bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas Turbine Icing in Cold Weather Pipeline Operation
Authors: Albone Trevor
Published: April 2015

The effect of ice formation and ingestion on ground based aircraft engine applications is described with a review of operating experience on a gas pipeline system. Measures introduced to reduce or eliminate the exposure of both the intake system and the engine are presented.
Compound Ejector Thrust Augmenter Development
Authors: Throndson L. W.
Published: April 2015

The basic simplicity of ejectors provides an advantageous form of engine thrust augmentation for V/STOL aircraft. Application requires careful internal aerodynamics development to provide high augmentation ratios in compact, short length, ejector installations. Development of the compound ejector through rig and wind tunnel tests is described wherein Coanda flow and improved central primary flow injection are combined. Several methods of reducing ejector volume are employed through increased mixing and diffusion rates while directing attention to loss sources such as inlet blockage.
U.S.C.G. Polar Star: Combination of a Diesel Electric Propulsion Plant With a Geared Gas Turbine Boost Plant
Authors: Finizio A. F.
Published: April 2015

The paper is a progress report on the selection and design of equipment for the U.S.C.G. Polar Icebreaker. A discussion of equipment concepts, designs, and modifications to off-the-shelf equipment is presented with a review of major design problem areas and solutions. The various modes of operation of the combined system with the attended degrees of flexibility and limitations of each are also defined.
Design and Application of Flexible Diaphragm Couplings to Industrial-Marine Gas Turbines
Authors: Rothfuss N. B.
Published: April 2015

This paper discusses the common needs of different industrial-marine gas turbine systems for flexible power transmission coupling shafts and shows how the flexible diaphragm coupling has been successfully applied to such gas turbines as the TPM FT-4, G. E.’s LM2500 and several others. Most aircraft derivatives and the larger industrial gas turbines require lightweight, maintenance-free, quiet flexible couplings. The diaphragm coupling will fill this need if properly designed and applied. Materials and methods of making preliminary natural frequency calculations and computer modeling of the diaphragm coupling are also discussed.
Real‐time markerless lung tumor tracking in fluoroscopic video: Handling overlapping of projected structures
Authors: Teske Hendrik , Mercea Paul , Schwarz Michael , Nicolay Nils H. , Sterzing Florian , Bendl Rolf
Published: April 2015

Purpose:

Fluoroscopic imaging is a well‐suited technique for online visualization of tumor motion in the thoracic region. Template‐based approaches for tumor tracking in such images are commonly used. However, overlapping of different structures, mainly bones, can lead to limited visibility of the projected tumor shape, which in turn can negatively affect the performance of the tracking method. In this study, a method based on multiple‐template matching was developed, providing fast and robust detection of tumor motion even under the influence of occurring tumor overlaps.

Methods:

A cohort of 14 patients with varying tumor sizes and locations was investigated. Image data from eight of these patients were used for evaluation. Based on the requirement of tumor visibility, the remaining datasets did not qualify for tracking. Generation of multiple templates was improved by implementation of an algorithm for automated selection of reference images containing the most characteristic tumor appearances. Various measures were taken to ensure real‐time capability of the algorithm. A prematching step was introduced in order to reduce dispensable comparison operations by selecting the most appropriate template. Subsequent matching was further optimized by using prior knowledge about likely tumor motion to effectively limit necessary matching tasks.

Results:

Tracking accuracy of the developed multiple‐template method was compared with that of single‐template. Mean errors of the multiple‐template approach were 0.6 ± 0.6 mm in left–right and 0.9 ± 0.9 mm in superior–inferior direction in the isocenter plane. The single‐template approach achieved mean errors of 0.7 ± 0.7 mm in left–right and 1.5 ± 1.3 mm in superior–inferior direction. These results derive from evaluation against manual tumor tracking performed by four expert observers. Computational times needed for tumor detection in a single fluoroscopic frame ranged between 1 and 29 ms depending on the tumor size and motion amplitude.

Conclusions:

This study shows that in case of tumor overlapping with dense structures, multiple‐template tracking provides more accurate results than a single‐template approach. The developed algorithm shows promising results in terms of suitability for real‐time application and robustness against frequently changing overlapping.
Characterization of a MOSkin detector for in vivo skin dose measurements during interventional radiology procedures
Authors: Safari M. J. , Wong J. H. D. , Ng K. H. , Jong W. L. , Cutajar D. L. , Rosenfeld A. B.
Published: April 2015

Purpose:

The MOSkin is a MOSFET detector designed especially for skin dose measurements. This detector has been characterized for various factors affecting its response for megavoltage photon beams and has been used for patient dose measurements during radiotherapy procedures. However, the characteristics of this detector in kilovoltage photon beams and low dose ranges have not been studied. The purpose of this study was to characterize the MOSkin detector to determine its suitability for in vivo entrance skin dose measurements during interventional radiology procedures.

