bluuebunny/crossref_metadata_2025 huggingface dataset:
Numbers of beam angles required for near‐optimal IMRT: Theoretical limits and numerical studies
Authors: Fenwick John D. , Pardo‐Montero Juan
Published: July 2011

Purpose:

To derive limits on the numbers of beams needed to deliver near‐optimal IMRT, and to assess the accuracy of the limits.

Methods:

The authors four different limits have been derived. One, KA, has been obtained by coupling Fourier techniques with a proof used to obtain Bortfeld's limit, K, that if all the cross‐profiles of a many‐field plan can be represented as polynomials of order (K−1) over the range [−R, + R], then within the radius R circle an identical dose‐distribution can be created using just K fields. Two further limits, KH and KN, have been obtained using sampling theory, the KN limit describing fields spaced at the Nyquist frequency. KN can be generalized to KN,Fbeamlet, a limit that accounts for the finite size of the beamlets from which modulated fields are constructed. Using Bortfeld's theoretical framework, the accuracy of the limits has been explored by testing how well the cross‐profiles of an 8 MV double‐Gaussian pencil beam and of 1 and 4 cm wide fields can be approximated by polynomials of orders equal to the different limits minus one. The dependence of optimized cost function values of IMRT plans, generated for a simple geometry and for a head‐and‐neck (oropharynx) case, on the numbers of beams used to construct the plans has also been studied.

Results:

The limits are all multiples of R/W (W being the 20%–80% penumbra‐width of a broad field) and work out at K = 27, KA = 43, KH = 34, and KN = 68 fields for R = 10 cm and W = 5.3 mm. All and none of the cross‐profiles are approximated well by polynomials of order KN−1 and K−1, respectively, suggesting some inaccuracy in the assumptions used to derive the limit K. Order KA−1 polynomials cannot accurately describe the pencil beam profile, but do approximate the 1‐ and 4‐cm profiles reasonably well because higher spatial frequencies are attenuated in these wider fields. All the profiles are represented well by polynomials of order KN,Fbeamlet−1, which decreases from KN as beamlet width increases. Cost functions generated in the IMRT planning study fall as greater numbers of fields are used, before plateauing out around KN,Fbeamlet fields.

Conclusions:

Numerical calculations suggest that the minimum number of fields required for near‐optimal IMRT lies around the generalized Nyquist limit KN,Fbeamlet. For a clinically realistic 20%–80% penumbra‐width of 5.3 mm and a radius of interest of 10 cm, KN,Fbeamlet falls from 68 to 47 fields as the beamlet width rises from 0 to 1 cm.
Response to Comment on “Activation of β-Catenin in Dendritic Cells Regulates Immunity Versus Tolerance in the Intestine”
Authors: Manicassamy Santhakumar , Pulendran Bali
Published: July 2011

Murphy argues that deletion of β-catenin in macrophages is a caveat to our interpretation that Wnt signaling programs dendritic cells (DCs) into a tolerogenic state in the gut. However, our data demonstrate that β-catenin–deficient DCs are greatly impaired in inducing regulatory T cells, and induce enhanced T helper 17 (T
H
17)/T
H
1 responses. Assessing the relative importance of DCs versus macrophages in intestinal tolerance must await tools that permit the genetic deletion of the numerous DC and macrophage subsets in the intestine.
7000 Years of
Emiliania huxleyi
Viruses in the Black Sea
Authors: Coolen Marco J. L.
Published: July 2011

Sequencing ancient DNA from a marine sediment traces population shifts of phytoplankton and their viruses over 7000 years.
Identity: Key to Children’s Understanding of Belief
Authors: Perner Josef , Mauer M. Christine , Hildenbrand Monika
Published: July 2011

“Theory of mind” is a domain-general cognitive capacity.
Structural Basis of Type II Topoisomerase Inhibition by the Anticancer Drug Etoposide
Authors: Wu Chyuan-Chuan , Li Tsai-Kun , Farh Lynn , Lin Li-Ying , Lin Te-Sheng , Yu Yu-Jen , Yen Tien-Jui , Chiang Chia-Wang , Chan Nei-Li
Published: July 2011

Inhibition of an enzyme that alters DNA topology with an anticancer agent should facilitate development of better cancer drugs.
Innovation in the Chinese Mode
Run of the Red Queen
Government, Innovation, Globalization, and Economic Growth in China

by Dan Breznitz and Michael Murphree

Yale University Press, New Haven, CT, 2011. 296 pp. $35, £25. ISBN 9780300152715.
Authors: Guthrie Doug
Published: July 2011

Examining factors behind China's economic growth, Breznitz and Murphree suggest that forms of innovation other than the invention of breakthrough products can yield bigger dividends.
Seeing the Trees in Your Terrace
Authors: Kubatko Laura S. , Pearl Dennis K.
Published: July 2011

Missing data creates “terraces” of phylogenetic trees with identical optimality scores.
New NSF Survey Tries to Separate Knowledge and Belief
Authors: Bhattacharjee Yudhijit
Published: July 2011

The National Science Board's attempt to distinguish between knowledge and belief in how people respond to a science literacy survey has drawn fire from critics who view the changes as surrendering scientific ground to religion.
Decrying CIA Vaccination Sham, Health Workers Brace for Backlash
Authors: Reardon Sara
Published: July 2011

