bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of high aspect ratio TiO2 and Al2O3 nanogratings by atomic layer deposition
Authors: Shkondin Evgeniy , Takayama Osamu , Lindhard Jonas Michael , Larsen Pernille Voss , Mar Mikkel Dysseholm , Jensen Flemming , Lavrinenko Andrei V.
Published: April 2016

The authors report on the fabrication of TiO2 and Al2O3 nanostructured gratings with an aspect ratio of up to 50. The gratings were made by a combination of atomic layer deposition (ALD) and dry etch techniques. The workflow included fabrication of a Si template using deep reactive ion etching followed by ALD of TiO2 or Al2O3. Then, the template was etched away using SF6 in an inductively coupled plasma tool, which resulted in the formation of isolated ALD coatings, thereby achieving high aspect ratio grating structures. SF6 plasma removes silicon selectively without any observable influence on TiO2 or Al2O3, thus revealing high selectivity throughout the fabrication. Scanning electron microscopy was used to analyze every fabrication step. Due to nonreleased stress in the ALD coatings, the top parts of the gratings were observed to bend inward as the Si template was removed, thus resulting in a gradual change in the pitch value of the structures. The pitch on top of the gratings is 400 nm, and it gradually reduces to 200 nm at the bottom. The form of the bending can be reshaped by Ar+ ion beam etching. The chemical purity of the ALD grown materials was analyzed by x-ray photoelectron spectroscopy. The approach presented opens the possibility to fabricate high quality optical metamaterials and functional nanostructures.
Kinetic mechanism of V-shaped twinning in 3C/4H-SiC heteroepitaxy
Authors: Xin Bin , Zhang Yu-Ming , Wu Hong-Ming , Feng Zhe Chuan , Lin Hao-Hsiung , Jia Ren-Xu
Published: April 2016

The authors investigated the kinetic mechanism of V-shaped twinning in 3C/4H-SiC heteroepitaxy. A fourfold V-shaped twinning complex was found, and its interface was measured with high-resolution transmission electron microscopy (HRTEM). Two linear coherent boundaries and a nonlinear incoherent boundary (also called the double-position boundary) were observed. On the basis of the HRTEM results, the authors proposed an adatom migration growth model, in which the activation barrier at the coherent boundary is much lower than that at the incoherent boundary. From a kinetic perspective, adatoms are prone to migrate to the side of the boundary with the lower potential energy if they have sufficient thermal energy to overcome the activation barrier. In the case of a coherent boundary, the growth rates of the domains either side of the boundary can be balanced through the intermigration of adatoms, leading to a linear boundary. Conversely, it is difficult for adatoms to migrate across an incoherent boundary, which results in asynchronous growth rates and a nonlinear boundary.
Biocompatible and target specific hydrophobically modified glycol chitosan nanoparticles
Authors: Yin Wei , Li Weiyi , Rubenstein David A. , Meng Yizhi
Published: April 2016

Cardiovascular disease is the leading cause of death in the United States. Atherosclerosis is a major cause for cardiovascular diseases. Drugs that treat atherosclerosis usually act nonspecifically. To enhance drug delivery specificity, the authors developed a hydrophobically modified glycol chitosan (HGC) nanoparticle that can specifically target activated endothelial cells. The biocompatibility of these nanoparticles toward red blood cells and platelets was evaluated through hemolysis, platelet activation, platelet thrombogenicity, and platelet aggregation assays. The biocompatibility of these nanoparticles toward vascular endothelial cells was evaluated by their effects on endothelial cell growth, metabolic activity, and activation. The results demonstrated that HGC nanoparticles did not cause hemolysis, or affect platelet activation, thrombogenicity, and aggregation capability in vitro. The nanoparticles did not impair vascular endothelial cell growth or metabolic activities in vitro, and did not cause cell activation either. When conjugated with intercellular adhesion molecular 1 antibodies, HGC nanoparticles showed a significantly increased targeting specificity toward activated endothelial cells. These results suggested that HGC nanoparticles are likely compatible toward red blood cells, platelets, and endothelial cells, and they can be potentially used to identify activated endothelial cells at atherosclerotic lesion areas within the vasculature, and deliver therapeutic drugs.
Kepler enlists relativity to find planets
Authors: Clery Daniel
Published: April 2016

Exotic search technique promises a small but rich harvest of extrasolar worlds.
How colonization by microbiota in early life shapes the immune system
Authors: Gensollen Thomas , Iyer Shankar S. , Kasper Dennis L. , Blumberg Richard S.
Published: April 2016

