bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Gram-Positive Cocci by Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry: Comparison of Different Preparation Methods and Implementation of a Practical Algorithm for Routine Diagnostics
Authors: Schulthess Bettina , Brodner Katharina , Bloemberg Guido V. , Zbinden Reinhard , Böttger Erik C. , Hombach Michael 
Published: April 2013

ABSTRACT

This study compared three sample preparation methods (direct transfer, the direct transfer-formic acid method with on-target formic acid treatment, and ethanol-formic acid extraction) for the identification of Gram-positive cocci with matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). A total of 156 Gram-positive cocci representing the clinically most important genera,
Aerococcus
,
Enterococcus
,
Staphylococcus
, and
Streptococcus
, as well as more rare genera, such as
Gemella
and
Granulicatella
, were analyzed using a Bruker MALDI Biotyper. The rate of correct genus-level identifications was approximately 99% for all three sample preparation methods. The species identification rate was significantly higher for the direct transfer-formic acid method and ethanol-formic acid extraction (both 77.6%) than for direct transfer (64.1%). Using direct transfer-formic acid compared to direct transfer, the total time to result was increased by 22.6%, 16.4%, and 8.5% analyzing 12, 48, and 96 samples per run, respectively. In a subsequent prospective study, 1,619 clinical isolates of Gram-positive cocci were analyzed under routine conditions by MALDI-TOF MS, using the direct transfer-formic acid preparation, and by conventional biochemical methods. For 95.6% of the isolates, a congruence between conventional and MALDI-TOF MS identification was observed. Two major limitations were found using MALDI-TOF MS: the differentiation of members of the
Streptococcus mitis
group and the identification of
Streptococcus dysgalactiae
. The Bruker MALDI Biotyper system using the direct transfer-formic acid sample preparation method was shown to be a highly reliable tool for the identification of Gram-positive cocci. We here suggest a practical algorithm for the clinical laboratory combining MALDI-TOF MS with phenotypic and molecular methods.
A Variant Macaque-Tropic Human Immunodeficiency Virus Type 1 Is Resistant to Alpha Interferon-Induced Restriction in Pig-Tailed Macaque CD4+T Cells
Authors: Thippeshappa Rajesh , Ruan Hongmei , Wang Weiming , Zhou Paul , Kimata Jason T. 
Published: April 2013

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) antagonizes innate restriction factors in order to infect and persistently replicate in a host. In a previous study, we demonstrated that HIV-1 NL4-3 with a simian immunodeficiency virus mne (SIVmne)vifgene substitution (HSIV-vif-NL4-3) could infect and replicate in pig-tailed macaques (PTM), indicating that APOBEC3 proteins are primary barriers to transmission. Because viral replication was persistent but low, we hypothesized that HSIV-vif-NL4-3 may be suppressed by type I interferons (IFN-I), which are known to upregulate the expression of innate restriction factors. Here, we demonstrate that IFN-α more potently suppresses HSIV-vif-NL4-3 in PTM CD4+T cells than it does pathogenic SIVmne027. Importantly, we identify a variant (HSIV-vif-Yu2) that is resistant to IFN-α, indicating that the IFN-α-induced barrier can be overcome by HSIV-vif chimeras in PTM CD4+T cells. Interestingly, HSIV-vif-Yu2 and HSIV-vif-NL4-3 are similarly restricted by PTM BST2/Tetherin, and neither virus downregulates it from the surface of infected PTM CD4+T cells. Resistance to IFN-α-induced restriction appears to be conferred by a determinant in HSIV-vif-Yu2 that includesenv su. Finally, we show that the Yu-2env suallele may overcome an IFN-α-induced barrier to entry. Together, our data demonstrate that the prototype macaque-tropic HIV-1 clones based on NL4-3 may not sufficiently antagonize innate restriction in PTM cells. However, variants with resistance to IFN-α-induced restriction factors in PTM CD4+T cells may enhance viral replication by overcoming a barrier early in the viral replication cycle.
Human La Protein Interaction with GCAC near the Initiator AUG Enhances Hepatitis C Virus RNA Replication by Promoting Linkage between 5′ and 3′ Untranslated Regions
Authors: Kumar Anuj , Ray Upasana , Das Saumitra 
Published: April 2013

