bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of Dimer Conformation by the Dengue Virus Core Protein α4-α4′ Helix Pair Is Critical for Nucleocapsid Formation and Virus Production
Authors: Teoh Pak-Guan , Huang Zhi-Shun , Pong Wen-Li , Chen Po-Chiang , Wu Huey-Nan 
Published: May 2014

ABSTRACT

The virion of dengue virus (DENV) is composed of a viral envelope covering a nucleocapsid formed by a complex of viral genomic RNA and core protein (CP). DENV CP forms a dimer via the internal α2 and α4 helices of each monomer. Pairing of α2-α2′ creates a continuous hydrophobic surface, while the α4-α4′ helix pair joins the homodimer via side-chain interactions of the inner-edge residues. However, the importance of dimer conformation and the α4 helix of DENV CP in relation to its function are poorly understood. Loss of association between CP and lipid droplets (LDs) due to mutation suggests that the CP hydrophobic surface was not exposed, offering a possible explanation for the absence of dimers. Further assays suggest the connection between CP folding and protein stability. Attenuation of full-length RNA-derived virus production is associated with CP mutation, since no significant defects were detected in virus translation and replication. The
in vitro
characterization assays further highlighted that the α4-α4′ helix pair conformation is critical in preserving the overall α-helical content, thermostability, and dimer formation ability of CP, features correlated with the efficiency of nucleocapsid formation. Addition of Tween 20 improves
in vitro
nucleocapsid-like particle formation, suggesting the role of the LD in nucleocapsid formation
in vivo
. This study provides the first direct link between the α4-α4′ helix pair interaction and the CP dimer conformation that is the basis of CP function, particularly in nucleocapsid formation during virion production.

IMPORTANCE
Structure-based mutagenesis study of the dengue virus core protein (CP) reveals that the α4-α4′ helix pair is the key to maintaining its dimer conformation, which is the basis of CP function in nucleocapsid formation and virus production. Attenuation of full-length RNA-derived virus production is associated with CP mutation, since no significant defects in virus translation and replication were detected.
In vitro
inefficiency and size of nucleocapsid-like particle (NLP) formation offer a possible explanation for
in vivo
virus production inefficiency upon CP mutation. Further, the transition of NLP morphology from an incomplete state to an intact particle shown by α4-α4′ helix pair mutants in the presence of a nonionic detergent suggests the regulatory role of the intracellular lipid droplet (LD) in CP-LD interaction and in promoting nucleocapsid formation. This study provides the first direct link between the α4-α4′ helix pair interaction and CP dimer conformation that is the fundamental requirement of CP function, particularly in nucleocapsid formation during virion production.
Molecularly Tagged Simian Immunodeficiency Virus SIVmac239 Synthetic Swarm for Tracking Independent Infection Events
Authors: Del Prete Gregory Q. , Park Haesun , Fennessey Christine M. , Reid Carolyn , Lipkey Leslie , Newman Laura , Oswald Kelli , Kahl Christoph , Piatak Michael , Quiñones Octavio A. , Alvord W. Gregory , Smedley Jeremy , Estes Jacob D. , Lifson Jeffrey D. , Picker Louis J. , Keele Brandon F. 
Published: May 2014

ABSTRACT
Following mucosal human immunodeficiency virus type 1 transmission, systemic infection is established by one or only a few viral variants. Modeling single-variant, mucosal transmission in nonhuman primates using limiting-dose inoculations with a diverse simian immunodeficiency virus isolate stock may increase variability between animals since individual variants within the stock may have substantial functional differences. To decrease variability between animals while retaining the ability to enumerate transmitted/founder variants by sequence analysis, we modified the SIVmac239 clone to generate 10 unique clones that differ by two or three synonymous mutations (molecular tags). Transfection- and infection-derived virus stocks containing all 10 variants showed limited phenotypic differences in 9 of the 10 clones. Twenty-nine rhesus macaques were challenged intrarectally or intravenously with either a single dose or repeated, limiting doses of either stock. The proportion of each variant within each inoculum and in plasma from infected animals was determined by using a novel real-time single-genome amplification assay. Each animal was infected with one to five variants, the number correlating with the dose. Longitudinal sequence analysis revealed that the molecular tags are highly stable with no reversion to the parental sequence detected in >2 years of follow-up. Overall, the viral stocks are functional and mucosally transmissible and the number of variants is conveniently discernible by sequence analysis of a small amplicon. This approach should be useful for tracking individual infection events in preclinical vaccine evaluations, long-term viral reservoir establishment/clearance research, and transmission/early-event studies.