Global health experts are worried that a sham vaccination campaign set up in Abbottabad by the CIA may make it more difficult for international health workers to deliver services in Pakistan.
Piloting Cancer Research With a Shrinking Budget
Authors: Kaiser Jocelyn
Published: July 2011

Harold Varmus's biggest challenge since taking the helm of the National Cancer Institute a year ago has been dealing with the grimmest budget in years.
Science
offers excerpts from a recent interview.
Antarctic Ice's Future Still Mired in Its Murky Past
Authors: Kerr Richard A.
Published: July 2011

As shrinking ice sheets raise sea level, estimates of how quickly the frozen continent is losing and gaining ice remain slippery.
In the Hands of Mummy Experts, Ancient Faces Gain New Life
Authors: Pringle Heather
Published: July 2011

At the meeting, researchers presented facial reconstructions of a British boy from the 18th century and a warrior from the Amazonian rainforest who died more than 80 years ago.
HLA-Associated Hemorrhagic Fever with Renal Syndrome Disease Progression in Slovenian Patients
Authors: Korva Miša , Saksida Ana , Kunilo Sabina , Vidan Jeras Blanka , Avšič-Županc Tatjana
Published: July 2011

Major histocompatibility complex (MHC) class I and class II genes regulate the balance between appropriate aggressive responses and invading pathogens while minimizing the destruction of host tissue. Several studies have shown that in hemorrhagic fever with renal syndrome (HFRS) patients, the disease outcome is determined by a complex interaction between the virus and immunopathologic and human genetic factors. In Slovenia, the severity of the disease caused by Puumala virus (PUUV) is significantly lower than that of HFRS due to Dobrava virus (DOBV). We have determined 23 different HLA-B and 12 different HLA-DRB1 types in Slovenian HFRS patients. Comparison of HLA frequencies between healthy individuals and HFRS patients showed no strong association with the susceptibility for hantaviral infection. Significant associations were recognized when the patient group was separated according to the virus responsible for the infection. DOBV-infected patients have a significantly higher frequency of HLA-B*35 than PUUV-infected patients. For HLA class II genes, the biggest difference between the PUUV- and DOBV-infected groups of patients was in HLA-DRB1*13, where this phenotype was more frequent in PUUV-infected patients, especially in the severe form of the disease. HLA-B*07 could play a protective role in PUUV-caused HFRS in the Slovenian population. Our study shows diverse associations of HLA molecules with DOBV- and PUUV-induced HFRS, and therefore, we presume that different hantaviruses are presented differently through the same HLA molecules and that this might lead to either a more severe or a milder form of the disease. In line with this idea, we have noticed that HLA-B*35 might be a genetic risk factor for DOBV infection in the Slovenian population.
Evaluation of Three Automated Systems for Susceptibility Testing of Enterobacteria Containing qnrB, qnrS, and/or aac(6′)-Ib-cr
Authors: Calvo Jorge , Cano María Eliecer , Pitart Cristina , Marco Francesc , Rodríguez-Martínez José Manuel , Pascual Álvaro , Martínez-Martínez Luis
Published: July 2011

The accuracy of the MicroScan WalkAway, BD Phoenix, and Vitek-2 systems for susceptibility testing of quinolones and aminoglycosides against 68 enterobacteria containing
qnrB
,
qnrS
, and/or
aac(6 ′)-Ib-cr
was evaluated using reference microdilution. Overall, one very major error (0.09%), 6 major errors (0.52%), and 45 minor errors (3.89%) were noted.
Serotyping of Streptococcus pneumoniae Isolates from Nasopharyngeal Samples: Use of an Algorithm Combining Microbiologic, Serologic, and Sequential Multiplex PCR Techniques
Authors: Miernyk Karen , DeByle Carolynn , Harker-Jones Marcella , Hummel Kimberlee Boyd , Hennessy Thomas , Wenger Jay , Rudolph Karen
Published: July 2011

We evaluated nasopharyngeal carriage of
Streptococcus pneumoniae
(pneumococci) in nine Alaskan communities and used an algorithm combining microbiologic, serologic, and sequential multiplex PCR (MP-PCR) techniques to serotype the isolates. After microbiological identification as pneumococci, isolates (
n
= 1,135) were serotyped using latex agglutination and Quellung tests (LA/Q) as well as a series of six sequential MP-PCR assays. Results from the two methods agreed for 94% (1,064/1,135) of samples. Eighty-six percent (61/71) of the discordant results were resolved. Discordant results occurred because (i) the MP-PCR gel was misread (31/61 [51%]), (ii) the LA/Q agglutination was misinterpreted (13/61 [21%]), (iii) two serotypes or sets of serotypes were identified by MP-PCR and only one of the two was identified by LA/Q (9/61 [15%]), (iv) different serotypes or sets of serotypes were identified by LA/Q and MP-PCR and both were correct (7/61 [11%]), and (v) the capsular polysaccharide locus (
cps
) did not amplify during the initial MP-PCR but was present upon retesting (1/61 [2%]). Overall, isolation of pneumococci followed by MP-PCR quickly and accurately identified pneumococcal serotypes in >97% of samples and made available isolates for additional tests such as antimicrobial susceptibility. Misinterpretation of the MP-PCR gel was identified as the main source of discordance. Increasing the number of MP-PCRs from six to seven and reducing the number of serotypes in each reaction may reduce this error. This method may be of use to laboratories characterizing large numbers of
S. pneumoniae
samples, especially when antimicrobial susceptibility data are needed.
Molecular Epidemiology of Autochthonous Dengue Virus Strains Circulating in Mexico
Authors: Rivera-Osorio Pilar , Vaughan Gilberto , Ramírez-González Jose Ernesto , Fonseca-Coronado Salvador , Ruíz-Tovar Karina , Cruz-Rivera Mayra Yolanda , Ruíz-Pacheco Juan Alberto , Vázquez-Pichardo Mauricio , Carpio-Pedroza Juan Carlos , Cázares Fernando , Escobar-Gutiérrez Alejandro
Published: July 2011