ABSTRACT

Human La protein has been implicated in facilitating the internal initiation of translation as well as replication of hepatitis C virus (HCV) RNA. Previously, we demonstrated that La interacts with the HCV internal ribosome entry site (IRES) around the GCAC motif near the initiator AUG within stem-loop IV by its RNA recognition motif (RRM) (residues 112 to 184) and influences HCV translation. In this study, we have deciphered the role of this interaction in HCV replication in a hepatocellular carcinoma cell culture system. We incorporated mutation of the GCAC motif in an HCV monocistronic subgenomic replicon and a pJFH1 construct which altered the binding of La and checked HCV RNA replication by reverse transcriptase PCR (RT-PCR). The mutation drastically affected HCV replication. Furthermore, to address whether the decrease in replication is a consequence of translation inhibition or not, we incorporated the same mutation into a bicistronic replicon and observed a substantial decrease in HCV RNA levels. Interestingly, La overexpression rescued this inhibition of replication. More importantly, we observed that the mutation reduced the association between La and NS5B. The effect of the GCAC mutation on the translation-to-replication switch, which is regulated by the interplay between NS3 and La, was further investigated. Additionally, our analyses of point mutations in the GCAC motif revealed distinct roles of each nucleotide in HCV replication and translation. Finally, we showed that a specific interaction of the GCAC motif with human La protein is crucial for linking 5′ and 3′ ends of the HCV genome. Taken together, our results demonstrate the mechanism of regulation of HCV replication by interaction of the
cis
-acting element GCAC within the HCV IRES with human La protein.
The Adenovirus L4-33K Protein Regulates both Late Gene Expression Patterns and Viral DNA Packaging
Authors: Wu Kai , Guimet Diana , Hearing Patrick 
Published: April 2013

ABSTRACT

The adenovirus (Ad) L4-33K protein has been linked to disparate functions during infection. L4-33K is a virus-encoded alternative RNA splicing factor which activates splicing of viral late gene transcripts that contain weak 3′ splice sites. Additionally, L4-33K has been indicated to play a role in adenovirus assembly. We generated and characterized an Ad5 L4-33K mutant virus to further explore its function(s) during infection. Infectivity, viral genome replication, and most viral gene expression of the L4-33K mutant virus are comparable to those of the wild-type virus, except for a prominent decrease in the levels of the late proteins IIIa and pVI. The L4-33K mutant virus produces only empty capsids, indicating a defect in viral DNA packaging. We demonstrate that L4-33K does not preferentially bind to viral packaging sequences
in vivo
, and mutation of L4-33K does not interfere with the binding of the known viral packaging proteins IVa2, L4-22K, L1-52/55K, and IIIa to the packaging sequences
in vivo
. Collectively, these results demonstrate that the phenotype of an Ad5 L4-33K mutant virus is complex. The L4-33K protein regulates the accumulation of selective Ad late gene mRNAs and is involved in the proper transition of gene expression during the late phase of infection. The L4-33K protein also plays a role in adenovirus morphogenesis by promoting the packaging of the viral genome into the empty capsid. These results demonstrate the multifunctional nature of the L4-33K protein and its involvement in several different and critical aspects of viral infection.
Structure of a Classical Broadly Neutralizing Stem Antibody in Complex with a Pandemic H2 Influenza Virus Hemagglutinin
Authors: Dreyfus Cyrille , Ekiert Damian C. , Wilson Ian A. 
Published: April 2013

ABSTRACT
We report the structural characterization of the first antibody identified to cross-neutralize multiple subtypes of influenza A viruses. The crystal structure of mouse antibody C179 bound to the pandemic 1957 H2N2 hemagglutinin (HA) reveals that it targets an epitope on the HA stem similar to those targeted by the recently identified human broadly neutralizing antibodies. C179 also inhibits the low-pH conformational change of the HA but uses a different angle of approach and both heavy and light chains.
Novel Recombinant Hepatitis B Virus Vectors Efficiently Deliver Protein and RNA Encoding Genes into Primary Hepatocytes
Authors: Hong Ran , Bai Weiya , Zhai Jianwei , Liu Wei , Li Xinyan , Zhang Jiming , Cui Xiaoxian , Zhao Xue , Ye Xiaoli , Deng Qiang , Tiollais Pierre , Wen Yumei , Liu Jing , Xie Youhua 
Published: April 2013