Methods:

The calibration and reproducibility of the MOSkin detector and its dependency on different radiation beam qualities were carried out using RQR standard radiation qualities in free‐in‐air geometry. Studies of the other characterization parameters, such as the dose linearity and dependency on exposure angle, field size, frame rate, depth‐dose, and source‐to‐surface distance (SSD), were carried out using a solid water phantom under a clinical x‐ray unit.

Results:

The MOSkin detector showed good reproducibility (94%) and dose linearity (99%) for the dose range of 2 to 213 cGy. The sensitivity did not significantly change with the variation of SSD (±1%), field size (±1%), frame rate (±3%), or beam energy (±5%). The detector angular dependence was within ±5% over 360° and the dose recorded by the MOSkin detector in different depths of a solid water phantom was in good agreement with the Markus parallel plate ionization chamber to within ±3%.

Conclusions:

The MOSkin detector proved to be reliable when exposed to different field sizes, SSDs, depths in solid water, dose rates, frame rates, and radiation incident angles within a clinical x‐ray beam. The MOSkin detector with water equivalent depth equal to 0.07 mm is a suitable detector for in vivo skin dosimetry during interventional radiology procedures.
Seeking tests for a contested brain disease
Authors: Underwood Emily
Published: April 2015

FDA warning to UCLA highlights struggle to diagnose chronic traumatic encephalopathy.
Plan for E.U. research funds raises ire
Authors: Rabesandratana Tania
Published: April 2015

European Parliament vows to shield science budget from stimulus package raid.
Clinical trials get practical
Authors: Couzin-Frankel Jennifer
Published: April 2015

Many clinical trials don't help doctors make decisions. A new breed of studies aims to change that.
Revealing the secrets of intractable cellular functions: All-in-one-well methods for studying protein interaction and secretion
Authors: Lundbäck Thomas , Coussens Nathan P.
Published: April 2015

Protein-based assays are essential tools for many laboratories in both industrial and academic settings. Protein targets of interest are often found at low abundance and can be complex in nature, making their analysis intractable. One of the considerable challenges when developing assays is that small sample sizes can limit the amount of relevant information that can be extracted. The ability to miniaturize an assay allows sufficient data to be collected from scarce samples, while being able to interrogate multiple proteins simultaneously through multiplexing enables researchers to extract more data from each experiment and improve the biological relevance of the results significantly. This multiplexing ability provides the opportunity to quantitatively profile multiple signaling pathways from minute samples derived from very small cell populations. Furthermore, having the tools to directly study protein target binding in cells allows biologically relevant information to be preserved, including subcellular localization, posttranslational modifications, and the occurrence of multiple interactions with different accessory proteins and other scaffolding molecules. In this webinar, two examples of such approaches will be discussed. The first is the use of a method to amplify the signal in a target engagement assay using small samples, utilized to interrogate modulators of cytokine secretion. The second involves a so-called cellular thermal shift assay (CETSA) to detect protein-ligand interactions without the need to modify either the ligand or receptor, or the necessity for recombinant cell lines.
Big names or big ideas: Do peer-review panels select the best science proposals?
Authors: Li Danielle , Agha Leila
Published: April 2015

Proof that peer review picks promising proposals

A key issue in the economics of science is finding effective mechanisms for innovation. A concern about research grants and other research and development subsidies is that the public sector may make poor decisions about which projects to fund. Despite its importance, especially for the advancement of basic and early-stage science, there is currently no large-scale empirical evidence on how successfully governments select research investments. Li and Agha analyze more than 130,000 grants funded by the U.S. National Institutes of Health during 1980–2008 and find clear benefits of peer evaluations, particularly for distinguishing high-impact potential among the most competitive applications.

Science
, this issue p. 434
A rhodium catalyst for single-step styrene production from benzene and ethylene
Authors: Vaughan Benjamin A. , Webster-Gardiner Michael S. , Cundari Thomas R. , Gunnoe T. Brent
Published: April 2015

A more direct way to synthesize styrene

Foam cups, foam pellets, plastic cutlery: All are made of polystyrene, which in turn is made of styrene. The massive manufacturing scale of this commodity chemical places a premium on the efficiency of its synthesis. The current industrial route requires three steps to make styrene from benzene and ethylene. Vaughan
et al.
present a rhodium catalyst that achieves the coupling in a single step by using a recyclable copper salt as an oxidant. Although the catalyst is slow for industrial application, it demonstrates the viability of a more direct process.