Dengue virus (DENV) is the most important arthropod-borne viral infection in humans. Here, the genetic relatedness among autochthonous DENV Mexican isolates was assessed. Phylogenetic and median-joining network analyses showed that viral strains recovered from different geographic locations are genetically related and relatively homogeneous, exhibiting limited nucleotide diversity.
Evaluation of Disk Approximation and Single-Well Broth Tests for Detection of Inducible Clindamycin Resistance in Streptococcus pneumoniae
Authors: Jorgensen James H. , McElmeel M. Leticia , Fulcher Letitia C. , McGee Lesley , Glennen Anita
Published: July 2011

This study evaluated an agar disk diffusion D-zone test and an erythromycin-clindamycin (ERY + CLI) single-well broth test for inducible CLI resistance in
Streptococcus pneumoniae
. The standard CLSI disk approximation test and a single-well combination test incorporating 1 plus 0.5 μg/ml ERY + CLI detected >96% of isolates containing the
ermB
determinant.
Carbapenemase Activity Detection by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry
Authors: Hrabák Jaroslav , Walková Radka , Študentová Vendula , Chudáčková Eva , Bergerová Tamara
Published: July 2011

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry is used for the determination of molecular weights of different chemical compounds. We describe here the use of MALDI-TOF mass spectrometry to detect a carbapenem antibiotic, meropenem, and its degradation products. Buffered meropenem solution (0.1 mM Tris-HCl, pH 6.8) was mixed with an overnight culture of bacteria. After 3-h incubation, the reaction mixture was centrifuged, and the supernatant was analyzed by MALDI-TOF mass spectrometry. The presence or absence of peaks representing meropenem and its sodium salts was crucial. The average turnaround time of this test, considering the use of overnight culture, is 4 h. We validated this method for the detection of resistance to carbapenems in
Enterobacteriaceae
and
Pseudomonas aeruginosa
mediated by carbapenemase production. A total of 124 strains, including 30 carbapenemase-producing strains, were used in the study. The sensitivity of this method is 96.67%, with a specificity of 97.87%. Our results demonstrate the ability of this method to routinely detect carbapenemases in
Enterobacteriaceae
and
Pseudomonas
spp. in laboratories. This assay is comparable with a labor-intensive imipenem-hydrolyzing spectrophotometric assay that is a reference method for the detection of carbapenemase. As demonstrated here, MALDI-TOF mass spectrometry may be used in microbiological laboratories not only for microbial identification but also for other applications, such as studies of mechanisms of antibiotic resistance.
Distribution of Classical and Nonclassical Virulence Genes in Enterotoxigenic Escherichia coli Isolates from Chilean Children and tRNA Gene Screening for Putative Insertion Sites for Genomic Islands
Authors: Del Canto Felipe , Valenzuela Patricio , Cantero Lidia , Bronstein Jonathan , Blanco Jesús E. , Blanco Jorge , Prado Valeria , Levine Myron , Nataro James , Sommerfelt Halvor , Vidal Roberto
Published: July 2011

Enterotoxigenic
Escherichia coli
(ETEC) is an important cause of diarrhea. Three adhesins (Tia, TibA, EtpA), an iron acquisition system (Irp1, Irp2, and FyuA), a GTPase (LeoA), and an autotransporter (EatA) are ETEC virulence-related proteins that, in contrast to the classical virulence factors (enterotoxins and fimbrial colonization factors) have not heretofore been targets in characterizing isolates from epidemiological studies. Here, we determined the occurrence of these nonclassical virulence genes in 103 ETEC isolates from Chilean children with diarrhea and described their association with O serogroups and classical virulence determinants. Because
tia
,
leoA
,
irp2
, and
fyuA
are harbored by pathogenicity islands inserted into the
selC
and
asnT
tRNA genes (tDNAs), we analyzed the regions flanking these loci. Ten additional tDNAs were also screened to identify hot spots for genetic insertions. Associations between the most frequent serogroups and classical colonization factor (CF)-toxin profiles included O6/LT-STh/CS1-CS3-CS21 (i.e., O6 serogroup, heat-labile [LT] and human heat-stable [STh] enterotoxins, and CFs CS1, -3 and -21), O6/LT-STh/CS2-CS3-CS21, and O104-O127/STh/CFAI-CS21. The
eatA
and
etpA
genes were detected in more than 70% of the collection, including diverse serogroups and virulence profiles. Sixteen percent of the ETEC strains were negative for classical and nonclassical adhesins, suggesting the presence of unknown determinants of adhesion. The
leuX
,
thrW
, and
asnT
tDNAs were disrupted in more than 65% of strains, suggesting they are hot spots for the insertion of mobile elements. Sequences similar to integrase genes were identified next to the
thrW
,
asnT
,
pheV
, and
selC
tDNAs. We propose that the
eatA
and
etpA
genes should be included in characterizations of ETEC isolates in future epidemiological studies to determine their prevalence in other geographical regions. Sequencing of tDNA-associated genetic insertions might identify new ETEC virulence determinants.
Separable Determinants of Subcellular Localization and Interaction Account for the Inability of Group O HIV-1 Vpu To Counteract Tetherin
Authors: Vigan Raphaël , Neil Stuart J. D.
Published: July 2011