ABSTRACT
Hepatitis B virus (HBV) has extremely restricted host and hepatocyte tropism. HBV-based vectors could form the basis of novel therapies for chronic hepatitis B and other liver diseases and would also be invaluable for the study of HBV infection. Previous attempts at developing HBV-based vectors encountered low yields of recombinant viruses and/or lack of sufficient infectivity/cargo gene expression in primary hepatocytes, which hampered follow-up applications. In this work, we constructed a novel vector based on a naturally occurring, highly replicative HBV mutant with a 207-bp deletion in the preS1/polymerase spacer region. By applying a novel insertion strategy that preserves the continuity of the polymerase open reading frame (ORF), recombinant HBV (rHBV) carrying protein or small interfering RNA (siRNA) genes were obtained that replicated and were packaged efficiently in cultured hepatocytes. We demonstrated that rHBV expressing a fluorescent reporter (DsRed) is highly infective in primary tree shrew hepatocytes, and rHBV expressing HBV-targeting siRNA successfully inhibited antigen expression from coinfected wild-type HBV. This novel HBV vector will be a powerful tool for hepatocyte-targeting gene delivery, as well as the study of HBV infection.
Chikungunya Virus Host Range E2 Transmembrane Deletion Mutants Induce Protective Immunity against Challenge in C57BL/6J Mice
Authors: Piper Amanda , Ribeiro Mariana , Smith Katherine M. , Briggs Caitlin M. , Huitt Emerson , Nanda Kavita , Spears Carla J. , Quiles Michelle , Cullen John , Thomas Malcolm E. , Brown Dennis T. , Hernandez Raquel 
Published: April 2013

ABSTRACT

A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (WT) virus via truncation of the transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice are a standard model system for ChikV disease and display the same symptoms of the disease seen in humans. Groups of mice were inoculated with one of three ChikV HR mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21 days after infection. Upon challenge with a highly pathogenic strain of ChikV, the mutant blocked viral replication in all tissues tested. This study identified a ChikV HR mutant that grows to high levels in insect cells but was restricted in the ability to assemble virus in mammalian cells
in vitro
. The study demonstrates that these HR strains are attenuated in the mammalian host and warrant further development as live-attenuated vaccine strains.
The isolated fourth ventricle
Authors: Ali Khalid , Nannapaneni Ravindra , Hamandi Khalid 
Published: April 2013

Isolated enlargement of the fourth ventricle, or ‘encysted’ fourth ventricle is a rare late complication following shunt insertion of the lateral ventricles for hydrocephalus. Caudal and rostral obstruction of the fourth ventricle and its subsequent dilation results in compression of adjacent cerebellum and brain stem structures; treatment with further shunt insertion directly to the fourth ventricle is invariably successful. There is potential for diagnostic delay, when clinical symptoms and signs of cerebellar and brain stem compromise are unrecognised or attributed to other factors, and attention on the CT is focused on the lateral ventricular system and the already existing ventriculoperitoneal shunt, which will appear unchanged from previous scans. We report two cases with isolated fourth ventricular obstruction and review the literature to highlight the importance of recognising this condition.
DEVELOPING A NEW PARAMETER TO REPRESENT THE FOOT ALIGNMENT IN SUBJECTS WITH FLAT ARCH
Authors: TAHERI A. R. , KARIMI M. T. , TAHMASEBI R. B. , SATVATI B. , FATOYE F. 
Published: April 2013

Background and aim: Flatfoot is characterized based on the height of the medial longitudinal arch of the foot relative to ground. The most common methods used to evaluate the severity of flatfoot and influences of the foot insole on the alignment of the foot structure in static situation are footprints and the use of X-ray. However, both of them have some limitations and cannot be used during walking while the subject uses the insole. Therefore, the aim of this research was to find a parameter which represents the alignment of the foot structure while walking. Methods: Two groups of normal and flat-arched subjects were recruited into this study. The location of center of ankle joint (COJ) and center of pressure (COP) while walking was obtained using Qualysis motion analysis system and a force plate. The area between COP and COJ in the medial side to the total area was the new parameter used in this study. Conclusion: The mean value of the new parameter was 74.65 ± 7.15 and 91.86 ± 12.4 for normal and flatfooted subjects, respectively. It appears that the new parameter can be used to check the alignment of the foot structure during walking. Clinical statement: The results of this research study can be used by clinicians to determine the alignment of the foot structure and the influence of the foot insole.
A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant Prostate Cancer and Bone Metastases
Authors: Lee Richard J. , Saylor Philip J. , Dror Michaelson M. , Michael Rothenberg S. , Smas Malgorzata E. , Miyamoto David T. , Gurski Carol A. , Xie Wanling , Maheswaran Shyamala , Haber Daniel A. , Goldin Jonathan G. , Smith Matthew R. 
Published: April 2013