Science
, this issue p. 421
Technology-driven layer-by-layer assembly of nanofilms
Authors: Richardson Joseph J. , Björnmalm Mattias , Caruso Frank
Published: April 2015

Thin-film fabrication

The deposition of thin films from multiple materials is essential to a range of materials fabrication processes. Layer-by-layer processes involve the sequential deposition of two or more materials that physically bond together. Richardson
et al.
review some of the techniques and materials that are used to make thin films, including sequential dip coating, spraying, and electrochemical deposition. Despite the versatility of the methods and the range of materials that can be deposited, the techniques remain mostly confined to the lab because of challenges in industrial scaling. But because there is tremendous scope for fine-tuning the structure and properties of the multilayers, there is interest in broadening the use of these techniques.

Science
, this issue
10.1126/science.aaa2491
Isolated compact elliptical galaxies: Stellar systems that ran away
Authors: Chilingarian Igor , Zolotukhin Ivan
Published: April 2015

Galaxies stripped down and evicted

It is easy to imagine that the relatively small and dense compact elliptical galaxies once had more to them. Especially when massive galactic neighbors are seen nearby that may have robbed them of their matter, but sometimes there are no such neighbors. Chilingarian and Zolotukhin have mined survey data to show that stripped-down galaxies are found in varied environments, with and without obvious disruptive companions. These isolated galaxies may still have been tidally stripped and then ejected from more crowded neighborhoods.

Science
, this issue p. 418
Translational tuning optimizes nascent protein folding in cells
Authors: Kim Soo Jung , Yoon Jae Seok , Shishido Hideki , Yang Zhongying , Rooney LeeAnn A. , Barral Jose M. , Skach William R.
Published: April 2015

Ribosomes help careful protein folding

Protein assembly in vitro is useful for studying small molecules but is problematic for studying the assembly of larger, more complex proteins. Kim
et al.
analyzed the biogenesis of the mutation-prone nucleotide-binding domain of the cystic fibrosis conductance regulator (CFTR) (see the Perspective by Puglisi). Newly synthesized polypeptides emerged relatively slowly from the ribosome and folded through a modulated pathway that ensured correct protein folding. Some parts of the protein chain folded immediately upon synthesis, whereas other segments did so more slowly. It appears that acquiring the correct conformation for this complex protein is partly guided by the ribosome itself.

Science
, this issue p. 444; see also p. 399
Genotype Considerations for Virus-Like Particle-Based Bivalent Norovirus Vaccine Composition
Authors: Malm Maria , Tamminen Kirsi , Lappalainen Suvi , Uusi-Kerttula Hanni , Vesikari Timo , Blazevic Vesna
Published: April 2015

Norovirus (NoV) genogroup I (GI) and GII are responsible for most human infections with NoV. Because of the high genetic variability of NoV, natural infection does not induce sufficient protective immunity to different genotypes or to variants of the same genotype and there is little or no cross-protection against different genogroups. NoV-derived virus-like particles (VLPs) are promising vaccine candidates that induce high levels of NoV-specific humoral and cellular immune responses. It is believed that a bivalent NoV vaccine consisting of a representative VLP from GI and GII is a minimum requirement for an effective vaccine. Here, we compared the abilities of monovalent immunizations with NoV GI.1-2001, GI.3-2002, GII.4-1999, and GII.4-2010 New Orleans VLPs to induce NoV type-specific and cross-reactive immune responses and protective blocking antibody responses in BALB/c mice. All of the VLPs induced comparable levels of type-specific serum IgG antibodies, as well as blocking antibodies to the VLPs used for immunization. However, the abilities of different VLP genotypes to induce cross-reactive IgG and cross-blocking antibodies varied remarkably. Our results confirm previous findings of a lack of cross-protective immune responses between GI and GII NoVs. These data support the rationale for including NoV GI.3 and GII.4-1999 VLPs in the bivalent vaccine formulation, which could be sufficient to induce protective immune responses across NoV genotypes in the two common genogroups in humans.
Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen Streptococcus suis
Authors: Gurung Mamata , Tamang Migma Dorji , Moon Dong Chan , Kim Su-Ran , Jeong Jin-Ha , Jang Geum-Chan , Jung Suk-Chan , Park Yong-Ho , Lim Suk-Kyung
Published: April 2015

Characterization of 227
Streptococcus suis
strains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to the
tet
gene,
erm
(B),
erm
(C),
mph
(C), and
mef
(A) and/or
mef
(E) genes,
aph(3′)-IIIa
and
aac(6′)-Ie-aph(2″)-Ia
genes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively.
Comparative Profile of Heme Acquisition Genes in Disease-Causing and Colonizing Nontypeable Haemophilus influenzae and Haemophilus haemolyticus
Authors: Hariadi Nurul I. , Zhang Lixin , Patel Mayuri , Sandstedt Sara A. , Davis Gregg S. , Marrs Carl F. , Gilsdorf Janet R.
Published: April 2015