Tetherin (BST-2/CD317) is thought to restrict retroviral particle release by cross-linking nascent viral and cellular membranes. Unlike the Vpu proteins encoded by human immunodeficiency virus type 1 (HIV-1) group M strains (M-Vpu), those from the nonpandemic HIV-1 group O (O-Vpu) are not able to counteract tetherin activity. Here, we characterized the basis of this defect in O-Vpu. O-Vpu differs from M-Vpu in that it fails to interact with tetherin and downregulate it from the cell surface. Unlike M-Vpu, O-Vpu localizes to the endoplasmic reticulum (ER) rather than the
trans
-Golgi network (TGN). Interestingly M-Vpu bearing an ER retention signal at the C terminus localizes similarly to O-Vpu. While it still interacts with tetherin, it fails to promote virus release, suggesting that O-Vpu deficiency correlates with its cellular distribution in the endoplasmic reticulum as well as its failure to bind tetherin. O-Vpu-M-Vpu chimeras were designed to identify the minimal changes required to restore tetherin antagonism. While several chimeric proteins bearing residues of the M-Vpu transmembrane domain into the O-Vpu transmembrane domain recovered tetherin binding in coimmunoprecipitation studies, efficient antagonism required an additional glutamic acid-to-lysine change in the membrane-proximal hinge region of the O-Vpu cytoplasmic tail that was sufficient to abolish ER retention and permit TGN localization.
The Acheta domesticus Densovirus, Isolated from the European House Cricket, Has Evolved an Expression Strategy Unique among Parvoviruses
Authors: Liu Kaiyu , Li Yi , Jousset Françoise-Xavière , Zadori Zoltan , Szelei Jozsef , Yu Qian , Pham Hanh Thi , Lépine François , Bergoin Max , Tijssen Peter
Published: July 2011

TheAcheta domesticusdensovirus (AdDNV), isolated from crickets, has been endemic in Europe for at least 35 years. Severe epizootics have also been observed in American commercial rearings since 2009 and 2010. The AdDNV genome was cloned and sequenced for this study. The transcription map showed that splicing occurred in both the nonstructural (NS) and capsid protein (VP) multicistronic RNAs. The splicing pattern of NS mRNA predicted 3 nonstructural proteins (NS1 [576 codons], NS2 [286 codons], and NS3 [213 codons]). The VP gene cassette contained two VP open reading frames (ORFs), of 597 (ORF-A) and 268 (ORF-B) codons. The VP2 sequence was shown by N-terminal Edman degradation and mass spectrometry to correspond with ORF-A. Mass spectrometry, sequencing, and Western blotting of baculovirus-expressed VPs versus native structural proteins demonstrated that the VP1 structural protein was generated by joining ORF-A and -B via splicing (splice II), eliminating the N terminus of VP2. This splice resulted in a nested set of VP1 (816 codons), VP3 (467 codons), and VP4 (429 codons) structural proteins. In contrast, the two splices within ORF-B (Ia and Ib) removed the donor site of intron II and resulted in VP2, VP3, and VP4 expression. ORF-B may also code for several nonstructural proteins, of 268, 233, and 158 codons. The small ORF-B contains the coding sequence for a phospholipase A2 motif found in VP1, which was shown previously to be critical for cellular uptake of the virus. These splicing features are unique among parvoviruses and define a new genus of ambisense densoviruses.
Some Human Immunodeficiency Virus Type 1 Vpu Proteins Are Able To Antagonize Macaque BST-2
In Vitro
and
In Vivo
: Vpu-Negative Simian-Human Immunodeficiency Viruses Are Attenuated
In Vivo
Authors: Shingai Masashi , Yoshida Takeshi , Martin Malcolm A. , Strebel Klaus
Published: July 2011

Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral particles from infected cells by targeting BST-2/tetherin, a cellular protein inhibiting virus release. The widely used HIV-1
NL4-3
Vpu functionally inactivates human BST-2 but not murine or monkey BST-2, leading to the notion that Vpu antagonism is species specific. Here we investigated the properties of the CXCR4-tropic simian-human immunodeficiency virus DH12 (SHIV
DH12
) and the CCR5-tropic SHIV
AD8
, each of which carries
vpu
genes derived from different primary HIV-1 isolates. We found that virion release from infected rhesus peripheral blood mononuclear cells was enhanced to various degrees by the Vpu present in both SHIVs. Transfer of the SHIV
DH12
Vpu transmembrane domain to the HIV-1
NL4-3
Vpu conferred antagonizing activity against macaque BST-2. Inactivation of the SHIV
DH12
and SHIV
AD8
vpu
genes impaired virus replication in 6 of 8 inoculated rhesus macaques, resulting in lower plasma viral RNA loads, slower losses of CD4
+
T cells, and delayed disease progression. The expanded host range of the SHIV
DH12
Vpu was not due to adaptation during passage in macaques but was an intrinsic property of the parental HIV-1
DH12
Vpu protein. These results demonstrate that the species-specific inhibition of BST-2 by HIV-1
NL4-3
Vpu is not characteristic of all HIV-1 Vpu proteins; some HIV-1 isolates encode a Vpu with a broader host range.
Systematic Analysis of the Amino Acid Residues of Human Papillomavirus Type 16 E7 Conserved Region 3 Involved in Dimerization and Transformation
Authors: Todorovic Biljana , Massimi Paola , Hung Katherine , Shaw Gary S. , Banks Lawrence , Mymryk Joe S.
Published: July 2011

