bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep sequencing identifies two genotypes and high viral genetic diversity of human pegivirus (GB virus C) in rural Ugandan patients
Authors: Ghai Ria R. , Sibley Samuel D. , Lauck Michael , Dinis Jorge M. , Bailey Adam L. , Chapman Colin A. , Omeja Patrick , Friedrich Thomas C. , O’Connor David H. , Goldberg Tony L.
Published: September 2013

Human pegivirus (HPgV), formerly ‘GB virus C’ or ‘hepatitis G virus’, is a member of the genus Flavivirus (Flaviviridae) that has garnered significant attention due to its inhibition of HIV, including slowing disease progression and prolonging survival in HIV-infected patients. Currently, there are six proposed HPgV genotypes that have roughly distinct geographical distributions. Genotypes 2 and 3 are the most comprehensively characterized, whereas those genotypes occurring on the African continent, where HPgV prevalence is highest, are less well studied. Using deep sequencing methods, we identified complete coding HPgV sequences in four of 28 patients (14.3 %) in rural Uganda, east Africa. One of these sequences corresponds to genotype 1 and is the first complete genome of this genotype from east Africa. The remaining three sequences correspond to genotype 5, a genotype that was previously considered exclusively South African. All four positive samples were collected within a geographical area of less than 25 km2, showing that multiple HPgV genotypes co-circulate in this area. Analysis of intra-host viral genetic diversity revealed that total single-nucleotide polymorphism frequency was approximately tenfold lower in HPgV than in hepatitis C virus. Finally, one patient was co-infected with HPgV and HIV, which, in combination with the high prevalence of HIV, suggests that this region would be a useful locale to study the interactions and co-evolution of these viruses.
Evolution of DS-1-like human G2P[4] rotaviruses assessed by complete genome analyses
Authors: Giammanco Giovanni M. , Bonura Floriana , Zeller Mark , Heylen Elisabeth , Van Ranst Marc , Martella Vito , Bányai Kristián , Matthijnssens Jelle , De Grazia Simona
Published: September 2013

Group A rotaviruses (RVAs) are a leading cause of viral gastroenteritis in children, with G2P[4] RVA being one of the most common human strains worldwide. The complete genome sequences of nine G2P[4] RVA strains, selected from a 26-year archival collection (1985–2011) established in Palermo, Italy, were determined. A strain associated with a peak of G2P[4] RVA activity in 1996 resembled a reassortant strain identified in Kenya in 1982 and differed completely in genomic make up from more recent strains that circulated during 2004–2011. Conversely, the 2004–2011 G2P[4] RVAs were genetically more similar to contemporary RVA strains circulating globally. Recent G2P[4] strains possessed either single or multiple genome segments (VP1, VP3 and/or NSP4) likely derived from ruminant viruses through intra-genotype reassortment. Amino acid substitutions were selected and maintained over time in the VP7 and VP8* antigenic proteins, allowing the circulation of two contemporary G2P[4] variants to be distinguished. Altogether, these findings suggest that major changes in the genomic composition of recent G2P[4] RVAs occurred in the early 2000s, leading to the appearance of a novel variant of the DS-1-like genotype constellation. Whether the modifications observed in the neutralizing antigens and in the genome composition of modern G2P[4] RVAs may affect the long-term effectiveness of the vaccination programmes remains to be explored.
New vaccinia virus promoter as a potential candidate for future vaccines
Authors: Di Pilato Mauro , Mejías-Pérez Ernesto , Gómez Carmen Elena , Perdiguero Beatriz , Sorzano Carlos Oscar S. , Esteban Mariano
Published: September 2013

Here we describe the design and strength of a new synthetic late-early optimized (LEO) vaccinia virus (VACV) promoter used as a transcriptional regulator of GFP expression during modified vaccinia Ankara infection. In contrast to the described synthetic VACV promoter (pS), LEO induced significantly higher levels of GFP expression in vitro within the first hour after infection, which correlated with an enhancement in the GFP-specific CD8 T-cell response detected in vivo, demonstrating its potential use in future vaccines.
Whole-genome sequences of two turkey adenovirus types reveal the existence of two unknown lineages that merit the establishment of novel species within the genus Aviadenovirus
Authors: Marek Ana , Ballmann Mónika Z. , Kosiol Carolin , Harrach Balázs , Schlötterer Christian , Hess Michael
Published: September 2013

There are eight species established for aviadenoviruses: Fowl adenovirus A–E, Goose adenovirus A, Falcon adenovirus A and Turkey adenovirus B. The aim of this study was to sequence and analyse the complete genomes of turkey adenovirus 4 (TAdV-4) and TAdV-5 (strain 1277BT) in addition to almost two-thirds of the genome of another TAdV-5 strain (strain D1648). By applying next-generation sequencing, the full genomes were found to be 42 940 and 43 686 bp and the G+C content was 48.5 and 51.6 mol% for TAdV-4 and TAdV-5, respectively. One fiber gene was identified in TAdV-4, whereas two fiber genes were found in TAdV-5. The genome organization of TAdV-4 resembled that of fowl adenovirus 5 (FAdV-5), but it had ORF1C near the left end of the genome. TAdV-4 also had five 123 bp tandem repeats followed by five 33 bp tandem repeats, but they occurred before and not after ORF8, as in several fowl adenoviruses. The genome organization of TAdV-5 was almost the same as that of FAdV-1 but with a possible difference in the splicing pattern of ORF11 and ORF26. Phylogenetic analyses and G+C content showed differences that seem to merit the establishment of two new species within the genus Aviadenovirus: Turkey adenovirus C (for TAdV-4) and Turkey adenovirus D (for TAdV-5). Our analyses suggest a common evolutionary origin of TAdV-5 and FAdV-1.
VP1 B–C and D–E loops of bovine enterovirus cluster B can effectively display foot-and-mouth disease virus type O-conserved neutralizing epitope
Authors: Chang Jitao , Li Yingli , Yang Decheng , Wang Fang , Jiang Zhigang , Yu Li
Published: September 2013