Nontypeable
Haemophilus influenzae
(NTHI) are Gram-negative bacteria that colonize the human pharynx and can cause respiratory tract infections, such as acute otitis media (AOM). Since NTHI require iron from their hosts for aerobic growth, the heme acquisition genes may play a significant role in avoiding host nutritional immunity and determining virulence. Therefore, we employed a hybridization-based technique to compare the prevalence of five heme acquisition genes (
hxuA
,
hxuB
,
hxuC
,
hemR
, and
hup
) between 514 middle ear strains from children with AOM and 235 throat strains from healthy children. We also investigated their prevalences in 148
Haemophilus haemolyticus
strains, a closely related species that colonizes the human pharynx and is considered to be nonpathogenic. Four out of five genes (
hxuA
,
hxuB
,
hxuC
, and
hemR
) were significantly more prevalent in the middle ear strains (96%, 100%, 100%, and 97%, respectively) than in throat strains (80%, 92%, 93%, and 85%, respectively) of NTHI, suggesting that strains possessing these genes have a virulence advantage over those lacking them. All five genes were dramatically more prevalent in NTHI strains than in
H. haemolyticus
, with 91% versus 9%
hxuA
, 98% versus 11%
hxuB
, 98% versus 11%
hxuC
, 93% versus 20%
hemR
, and 97% versus 34%
hup
, supporting their potential role in virulence and highlighting their possibility to serve as biomarkers to distinguish
H. influenzae
from
H. haemolyticus
. In summary, this study demonstrates that heme acquisition genes are more prevalent in disease-causing NTHI strains isolated from the middle ear than in colonizing NTHI strains and
H. haemolyticus
isolated from the pharynx.
High-Level Pan-Azole-Resistant Aspergillosis
Authors: van Ingen Jakko , van der Lee Henrich A. L. , Rijs Antonius J. M. M. , Snelders Eveline , Melchers Willem J. G. , Verweij Paul E.
Published: April 2015

High-level pan-azole-resistant
Aspergillus fumigatus
was recovered from four patients with chronic lung disease. In one patient, the development of progressive resistance followed long-term azole therapy and switching between antifungal azoles. The high-level pan-azole-resistant phenotypes were not associated with a specific
cyp51A
gene mutation. New strategies that avoid the development of progressive azole resistance are needed.
Impact of the MRN Complex on Adeno-Associated Virus Integration and Replication during Coinfection with Herpes Simplex Virus 1
Authors: Millet Rachel , Jolinon Nelly , Nguyen Xuan-Nhi , Berger Gregory , Cimarelli Andrea , Greco Anna , Bertrand Pascale , Odenthal Margarete , Büning Hildegard , Salvetti Anna
Published: April 2015

Adeno-associated virus (AAV) is a helper-dependent parvovirus that requires coinfection with adenovirus (AdV) or herpes simplex virus 1 (HSV-1) to replicate. In the absence of the helper virus, AAV can persist in an episomal or integrated form. Previous studies have analyzed the DNA damage response (DDR) induced upon AAV replication to understand how it controls AAV replication. In particular, it was shown that the Mre11-Rad50-Nbs1 (MRN) complex, a major player of the DDR induced by double-stranded DNA breaks and stalled replication forks, could negatively regulate AdV and AAV replication during coinfection. In contrast, MRN favors HSV-1 replication and is recruited to AAV replication compartments that are induced in the presence of HSV-1. In this study, we examined the role of MRN during AAV replication induced by HSV-1. Our results indicated that knockdown of MRN significantly reduced AAV DNA replication after coinfection with wild-type (wt) HSV-1 or HSV-1 with the polymerase deleted. This effect was specific to wt AAV, since it did not occur with recombinant AAV vectors. Positive regulation of AAV replication by MRN was dependent on its DNA tethering activity but did not require its nuclease activities. Importantly, knockdown of MRN also negatively regulated AAV integration within the human AAVS1 site, both in the presence and in the absence of HSV-1. Altogether, this work identifies a new function of MRN during integration of the AAV genome and demonstrates that this DNA repair complex positively regulates AAV replication in the presence of HSV-1.

IMPORTANCE
Viral DNA genomes trigger a DNA damage response (DDR), which can be either detrimental or beneficial for virus replication. Adeno-associated virus (AAV) is a defective parvovirus that requires the help of an unrelated virus such as adenovirus (AdV) or herpes simplex virus 1 (HSV-1) for productive replication. Previous studies have demonstrated that the cellular Mre11-Rad50-Nbs1 (MRN) complex, a sensor and regulator of the DDR, negatively regulates AAV replication during coinfection with AdV, which counteracts this effect by inactivating the complex. Here, we demonstrate that MRN positively regulates AAV replication during coinfection with HSV-1. Importantly, our study also indicates that MRN also favors integration of AAV genomes within the human AAVS1 site. Altogether, this work indicates that MRN differentially regulates AAV replication depending on the helper virus which is present and identifies a new function of this DNA repair complex during AAV integration.
Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection
Authors: Jochems Simon P. , Jacquelin Beatrice , Chauveau Lise , Huot Nicolas , Petitjean Gaël , Lepelley Alice , Liovat Anne-Sophie , Ploquin Mickaël J. , Cartwright Emily K. , Bosinger Steven E. , Silvestri Guido , Barré-Sinoussi Françoise , Lebon Pierre , Schwartz Olivier , Müller-Trutwin Michaela C.
Published: April 2015

Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4
+
T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV
in vivo
identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor.