The human papillomavirus (HPV) E7 oncoprotein exists as a dimer and acts by binding to many cellular factors, preventing or retargeting their function and thereby making the infected cell conducive for viral replication. Dimerization of E7 is attributed primarily to the C-terminal domain, referred to as conserved region 3 (CR3). CR3 is highly structured and is necessary for E7's transformation ability. It is also required for binding of numerous E7 cellular targets. To systematically analyze the molecular mechanisms by which HPV16 E7 CR3 contributes to carcinogenesis, we created a comprehensive panel of mutations in residues predicted to be exposed on the surface of CR3. We analyzed our novel collection of mutants, as well as mutants targeting predicted hydrophobic core residues of the dimer, for the ability to dimerize. The same set of mutants was also assessed functionally for transformation capability in a baby rat kidney cell assay in conjugation with activated
ras
. We show that some mutants of HPV16 E7 CR3 failed to dimerize yet were still able to transform baby rat kidney cells. Our results identify several novel E7 mutants that abrogate transformation and also indicate that E7 does not need to exist as a stable dimer in order to transform cells.
DNA/NYVAC Vaccine Regimen Induces HIV-Specific CD4 and CD8 T-Cell Responses in Intestinal Mucosa
Authors: Perreau Matthieu , Welles Hugh C. , Harari Alexandre , Hall Olivia , Martin Ricardo , Maillard Michel , Dorta Gian , Bart Pierre-Alexandre , Kremer Eric J. , Tartaglia Jim , Wagner Ralf , Esteban Mariano , Levy Yves , Pantaleo Giuseppe
Published: July 2011

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed α4β7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.
Ocular Tropism of Influenza A Viruses: Identification of H7 Subtype-Specific Host Responses in Human Respiratory and Ocular Cells
Authors: Belser Jessica A. , Zeng Hui , Katz Jacqueline M. , Tumpey Terrence M.
Published: July 2011

Highly pathogenic avian influenza (HPAI) H7 virus infection in humans frequently results in conjunctivitis as a major symptom. However, our understanding of what properties govern virus subtype-specific tropism, and of the host responses responsible for eliciting ocular inflammation and pathogenicity following influenza virus infection, are not well understood. To study virus-host interactions in ocular tissue, we infected primary human corneal and conjunctival epithelial cells with H7, H5, and H1 subtype viruses. We found that numerous virus subtypes were capable of infecting and replicating in multiple human ocular cell types, with the highest titers observed with highly pathogenic H7N7 and H5N1 viruses. Similar patterns of proinflammatory cytokine and chemokine production following influenza virus infection were observed in ocular and respiratory cells. However, primary ocular cells infected with HPAI H7N7 viruses were found to have elevated levels of interleukin-1β (IL-1β), a cytokine previously implicated in ocular disease pathology. Furthermore, H7N7 virus infection of corneal epithelial cells resulted in enhanced and significant increases in the expression of genes related to NF-κB signal transduction compared with that after H5N1 or H1N1 virus infection. The differential induction of cytokines and signaling pathways in human ocular cells following H7 virus infection marks the first association of H7 subtype-specific host responses with ocular tropism and pathogenicity. In particular, heightened expression of genes related to NF-κB-mediated signaling transduction following HPAI H7N7 virus infection in primary corneal epithelial cells, but not respiratory cells, identifies activation of a signaling pathway that correlates with the ocular tropism of influenza viruses within this subtype.
CD11c Controls Herpes Simplex Virus 1 Responses To Limit Virus Replication during Primary Infection
Authors: Allen Sariah J. , Mott Kevin R. , Chentoufi Aziz A. , BenMohamed Lbachir , Wechsler Steven L. , Ballantyne Christie M. , Ghiasi Homayon
Published: July 2011

CD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c+DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8+T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8+T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8+T cell responses.
APOBEC1-Mediated Editing and Attenuation of Herpes Simplex Virus 1 DNA Indicate That Neurons Have an Antiviral Role during Herpes Simplex Encephalitis
Authors: Gee Peter , Ando Yoshinori , Kitayama Hiroko , Yamamoto Seiji P. , Kanemura Yuka , Ebina Hirotaka , Kawaguchi Yasushi , Koyanagi Yoshio
Published: July 2011