On the basis of generation of an infectious cDNA clone for the BHM26 strain of bovine enterovirus cluster B (BEV-B), 22 sites on different loops of the BHM26 capsid were selected according to an alignment of its sequence with the structural motifs of BEV-A strain VG-5-27 for insertion of the foot-and-mouth disease virus (FMDV) type O-conserved neutralizing epitope 8E8. Two recombinant viruses, rBEV-A1 and rBEV-DE, in which the FMDV epitope was inserted into the VP1 B–C or D–E loops, were rescued by transfection of BHK-21 cells with the in vitro-transcribed RNA of the recombinant BHM26 genome-length cDNA constructs. The two epitope-inserted viruses were genetically stable and exhibited growth properties similar to those of their parental virus in BHK-21 and IBRS-2 cells, which are susceptible to both BEV and FMDV. However, the two recombinant BEVs (rBEVs) had a significantly lower growth titre than those of the parental virus BHM26 in MDBK and Marc145 cells, which are susceptible to BEV but not to FMDV. These results indicated that insertion of the FMDV epitope into the VP1 B–C or D–E loops of the BEV particle altered the replication properties of BEV. In addition, the two rBEVs were sensitive to neutralization by the FMDV type O-specific mAb 8E8, and anti-FMDV IgG antibodies were induced in mice by intramuscular inoculation with the rBEV-A1 and rBEV-DE viruses. Our results demonstrate that the VP1 B–C and D–E loops of the BEV-B particle can effectively display a foreign epitope, making this an attractive approach for the design of BEV-vectored and epitope-based vaccines.
Antigenicity and transmissibility of a novel clade 2.3.2.1 avian influenza H5N1 virus
Authors: Xu Lili , Bao Linlin , Yuan Jing , Li Fengdi , Lv Qi , Deng Wei , Xu Yanfeng , Yao Yanfeng , Yu Pin , Chen Honglin , Yuen Kwok-Yung , Qin Chuan
Published: September 2013

A genetic variant of the H5N1 influenza virus, termed subclade 2.3.2.1, was first identified in Bulgaria in 2010 and has subsequently been found in Vietnam and Laos. Several cases of human infections with this virus have been identified. Thus, it is important to understand the antigenic properties and transmissibility of this variant. Our results showed that, although it is phylogenetically closely related to other previously characterized clade 2.3 viruses, this novel 2.3.2.1 variant exhibited distinct antigenic properties and showed little cross-reactivity to sera raised against other H5N1 viruses. Like other H5N1 viruses, this variant bound preferentially to avian-type receptors, but contained substitutions at positions 190 and 158 of the haemagglutinin (HA) protein that have been postulated to facilitate HA binding to human-type receptors and to enhance viral transmissibility among mammals, respectively. However, this virus did not appear to have acquired the capacity for airborne transmission between ferrets. These findings highlight the challenges in selecting vaccine candidates for H5N1 influenza because these viruses continue to evolve rapidly in the field. It is important to note that some variants have obtained mutations that may gain transmissibility between model animals, and close surveillance of H5N1 viruses in poultry is warranted.
Computational Fluid Dynamics Assisted Control System Design With Applications to Central Processing Unit Chip Cooling
Authors: Zhang R. , Zhang C. , Jiang J.
Published: October 2013

In this paper, a computational fluid dynamics (CFD) assisted control system design methodology has been described in detail. The entire design and evaluation procedure has been illustrated through a feedback control system synthesis for a central processing unit (CPU) chip cooling system. The design methodology starts with a full-scale CFD simulation of the nonlinear dynamic process to generate the input and output databases of the process. Using this data set, linear dynamic models around specified operating points are obtained using system identification techniques. Based on these models, one can design appropriate control systems to meet the required closed-loop control system specifications. To illustrate the effectiveness of this technique, it has been used to design a controller for a PC chip cooling system. In particular, the coupling issues between ‘real-time’ dynamic controllers with non real-time CFD simulation have been resolved. A physical experimental test bench based on a cooling system of a Pentium III CPU has been constructed. The feedback linear control systems designed by the proposed CFD approach have been evaluated experimentally for six CPU load conditions.
A super‐resolution ultrasound method for brain vascular mapping
Authors: OˈReilly Meaghan A. , Hynynen Kullervo
Published: October 2013

Purpose:

High‐resolution vascular imaging has not been achieved in the brain due to limitations of current clinical imaging modalities. The authors present a method for transcranial ultrasound imaging of single micrometer‐size bubbles within a tube phantom.

Methods:

Emissions from single bubbles within a tube phantom were mapped through anex vivo human skull using a sparse hemispherical receiver array and a passive beamforming algorithm. Noninvasive phase and amplitude correction techniques were applied to compensate for the aberrating effects of the skull bone. The positions of the individual bubbles were estimated beyond the diffraction limit of ultrasound to produce a super‐resolution image of the tube phantom, which was compared with microcomputed tomography (micro‐CT).