IMPORTANCE
The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I interferon (IFN-I) upon heterologous SIVmac/HIV type 1 (HIV-1) encounter, while they sensed autologous SIVagm isolates. Pseudotyping SIVmac/HIV-1 overcame this deficiency, suggesting that reduced uptake of heterologous viral strains underlays this lack of sensing. The distinct IFN-I responses depending on host species and HIV/SIV isolates reveal the host/virus species specificity of pDC sensing.
Particle-to-PFU Ratio of Ebola Virus Influences Disease Course and Survival in Cynomolgus Macaques
Authors: Alfson Kendra J. , Avena Laura E. , Beadles Michael W. , Staples Hilary , Nunneley Jerritt W. , Ticer Anysha , Dick Edward J. , Owston Michael A. , Reed Christopher , Patterson Jean L. , Carrion Ricardo , Griffiths Anthony
Published: April 2015

This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (
Macaca fascicularis
) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease
in vivo
. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures.

IMPORTANCE
Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks possessing either high or low specific infectivities. Interestingly, some particles that did not yield plaques in cell culture assays were able to result in lethal disease
in vivo
. Furthermore, the number of PFU needed to induce lethal disease in animals was very low. Our results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures.
Nonneutralizing Antibodies Induced by the HIV-1 gp41 NHR Domain Gain Neutralizing Activity in the Presence of the HIV Fusion Inhibitor Enfuvirtide: a Potential Therapeutic Vaccine Strategy
Authors: Wang Qian , Bi Wenwen , Zhu Xiaojie , Li Haoyang , Qi Qianqian , Yu Fei , Lu Lu , Jiang Shibo
Published: April 2015

A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines.
Move Over, Bacteria! Viruses Make Their Mark as Mutualistic Microbial Symbionts
Authors: Roossinck Marilyn J.
Published: April 2015

Viruses are being redefined as more than just pathogens. They are also critical symbiotic partners in the health of their hosts. In some cases, viruses have fused with their hosts in symbiogenetic relationships. Mutualistic interactions are found in plant, insect, and mammalian viruses, as well as with eukaryotic and prokaryotic microbes, and some interactions involve multiple players of the holobiont. With increased virus discovery, more mutualistic interactions are being described and more will undoubtedly be discovered.
A cluster randomised trial of cloth masks compared with medical masks in healthcare workers
Authors: MacIntyre C Raina , Seale Holly , Dung Tham Chi , Hien Nguyen Tran , Nga Phan Thi , Chughtai Abrar Ahmad , Rahman Bayzidur , Dwyer Dominic E , Wang Quanyi
Published: April 2015

Editor's Note

The authors of this article, published in 2015, have written a response to their work in light of the COVID-19 pandemic. We urge our readers to consider the response when reading the article.https://bmjopen.bmj.com/content/5/4/e006577.responses#covid-19-shortages-of-masks-and-the-use-of-cloth-masks-as-a-last-resort

Objective

The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks.

Setting

14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam.

Participants

1607 hospital HCWs aged ≥18 years working full-time in selected high-risk wards.

Intervention

Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks.

Main outcome measure

Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection.

Results

The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%.

Conclusions

This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated.

Trial registration number

Australian New Zealand Clinical Trials Registry: ACTRN12610000887077.
Paediatric reference interval and biological variation trends of thyrotropin (TSH) and free thyroxine (T4) in an Asian population
Authors: Loh Tze Ping , Sethi Sunil Kumar , Metz Michael Patrick
Published: April 2015

Aims

To describe the reference intervals and biological variation data for thyrotropin (TSH) and free thyroxine (FT4) in a mixed Asian population using an indirect sampling approach and to compare them with published reports.

Methods

TSH and FT4 of children measured once or twice over a 7-year period (2008–2014) at primary-care and tertiary-care settings were extracted from the laboratory information system. After excluding outliers, age-related reference intervals were derived using the Lambda-Mu-Sigma (LMS) approach, while age-partitioned biological variation data were obtained according to recommendations by Fraser and Harris.

Results

Both TSH and FT4 were very high at birth and declined with age. Similarly within-individual and between-individual biological variations were higher for both TSH and FT4 at birth and also declined with age. Our data were broadly similar to previous studies. Significant heterogeneity in study population and methods prohibited direct numerical comparison between this and previously published studies.