APOBEC1 (A1) is a cytidine deaminase involved in the regulation of lipids in the small intestine. Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen that is capable of infecting neurons in the brain, causing encephalitis. Here, we show that A1 is induced during encephalitis in neurons of rats infected with HSV-1. In cells stably expressing A1, HSV-1 infection resulted in significantly reduced virus replication compared to that in control cells. Infectivity could be restored to levels comparable to those observed for control cells if A1 expression was silenced by specific A1 short hairpin RNAs (shRNA). Moreover, cytidine deaminase activity appeared to be essential for this inhibition and led to an impaired accumulation of viral mRNA transcripts and DNA copy numbers. The sequencing of viral gene UL54 DNA, extracted from infected A1-expressing cells, revealed G-to-A and C-to-T transitions, indicating that A1 associates with HSV-1 DNA. Taken together, our results demonstrate a model in which A1 induction during encephalitis in neurons may aid in thwarting HSV-1 infection.
Tempo and Mode of Plant RNA Virus Escape from RNA Interference-Mediated Resistance
Authors: Lafforgue Guillaume , Martínez Fernando , Sardanyés Josep , de la Iglesia Francisca , Niu Qi-Wen , Lin Shih-Shun , Solé Ricard V. , Chua Nam-Hai , Daròs José-Antonio , Elena Santiago F.
Published: July 2011

A biotechnological application of artificial microRNAs (amiRs) is the generation of plants that are resistant to virus infection. This resistance has proven to be highly effective and sequence specific. However, before these transgenic plants can be deployed in the field, it is important to evaluate the likelihood of the emergence of resistance-breaking mutants. Two issues are of particular interest: (i) whether such mutants can arise in nontransgenic plants that may act as reservoirs and (ii) whether a suboptimal expression level of the transgene, resulting in subinhibitory concentrations of the amiR, would favor the emergence of escape mutants. To address the first issue, we experimentally evolved independent lineages of
Turnip mosaic virus
(TuMV) (family
Potyviridae
) in fully susceptible wild-type
Arabidopsis thaliana
plants and then simulated the spillover of the evolving virus to fully resistant
A. thaliana
transgenic plants. To address the second issue, the evolution phase took place with transgenic plants that expressed the amiR at subinhibitory concentrations. Our results show that TuMV populations replicating in susceptible hosts accumulated resistance-breaking alleles that resulted in the overcoming of the resistance of fully resistant plants. The rate at which resistance was broken was 7 times higher for TuMV populations that experienced subinhibitory concentrations of the antiviral amiR. A molecular characterization of escape alleles showed that they all contained at least one nucleotide substitution in the target sequence, generally a transition of the G-to-A and C-to-U types, with many instances of convergent molecular evolution. To better understand the viral population dynamics taking place within each host, as well as to evaluate relevant population genetic parameters, we performed
in silico
simulations of the experiments. Together, our results contribute to the rational management of amiR-based antiviral resistance in plants.
Gainfully employed? An inquiry into bidi-dependent livelihoods in Bangladesh
Authors: Roy Anupom , Efroymson Debra , Jones Lori , Ahmed Saifuddin , Arafat Islam , Sarker Rashmi , FitzGerald Sian
Published: July 2011

Objectives

This study sought to increase government, civil society and media attention to the tobacco–poverty connection in Bangladesh, particularly as it relates to bidi-dependent livelihoods.

Data sources

This study consisted of a literature review that examined the socioeconomic impacts of tobacco farming, the working conditions of tobacco workers and the impact of tobacco on consumers, and a primary research study among bidi workers and users. The research included in-depth and semistructured interviews and focus group discussions among bidi workers and a closed-ended quantitative survey among bidi users.

Data synthesis

Most bidi worker families earn about $6.40 per 7-day work week, leaving them below the poverty line. The majority of bidi workers are women and children, classified as unpaid assistants, who toil long hours in toxic environments. Bidi users are primarily low-income earners who spend up to 10% of their daily income on bidis; the average proportion of income spent on bidis decreased as income increased. If bidi expenditures were reduced and spent instead on food or local transportation, many higher value jobs could be created. This could also mean better health and nutrition for those currently engaged in bidi work.

Conclusions

The results of this study illustrate the linkages between tobacco and poverty. Tobacco control is not simply about health and the environment, but also about the living conditions of the poorest of the poor. If we are to improve the lives of the poor, we must address the root causes of poverty, which include the production and use of tobacco.
NO-WALL HOLOGRAPHIC MODEL FOR QCD
Authors: AFONIN S. S.
Published: July 2011

We propose a new type of bottom-up holographic model describing the Regge-like spectrum of mesons. This type of spectrum emerges due to condensation of a scalar field in the bulk anti-de Sitter space. The gauge invariance of the action describing the vector mesons requires that the bulk scalar field must correspond to an operator of canonical dimension two. This is not necessary for the description of the scalar sector where the generation of the mass spectrum can be directly related to the formation of gluon condensate in QCD. It is also demonstrated that such an explicit introduction of local dimension-2 operator into the model leads to disappearance of the corresponding contribution from the dimension-2 condensate in the power expansion of the gauge-invariant vector correlator as required by QCD.
DIMENSION EMERGENCE, HOLOGRAPHY AND QUANTUM GRAVITY
Authors: FENG YU-LEI , XU LI-XIN , WANG YU-TING
Published: July 2011

In this paper, we try to give an alternative interpretation of the holography principle. We argue that the space or time may be regarded as emerging from quantum mechanics as an evolutive parameter. The lower D-dimensional theory is related to a corresponding (D+1)-theory by a mysterious quantum system. Then from the higher-dimensional theory, under a new dimension reduction mechanism we obtain the corresponding results. We also try to incorporate the gauge field into the reduction, roughly identifying Aμ with Nμ which is the shift vector in the ADM-like decomposition of space–time metric. In the end, we extend to the gravitational field, and obtain a relation [Formula: see text] with a cutoff factor κ, from a different view.
WAVE-PACKET SCATTERING OFF THE KINK-SOLUTION
Authors: ABDELHADY A. M. H. H. , WEIGEL H.
Published: July 2011