Results:

The resulting super‐resolution ultrasound image is comparable to results obtained via the micro‐CT for small tissue specimen imaging.

Conclusions:

This method provides superior resolution to deep‐tissue contrast ultrasound and has the potential to be extended to provide complete vascular network imaging in the brain.
Allele-Specific Silencing of Mutant
Myh6
Transcripts in Mice Suppresses Hypertrophic Cardiomyopathy
Authors: Jiang Jianming , Wakimoto Hiroko , Seidman J. G. , Seidman Christine E.
Published: October 2013

Silencing a Silent Killer

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death in young athletes. HCM is caused by dominant mutations in genes encoding constituents of the cardiac sarcomere, the contractile unit that keeps the heart pumping. Studying a mouse model that recapitulates a severe form of HCM caused by a mutation in a β myosin heavy chain gene,

Jiang
et al.

(p.
111
) investigated whether sarcomere dysfunction could be corrected by selectively silencing expression of the mutant allele. Mice treated shortly after birth with a viral vector encoding an appropriately designed RNA interference cassette did not develop cardiac hypertrophy or myocardial fibrosis—the pathologic manifestations of HCM—for at least 6 months.
A Looser Clock to Cure Jet Lag
Authors: Hastings Michael H.
Published: October 2013

A neuropeptide that signals in the brain's master circadian clock may be the key to overcoming the symptoms of malaise associated with jet lag.

[Also see Research Article by

Yamaguchi
et al.

]
Public Science 2.0—Back to the Future
Authors: Könneker Carsten , Lugger Beatrice
Published: October 2013

Modern dialog formats in science communication are reminiscent of a culture of public discourse and involvement in past centuries.
Lock Up the Genome, Lock Down Research?
Authors: Marshall Eliot
Published: October 2013

Researchers say that gene patents impede data sharing and innovation; patent lawyers say there's no evidence for this.
Novel Secreted Antigens of Mycobacterium paratuberculosis as Serodiagnostic Biomarkers for Johne's Disease in Cattle
Authors: Facciuolo Antonio , Kelton David F. , Mutharia Lucy M.
Published: October 2013

Johne's disease is a chronic gastroenteritis of cattle caused by
Mycobacterium avium
subsp.
paratuberculosis
that afflicts 40% of dairy herds worldwide.
M. avium
subsp.
paratuberculosis
-infected cattle can remain asymptomatic for years while transmitting the pathogen via fecal contamination and milk. Current serodiagnosis with enzyme-linked immunosorbent assays (ELISAs) fails to detect asymptomatic
M. avium
subsp.
paratuberculosis
-infected cattle due to the use of poorly defined antigens and knowledge gaps in our understanding of
M. avium
subsp.
paratuberculosis
components eliciting pathogen-specific immune responses. We set out to (i) define a subset of proteins that contain putative antigenic targets and (ii) screen these antigen pools for immunogens relevant in detecting infection. To accomplish our first objective, we captured and resolved
M. avium
subsp.
paratuberculosis
-secreted proteins using a 2-step fractionation method and reverse-phase liquid chromatography to identify 162 unique proteins, of which 66 had not been previously observed in
M. avium
subsp.
paratuberculosis
culture filtrates. Subsequent screening of
M. avium
subsp.
paratuberculosis
-secreted proteins showed four antigens, of which one or more reacted on immunoblotting with individual serum samples from 35
M. avium
subsp.
paratuberculosis
-infected cows. Moreover, these novel antigens reacted with sera from 6 low
M. avium
subsp.
paratuberculosis
shedders and 3 fecal-culture-positive cows labeled as ELISA seronegative. The specificity of these antigens was demonstrated using negative-control sera from uninfected calves (
n
= 5) and uninfected cows (
n
= 5), which did not react to any of these antigens in immunoblotting. As three of the four antigens are novel, their characterization and incorporation into an ELISA-based format will aid in detecting asymptomatic cattle in early or subclinical stages of disease.
Multicenter Evaluation of the Verigene Clostridium difficile Nucleic Acid Assay
Authors: Carroll Karen C. , Buchan Blake W. , Tan Sokha , Stamper Paul D. , Riebe Katherine M. , Pancholi Preeti , Kelly Cheryl , Rao Arundhati , Fader Robert , Cavagnolo Robert , Watson Wendy , Goering Richard V. , Trevino Ernest A. , Weissfeld Alice S. , Ledeboer Nathan A.
Published: October 2013