Microbial colonization of mucosal tissues during infancy plays an instrumental role in the development and education of the host mammalian immune system. These early-life events can have long-standing consequences: facilitating tolerance to environmental exposures or contributing to the development of disease in later life, including inflammatory bowel disease, allergy, and asthma. Recent studies have begun to define a critical period during early development in which disruption of optimal host-commensal interactions can lead to persistent and in some cases irreversible defects in the development and training of specific immune subsets. Here, we discuss the role of early-life education of the immune system during this “window of opportunity,” when microbial colonization has a potentially critical impact on human health and disease.
Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens
Authors: Pamer Eric G.
Published: April 2016

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria.
Parenteral Vaccination Can Be an Effective Means of Inducing Protective Mucosal Responses
Authors: Clements John D. , Freytag Lucy C.
Published: April 2016

The current paradigm in vaccine development is that nonreplicating vaccines delivered parenterally fail to induce immune responses in mucosal tissues. However, both clinical and experimental data have challenged this concept, and numerous studies have shown that induction of mucosal immune responses after parenteral vaccination is not a rare occurrence and might, in fact, significantly contribute to the protection against mucosal infections afforded by parenteral vaccines. While the mechanisms underlying this phenomenon are not well understood, the realization that parenteral vaccination can be an effective means of inducing protective mucosal responses is paradigm-shifting and has potential to transform the way vaccines are designed and delivered.
Comparison of Culture-Based Methods for Identification of Colonization with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in the Context of Cocolonization
Authors: Davis Meghan F. , Hu Baofeng , Carroll Karen C. , Bilker Warren B. , Tolomeo Pam , Cluzet Valerie C. , Baron Patrick , Ferguson Jacqueline M. , Morris Daniel O. , Rankin Shelley C. , Lautenbach Ebbing , Nachamkin Irving
Published: April 2016

Two screening methods to detect staphylococcal colonization in humans were compared. Direct plating to CHROMagar (BD Diagnostics) was compared to a broth preenrichment followed by plating to Baird-Parker agar. The broth-enrichment method was comparable to CHROMagar for methicillin-resistant
Staphylococcus aureas
(MRSA) detection, but the enrichment method was optimum for recovery of coagulase-positive
Staphylococcus
spp.
Use of Shotgun Metagenome Sequencing To Detect Fecal Colonization with Multidrug-Resistant Bacteria in Children
Authors: Andersen Heidi , Connolly Natalia , Bangar Hansraj , Staat Mary , Mortensen Joel , Deburger Barbara , Haslam David B.
Published: April 2016

Prevention of multidrug-resistant (MDR) bacterial infections relies on accurate detection of these organisms. We investigated shotgun metagenome sequencing for the detection of methicillin-resistant
Staphylococcus aureus
(MRSA), vancomycin-resistant
Enterococcus
(VRE), and MDR
Enterobacteriaceae
. Fecal metagenomes were analyzed from high-risk inpatients and compared to those of low-risk outpatients and controls with minimal risk for a MDR bacterial infection. Principal-component analysis clustered patient samples into distinct cohorts, confirming that the microbiome composition was significantly different between cohorts (
P
= 0.006). Microbial diversity and relative anaerobe abundance were preserved in outpatients compared to those in controls. Relative anaerobe abundance was significantly reduced in inpatients compared to that in outpatients (
P
= 0.006). Although the potential for MDR bacteria was increased in inpatients and outpatients compared to that in controls (
P
< 0.001), there was no difference between inpatients and outpatients. However, 9 (53%) inpatients had colonization with a MDR bacterium that was not identified by culture. Unlike culture, shotgun sequencing quantitatively characterizes the burdens of multiple MDR bacteria relative to all of the microbiota within the intestinal community. We propose consideration of key microbiome features, such as diversity and relative anaerobe abundance, in addition to the detection of MDR bacteria by shotgun metagenome sequencing as a novel method that might better identify patients who are at increased risk of a MDR infection.
Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins
Authors: Bronnimann Matthew P. , Calton Christine M. , Chiquette Samantha F. , Li Shuaizhi , Lu Mingfeng , Chapman Janice A. , Bratton Kristin N. , Schlegel Angela M. , Campos Samuel K.
Published: April 2016