We investigate the propagation of a wave-packet in the ϕ4 model. We solve the time-dependent equation of motion for two distinct initial conditions: The wave-packet in a trivial vacuum background and in the background of the kink soliton solution. We extract the scattering matrix from the wave-packet in the kink background at very late times and compare it with the result from static potential scattering in the small amplitude approximation. We vary the size of the initial wave-packet to identify nonlinear effects as, for example, the replacement of the center of the kink.
TIME AND INTERPRETATIONS OF QUANTUM GRAVITY
Authors: KUCHAŘ KAREL V.
Published: July 2011

In canonical quantization of gravity, the state functional does not seem to depend on time. This hampers the physical interpretation of quantum gravity. I critically examine ten major attempts to circumvent this problem and discuss their shortcomings.
THE DISCOVERY OF THE EXPANDING UNIVERSE AND 80 YEARS OF BIG BANG
Authors: NUSSBAUMER HARRY
Published: July 2011

Modern cosmology began in 1917 when Einstein published his model of a static Universe built on general relativity. A few months later de Sitter came forward with a competing, but also static model which contained no matter but had the intriguing quality that the spectrum of a test particle appeared redshifted to a distant observer. It was thought that de Sitter's model might explain the redshifted spectra observed by Slipher in spiral nebulae. However, in 1927 Lemaître showed that de Sitter's model violated the principle of homogeneity. He then formulated a dynamical cosmological model and combined it with the available observations, showing that our Universe is expanding. He theoretically derived the linear distance–velocity relationship which today is called the "Hubble-relation." Hubble confirmed the relation in 1929 on purely observational grounds. 80 years ago, in 1931 in a letter to Nature, Lemaître suggested that the Universe had a definite beginning in a rapid expansion out of a highly condensed state: the primeval atom. This event became later known as the Big Bang.
SOME COMMENTS ON RELATIVISTIC HYDRODYNAMICS AND FUZZY BAGS
Authors: ANDREEV OLEG
Published: July 2011

Three subjects are considered here: the relativistic hydrodynamics equations for a boost-invariant expanding fluid; the fuzzy bag model for the pressure which recently appeared in (QCD) phenomenology; and the early space-time evolution of the QCD matter, drawn from model studies, which can also be expected to arise in realistic fluid dynamics relevant to heavy ion collisions at LHC.
NEGATIVE ENERGY SOLUTIONS AND SYMMETRIES
Authors: SIDHARTH B. G.
Published: July 2011

We revisit the negative energy solutions of the Dirac (and Klein–Gordon) equation, which become relevant at very high energies in the context of the Feshbach–Villars formulation, and study several symmetries which follow therefrom. Significant consequences are briefly examined.
MARGIN AND DOMAIN INTEGRATED CLASSIFICATION FOR IMAGES
Authors: CHEN YEN-LUN , ZHENG YUAN F. , LIU YI
Published: July 2011

Multi-category classification is an ongoing research topic in image acquisition and processing for numerous applications. In this paper, a novel approach called margin and domain integrated classifier (MDIC) is addressed. It merges the conventional support vector machine (SVM) and support vector domain description (SVDD) classifiers, and handles multi-class problems as a combination of several target classes plus outliers. The basic idea behind the proposed approach is that target classes possess structured characteristics while outliers scatter around in the feature space. In our approach, the domain description and large-margin discrimination are adjustable and therefore yield higher classification accuracy which leads to better performance than conventional classifiers. The properties of MDIC are analyzed and the performance comparisons using synthetic and real data are presented.
Disk Scrubbing Versus Intradisk Redundancy for RAID Storage Systems
Authors: Iliadis Ilias , Haas Robert , Hu Xiao-Yu , Eleftheriou Evangelos
Published: July 2011

Two schemes proposed to cope with unrecoverable or latent media errors and enhance the reliability of RAID systems are examined. The first scheme is the established, widely used, disk scrubbing scheme, which operates by periodically accessing disk drives to detect media-related unrecoverable errors. These errors are subsequently corrected by rebuilding the sectors affected. The second scheme is the recently proposed intradisk redundancy scheme, which uses a further level of redundancy inside each disk, in addition to the RAID redundancy across multiple disks. A new model is developed to evaluate the extent to which disk scrubbing reduces the unrecoverable sector errors. The probability of encountering unrecoverable sector errors is derived analytically under very general conditions regarding the characteristics of the read/write process of uniformly distributed random workloads and for a broad spectrum of disk scrubbing schemes, which includes the deterministic and random scrubbing schemes. We show that the deterministic scrubbing scheme is the most efficient one. We also derive closed-form expressions for the percentage of unrecoverable sector errors that the scrubbing scheme detects and corrects, the throughput performance, and the minimum scrubbing period achievable under operation with random, uniformly distributed I/O requests. Our results demonstrate that the reliability improvement due to disk scrubbing depends on the scrubbing frequency and the load of the system, and, for heavy-write workloads, may not reach the reliability level achieved by a simple interleaved parity-check (IPC)-based intradisk redundancy scheme, which is insensitive to the load. In fact, for small unrecoverable sector error probabilities, the IPC-based intradisk redundancy scheme achieves essentially the same reliability as that of a system operating without unrecoverable sector errors. For heavy loads, the reliability achieved by the scrubbing scheme can be orders of magnitude less than that of the intradisk redundancy scheme. Finally, the I/O and throughput performances are evaluated by means of analysis and event-driven simulation.
Complexity of conservative constraint satisfaction problems
Authors: Bulatov Andrei A.
Published: July 2011