IMPORTANCE
Human immunodeficiency virus type 1 transmission is established by one or only a few viral variants. Modeling of limited variant transmission in nonhuman primates with a diverse simian immunodeficiency virus isolate stock may increase the variability between animals because of functional differences in the individual variants within the stock. To decrease such variability while retaining the ability to distinguish and enumerate transmitted/founder variants by sequence analysis, we generated a viral stock with 10 sequence-identifiable but otherwise genetically identical variants. This virus was characterized
in vitro
and
in vivo
and shown to allow discrimination of distinct transmission events. This approach provides a novel nonhuman primate challenge system for the study of viral transmission, evaluation of vaccines and other prevention approaches, and characterization of viral reservoirs and strategies to target them.
Financial incentives
Authors: Main David 
Published: May 2014

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Financial incentives’, was submitted and is discussed by David Main. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Giraffes’ greater good?’, which was published in the April issue of In Practice, appears on page 263.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
AREA-EFFICIENT DIGIT SERIAL–SERIAL TWO'S COMPLEMENT MULTIPLIER
Authors: ELSAYED ESSAM , EL-BOGHDADI HATEM 
Published: May 2014

Although parallel multipliers are optimal for speed, they occupy considerable chip area. For applications with lengthy operands as cryptography, the required area grows further. On the other hand, digit multipliers reduce chip area at the expense of the number of cycles required to complete the multiplication. In such multipliers, one-or-both inputs are received serially one digit per cycle. Digit multiplier designs are flexible with respect to the digit width enabling designers to select the most suitable compromise between area and cycle count for the application under consideration. This paper proposes a new digit serial–serial multiplier that is more area efficient compared to other functionally-similar multipliers. First, we propose a new unsigned digit serial–serial multiplier that is area efficient. The multiplier has the ability to handle unequal-width operands. That is, one operand can be of dynamic width (unlimited digit count) and the other operand is of fixed width. Moreover, with a small modification, the multiplier can operate on two's complement operands. Then, the design is extended to support bit-level pipelining: the critical path of the multiplier pipeline stage is independent of the operand width and the digit width. Simulation results show that the proposed multiplier reduces the area over similar multipliers by up to 28% and reduces power by up to 31%.
Validation of Methylation Biomarkers that Distinguish Normal Colon Mucosa of Cancer Patients from Normal Colon Mucosa of Patients without Cancer
Authors: Cesaroni Matteo , Powell Jasmine , Sapienza Carmen 
Published: May 2014

Abstract
We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate–strong correlation (Pearson coefficients r = 0.253–0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. Cancer Prev Res; 7(7); 717–26. ©2014 AACR.
It Is Time to Regulate Carcinogenic Tobacco-Specific Nitrosamines in Cigarette Tobacco
Authors: Hecht Stephen S. 
Published: May 2014

Abstract
The Family Smoking Prevention and Tobacco Control Act gives the U.S. Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and nonsmokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15- to 20-fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States. Cancer Prev Res; 7(7); 639–47. ©2014 AACR.
Investigating the Ice Water Path in Convective Cloud Life Cycles to Improve Passive Microwave Rainfall Retrievals
Authors: Braga Ramon Campos , Vila Daniel Alejandro 
Published: May 2014