The Verigene
Clostridium difficile
Nucleic Acid test (Verigene CDF test) (Nanosphere, Northbrook, IL) is a multiplex qualitative PCR assay that utilizes a nanoparticle-based array hybridization method to detect
C. difficile
tcdA
and
tcdB
in fecal specimens. In addition, the assay detects binary toxin gene sequences and the single base pair deletion at nucleotide 117 (Δ 117) in
tcdC
to provide a presumptive identification of the epidemic strain 027/NAP1/BI (referred to here as ribotype 027). This study compared the Verigene CDF test with anaerobic direct and enriched toxigenic culture on stool specimens from symptomatic patients among five geographically diverse laboratories within the United States. The Verigene CDF test was performed according to the manufacturer's instructions, and the reference methods performed by a central laboratory included direct culture onto cycloserine cefoxitin fructose agar (CCFA) and enriched culture using cycloserine cefoxitin mannitol broth with taurocholate and lysozyme. Recovered isolates were identified as
C. difficile
using gas liquid chromatography and were tested for toxin using a cell culture cytotoxicity neutralization assay. Strains belonging to ribotype 027 were determined by PCR ribotyping and bidirectional sequencing for Δ 117 in
tcdC
. A total of 1,875 specimens were evaluable. Of these, 275 specimens (14.7%) were culture positive by either direct or enriched culture methods. Compared to direct culture alone, the overall sensitivity, specificity, positive predictive value, and negative predictive value for the Verigene CDF test were 98.7%, 87.5%, 42%, and 99.9%, respectively. Compared to combined direct and enriched culture results, the sensitivity, specificity, positive predictive value, and negative predictive values of the Verigene CDF test were 90.9%, 92.5%, 67.6%, and 98.3%, respectively. Of the 250 concordantly culture-positive specimens, 59 (23.6%) were flagged as “hypervirulent”; 53 were confirmed as ribotype 027, and all 59 possessed Δ 117 in
tcdC
. Time to results was approximately 2.5 h per specimen. The Verigene CDF test is a novel nucleic acid microarray that reliably detects both
C. difficile
toxins A and B in unformed stool specimens and appears to adequately identify ribotype 027 isolates.
Superior Sensitivity and Decreased Time to Detection with the Bactec Peds Plus/F System Compared to the BacT/Alert Pediatric FAN Blood Culture System
Authors: Sullivan K. V. , Turner N. N. , Lancaster D. P. , Shah A. R. , Chandler L. J. , Friedman D. F. , Blecker-Shelly D. L.
Published: October 2013

Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were
Staphylococcus epidermidis
and vancomycin, methicillin-resistant
Staphylococcus aureus
and vancomycin,
Streptococcus pneumoniae
, vancomycin, and ceftriaxone,
Streptococcus agalactiae
, ampicillin, and cefotaxime,
Escherichia coli
, cefotaxime, and cefepime,
Pseudomonas aeruginosa
, piperacillin-tazobactam, cefepime, and gentamicin,
Neisseria meningitidis
and ceftriaxone, and
Haemophilus influenzae
and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with
S. pneumoniae
,
S. agalactiae
,
E. coli
,
N. meningitidis
, or
H. influenzae
in combination with cefotaxime or ceftriaxone. The Peds Plus system detected
P. aeruginosa
in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h;
P
= 0.001) and the test bottles (14.3 versus 17.8 h;
P
= 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.
Emergence of an Oseltamivir-Resistant Influenza A/H3N2 Virus in an Elderly Patient Receiving a Suboptimal Dose of Antiviral Prophylaxis
Authors: Roussy Jean-François , Abed Yacine , Bouhy Xavier , Boivin Guy
Published: October 2013

We report the emergence of an influenza virus A/H3N2-E119V neuraminidase variant from an elderly patient with renal dysfunction who received a suboptimal dose of oseltamivir prophylaxis. In neuraminidase inhibition assays, the E119V variant showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and grew at titers comparable to those of the wild typein vitro.
Therapeutic Vaccination against the Rhesus Lymphocryptovirus EBNA-1 Homologue, rhEBNA-1, Elicits T Cell Responses to Novel Epitopes in Rhesus Macaques
Authors: Silveira Eduardo L. V. , Fogg Mark H. , Leskowitz Rachel M. , Ertl Hildegund C. , Wiseman Roger W. , O'Connor David H. , Lieberman Paul , Wang Fred , Villinger Francois
Published: October 2013

Epstein-Barr virus (EBV) is a vaccine/immunotherapy target due to its association with several human malignancies. EBNA-1 is an EBV protein consistently expressed in all EBV-associated cancers. Herein, EBNA-1-specific T cell epitopes were evaluated after AdC–rhEBNA-1 immunizations in chronically lymphocryptovirus-infected rhesus macaques, an EBV infection model. Preexisting rhEBNA-1-specific responses were augmented in 4/12 animals, and new epitopes were recognized in 5/12 animals after vaccinations. This study demonstrated that EBNA-1-specific T cells can be expanded by vaccination.
Highly Divergent Strains of Porcine Reproductive and Respiratory Syndrome Virus Incorporate Multiple Isoforms of Nonstructural Protein 2 into Virions
Authors: Kappes Matthew A. , Miller Cathy L. , Faaberg Kay S.
Published: October 2013

Viral structural proteins form the critical intermediary between viral infection cycles within and between hosts, function to initiate entry, participate in immediate early viral replication steps, and are major targets for the host adaptive immune response. We report the identification of nonstructural protein 2 (nsp2) as a novel structural component of the porcine reproductive and respiratory syndrome virus (PRRSV) particle. A set of custom α-nsp2 antibodies targeting conserved epitopes within four distinct regions of nsp2 (the PLP2 protease domain [OTU], the hypervariable domain [HV], the putative transmembrane domain [TM], and the C-terminal region [C]) were obtained commercially and validated in PRRSV-infected cells. Highly purified cell-free virions of several PRRSV strains were isolated through multiple rounds of differential density gradient centrifugation and analyzed by immunoelectron microscopy (IEM) and Western blot assays using the α-nsp2 antibodies. Purified viral preparations were found to contain pleomorphic, predominantly spherical virions of uniform size (57.9 nm ± 8.1 nm diameter;
n
= 50), consistent with the expected size of PRRSV particles. Analysis by IEM indicated the presence of nsp2 associated with the viral particle of diverse strains of PRRSV. Western blot analysis confirmed the presence of nsp2 in purified viral samples and revealed that multiple nsp2 isoforms were associated with the virion. Finally, a recombinant PRRSV genome containing a
myc
-tagged nsp2 was used to generate purified virus, and these particles were also shown to harbor
myc
-tagged nsp2 isoforms. Together, these data identify nsp2 as a virion-associated structural PRRSV protein and reveal that nsp2 exists in or on viral particles as multiple isoforms.
Four-year follow-up of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome
Authors: Zamora Tara G , Roberts Kari D
Published: October 2013

