in UNX solvent and UNX calcitriol compared with sham-operated and UNX paricalcitol animals. Treatment with both paricalcitol and calcitriol caused significant elevation of VDR expression in the aorta. While at the dose employed paricalcitol significantly reduced TGF-β expression in plaques, calcitriol in contrast caused significant vascular calcification and elevated expression of related proteins (BMP2, RANKL, and Runx2).
Encoding of Eye Position in the Goldfish Horizontal Oculomotor Neural Integrator
Authors: Debowy Owen , Baker Robert
Published: December 2010

Monocular organization of the goldfish horizontal neural integrator was studied during spontaneous scanning saccadic and fixation behaviors. Analysis of neuronal firing rates revealed a population of ipsilateral (37%), conjugate (59%), and contralateral (4%) eye position neurons. When monocular optokinetic stimuli were employed to maximize disjunctive horizontal eye movements, the sampled population changed to 57, 39, and 4%. Monocular eye tracking could be elicited at different gain and phase with the integrator time constant independently modified for each eye by either centripetal (leak) or centrifugal (instability) drifting visual stimuli. Acute midline separation between the hindbrain oculomotor integrators did not affect either monocularity or time constant tuning, corroborating that left and right eye positions are independently encoded within each integrator. Together these findings suggest that the “ipsilateral” and “conjugate/contralateral” integrator neurons primarily target abducens motoneurons and internuclear neurons, respectively. The commissural pathway is proposed to select the conjugate/contralateral eye position neurons and act as a feedfoward inhibition affecting null eye position, oculomotor range, and saccade pattern.
Tunga Penetrans: Painful Lesions on the Feet—The First Imported Case from Guinea-Bissau
Authors: Rosmaninho A. , Vilaça S. , Costa V. , Sarmento A. , Amorim I. , Selores M.
Published: December 2010

Tungiasis is an endemic disease in certain poor areas around the world. Imported infestations in travelers are becoming more frequent and can lead to considerable morbidity. We report a case of a 50 year-old-man who returned from a trip to Guinea-Bissau with an infection caused byTunga penetrans.
CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy
Authors: Saif Muhammad Wasif , Makrilia Nektaria , Syrigos Kostas
Published: December 2010

Intracellular reduced folate exists as a “pool” of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH2THF), is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS). This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU) exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV) has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl)-5,10,-methylenepteroyl-monoglutamate calcium salt) is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies.
The Impact of Insurance on Access to Cancer Clinical Trials at a Comprehensive Cancer Center
Authors: Klamerus Justin F. , Bruinooge Suanna S. , Ye Xiaobu , Klamerus Mandi L. , Damron Dorothy , Lansey Dina , Lowery John C. , Diaz Luis A. , Ford Jean G. , Kanarek Norma , Rudin Charles M.
Published: December 2010

Purpose: Cancer patients at Johns Hopkins undergo insurance clearance to verify coverage for enrollment to interventional clinical trials. We sought to explore the impact of insurance clearance on disparities in access to cancer clinical trials at this urban comprehensive cancer center.

Experimental Design: We evaluated the frequency of insurance-based denial of access to cancer clinical trials over a 5-year period after initiation of a formal insurance clearance process. We used a case-control design to compare demographic and clinical parameters of patients denied or approved for clinical trials participation by their insurance company in a 3-year interval.

Results: From July 2003 to July 2008, insurance requests for clinical trial participation were submitted on 4,617 consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with health insurance were denied therapeutic trial enrollment owing to lack of insurance coverage for participation. A total of 254 patients denied enrollment from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly selected patients approved for clinical trial participation served as controls. Patients approved were on average older (59.2 versus 54.9 years) than patients denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating cancer clinical trial coverage for residents, were overrepresented among the denied patients (P = 0.0009). No statistically significant variance in the likelihood of insurance denial was found on the basis of sex, race, stage of disease, or presence of comorbidities.

Conclusions: Denial of access to therapeutic clinical trials, even among insured patients, is a significant barrier to clinical cancer research. This barrier spans racial, ethnic, and gender categories. Clin Cancer Res; 16(24); 5997–6003. ©2010 AACR.
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Authors: Aziz Saadia A. , Jilaveanu Lucia B. , Zito Christopher , Camp Robert L. , Rimm David L. , Conrad Patricia , Kluger Harriet M.
Published: December 2010

Purpose: Melanoma is relatively resistant to chemotherapy; improved targeting of molecules critical for cell proliferation and survival are needed. Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K.