In a constraint satisfaction problem (CSP), the aim is to find an assignment of values to a given set of variables, subject to specified constraints. The CSP is known to be NP-complete in general. However, certain restrictions on the form of the allowed constraints can lead to problems solvable in polynomial time. Such restrictions are usually imposed by specifying a constraint language, that is, a set of relations that are allowed to be used as constraints. A principal research direction aims to distinguish those constraint languages that give rise to tractable CSPs from those that do not.

We achieve this goal for the important version of the CSP, in which the set of values for each individual variable can be restricted arbitrarily. Restrictions of this type can be studied by considering those constraint languages which contain all possible unary constraints; we call such languages
conservative
. We completely characterize conservative constraint languages that give rise to polynomial time solvable CSP classes. In particular, this result allows us to obtain a complete description of those (directed) graphs
H
for which the List
H
-Coloring problem is solvable in polynomial time. The result, the solving algorithm, and the proofs heavily use the algebraic approach to CSP developed in Jeavons et al. [1997], Jeavons [1998], Bulatov et al. [2005], and Bulatov and Jeavons [2001b, 2003].
Logic programs with propositional connectives and aggregates
Authors: Ferraris Paolo
Published: July 2011

Answer set programming (ASP) is a logic programming paradigm that can be used to solve complex combinatorial search problems. Aggregates are an ASP construct that plays an important role in many applications. Defining a satisfactory semantics of aggregates turned out to be a difficult problem, and in this article we propose a new approach, based on an analogy between aggregates and propositional connectives. First we extend the definition of an answer set/stable model to cover arbitrary propositional theories; then we define aggregates on top of them both as primitive constructs and as abbreviations for formulas. Our definition of an aggregate combines expressiveness and simplicity, and it inherits many theorems about programs with nested expressions, such as theorems about strong equivalence and splitting.
Two-variable logic on data words
Authors: Bojańczyk Mikołaj , David Claire , Muscholl Anca , Schwentick Thomas , Segoufin Luc
Published: July 2011

In a
data word
each position carries a label from a finite alphabet and a data value from some infinite domain. This model has been already considered in the realm of semistructured data, timed automata, and extended temporal logics.

This article shows that satisfiability for the two-variable fragment FO
2
(∼,<,+1) of first-order logic with data equality test ∼ is decidable over finite and infinite data words. Here +1 and < are the usual successor and order predicates, respectively. The satisfiability problem is shown to be at least as hard as reachability in Petri nets. Several extensions of the logic are considered; some remain decidable while some are undecidable.
Logics for information systems and their dynamic extensions
Authors: Khan Md. Aquil , Banerjee Mohua
Published: July 2011

The article proposes logics for
information systems
, which provide information about a set of objects regarding a set of attributes. Both “
complete
” and “
incomplete
” information systems are dealt with. The language of these logics contains modal operators, and constants corresponding to attributes and attribute values. Sound and complete deductive systems for these logics are presented, and the problem of decidability is addressed. Furthermore, notions of
information
and
information update
are defined, and dynamic extensions of the above logics are presented to accommodate these notions. A set of reduction axioms enables us to obtain a complete axiomatization of the dynamic logics.
From the presidents of the IEEE Computer Society and ACM
Authors: Reisman Sorel , Chesnais Alain
Published: July 2011

As most members of our organizations probably know, there is a great deal of overlap between the products and services offered by the IEEE CS and ACM. In fact, about 27% of ACM members belong to IEEE CS.
In the Virtual Extension
Authors: CACM Staff
Published: July 2011

To ensure the timely publication of articles,
Communications
created the Virtual Extension (VE) to expand the page limitations of the print edition by bringing readers the same high-quality articles in an online-only format. VE articles undergo the same rigorous review process as those in the print edition and are accepted for publication on merit. The following synopses are from articles now available in their entirety to ACM members via the Digital Library.
Stonebraker on NoSQL and enterprises
Authors: Stonebraker Michael
Published: July 2011

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Michael Stonebraker discusses several reasons why NoSQL has not caught on with enterprise users.
Supercomputing's exaflop target
Authors: Geller Tom
Published: July 2011

The twin challenges of parallelism and energy consumption are enlivening supercomputers' progress.
As simple as possible---but not more so
Authors: Bellovin S. M. , Bradner S. O. , Diffie W. , Landau S. , Rexford J.
Published: July 2011

An assessment of the U.S. government's EINSTEIN project.
Journals for certification, conferences for rapid dissemination
Authors: Halpern Joseph Y. , Parkes David C.
Published: July 2011

Rethinking the role of journals in computer science.
An overview of business intelligence technology
Authors: Chaudhuri Surajit , Dayal Umeshwar , Narasayya Vivek
Published: July 2011

BI technologies are essential to running today's businesses and this technology is going through sea changes.