Conclusions

This study fills two important gaps in our knowledge of paediatric thyroid function by reporting the centile trends (and reference values) in a mixed Asian population, as well as providing age-partitioned biological variation data. The variation in published reference intervals highlights the difficulty in harmonising paediatric thyroid reference intervals or recommending universal clinical cut-offs.
Behaviourally designed treatments that increase willingness to treatment from families with children suffering from autism spectrum disorder
Authors: Bogliacino Francesco , Parra Forero Israel Andrés
Published: April 2015

Background

Autism spectrum disorder is a lifelong disability that is not well known by the general population and tends to be associated with social stigma; also, because it involves children, it may get highly emotionally charged. These stylised facts engender a number of possible heuristics and biases at the moment of deciding on following a treatment or looking for a diagnosis, which should be considered in the presentation of information. Using insights from Behavioural Economics, three treatments are designed to present the information regarding possible therapies.

Methods

Between-subjects design with one level of variation. Interviews were performed with a convenience sample of 154 households from the metropolitan area of Bogotá (Colombia). The treatments include: use of default option, use of professional interviewer to illustrate the therapy and emotionally charged presentation.

Results

Kruskal-Wallis test of the intention to be treated rejects the null hypothesis (χ2=22.14, p=0.00). The cognitive processing of the information is not a determinant, supporting the claim that genuine framing effects shape the choice. The strongest effect of the treatment with a professional suggests a key role for asymmetry of the information, which is confirmed indirectly through the postexperiment questionnaire.

Conclusions

Bad healthcare decisions are not necessarily driven by lack of information. Asymmetric information (eg, delegating the decision to a professional) improves choices, especially when social stigma is involved. Cognitive processing of information seems to be less relevant than the framing effect.
Root system development and architecture in various genotypes of the Solanaceae family
Authors: Bui Hong Hai , Serra Valérie , Pagès Loïc
Published: April 2015

We present an extensive, dynamic, and quantitative study of the root system architecture of Solanaceae based on 29 genotypes from three important groups (aubergines, capsicums, and tomatoes). Quantitative traits were essentially obtained from measurements made on high resolution images of different plant parts at several stages. The developmental schema was common to all genotypes. Several traits showed significant genetic variations: root apical diameter (reflecting meristem size), interbranch distances, slopes of the regression lines of elongation rate versus apical diameter, and ratios of diameters of laterals to mother roots. On all genotypes, the initial root system was complemented by a strong adventitious system emerging near the plant collar, made up of a set of fast growing roots with large apical diameters. Correlations between traits were evidenced within the root systems on one hand (e.g., interbranch distance and diameter ratio of laterals to their mother) and between shoot and root on the other hand (e.g., leaf area growth rate and root elongation rate). They revealed both trade-offs in developmental processes and coordination between plant parts. Beyond these results, we demonstrated the importance of characterizing phenotypes through multiple criteria, considering the whole plant and including late stages.
Enhancing plant productivity while suppressing biofilm growth in a windowfarm system using beneficial bacteria and ultraviolet irradiation
Authors: Lee Seungjun , Ge Chongtao , Bohrerova Zuzana , Grewal Parwinder S. , Lee Jiyoung
Published: April 2015

Common problems in a windowfarm system (a vertical and indoor hydroponic system) are phytopathogen infections in plants and excessive buildup of biofilms. The objectives of this study were (i) to promote plant health by making plants more resistant to infection by using beneficial biosurfactant-producing Pseudomonas chlororaphis around the roots and (ii) to minimize biofilm buildup by ultraviolet (UV) irradiation of the water reservoir, thereby extending the lifespan of the whole system with minimal maintenance. Pseudomonas chlororaphis-treated lettuce grew significantly better than nontreated lettuce, as indicated by enhancement of color, mass, length, and number of leaves per head (p < 0.05). The death rate of the lettuce was reduced by ∼50% when the lettuce was treated with P. chlororaphis. UV irradiation reduced the bacteria (4 log reduction) and algae (4 log reduction) in the water reservoirs and water tubing systems. Introduction of P. chlororaphis into the system promoted plant growth and reduced damage caused by the plant pathogen Pythium ultimum. UV irradiation of the water reservoir reduced algal and biofilm growth and extended the lifespan of the system.
IS256 abolishes gelatinase activity and biofilm formation in a mutant of the nosocomial pathogen Enterococcus faecalis V583
Authors: Perez Marta , Calles-Enríquez Marina , del Rio Beatriz , Ladero Victor , Martín María Cruz , Fernández María , Alvarez Miguel A.
Published: April 2015