Despite an abundance of evidence supporting an important role for the cleavage of minor capsid protein L2 by cellular furin, direct cleavage of capsid-associated L2 during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved cleavage site, close to the L2 N terminus, confounds observation and quantification of the small cleavage product by SDS-PAGE. To overcome this difficulty, we increased the size shift by fusing a compact protein domain, the
Propionibacterium shermanii
transcarboxylase domain (PSTCD), to the N terminus of L2. The infectious PSTCD-L2 virus displayed an appreciable L2 size shift during infection of HaCaT keratinocytes. Cleavage under standard cell culture conditions rarely exceeded 35% of total L2. Cleavage levels were enhanced by the addition of exogenous furin, and the absolute levels of infection correlated to the level of L2 cleavage. Cleavage occurred on both the HaCaT cell surface and extracellular matrix (ECM). Contrary to current models, experiments on the involvement of cyclophilins revealed little, if any, role for these cellular enzymes in the modulation of furin cleavage. HPV16 L2 contains two consensus cleavage sites, Arg5 (
2
RHKR
5
) and Arg12 (
9
RTKR
12
). Mutant PSTCD-L2 viruses demonstrated that although furin can cleave either site, cleavage must occur at Arg12, as cleavage at Arg5 alone is insufficient for successful infection. Mutation of the conserved cysteine residues revealed that the Cys22-Cys28 disulfide bridge is not required for cleavage. The PSTCD-L2 virus or similar N-terminal fusions will be valuable tools to study additional cellular and viral determinants of furin cleavage.

IMPORTANCE
Furin cleavage of minor capsid protein L2 during papillomavirus infection has been difficult to directly visualize and quantify, confounding efforts to study this important step of HPV infection. Fusion of a small protein domain to the N terminus greatly facilitates direct visualization of the cleavage product, revealing important characteristics of this critical process. Contrary to the current model, we found that cleavage is largely independent of cyclophilins, suggesting that cyclophilins act either in parallel to or downstream of furin to trigger exposure of a conserved N-terminal L2 epitope (RG-1) during infection. Based on this finding, we strongly caution against using L2 RG-1 epitope exposure as a convenient but indirect proxy of furin cleavage.
Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry
Authors: Rhein Bethany A. , Brouillette Rachel B. , Schaack Grace A. , Chiorini John A. , Maury Wendy
Published: April 2016

Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the
Filoviridae
family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion–TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions.

IMPORTANCE
With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor.
Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets
Authors: Sun Honglei , Pu Juan , Wei Yandi , Sun Yipeng , Hu Jiao , Liu Litao , Xu Guanlong , Gao Weihua , Li Chong , Zhang Xuxiao , Huang Yinhua , Chang Kin-Chow , Liu Xiufan , Liu Jinhua
Published: April 2016

Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans.

IMPORTANCE
Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored.
Evolution of Neuroadaptation in the Periphery and Purifying Selection in the Brain Contribute to Compartmentalization of Simian Immunodeficiency Virus (SIV) in the Brains of Rhesus Macaques with SIV-Associated Encephalitis
Authors: Rife Brittany D. , Nolan David J. , Lamers Susanna L. , Autissier Patrick , Burdo Tricia , Williams Kenneth C. , Salemi Marco
Published: April 2016

The emergence of a distinct subpopulation of human or simian immunodeficiency virus (HIV/SIV) sequences within the brain (compartmentalization) during infection is hypothesized to be linked to AIDS-related central nervous system (CNS) neuropathology. However, the exact evolutionary mechanism responsible for HIV/SIV brain compartmentalization has not been thoroughly investigated. Using extensive viral sampling from several different peripheral tissues and cell types and from three distinct regions within the brain from two well-characterized rhesus macaque models of the neurological complications of HIV infection (neuroAIDS), we have been able to perform in-depth evolutionary analyses that have been unattainable in HIV-infected subjects. The results indicate that, despite multiple introductions of virus into the brain over the course of infection, brain sequence compartmentalization in macaques with SIV-associated CNS neuropathology likely results from late viral entry of virus that has acquired through evolution in the periphery sufficient adaptation for the distinct microenvironment of the CNS.