Abstract
This study focuses on the possible relationship between ice water path (IWP) retrievals using high-frequency channels (89 and 150 GHz) from the Advanced Microwave Sounding Unit-B and Moisture Humidity Sounder sensors (NOAA-16–NOAA-19) and the life cycle stage of convective clouds. In the first part of this study, the relationship between IWP and the cloud area expansion rate is analyzed using the 235-K isotherm from Geostationary Operational Environmental Satellite-12 (GOES-12) thermal infrared images (10.7 μm). Next, the relationships between cloud convective fraction, rain rates (from ground radar), and cloud life cycle are analyzed. The selected area and time period coincide with the research activities of the Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud Resolving Modeling and to the Global Precipitation Measurement (CHUVA)–Geostationary Lightning Mapper (GLM) project at São José dos Campos, Brazil. The results show that 84% of precipitating clouds contain ice, according to the Microwave Surface and Precipitation Products System (MSPPS) algorithm. Convective systems in the intensifying stage (when the area is expanding and the minimum temperature is decreasing) tend to have larger IWPs than systems in the dissipating stage. Larger rain rates and convective fractions are also observed from radar retrievals in the early stage of convection compared with mature systems. Hydrometeor retrieval data from polarimetric X-band radar suggest that particle effective diameter De and IWP patterns inferred with the MSPPS algorithm could be used to determine the life cycle stage of a given convective system. Using this information, a new set of equations is evaluated for rainfall retrievals using De and IWP from the current retrieval algorithm. This new approach outperforms the current algorithm in the studied region.
Balloon Launch and Flight Operation from the Research Vessel Hakuho Maru for Stratospheric Air Sampling over the Eastern Pacific Equator
Authors: Fuke Hideyuki , Iijima Issei , Izutsu Naoki , Matsuzaka Yukihiko , Kato Yoichi , Kakehashi Yuya , Shoji Yasuhiro , Yoshida Tetsuya , Honda Hideyuki , Aoki Shuji , Inai Yoichi , Morimoto Shinji 
Published: May 2014

Abstract
A balloon-borne cryogenic air sampling experiment was carried out over the ocean near the equator to elucidate the transport process of greenhouse gases in the stratosphere. Four air samplers were launched from the deck of the Research Vessel Hakuho Maru by four individual balloons. To realize a balloon launch from this vessel’s narrow deck, a new launch method was developed, based on the conventional static launch method. After the balloon flight, each of the four samplers parachuted down to the sea and was recovered by the vessel itself. Details of this successful shipboard balloon operation, including the new launch method, are described.
Match Between Classroom Dimensions and Students’ Anthropometry
Authors: Macedo Angela C. , Morais André V. , Martins Henriqueta F. , Martins João C. , Pais Silvina M. , Mayan Olga S. 
Published: May 2014

Objective: The aim of this study was to investigate mismatch between students and classroom furniture dimensions and evaluate the improvement in implementing the European furniture standard. Background: In Portugal, school furniture does not meet any national ergonomic criteria, so it cannot fit students’ anthropometric measures. Method: A total of 893 students belonging to third (7th through 9th grades) and secondary (10th through 12th grades) cycles participated in the study. Anthropometric measurements of the students were gathered in several physical education classes. The furniture dimensions were measured for two models of tables and seats. Several two-way equations for match criteria based on published studies were applied to data. Results: The percentage of students who match with classroom furniture dimensions is low (24% and 44% between table and students, 4% and 9% between seat and students at 7th and 12th grades, respectively). Table is high for the third cycle, seat is high for both cycles, and seat depth fits well to students. No significant relationship was found between ergonomic mismatch and prevalence of pain. Conclusion: For each cycle, at least two different sizes indicated in the European standard should be available to students, considering the large variability in body dimensions within each cycle. The match criteria used gives a large percentage of students without pain in a mismatch situation. Application: Future measures applying to secondary schools should revise the decision of selecting a single size of classroom furniture and improve the implementation of the European standard. New criteria for ergonomic mismatch are needed that more closely model the responses about discomfort/pain.
Six-Step Recanalization Manual Therapy
Authors: Zhao Chunying , Tang Rui , Wang Jiandong , Guan Xiao , Zheng Jie , Hu Junyan , Hu Gaowu , Song Cong 
Published: May 2014

Background: Plugged ducts are a common, painful condition in lactating women, but no standard treatment is currently available. Objective: This study aimed to evaluate the clinical efficacy of a newly established 6-step recanalization manual therapy (SSRMT) for treating plugged ducts. Methods: This observational study included 3497 lactating women with plugged ducts. The SSRMT comprised the following well-defined steps: (1) preparation, (2) clearing the plugged duct outlets, (3) nipple manipulation, (4) pushing and pressing the areola, (5) pushing and kneading the breast, and (6) checking for residual milk stasis. The response to the treatment was graded as I (complete resolution), II (marked improvement), III (improvement), or IV (no response). Results: Of the 3497 patients, the mean age was 26.7 years and 3284 (93.9%) patients were primiparas. Fever was present in 1231 (35.2%) patients. After a single SSRMT treatment, 3189 (91.2%), 173 (4.9%), and 83 (2.4%) patients achieved grade I, II, and III responses, respectively, with only 52 (1.5%) showing unresponsiveness. For the 308 (8.8% of total) non-grade I patients, a second SSRMT given 3 days later resulted in grade I, II, and III responses in 267 (7.6% of total), 28 (0.8% of total), and 13 (0.4% of total) patients, respectively, and none were absolutely unresponsive. No complications with clinical significance were observed. Conclusion: Based on this large-scale clinical observation, SSRMT appears to be a useful, safe, low-cost treatment for postpartum plugged milk ducts.
Perceptions of recovery and prognosis from long-term conditions: The relevance of hope and imagined futures
Authors: Brooks Helen L , Rogers Anne , Sanders Caroline , Pilgrim David 
Published: May 2014