Abstract
Background: Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100 mg daily) showed improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses.
Experimental Design: An adaptive design was used to determine the lowest active daily dose among 60, 40, and 20 mg. The primary endpoint was week 6 bone scan response, defined as ≥30% decrease in bone scan lesion area. The secondary endpoint was change in circulating tumor cells (CTC).
Results: Among 11 evaluable subjects enrolled at 40 mg, there were 9 partial responses (PR), 1 complete response, and 1 stable disease (SD). Of 10 subjects subsequently enrolled at 20 mg, there were 1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40 mg expansion cohort, there were 6 PRs and 7 SDs. No subjects required dose reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0 discontinued due to AEs by 12 weeks. At 40 mg, median treatment duration was 27 weeks. 58% of subjects with ≥5 CTCs/7.5mL at baseline converted to &lt;5.
Conclusions: Cabozantinib 40 mg daily was associated with a high rate of bone scan response. Cabozantinib 40 mg daily was associated with better tolerability than previously reported for cabozantinib 100 mg daily. These observations informed the design of phase III studies of cabozantinib in mCRPC. Clin Cancer Res; 19(11); 3088–94. ©2013 AACR.
Identifying Locations for Public Access Defibrillators Using Mathematical Optimization
Authors: Chan Timothy C.Y. , Li Heyse , Lebovic Gerald , Tang Sabrina K. , Chan Joyce Y.T. , Cheng Horace C.K. , Morrison Laurie J. , Brooks Steven C. 
Published: April 2013

Background—
Geospatial methods using mathematical optimization to identify clusters of cardiac arrests and prioritize public locations for defibrillator deployment have not been studied. Our objective was to develop such a method and test its performance against a population-guided approach.

Methods and Results—
All public location cardiac arrests in Toronto, Ontario, Canada, from December 16, 2005, to July 15, 2010, and all automated external defibrillator (AED) locations registered with Toronto Emergency Medical Services as of September 2009 were plotted geographically. Current AED coverage was quantified by determining the number of cardiac arrests occurring within 100 m of a registered AED. Clusters of cardiac arrests without a registered AED within 100 m were identified. With the use of mathematical optimization techniques, cardiac arrest coverage improvements were computed and shown to be superior to results from a population-guided deployment method. There were 1310 eligible public location cardiac arrests and 1669 registered AEDs. Of the eligible cardiac arrests, 304 were within 100 m of at least 1 registered AED (23% coverage). The average distance from a cardiac arrest to the closest AED was 281 m. With AEDs deployed in the top 30 locations, an additional 112 historical cardiac arrests would be covered (32% total coverage), and the average distance to the closest AED would be 262 m.

Conclusions—
Geographic clusters of cardiac arrests can be easily identified and prioritized with the use of mathematical modeling. Optimized AED deployment can increase cardiac arrest coverage and decrease the distance to the closest AED. Mathematical modeling can augment public AED deployment programs.
First the Revolutionary Culture
Authors: Scarritt Arthur 
Published: April 2013