A male infant was born by emergent caesarean section at 39 weeks gestational age secondary to maternal and fetal distress. Initial physical examination was notable for macrocephaly (greater than+2SD), postaxial polydactyly of the hands and facial dysmorphism. Head imaging demonstrated diffuse polymicrogyria without hydrocephalus. All findings were consistent with a diagnosis of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome. At the 4-year follow-up, megalencephaly persisted without evidence of hydrocephalus. The child was severely delayed with a stable seizure disorder controlled with dual antiepileptic therapy. This case meets the classic criteria for MPPH syndrome, adding to the limited experience with this disease. The 4-year follow-up and absence of hydrocephalus, once thought to be a key diagnostic criterion, adds to our understanding of the long-term sequelae.
Extensive acute disseminated encephalomyelitis in a young girl responding to intravenous methylprednisolone
Authors: Verma Rajesh , Patil Tushar B , Lalla Rakesh , Kumar Manoj
Published: October 2013

Acute disseminated encephalomyelitis (ADEM) is a monophasic clinical syndrome, characterised by immune-mediated demyelination of the central nervous system. Differentiating ADEM from acute viral encephalomyelitis may pose a difficult clinical challenge. We describe a 3-year-old girl who presented with fever, weakness in all four limbs, urinary retention, respiratory distress and altered sensorium. MRI of the brain showed multiple cerebral T2-hyperintense signals with bilateral thalamic and basal ganglia involvement. MRI of the spine showed extensive T2-hyperintensities from cervical to lumbar spinal cord. Cerebrospinal fluid examination was normal. The patient was diagnosed as ADEM and treated with intravenous methylprednisolone. She showed complete clinical and radiological improvement at the end of 1-month follow-up.
Disassociation at the head–trunnion interface: an unseen complication of modular hip hemiarthroplasty
Authors: Moores Thomas Steven , Blackwell John R , Chatterton Benjamin Dougal , Eisenstein Neil
Published: October 2013

A woman in her mid-90s underwent a left uncemented bipolar hemiarthroplasty for an intracapsular femoral neck fracture. Postoperative radiographs at 48h showed a disassociation of the left femoral prosthesis at the head–trunnion interface, with the bipolar head remaining in the acetabulum. There was no preceding trauma and the patient had mobilised postoperatively. The hip was revised to a monopolar head, and the patient's hip was protected postoperatively in a brace limiting flexion and external rotation. At 30 days following revision she was mobilising pain-free with a stable hip. Disassociation at the head–trunnion interface has never been reported in hip hemiarthroplasty, and is only described in relation to primary or revision total hip replacements (THR) following dislocation or trauma to the THR. This demonstrates a potential complication of modular prostheses for trauma.
Vesicovaginal fistula due to vaginal herb for primary infertility: could it be devastating?
Authors: Paul Sagorika , Singh Vishwajeet , Sinha Rahul Janak , Kumar Arvind
Published: October 2013

Vesicovaginal fistula (VVF) is a very commonly encountered urogynaecological entity in developing countries such as India. The most common cause of VVF in developing counties is secondary to obstructive labour. We report a very unusual case of VVF in a young woman that developed due to insertion of an unknown vaginal herb for treatment of primary infertility. Cystoscopy showed a single trigonal fistula measuring 3×2 cm just near the bladder neck. Vaginoscopy revealed cicatrised less capacious vagina and unhealthy vaginal mucosa. She was treated with transvaginal VVF repair using Martius flap interposition which leaked on 10th postoperative day. She underwent re-evaluation and another transvaginal fistula repair for small trigonal residual fistula after 3 months. She is doing well during the follow-up of 2 years. She attained sexual activity after 3 months of surgical repair but could not conceive.
Haemagglutinin and nucleoprotein replicon particle vaccination of swine protects against the pandemic H1N1 2009 virus
Authors: Vander Veen R. L. , Mogler M. A. , Russell B. J. , Loynachan A. T. , Harris D. L. H. , Kamrud K. I.
Published: September 2013

The recent emergence of the pandemic H1N1 (pH1N1) and H3N2 variant influenza A viruses (IAV) in 2009 and 2011–2012, respectively, highlight the zoonotic potential of influenza viruses and the need for vaccines capable of eliciting heterosubtypic protection. In these studies, single‐cycle, propagation‐defective replicon particle (RP) vaccines expressing IAV haemagglutinin (HA) and nucleoprotein (NP) genes were constructed and efficacy was evaluated in homologous and heterologous pig challenge studies with the pH1N1 2009 influenza virus (A/California/04/2009). Homologous HA RP vaccination eliminated virus shedding and decreased pulmonary pathology in pigs following pH1N1 2009 challenge. An RP vaccine expressing an H3N2‐derived NP gene was able to decrease nasal shedding and viral load following heterosubtypic pH1N1 2009 challenge in pigs. These studies indicate that although homologous vaccination of swine remains the most effective means of preventing IAV infection, other vaccine alternatives do offer a level of heterosubtypic protection, and should continue to be evaluated for their ability to provide broader protection.
Robust synchronization of delay differential systems
Authors: Ray Anirban , Chowdhury A. Roy
Published: September 2013