Objective Analyses of the experiences of chronic conditions demonstrate the importance of moral worth and social meaning linked to undertaking self-management practices. Rather less attention has been paid to the contemplation and significance of adopting, embedding and continuing with established practices overtime. This study explored perceptions about recovery and prognosis from the point of view of people with long-term physical health conditions and compared these findings with the mental health literature. Methods A longitudinal qualitative study was conducted incorporating semi-structured interviews and thematic analysis. Thirty-two participants identified as having a chronic long-term physical health condition such as heart disease and diabetes were included in the study. Results In line with the notions of recovery in the mental health field, respondents viewed recovery as a complex journey related to the ability to undertake things of value in everyday life. However, there were differences in relation to reflections on trajectories and imagined futures centred on physical health. Discussion These findings are discussed in the context of literature from the mental and physical health fields and recent health policies for those with long-term conditions. The study adds to existing literature by examining the similarities and differences in the experience of chronic physical and mental health conditions.
Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells
Authors: Makarona Kalliopi , Caputo Valentina S. , Costa Joana R. , Liu Binbin , O’Connor David , Iskander Deena , Roper David , Robertson Lynn , Bhatnagar Neha , Terpos Evangelos , Georgiou Elisabeth , Papaioannou Maria , Layton D. Mark , Luzzatto Lucio , Roberts Irene , Karadimitris Anastasios 
Published: May 2014

Key Points
Increase in HDAC binding is required for HDAC inhibitors to enhance gene transcription. G6PD deficiency in erythroid precursors can be restored by HDAC inhibitor-mediated increased transcription of the variant gene.
A note on norm inequalities for positive operators
Authors: Huang Jiewu , Peng Yang , Zou Limin 
Published: May 2014

Abstract
In this short note, we present a generalization of a norm inequality due to Bhatia and Kittaneh (Lett. Math. Phys. 43:225-231, 1998), which is also a refinement and a generalization of a result obtained by Kittaneh (Commun. Math. Phys. 104:307-310, 1986).

MSC:15A42, 47A63.
One-stage dorsal inlay oral mucosa graft urethroplasty for anterior urethral stricture
Authors: Liu Yidong , Zhuang Likai , Ye Weijing , Ping Ping , Wu Ming 
Published: May 2014

Abstract

Background
Anterior urethral stricture remains a great challenge. We reported our clinical technique and results by using inlay dorsal buccal mucosal graft urethroplasty for repair of anterior urethral stricture.

Methods
From January 2005 to July 2008, 87 male patients (range from 9 to 72 years old) with anterior urethral stricture have been treated by one-stage dorsal inlay oral mucosal graft (OMG) urethroplasty. All patients gave written informed consent for their participation. All patients showed that urethral plate had been either scarred or removed previously. In our surgery, the urethra was dissected dorsally and scar of the urethral plate was removed. The remnant urethral plate was split at midline and a buccal mucosa patch was inserted between the two parts. Neourethra was tubularized and covered with dartos flap. The pre-operative assessments included clinical data, urine analysis, uroflowmetry, retrograde and voiding cystogram, urethral ultrasonography and endoscopy. Postoperatively, the flow rate and void residual volume were analyzed by uroflowmetry and sonography. Any further instrumentation to assist voiding was considered as failure.

Results
After 12 to 48 months (mean: 25.8 months), 78 patients (89.66%) have shown good results by the one-stage urethroplasty. However, 9 patients (10.3%) required further treatment due to recurrence, while 6 patients (6.9%) had fistula.

Conclusions
This one-stage dorsal inlay approach using dorsal oral mucosal grafts is a reliable method to create a substitute urethral plate for tubularization. This approach represents a safe option for anterior urethral stricture patients especially with grossly scarred urethral plate.