The long-standing marginalization of highland Peru, coupled with the terrible violence of the 1980s and 1990s civil war, make it a difficult place for political mobilization. Nevertheless, one village successfully asserted its self-determination in the face of an exploitative political economy through conversion to Evangelical Christianity. A revolutionary cultural break from the mainstream created a vibrant local subculture that stressed brotherhood and provided meaning to adherents, allowing them to seize local opportunities to assert a more egalitarian social reality. While specific to this village’s conditions, these experiences speak to broader possibilities for innovative social change through novel combinations of cultural practices and political concerns. La marginalización de larga data del altiplano peruano, junto con la terrible violencia de la guerra civil de las décadas de 1980 y 1990, dificulta la movilización política. Sin embargo, un pueblo hizo valer exitosamente su auto-determinación frente a una economía política explotador a través de la conversión al cristianismo evangélico. Una separación cultural revolucionaria de la corriente principal creó una vibrante subcultura que ponía énfasis en la hermandad y proporcionó sentido a los adherentes, permitiéndoles aprovechar de oportunidades locales para imponer una realidad social más igualitaria. Aunque fueron particulares a las condiciones de este pueblo, estas experiencias anuncian posibilidades más extensas de cambio social a través de combinaciones novedosas de prácticas culturales y asuntos políticos.
Supraclavicular Artery Island Flap (SCAIF) vs Free Fasciocutaneous Flaps for Head and Neck Reconstruction
Authors: Granzow Jay W. , Suliman Ahmed , Roostaeian Jason , Perry Adam , Boyd J. Brian 
Published: April 2013

ObjectiveAt our institution, the supraclavicular artery island flap (SCAIF) has become a reliable option for fasciocutaneous coverage of complex head and neck (H&N) defects. We directly compare the outcomes of reconstructions performed with SCAIFs and free fasciocutaneous flaps (FFFs), which have not been reported previously.Study DesignRetrospective chart review.SettingTertiary academic medical center.Subjects and MethodsRetrospective review of consecutive single‐surgeon H&N reconstructions using fasciocutaneous flaps over 5 years. Reconstructions were divided into 2 groups: SCAIFs and FFFs. Patient demographics, surgical parameters, and outcomes were compared statistically between groups.ResultsThirty‐four flaps were used in H&N reconstruction (18 SCAIFs and 16 FFFs). There was no difference in patient demographics, distribution of defects, or follow‐up (SCAIF 9.2 vs FFF 15.13 months, P =. 65) between the 2 groups. The SCAIFs were larger than the FFFs (164.6 ± 60 vs 111 ± 68 cm2, P <. 05) and had shorter total operative times (588 ± 131 vs 816 ± 149 minutes, P <. 05). Intensive care unit (ICU) length of stay was shorter for the SCAIF vs the FFF group (1.8 vs 5.6 days, P <. 05). Overall morbidity was not significantly different (SCAIF 39% vs FFF 44%, P = NS).ConclusionThe SCAIF is a technically simpler and equally reliable sensate fasciocutaneous flap for H&N reconstruction with comparable outcomes, shorter operative time, less ICU stay, and no need for postoperative monitoring when compared with using FFFs. It should be considered a first‐choice reconstructive option for complex H&N defects.
Evaluation of in vitro and in vivo genotoxicity of single-walled carbon nanotubes
Authors: Kim Jin Sik , Song Kyung Seuk , Yu Il Je 
Published: April 2013

Single-walled carbon nanotubes (SWCNTs) have extensive potential industrial applications due to their unique physical and chemical properties; yet this also increases the chance of human and environment exposure to SWCNTs. Due to the current lack of hazardous effect information on SWNCTs, a standardized genotoxicity battery test was conducted to clarify the genetic toxicity potential of SWCNTs (diameter: 1–1.2 nm, length: ∼20 μm) according to Organization for Economic Cooperation and Development test guidelines 471 (bacterial reverse mutation test), 473 ( in vitro chromosome aberration test), and 474 ( in vivo micronuclei test) with a good laboratory practice system. The test results showed that the SWCNTs did not induce significant bacterial reverse mutations at 31.3–500 μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 or in Escherichia coli strain WP2uvrA, with and without a metabolic activation system. Furthermore, the in vitro chromosome aberration test showed no significant increase in structural or numerical chromosome aberration frequencies at SWCNT dose levels of 12.5–50 μg/ml in the presence and absence of metabolic activation. However, dose-dependent cell growth inhibition was found at all the SWCNT dose levels and statistically significant cytotoxic effects observed at certain concentrations in the presence and absence of metabolic activation. Finally, the SWCNTs did not evoke significant in vivo micronuclei frequencies in the polychromatic erythrocytes of an imprinting control region mice at 25–100 mg/kg. Thus, according to the results of the present study, the SWCNTs were not found to have a genotoxic effect on the in vitro and in vivo test systems.