The methodology of open-plus-close-loop (OPCL), which is up till now mainly used for the case of ordinary dynamical systems is extended for the first time to the case of delay dynamical process, to achieve complete, lag synchronization. Both the one and two way couplings are examined in detail, with the help of delay logistics, Ikeda and Mackey–Glass system. Robustness of the process is exhibited when the same analysis is done in presence of Gaussian noise. Influence of the strength of such a noise is shown. Our procedure opens up a potentially new approach for the synchronization study of delay dynamical systems.
ON CRITICAL HEEGAARD SPLITTINGS OF TUNNEL NUMBER TWO COMPOSITE KNOT EXTERIORS
Authors: KIM JUNGSOO
Published: September 2013

In this paper, we prove that a tunnel number two knot induces a critical Heegaard splitting in its exterior if there are two weak reducing pairs such that each weak reducing pair contains the cocore disk of each tunnel. Moreover, we prove that a connected sum of two 2-bridge knots or more generally that of two (1,1)-knots always contains a critical Heegaard splitting in its exterior as the examples of the main theorem.
ON 2-ADJACENCY OF CLASSICAL PRETZEL KNOTS
Authors: TAO ZHI-XIONG
Published: September 2013

For classical (3-strand) pretzel knots (including even type and odd type), we study their 2-adjacency using Conway polynomial and Jones polynomial. We show that only the trefoil knot and the figure-eight knot in these knots are 2-adjacent.
A MULTI-OBJECTIVE APPROACH TO FUZZY LINEAR PRODUCTION GAMES
Authors: HINOJOSA M. A. , MÁRMOL A. M. , MONROY L. , FERNÁNDEZ F. R.
Published: October 2013

In a real-world production problem, some of the parameters involved, namely the availability of the resources, technological coefficients and the incomes associated with each product, may not be perfectly determined thus reflecting some ambiguity or fuzzy understanding of their nature. Therefore these parameters may admit a representation as fuzzy numbers. In this paper, we show how multi-criteria decision theory can be used to deal with a fuzzy linear production problem and with the associated fuzzy linear production game.
AN INTERACTIVE PARTITIONING APPROACH FOR MULTIOBJECTIVE DECISION MAKING UNDER A GENERAL MONOTONE UTILITY FUNCTION
Authors: KARASAKAL ESRA , KÖKSALAN MURAT
Published: October 2013

We develop an interactive partitioning approach for solving the multiobjective decision making problem of a decision maker (DM) who has an implicit general monotone utility function. The approach reduces feasible solution space using the DM's preferences. Hypothetical solutions called partition ideals (PIs) that dominate portions of the efficient frontier are generated and those that are inferior to a feasible solution are used to eliminate the dominated regions. We investigate the issues in representation of the reduced feasible solution space. We develop procedures for locating PIs and measuring the size of feasible solution space. We incorporate these ideas into an approach that converges to a neighborhood of the most preferred solution of the DM. We demonstrate the approach on an example problem.
COGNITIVE MECHANISMS OF THE MIND
Authors: KUVICH GARY , PERLOVSKY LEONID
Published: October 2013

Successes of information and cognitive science brought a growing understanding that mind is based on intelligent cognitive processes, which are not limited by language and logic only. A nice overview can be found in the excellent work of Jeff Hawkins "On Intelligence." This view is that thought is a set of informational processes in the brain, and such processes have the same rationale as any other systematic informational processes. Their specifics are determined by the ways of how brain stores, structures and process this information. Systematic approach allows representing them in a diagrammatic form that can be formalized and programmed. Semiotic approach allows for the universal representation of such diagrams. In our approach, logic is just a way of synthesis of such structures, which is a small but clearly visible top of the iceberg. However, most of the efforts were traditionally put into logics without paying much attention to the rest of the mechanisms that make the entire thought system working autonomously. Dynamic fuzzy logic is reviewed and its connections with semiotics are established. Dynamic fuzzy logic extends fuzzy logic in the direction of logic-processes, which include processes of fuzzification and defuzzification as parts of logic. This extension of fuzzy logic is inspired by processes in the brain-mind. The paper reviews basic cognitive mechanisms, including instinctual drives, emotional and conceptual mechanisms, perception, cognition, language, a model of interaction between language and cognition upon the new semiotic models. The model of interacting cognition and language is organized in an approximate hierarchy of mental representations from sensory percepts at the "bottom" to objects, contexts, situations, abstract concepts-representations, and to the most general representations at the "top" of mental hierarchy. Knowledge instinct and emotions are driving feedbacks for these representations. Interactions of bottom-up and top-down processes in such hierarchical semiotic representation are essential for modeling cognition. Dynamic fuzzy logic is analyzed as a fundamental mechanism of these processes. In this paper we are trying to formalize cognitive processes of the human mind using approaches above, and provide interfaces that could allow for their practical realization in software and hardware. Future research directions are discussed.
A NEW APPROACH TO DERIVE NORMALIZED PRESSURE IMPULSE CURVES FOR ELASTIC MEMBERS
Authors: DRAGOS JONATHON , WU CHENGQING
Published: October 2013