IMPORTANCEHIV-associated neurocognitive disorders remain prevalent among HIV type 1-infected individuals, whereas our understanding of the critical components of disease pathogenesis, such as virus evolution and adaptation, remains limited. Building upon earlier findings of specific viral subpopulations in the brain, we present novel yet fundamental results concerning the evolutionary patterns driving this phenomenon in two well-characterized animal models of neuroAIDS and provide insight into the timing of entry of virus into the brain and selective pressure associated with viral adaptation to this particular microenvironment. Such knowledge is invaluable for therapeutic strategies designed to slow or even prevent neurocognitive impairment associated with AIDS.
Colony-Stimulating Factor 1 Receptor Antagonists Sensitize Human Immunodeficiency Virus Type 1-Infected Macrophages to TRAIL-Mediated Killing
Authors: Cunyat Francesc , Rainho Jennifer N. , West Brian , Swainson Louise , McCune Joseph M. , Stevenson Mario
Published: April 2016

Strategies aimed at eliminating persistent viral reservoirs from HIV-1-infected individuals have focused on CD4
+
T-cell reservoirs. However, very little attention has been given to approaches that could promote elimination of tissue macrophage reservoirs. HIV-1 infection of macrophages induces phosphorylation of colony-stimulating factor 1 receptor (CSF-1R), which confers resistance to apoptotic pathways driven by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thereby promoting viral persistence. In this study, we assessed whether CSF-1R antagonists (PLX647, PLX3397, and PLX5622) restored apoptotic sensitivity of HIV-1-infected macrophages
in vitro
. PLX647, PLX3397, and PLX5622 at clinically relevant concentrations blocked the activation of CSF-1R and reduced the viability of infected macrophages, as well as the extent of viral replication. Our data show that strategies targeting monocyte colony-stimulating factor (MCSF) signaling could be used to promote elimination of HIV-1-infected myeloid cells and to contribute to the elimination of persistent viral reservoirs.

IMPORTANCE
As the HIV/AIDS research field explores approaches to eliminate HIV-1 in individuals on suppressive antiviral therapy, those approaches will need to eliminate both CD4
+
T-cell and myeloid cell reservoirs. Most of the attention has focused on CD4
+
T-cell reservoirs, and scant attention has been paid to myeloid cell reservoirs. The distinct nature of the infection in myeloid cells versus CD4
+
T cells will likely dictate different approaches in order to achieve their elimination. For CD4
+
T cells, most strategies focus on promoting virus reactivation to promote immune-mediated clearance and/or elimination by viral cytopathicity. Macrophages resist viral cytopathic effects and CD8
+
T-cell killing. Therefore, we have explored clearance strategies that render macrophages sensitive to viral cytopathicity. This research helps inform the design of strategies to promote clearance of the macrophage reservoir in infected individuals on suppressive antiviral therapy.
Human Norovirus Interactions with Histo-Blood Group Antigens and Human Milk Oligosaccharides
Authors: Schroten Horst , Hanisch Franz-Georg , Hansman Grant S.
Published: April 2016

Human noroviruses interact with both human histo-blood group antigens (HBGAs) and human milk oligosaccharides (HMOs). The former are believed to be important for a virus infection, while the latter might act as natural decoys in the host during an infection. However, certain noroviruses are known to bind poorly to HBGAs and yet still cause infections; some interact with numerous HBGA types but are nonprevalent; and yet others bind HBGAs and seem to be increasing in prevalence. HBGAs and HMOs can be found as soluble antigens in humans, can be structurally alike, and can interact with equivalent residues at identical binding pockets on the capsid. In this Gem, we discuss HBGA and HMO binding studies for human noroviruses, concentrating on the clinically important genogroup II noroviruses. In short, the roles of HBGA and HMO interactions in norovirus infections are still unclear.
Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies
Authors: von Bredow Benjamin , Arias Juan F. , Heyer Lisa N. , Moldt Brian , Le Khoa , Robinson James E. , Zolla-Pazner Susan , Burton Dennis R. , Evans David T.
Published: April 2016

Although antibodies to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been studied extensively for their ability to block viral infectivity, little data are currently available on nonneutralizing functions of these antibodies, such as their ability to eliminate virus-infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 Env-specific antibodies of diverse specificities, including potent broadly neutralizing and nonneutralizing antibodies, were therefore tested for ADCC against cells infected with a lab-adapted HIV-1 isolate (HIV-1NL4-3), a primary HIV-1 isolate (HIV-1JR-FL), and a simian-human immunodeficiency virus (SHIV) adapted for pathogenic infection of rhesus macaques (SHIVAD8-EO). In accordance with the sensitivity of these viruses to neutralization, HIV-1NL4-3-infected cells were considerably more sensitive to ADCC, both in terms of the number of antibodies and magnitude of responses, than cells infected with HIV-1JR-FLor SHIVAD8-EO. ADCC activity generally correlated with antibody binding to Env on the surfaces of virus-infected cells and with viral neutralization; however, neutralization was not always predictive of ADCC, as instances of ADCC in the absence of detectable neutralization, and vice versa, were observed. These results reveal incomplete overlap in the specificities of antibodies that mediate these antiviral activities and provide insights into the relationship between ADCC and neutralization important for the development of antibody-based vaccines and therapies for combating HIV-1 infection.