Enterococcus faecalis is one of the most controversial species of lactic acid bacteria. Some strains are used as probiotics, while others are associated with severe and life-threatening nosocomial infections. Their pathogenicity depends on the acquisition of multidrug resistance and virulence factors. Gelatinase, which is required in the first steps of biofilm formation, is an important virulence determinant involved in E. faecalis pathogenesis, including endocarditis and peritonitis. The gene that codes for gelatinase (gelE) is controlled by the Fsr quorum-sensing system, whose encoding genes (fsrA, fsrB, fsrC, and fsrD) are located immediately upstream of gelE. The integration of a DNA fragment into the fsr locus of a derived mutant of E. faecalis V583 suppressed the gelatinase activity and prevented biofilm formation. Sequence analysis indicated the presence of IS256 integrated into the fsrC gene at nucleotide position 321. Interestingly, IS256 is also associated with biofilm formation in Staphylococcus epidermidis and Staphylococcus aureus. This is the first description of an insertion sequence that prevents biofilm formation in E. faecalis.
Amelioration of palmitate-induced metabolic dysfunction in L6 muscle cells expressing low levels of receptor-interacting protein 140
Authors: Constantinescu Silvana , Turcotte Lorraine P.
Published: April 2015

We have shown that reduced expression of receptor-interacting protein 140 (RIP140) alters the regulation of fatty-acid (FA) oxidation in muscle. To determine whether a high level of FA availability alters the effects of RIP140 on metabolic regulation, L6 myotubes were transfected with or without RNA interference oligonucleotide sequences to reduce RIP140 expression, and then incubated with high levels of palmitic acid, with or without insulin. High levels of palmitate reduced basal (53%–58%) and insulin-treated (24%–44%) FA uptake and oxidation, and increased basal glucose uptake (88%). In cells incubated with high levels of palmitate, low RIP140 increased basal FA uptake and insulin-treated FA oxidation and glucose uptake, and decreased basal glucose uptake and insulin-treated FA uptake. Under basal conditions, low RIP140 increased the mRNA content of FAT/CD36 (159%) and COX4 (61%), as well as the protein content of Nur77 (68%), whereas the mRNA expression of FGF21 (50%) was decreased, as was the protein content of CPT1b (35%) and FGF21 (44%). Under insulin-treated conditions, low RIP140 expression increased the mRNA content of MCAD (84%) and Nur77 (84%), as well as the protein content of Nur77 (23%). Thus, a low level of RIP140 restores the rates of FA uptake in the basal state, in part via a reduction in upstream insulin signaling. Our data also indicate that the protein expression of Nur77 may be modulated by RIP140 when muscle cells are metabolically challenged by high levels of palmitate.
Unbounded energies of debris from head-on particle collisions near black holes
Authors: Zaslavskii O. B.
Published: April 2015

If two particles move toward a black hole and collide near the horizon, the energy E c.m. in the centre of mass can grow unbounded. This is a so-called Bañados–Silk–West (BSW) effect. One of the problems creating obstacles to the possibility of its observation consists in that individual energy E of a fragment at infinity remains finite because of redshift. We show that in the case of head-on collision, debris may have unbounded energy E. An essential ingredient of this scenario is a particle moving away from a black hole in the near-horizon region. It can appear due to precedent collision that implies multiple scattering.
Design of a 10-Bit High Performance Current-Steering DAC with a Novel Nested Decoder Based on Domino Logic
Authors: Nazari Masoud , Sharifi Leila , Akbari Meysam , Hashemipour Omid
Published: April 2015

In this paper, a 10-bit 8-2 segmented current-steering digital-to-analog converter (DAC) is presented which uses a novel nested binary to thermometer (BT) decoder based on domino logic gates. High accuracy and high performances are achieved with this structure. The proposed decoder has a pipelining scheme and it is designed symmetrically in three stages with repeatable logic gates. Thus, power consumption, chip area and the number of control signals are reduced. The proposed DAC is simulated in 0.18-μm CMOS technology and the spurious-free dynamic range (SFDR) is 65.3 dB over a 500 MHz output bandwidth at 1 GS/s. Total power consumption of the designed DAC is only 23.4 mW while the digital and analog supply voltages are 1.2 and 1.8 V, respectively. The active area of the proposed DAC is equal to 0.3 mm2.
Interacting dark energy in f(T) cosmology: A dynamical system analysis
Authors: Biswas Sujay Kr. , Chakraborty Subenoy
Published: April 2015

This paper deals with an interacting dark energy (DE) model in the framework of f(T) cosmology. A cosmologically viable form of f(T) is chosen (T is the torsion scalar in teleparallelism) in the background of flat homogeneous and isotropic Friedmann–Robertson–Walker (FRW) spacetime model of the universe. The matter content of the universe is chosen as dust interacting with minimally coupled scalar field. The evolution equations are reduced to an autonomous system of ordinary differential equations by suitable transformation of variables. The nature of critical points is analyzed by evaluating the eigenvalues of the linearized Jacobi matrix and stable attractors are examined from the point of view of cosmology. Finally, both classical and quantum stability of the model have been discussed.
Fluid sphere: Stability problem and dimensional constraint
Authors: Rahaman Farook , Pradhan Anirudh , Ahmed Nasr , Ray Saibal , Saha Bijan , Rahaman Mosiur
Published: April 2015