A pressure impulse (PI) diagram is a useful preliminary design tool for structural members against blasts. An extensive amount of investigation has been undertaken to generalize PI curves, using single degree of freedom (SDOF) theory, for elastic structural members. In this study, a new original approach also using SDOF theory, relying on the concept of effective pulse shape, is presented for determining a PI curve for any elastic member. The advantage of this approach is that it can be applied to any given type of blast load. The techniques and equations involved in this approach are outlined. Then, to assess the accuracy of this approach, elastic normalized PI curves generated using the new approach are compared against those obtained using the traditional methods. Finally, this approach is compared against other simplified techniques for determining elastic normalized PI curves.
AN IMPROVED RANDOM WALK SEGMENTATION ON THE LUNG NODULES
Authors: GUO LI , ZHANG YUNTING , ZHANG ZEWEI , LI DONGYUE , LI YING
Published: September 2013

In this paper, we proposed a semi-automatic technique with a marker indicating the target to locate and segment nodules. For the lung nodule detection, we develop a Gabor texture feature by FCM (Fuzzy C Means) segmentation. Given a marker indicating a rough location of the nodules, a decision process is followed by applying an ellipse fitting algorithm. From the ellipse mask, the foreground and background seeds for the random walk segmentation can be automatically obtained. Finally, the edge of the nodules is obtained by the random walk algorithm. The feasibility and effectiveness of the proposed method are evaluated with the various types of the nodules to identify the edges, so that it can be used to locate the nodule edge and its growth rate.
A SET OF NEW PARANORMED DIFFERENCE SEQUENCE SPACES AND THEIR MATRIX TRANSFORMATIONS
Authors: Baliarsingh P.
Published: October 2013

In this paper, by using a new difference operator Δj, the author likes to introduce new classes of paranormed difference sequence spaces X(Δj, u, v; p) for X ∈ {ℓ∞, c, c0} and investigates their topological structures, where (un) and (vn) are two sequences satisfying certain conditions. The difference operator Δjis defined by Δj(xj) = jxj- (j + 1)xj+1for all j ∈ ℕ, the set of positive integers. Also, we determine the α-, β- and γ-duals of these classes. Furthermore, the matrix transformations from these classes to the sequence spaces ℓ∞(q), c0(q) and c(q) have been characterized.
The modification of natural pyrite and its electrochemical properties in Li/FeS2 batteries
Authors: Zhao Honggang , Wang Shengping , Fan Liren , Wu Jinping
Published: September 2013

The crystal structure and electrochemical properties of modified pyrite are introduced in this study. The structural properties, morphology and thermal stability of synthesized materials were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Impurities in the modified pyrite were measured using an energy dispersive spectrometer (EDS) and an inductively coupled plasma mass spectrometer (ICP-MS). In addition, the electrochemical performance of the modified pyrite in Li / FeS 2 primary batteries was evaluated by cyclic voltammetry, electrochemical impedance spectroscopy and a galvanostatic discharge test. The results show that the capacity density of modified FeS 2(717.45 mAh g-1) is 1.77 times greater compared with natural FeS 2(570.4 mAh g-1). Therefore, modified natural pyrite has potentially useful significance.
Cell transformations and physical design techniques for 3D monolithic integrated circuits
Authors: Bobba Shashikanth , Chakraborty Ashutosh , Thomas Olivier , Batude Perrine , Micheli Giovanni de
Published: October 2013

3D Monolithic Integration (3DMI), also termed as sequential integration, is a potential technology for future gigascale circuits. In 3DMI technology the 3D contacts, connecting different active layers, are in the order of few 100nm. Given the advantage of such small contacts, 3DMI enables fine-grain (gate-level) partitioning of circuits. In this work we present three cell transformation techniques for standard cell-based ICs with 3DMI technology. As a major contribution of this work, we propose a design flow comprising of a cell transformation technique,
cell-on-cell stacking
, and a physical design technique (CELONCEL
PD
) aimed at placing cells transformed with
cell-on-cell
stacking. We analyze and compare various cell transformation techniques for 3DMI technology without disrupting the regularity of the IC design flow. Our experiments demonstrate the effectiveness of CELONCEL design technique, yielding us an area reduction of 37.5%, 16.2% average reduction in wirelength, and 6.2% average improvement in overall delay, compared with a 2D case when benchmarked across various designs in 45nm technology node.
ILP formulations for variation/defect-tolerant logic mapping on crossbar nano-architectures
Authors: Zamani Masoud , Mirzaei Hanieh , Tahoori Mehdi B.
Published: October 2013

Several emerging nano-technologies, including crossbar nano-architectures, have recently been studied as possible replacement or supplement to CMOS technology in the future. However, extreme process variation and high failure rates, mainly due to atomic device sizes, are major challenges for crossbar nano-architectures.