Methods: Using a method of quantitative immunofluorescence to measure mTOR expression in a large melanoma cohort, we studied associations with PI3K subunits, p85 and p110α. We assessed addition of the mTOR inhibitor rapamycin to 2 PI3KIs, NVP-BKM120 and LY294002. We studied in vitro activity of a novel dual PI3K/mTOR inhibitor NVP-BEZ235 and activity of the combination of NVP-BEZ235 and the MAP/ERK kinase (MEK) inhibitor AZD6244.

Results: Strong coexpression of mTOR and p110α was observed (ρ = 0.658; P < 0.0001). Less coexpression was seen with p85 (ρ = 0.239; P < 0.0001). Strong synergism was shown between rapamycin and both PI3KIs. Activity of both PI3KIs was similarly enhanced with all rapamycin concentrations used. The dual PI3K/mTOR inhibitor effectively inhibited viability in 23 melanoma cell lines (IC50 values in the nanomolar range), regardless of B-Raf mutation status, with resultant reduction in clonogenicity and downregulation of pAkt and pP70S6K. Synergism was seen when combining NVP-BEZ235 and AZD6244, with resultant increases in poly(ADP-ribose) polymerase and caspase-2 cleavage.

Conclusions: mTOR and p110α are coexpressed in melanoma. Rapamycin concentrations as low as 1 nmol/L enhance activity of PI3KIs. The dual PI3K/mTOR inhibitor NVP-BEZ235 is highly active in melanoma cells in vitro, suggesting that concurrent PI3K and mTOR targeting in melanoma warrants further investigation, both alone and in combination with MEK inhibitors.
Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study
Authors: O'Brien Katie M. , Cole Stephen R. , Tse Chiu-Kit , Perou Charles M. , Carey Lisa A. , Foulkes William D. , Dressler Lynn G. , Geradts Joseph , Millikan Robert C.
Published: December 2010

Purpose: Previous research identified differences in breast cancer–specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2+/ER−).

Experimental Design: We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years.

Results: Cancer subtypes luminal A, luminal B, basal-like, and HER2+/ER− were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2+/ER− and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer–specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2–3.4) than African Americans (HR = 1.5, 95% CI: 1.0–2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5–10.0).

Conclusions: Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. Clin Cancer Res; 16(24); 6100–10. ©2010 AACR.
Evaluating Patient-Centered Outcomes in the Randomized Controlled Trial and Beyond: Informing the Future with Lessons from the Past
Authors: Booth Christopher M.
Published: December 2010

In the era of molecular oncology, patients still define a useful therapy as one that allows them to live longer and helps them to live better. Although patient outcomes have clearly improved as a result of randomized controlled trials (RCT), it is critical that contemporary trials retain the perspective of these fundamental patient-centered outcomes. Trends in study design, results, and interpretation of oncology RCTs from the past provide a useful framework in which to consider how the research community may approach trial design in the future. Although the RCT remains the standard for establishing efficacy, this article also considers how population-based outcome studies can provide insight into effectiveness of new therapies and explores how the results of RCTs translate into benefit in the general population. Clin Cancer Res; 16(24); 5963–71. ©2010 AACR.
Aerosolized Bexarotene Inhibits Lung Tumorigenesis without Increasing Plasma Triglyceride and Cholesterol Levels in Mice
Authors: Zhang Qi , Pan Jing , Zhang Jingjie , Liu Pengyuan , Chen Ruth , Chen Da-ren , Lubet Ronald , Wang Yian , You Ming
Published: December 2010

Prior studies have shown the retinoid X receptor (RXR) agonist bexarotene has preventive efficacy in rodent models of mammary and lung tumorigenesis albeit causing hypertriglyceridemia and hypercholesterolemia. We reasoned that bexarotene delivered by inhalation may provide sufficient dose directly to the respiratory tract to achieve efficacy while avoiding these side effects. In this study, the chemopreventive activity of aerosolized bexarotene was investigated in the benzo(a)pyrene [B(a)P]-induced mouse lung tumor model as assessed by tumor multiplicity and tumor load. Aerosolized bexarotene significantly decreased tumor multiplicity and tumor load by 43% and 74%, respectively. Our data showed that bexarotene can both inhibit proliferation and promote apoptosis in vivo. Our data also show that aerosolized bexarotene did not increase plasma total cholesterol and triglyceride level compared with diet group. These results indicate that aerosolization may be a safe and effective route of administering bexarotene for chemoprevention of lung cancer. Cancer Prev Res; 4(2); 270–6. ©2010 AACR.
Effect of Psychiatric Severity on the Outcome of Methadone Maintenance Treatment
Authors: Pani Pier Paolo , Maremmani Icro , Pacini Matteo , Lamanna Francesco , Maremmani Angelo G.I. , dell’Osso Liliana
Published: December 2010

While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.