IMPORTANCEThis study provides fundamental insights into the relationship between antibody-dependent cell-mediated cytotoxicity (ADCC) and virus neutralization that may help to guide the development of antibody-based vaccines and immunotherapies for the prevention and treatment of HIV-1 infection.
Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection
Authors: Jiang Jingwen , Li Jing , Fan Wenhui , Zheng Weinan , Yu Meng , Chen Can , Sun Lei , Bi Yuhai , Ding Chan , Gao George F. , Liu Wenjun
Published: April 2016

Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins.

IMPORTANCE
Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination.
Biphasic CD8
+
T-Cell Defense in Simian Immunodeficiency Virus Control by Acute-Phase Passive Neutralizing Antibody Immunization
Authors: Iseda Sumire , Takahashi Naofumi , Poplimont Hugo , Nomura Takushi , Seki Sayuri , Nakane Taku , Nakamura Midori , Shi Shoi , Ishii Hiroshi , Furukawa Shota , Harada Shigeyoshi , Naruse Taeko K. , Kimura Akinori , Matano Tetsuro , Yamamoto Hiroyuki
Published: April 2016

Identifying human immunodeficiency virus type 1 (HIV-1) control mechanisms by neutralizing antibodies (NAbs) is critical for anti-HIV-1 strategies. Recent
in vivo
studies on animals infected with simian immunodeficiency virus (SIV) and related viruses have shown the efficacy of postinfection NAb passive immunization for viremia reduction, and one suggested mechanism is its occurrence through modulation of cellular immune responses. Here, we describe SIV control in macaques showing biphasic CD8
+
cytotoxic T lymphocyte (CTL) responses following acute-phase NAb passive immunization. Analysis of four SIV
mac239
-infected rhesus macaque pairs matched with major histocompatibility complex class I haplotypes found that counterparts receiving day 7 anti-SIV polyclonal NAb infusion all suppressed viremia for up to 2 years without accumulating viral CTL escape mutations. In the first phase of primary viremia control attainment, CD8
+
cells had high capacities to suppress SIVs carrying CTL escape mutations. Conversely, in the second, sustained phase of SIV control, CTL responses converged on a pattern of immunodominant CTL preservation. During this sustained phase of viral control, SIV epitope-specific CTLs showed retention of phosphorylated extracellular signal-related kinase (ERK)
hi
/phosphorylated AMP-activated protein kinase (AMPK)
lo
subpopulations, implying their correlation with SIV control. The results suggest that virus-specific CTLs functionally boosted by acute-phase NAbs may drive robust AIDS virus control.

IMPORTANCE
In early HIV infection, NAb responses are lacking and CTL responses are insufficient, which leads to viral persistence. Hence, it is important to identify immune responses that can successfully control such HIV replication. Here, we show that monkeys receiving NAb passive immunization in early SIV infection strictly control viral replication for years. Passive infusion of NAbs with CTL cross-priming capacity resulted in induction of functionally boosted early CTL responses showing enhanced suppression of CTL escape mutant virus replication. Accordingly, the NAb-infused animals did not show accumulation of viral CTL escape mutations during sustained SIV control, and immunodominant CTL responses were preserved. This early functional augmentation of CTLs by NAbs provides key insights into the design of lasting and viral escape mutation-free protective immunity against HIV-1 infection.
GcsR, a TyrR-Like Enhancer-Binding Protein, Regulates Expression of the Glycine Cleavage System in Pseudomonas aeruginosa PAO1
Authors: Sarwar Zaara , Lundgren Benjamin R. , Grassa Michael T. , Wang Michael X. , Gribble Megan , Moffat Jennifer F. , Nomura Christopher T.
Published: April 2016

Glycine is required for various cellular functions, including cell wall synthesis, protein synthesis, and the biosynthesis of several important metabolites. Regulating levels of glycine metabolism allows
P. aeruginosa
to maintain the metabolic flux of glycine through several pathways, including the metabolism of glycine to produce other amino acids, entry into the trichloroacetic acid cycle, and the production of virulence factors such as hydrogen cyanide. In this study, we characterized GcsR, a transcriptional regulator that activates the expression of genes involved in
P. aeruginosa
PAO1 glycine metabolism. Our work reveals that GcsR is the founding member of a novel class of TyrR-like EBPs that likely regulate glycine metabolism in
Pseudomonadales
.
Fully automated PCR detection of KRAS mutations on pancreatic endoscopic ultrasound fine-needle aspirates
Authors: de Biase Dario , de Luca Caterina , Gragnano Gianluca , Visani Michela , Bellevicine Claudio , Malapelle Umberto , Tallini Giovanni , Troncone Giancarlo
Published: April 2016

Aims

In cystic and solid pancreatic lesions,KRASmutational status refines the diagnosis of uncertain endoscopic ultrasound (EUS) aspirates. This test should have a fast turnaround time and ideally be performed at the centre where the patient is diagnosed. The Idylla KRAS Mutation Test enables standardisation even in units without molecular expertise.