We study different dimensional fluids inspired by noncommutative geometry which admit conformal Killing vector (CKV). The solutions of the Einstein field equations were examined specifically for five different set of spacetime. We calculate the active gravitational mass and impose stability conditions of the fluid sphere. The analysis thus carried out immediately indicates that at four dimension only one can get a stable configuration for any spherically symmetric stellar system and any other dimension, lower or higher, becomes untenable as far as the stability of a system is concerned.
Mechanotransduction of trigeminal ganglion neurons innervating inner walls of rat anterior eye chambers
Authors: Meng Qingli , Fang Peng , Hu Zhuangli , Ling Yun , Liu Haixia
Published: April 2015

To address mechanoreceptive roles of trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior eye chambers, we investigated the mechanotransduction process and mechanosensitive (MS) channel on somata of TG neurons innervating this area in vitro. Rat TG neurons innervating inner walls of anterior chambers were labeled by anterior chamber injection of 1,1′-dilinoleyl-3,3,3′,3′-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (FAST DiI). The neuronal cell bodies were voltage clamped using a whole cell patch-clamp technique, while it was deformed by ejection of bath solution to verify mechanotransduction. Immunofluorescence staining was performed on sections of TG ganglia to determine the specific MS channel proteins. Mechanical stimuli induced MS currents in 55 out of 96 FAST DiI-labeled TG neurons. The MS currents exhibited mechanical intensity-dependent and clamp voltage-dependent characteristics. Mechanical stimulation further enhanced the membrane potential and increased the frequency of action potentials. Transient receptor potential ankyrin 1 (TRPA1), TRP vanilloid 4 (TRPV4), acid-sensing ion channel (ASIC) 2 and ASIC3 channel proteins were expressed in FAST DiI-labeled TG neurons. The inhibitory effect of HC-030031, a specific inhibitor of TRPA1, on MS currents demonstrated that TRPA1 was an essential MS channel protein. Taken together, our results show that mechanical stimuli induce MS currents via MS channels such as TRPA1 to trigger mechanotransduction in TG neurons innervating inner walls of anterior chambers. Our results indicate the existence of mechanoreceptive TG nerve endings in inner walls of anterior chambers. Whether the mechanoreceptive TG nerve endings play a role in intraocular pressure sensation warrants further investigation.
Cardiovascular responses to forearm muscle metaboreflex activation during hypercapnia in humans
Authors: Delliaux Stephane , Ichinose Masashi , Watanabe Kazuhito , Fujii Naoto , Nishiyasu Takeshi
Published: April 2015

We characterized the cardiovascular responses to forearm muscle metaboreflex activation during hypercapnia. Ten healthy males participated under three experimental conditions: 1) hypercapnia (HCA, PetCO2: +10 mmHg, by inhalation of a CO2-enriched gas mixture); 2) muscle metaboreflex activation (MMA, by 5 min of local circulatory occlusion after 1 min of 50% maximum voluntary contraction isometric handgrip under normocapnia); and 3) HCA+MMA. We measured mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO); calculated stroke volume (SV), and total peripheral resistance (TPR); and evaluated myocardial oxygen consumption (MV̇o2) and cardiac work (CW) noninvasively. MAP increased in the three experimental conditions but HCA+MMA led to the highest MAP, CO, and HR. Moreover, HCA+MMA increased SV and was associated with the highest MV̇o2and CW. HCA and MMA exhibited inhibitory interactions with MAP, HR, TPR, MV̇o2, and CW, increases of which were smaller during HCA+MMA than the sum of the increases during HCA and MMA alone (MAP: +28 ± 2 vs. +34 ± 2 mmHg, P < 0.001; HR: +15 ± 2 vs. +22 ± 3 bpm, P < 0.01; TPR: +1.1 ± 1.4 vs. +3.0 ± 1.5 mmHg·l·min−1, P < 0.05; MV̇o2: +50.25 ± 4.74 vs. +59.48 ± 5.37 mmHg·min−1·10−2, P < 0.01; CW: +59.10 ± 7.52 vs. +63.67 ± 7.71 ml mmHg·min−1·10−4, P < 0.05). Oppositely, HCA and MMA interactions were linearly additive for CO (+2.3 ± 0.4 l/min) and SV (+13 ± 4 ml). We showed that muscle metaboreflex and hypercapnia interact in healthy humans, reducing vasoconstriction but enhancing SV.