This article presents variation- and defect-tolerant logic mapping on crossbar nano-architectures. Since variation/defect-aware mapping is an NP-hard problem, we introduce a set of
Integer Linear Programming
(ILP) formulations to effectively solve the problem in a reasonable time. The proposed ILP formulations can be used for both diode-based and FET-based crossbars. Experimental results on benchmark circuits show that our approach can reduce the critical-path delay 39% compared to the
Simulated Annealing (SA)
method. It can also successfully achieve 97% defect-free mapping with 40% defect density. It can tolerate process variations to meet timing constraints in 95% of the cases, compared to only 77% achieved by SA.
Activin A induction of erythroid differentiation sensitizes K562 chronic myeloid leukemia cells to a subtoxic concentration of imatinib
Authors: Huang Yu-Wen , Lee Wei-Hwa , Tsai Yu-Hui , Huang Huei-Mei
Published: October 2013

Chronic myeloid leukemia (CML) is a hematopoietic stem/progenitor cell disorder in which Bcr-Abl oncoprotein inhibits cell differentiation. Differentiation induction is considered an alternative strategy for treating CML. Activin A, a member of the transforming growth factor-β superfamily, induces erythroid differentiation of CML cells through the p38 MAPK pathway. In this study, treatment of the K562 CML stem/progenitor cell line with activin A followed by a subtoxic concentration of the Bcr-Abl inhibitor imatinib strongly induced growth inhibition and apoptosis compared with simultaneous treatment with activin A and imatinib. Imatinib-induced growth inhibition and apoptosis following activin A pretreatment were dose- and time-dependent. Imatinib-induced growth inhibition and apoptosis were also dependent on the pretreatment dose of activin A. More than 90% of the activin A-induced increases in glycophorin A-positive cells were sensitive to imatinib. However, only some of original glycophorin A-positive cells in the activin A treatment group were sensitive to imatinib. Sequential treatment with activin A and imatinib decreased Bcr-Abl, procaspase-3, Mcl-1, and Bcl-xL and also induced cleavage of procaspase-3/poly(ADP-ribose)polymerase. The reduction of erythroid differentiation in p38 MAPK dominant-negative mutants or by short hairpin RNA knockdown of p38 MAPK decreased the growth inhibition and apoptosis mediated by sequential treatment with activin A and imatinib. Furthermore, the same inhibition level of multidrug resistance 1 expression was observed in cells treated with activin A alone, treated sequentially with activin A and imatinib, or treated simultaneously with activin A and imatinib. The p38 MAPK inhibitor SB-203580 can restore activin A-inhibited multidrug resistance 1 expression. Taken together, our results suggest that a subtoxic concentration of imatinib could exhibit strong cytotoxicity against erythroid-differentiated K562 CML cells.
Calmodulin-dependent binding to the NHE1 cytosolic tail mediates activation of the Na+/H+ exchanger by Ca2+ and endothelin
Authors: Li Xiuju , Prins Daniel , Michalak Marek , Fliegel Larry
Published: October 2013

The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that regulates intracellular pH by removing a single proton (H+) in exchange for one extracellular Na+. The human protein contains a ∼500-amino acid membrane domain and a regulatory, ∼315-amino acid cytosolic domain. NHE1 is activated by a number of hormones including endothelin (ET) and by Ca2+. The regulatory tail possesses an inhibitory calmodulin (CaM)-binding domain, and inhibition of NHE1 is relieved by binding of a Ca2+-CaM complex. We examined the dynamics of ET-1 and Ca2+ regulation of binding to NHE1 in vivo. CFP was linked to the NHE1 protein cytoplasmic COOH terminus. This was stably transfected into AP-1 cells that are devoid of their own NHE1 protein. The protein was expressed and targeted properly and retained NHE1 activity comparable to the wild-type protein. We examined the in vivo coupling of NHE1 to CaM by Förster resonance energy transfer using CaM linked to the fluorescent protein Venus. CaM interaction with NHE1 was dynamic. Removal of serum reduced CaM interaction with NHE1. Addition of the Ca2+ ionophore ionomycin increased the interaction between CaM and NHE1. We expressed an ET receptor in AP-1 cells and also found a time-dependent association of NHE1 with CaM in vivo that was dependent on ET treatment. The results are the first demonstration of the in vivo association of NHE1 and CaM through ET-dependent signaling pathways.
Paradoxical effects of heme arginate on survival of myocutaneous flaps
Authors: Edmunds Marie-Claire , Czopek Alicja , Wigmore Stephen J. , Kluth David C.
Published: October 2013

Ischemia reperfusion injury (IRI) contributes to partial flap and solid organ transplant failure. Heme-oxygenase 1 (HO-1) is an inducible, cytoprotective enzyme which protects against IRI in solid organ transplant models. Heme arginate (HA), a HO-1 inducer, is a promising, translatable, preconditioning agent. This study investigated the effects of preconditioning with HA on the clinical outcome of a myocutaneous IRI model. Forty male Lewis rats were randomized to intravenously receive 1) Control-NaCl, 2) HA, 3) HA and tin mesoporphyrin (SnMP), a HO-1 inhibitor; and 4) SnMP alone. Twenty-four hours later, an in situ transverse rectus abdominis myocutaneous flap was performed under isoflurane anesthesia. Viability of flaps was measured clinically and by laser-Doppler perfusion scanning. In vitro work on human epidermal keratinocytes (HEKa) assessed the effects of HA, SnMP, and the iron chelator desferrioxamine on 1) cytotoxicity, 2) intracellular reactive oxygen species (ROS) concentration, and 3) ROS-mediated DNA damage. In contrast to our hypothesis, HA preconditioning produced over 30% more flap necrosis at 48 h compared with controls ( P = 0.02). HA-containing treatments produced significantly worse flap perfusion at all postoperative time points. In vitro work showed that HA is cytotoxic to keratinocytes. This cytotoxicity was independent of HO-1 and was mediated by the generation of ROS by free heme. In contrast to solid organ data, pharmacological preconditioning with HA significantly worsened clinical outcome, thus indicating that this is not a viable approach in free flap research.