Methods

The Idylla test was designed for use with formalin-fixed paraffin-embedded (FFPE) sections. However, we directly pipetted 3 µL (corresponding to 1/10th of a DNA preparation from the aspirate sample) in the cartridge, which was automatically run as if an FFPE sample had been inserted. The performance was compared with Sanger sequencing, Allele Specific Locked Nucleic Acid PCR (ASLNAqPCR), and 454 Next Generation Sequencing (454-NGS) in light of clinicopathological end points.

Results

Idylla yielded valid results in 49/52 (94.2%) cases, in 2 h. A total of 18/49 cases showed mutation either in KRAS exon 2 (14/18) or in exon 3 (4/18). Idylla KRAS test had 100% specificity and a sensitivity (55.1%) higher than Sanger sequencing (41.3%) and identical to ASLNAqPCR (55.1%). When the low-abundant mutant allele (<5%) cases were excluded from the analysis, the Idylla KRAS Mutation Test clinical sensitivity increased to 61.9% approaching that of 454-NGS (66.6%).

Conclusions

This is the first study that applied the novel Idylla KRAS test to the clinical setting of pancreatic cancer. In particular, this system can be easily implemented in the routine assessment of pancreatic EUS-fine-needle aspiration-derived DNA samples to quickly provide information on KRAS mutational status to supplement cytological evaluation.
Positivity of metrics on conic neighborhoods of 1-convex submanifolds
Authors: Prezelj Jasna
Published: April 2016

Let [Formula: see text] be a holomorphic submersion from a complex manifold [Formula: see text] onto a 1-convex manifold [Formula: see text] with exceptional set [Formula: see text] and [Formula: see text] a holomorphic section. Let [Formula: see text] be a plurisubharmonic exhaustion function which is strictly plurisubharmonic on [Formula: see text] with [Formula: see text] For every holomorphic vector bundle [Formula: see text] there exists a neighborhood [Formula: see text] of [Formula: see text] for [Formula: see text] conic along [Formula: see text] such that [Formula: see text] can be endowed with Nakano strictly positive Hermitian metric. Let [Formula: see text] [Formula: see text] be a given holomorphic function. There exist finitely many bounded holomorphic vector fields defined on a Stein neighborhood [Formula: see text] of [Formula: see text] conic along [Formula: see text] with zeroes of arbitrary high order on [Formula: see text] and such that they generate [Formula: see text] Moreover, there exists a smaller neighborhood [Formula: see text] such that their flows remain in [Formula: see text] for sufficiently small times thus generating a local dominating spray.
The hypergeometric systems and the contiguity operators on the Grassmannian manifold and on the associated configuration space
Authors: Mimachi Katsuhisa , Sasaki Takeshi
Published: April 2016

The hypergeometric system [Formula: see text] and the contiguity operators defined on the space of [Formula: see text] matrices [Formula: see text] induce the systems and the contiguity operators on the Grassmannian manifold [Formula: see text] and on the configuration space [Formula: see text] where [Formula: see text] is the group consisting of diagonal matrices of size [Formula: see text]. The first purpose of this paper is to give a rigorous treatment of these systems and contiguity operators, the second is to derive a condition that the system [Formula: see text] is reducible, and the third is to derive the contiguity relations and the contiguous relations satisfied by the solutions of the system on [Formula: see text] or the solutions of the system on [Formula: see text]
The influence of bus stop on traffic flow with velocity-difference-separation model
Authors: Zheng Pengjun , Wang Wei , Ge Hongxia
Published: April 2016

Based on velocity-difference-separation model, the mixed traffic flow on two-lane road is investigated. For a fixed road length, the influence of bus and bus stops on traffic flow is studied with the increasing traffic density. Compared with the result without bus stops given by Li et al., a new traffic state is found, which is valuable for studying the impacts of public transport on urban traffic flow.
Simple prescription for computing the nonrelativistic interparticle potential energy related to dual models
Authors: de Gracia G. B. , de Brito G. P.
Published: April 2016

