bluuebunny/crossref_metadata_2025_split 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.
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

ABSTRACTMajor 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

ABSTRACT

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

ABSTRACT

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

ABSTRACT
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACTTheAcheta 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

ABSTRACT

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

ABSTRACT

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

ABSTRACTIn 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

ABSTRACT
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.