Following a procedure recently utilized by Accioly et al. to obtain the D-dimensional interparticle potential energy for electromagnetic models in the nonrelativistic limit, and relaxing the condition assumed by the authors concerning the conservation of the external current, the prescription found out by them is generalized so that dual models can also be contemplated. Specific models in which the interaction is mediated by a spin-0 particle described first by a vector field and then by a higher-derivative vector field, are analyzed. Systems mediated by spin-1 particles described, respectively, by symmetric rank-2 tensors, symmetric rank-2 tensors augmented by higher derivatives and antisymmetric rank-2 tensors, are considered as well.
Detection of shape and sizes of magnetic impurity based on the shape of magnetic domain configuration
Authors: Akimov M. L. , Polyakov P. A. , Banishev A. A. , Usmanov N. N.
Published: April 2016

The phenomenon of domain magnetic shielding by the magnetic sample of external and intrinsic magnetostatic field has been revealed. In this work, we investigate the possibility for detection of the shape and size of magnetic impurity based on the shape of magnetic domain configuration in magnetic film. We show that due to the influence of magnetostatic field of stripe domain structure in magnetic film on the magnetostatic field of magnetic impurity, one can determine the shape and size of this impurity.
Design of a High-Frequency Very Low-Power Direct Digital Frequency Synthesizer
Authors: Hasannezhad Mojtaba , Jannesari Abumoslem , Lotfizad Mojtaba
Published: April 2016

This paper presented a low-power Direct Digital Frequency Synthesizer (DDFS) using non-uniform sine-weighted digital-to-analog convertor (DAC). To avoid the need for a sharp filter to generate signals near and beyond the Nyquist frequency, parallel DACs, which cause to speed relaxation in a single DAC as well, and return-to-zero (RZ) technique were used. To reduce the area and power in parallel DACs, non-uniform sine-weighted DAC design method was proposed. This technique causes to reduce power consumption in DACs up to 48.47%, and nearly the same amount of reduction in the area. Meanwhile, by modifying weights of DAC cells, Gilbert cell, the latter block in DDFS structure, was omitted. Although these proposed methods are quite frequency independent, simulations with MATLAB and Cadence in 0.18[Formula: see text][Formula: see text]m CMOS technology were used to demonstrate those. Then, the designed DDFS with 5-bit frequency resolution could generate different output sine signals with acceptable spurious free dynamic range (SFDR).
Formally Modeling and Analyzing the Reliability of Cloud Applications
Authors: Fan Guisheng , Yu Huiqun , Chen Liqiong
Published: April 2016

Cloud computing has become an important, useful paradigm for building applications with cloud services. However, cloud services exist in heterogeneous environments on the Internet. It is challenging to guarantee the reliability of cloud applications. Although there are efforts studying cloud and grid service reliability, very few have considered the modeling and analysis of the reliability of cloud applications. To address this emerging, important problem, we propose the first systematic approach that considers both cloud application elements and their running environment so as to faithfully model the dynamics of cloud computing.

First, we present a formal description language to model the different components of a cloud application, and use it to analyze the static and dynamic factors affecting the reliability of cloud applications. Second, we propose reliability assurance strategies to ensure that cloud applications dynamically meet their required reliability. Third, Computation Tree Logic (CTL) is used to convert the reliability assurance strategy into the CTL formulas. We present operational semantics and related theories of Petri nets for establishing the correctness of our proposed method. Finally, a series of simulations are performed to evaluate the efficiency of our proposed approach.
SEPARABLE LOCAL FRACTIONAL DIFFERENTIAL EQUATIONS
Authors: KOLWANKAR KIRAN M.
Published: April 2016

The concept of local fractional derivative was introduced in order to be able to study the local scaling behavior of functions. However it has turned out to be much more useful. It was found that simple equations involving these operators naturally incorporate the fractal sets into the equations. Here, the scope of these equations has been extended further by considering different possibilities for the known function. We have also studied a separable local fractional differential equation along with its method of solution.
TEMPERATURE EFFECT ON MICROSTRUCTURE AND AGGREGATION BEHAVIOR OF GOLD ATOMIC AGGREGATES ON SILICONE OIL SURFACE
Authors: FENG YUANXIN , ZHANG CHUHANG
Published: April 2016

By thermal evaporation method, gold (Au) atomic aggregates were fabricated on a silicone oil surface and the aggregation mechanism was investigated. It is found that the apparent surface coverage ([Formula: see text]) of the Au aggregates dropped obviously, from 15% to 12% as the oil temperature (T) increased from 285[Formula: see text]K to 353[Formula: see text]K. Meanwhile, the average width of the aggregates gradually increased from 0.36[Formula: see text][Formula: see text]m to 0.50[Formula: see text][Formula: see text]m, indicating the aggregates combine with each other as T increased. By the atomic force microscopy observation, Au nanoparticles with diameter around 45.0 nm were observed in the aggregates, which were independent with T. Similarly, the average height of the aggregates found remain unchanged at around 10.0[Formula: see text]nm as T increased. The anomalous aggregation mechanism of Au aggregates suggests that a compact microstructure for Au aggregates is preferred at high T rather than three-dimensional (3D) growth, which is quite different from that of Ag aggregates.
Multi-Objective Optimization of Wire Electrical Discharge Machining (WEDM) Process Parameters Using Weighted Sum Genetic Algorithm Approach
Authors: Padhi P. C. , Mahapatra S. S. , Yadav S. N. , Tripathy D. K.
Published: April 2016

The present work is aimed at optimizing the cutting rate (CR), surface roughness (Ra) and dimensional deviation (DD) in wire electrical discharge machining (WEDM) of EN-31 steel considering various input parameters such as pulse-on-time, pulse-off-time, wire tension, spark gap set voltage and servo feed. A face centered central composite design of response surface methodology (RSM) has been adopted to develop the empirical model for the responses. It is often desired to obtain a single parameter setting that can decrease Ra and DD and increase CR simultaneously. Since the responses are conflicting in nature, it is difficult to obtain a single combination of cutting parameters satisfying all the objectives in any one solution. The optimum search of the machining parameter values for maximization of CR and minimization of Ra and DD are formulated as a multi-objective, multi-variable, nonlinear optimization problem using genetic algorithm weighted sum method to evaluate the performance.
Two-party quantum key agreement based on four-particle GHZ states
Authors: He Ye-Feng , Ma Wen-Ping
Published: April 2016

Based on four-particle GHZ states, the double CNOT operation and the delayed measurement technique, a two-party quantum key agreement (QKA) protocols is proposed. The double CNOT operation makes each four-particle GHZ state collapse into two independent quantum states without any entanglement. Furthermore, one party can directly know the two quantum states and the other party can be aware of the two quantum states by using the corresponding measurement. According to the initial states of the two quantum states, two parties can extract the secret keys of each other by using the publicly announced value or by performing the delayed measurement, respectively. Then the protocol achieves the fair establishment of a shared key. The security analysis shows that the new protocol can resist against participant attacks, the Trojan horse attacks and other outsider attacks. Furthermore, the new protocol also has no information leakage problem and has high qubit efficiency.
Reactive Collision Avoidance of UAVs with Simple Pin-hole Camera Based Passive Stereovision Sensing
Authors: Tripathi Amit Kumar , Padhi Radhakant
Published: April 2016

An effective reactive collision avoidance algorithm is presented in this paper for unmanned aerial vehicles (UAVs) using two simple inexpensive pinhole cameras. The vision sensed data, which consists of the azimuth and elevation angles at the two camera positions, is first processed through a Kalman filter formulation to estimate the position and velocity of the obstacle. Once the obstacle position is estimated, the collision cone philosophy is used to predict the collision over a short period of time. In case a collision is predicted, steering guidance commands are issued to the vehicle to steer its velocity vector away using the nonlinear differential geometric guidance. A new cubic spline based post-avoidance merging algorithm is also presented so that the vehicle rejoins the intended global path quickly in a smooth manner after avoiding the obstacle. The overall algorithm has been validated using the point mass model of a prototype UAV with first-order autopilot delay. Both extended Kalman filtering (EKF) and unscented Kalman filtering (UKF) have been experimented. Both are found to be quite effective. However, performance of UKF was found to be better than EKF with minor compromise in computational efficiency and hence it can be a better choice. Note that because of two cameras, stereovision signature gets associated with optical flow signature thereby making the overall signature quite strong for obstacle position estimation. This leads to a good amount of success as compared to the usage of a single pinhole camera, results of which has been published earlier.
Timing analysis of P-FRP systems
Authors: Underwood Danielle , Cheng Albert M. K.
Published: April 2016

P-FRP systems are relatively new, so little research has been done on how tasks are best scheduled using the P-FRP paradigm. This paper provides a background of the subjects that timing analysis must cover, and concludes with suggestions for future research to be done in this field.