bluuebunny/crossref_metadata_2025 huggingface dataset:
Stresses in Half-Elliptic Curved Beams Subjected to Transverse Tip Forces
Authors: Velazquez Eduardo , Kosmatka J. B.
Published: June 2012

In-plane bending of curved beams produces substantial through-thickness normal and shear stresses that can result in structural failures. A half-elliptic curved beam, having a known prescribed variable radius of curvature, is studied as an extension of the previously published circular arc beam. The equations for the normal, tangential, and shear stresses are developed for a curved beam outlined by two confocal half ellipses loaded by a pair of concentrated perpendicular forces on its ends. Closed-form analytical solutions for the stresses are found using an elasticity approach, where the solution is found by using selected terms of the biharmonic equation in elliptic coordinates. For the case of an elliptic beam with an aspect ratio of very close to unity, the solution closely agrees with published circular beam solutions. For other elliptic beam aspect ratios, the calculated stresses display good correlation to detailed finite element model solutions for thickness to semi-axis ratios < 0.1. A parametric study revealed that the maximum normal stress is located at the midplane for high-aspect ratio (a/b ≥ 1) half-elliptic beams, but shifts toward the load tip for low aspect ratio (a/b < 1) beams due to local curvature effects. Moreover, the peak shear stress location moves toward the midplane and the magnitude greatly increases as the aspect ratio is increased. Thus, there are large normal and shear stress interactions occurring near the midplane for high-aspect ratio half-elliptic beams, which is not observed for circular beams. These stress interactions can produce unique failures in materials having low shear strength and through-thickness strength. The current closed-form solution is an improvement on previously published approximate solutions.
On Thermodynamic Restrictions in Peridynamics
Authors: Ostoja-Starzewski M. , Demmie P. N. , Zubelewicz A.
Published: June 2012

This note examines restrictions imposed by the second law of thermodynamics on peridynamics in both the bond-based and the state-based formulations. Our study was carried out in the framework of thermomechanics with internal variables. In bond-based peridynamics, there are two possible thermomechanical interpretations of the dissipation function. One interpretation only admits a thermodynamic orthogonality of Ziegler, while the other admits powerless forces within a representation theory of Edelen. The latter interpretation is admissible in state-based peridynamics. Since the dissipation function of peridynamics is set up in velocity space, a link to statistical mechanics of irreversible phenomena does not appear possible.
Highly Nonlinear Solitary Waves for the Assessment of Dental Implant Mobility
Authors: Berhanu Bruk , Rizzo Piervincenzo , Ochs Mark
Published: June 2012

In this paper we present a noninvasive technique based on the propagation of highly nonlinear solitary waves (HNSWs) to monitor the stability of dental implants. HNSWs are nondispersive mechanical waves that can form and travel in highly nonlinear systems, such as one-dimensional chains of spherical particles. The technique is based on the hypothesis that the mobility of a dental implant affects certain characteristics of the HNSWs reflected at the interface between a crystal-based transducer and the implant. To validate the research hypothesis we performed two experiments: first we observed the hydration of commercial plaster to simulate at large the osseointegration process that occurs in the oral connective tissue once a dental-endosteal threaded implant is surgically inserted; then, we monitored the decalcification of treated bovine bones immersed in an acid bath to simulate the inverse of the osseointegration process. In both series, we found a good correlation between certain characteristics of the HNSWs and the stiffness of the material under testing.
Quantum Information Storage for over 180 s Using Donor Spins in a
28
Si “Semiconductor Vacuum”
Authors: Steger M. , Saeedi K. , Thewalt M. L. W. , Morton J. J. L. , Riemann H. , Abrosimov N. V. , Becker P. , Pohl H.-J.
Published: June 2012

Extending Quantum Memory

Practical applications in quantum communication and quantum computation require the building blocks—quantum bits and quantum memory—to be sufficiently robust and long-lived to allow for manipulation and storage (see the Perspective by

Boehme and McCarney

).

Steger
et al.

(p.
1280
) demonstrate that the nuclear spins of
31
P impurities in an almost isotopically pure sample of
28
Si can have a coherence time of as long as 192 seconds at a temperature of ∼1.7 K. In diamond at room temperature,

Maurer
et al.

(p.
1283
) show that a spin-based qubit system comprised of an isotopic impurity (
13
C) in the vicinity of a color defect (a nitrogen-vacancy center) could be manipulated to have a coherence time exceeding one second. Such lifetimes promise to make spin-based architectures feasible building blocks for quantum information science.
Templating Three-Dimensional Self-Assembled Structures in Bilayer Block Copolymer Films
Authors: Tavakkoli K. G. A. , Gotrik K. W. , Hannon A. F. , Alexander-Katz A. , Ross C. A. , Berggren K. K.
Published: June 2012

To the Next Level

Block copolymers will spontaneously separate into a range of microstructures that depend on the polymer block lengths and chemical compositions, and have been used as a templating material because one can selectively etch or functionalize one of the blocks. However, creating a template that is more than one layer thick is challenging.

Tavakkoli K. G.
et al.

(p.
1294
) used an array of posts to provide independent and simultaneous control of the morphology and orientation of two layers of block copolymers and were able to create local variations in the curvature and spacing of the domains.
Bright Coherent Ultrahigh Harmonics in the keV X-ray Regime from Mid-Infrared Femtosecond Lasers
Authors: Popmintchev Tenio , Chen Ming-Chang , Popmintchev Dimitar , Arpin Paul , Brown Susannah , Ališauskas Skirmantas , Andriukaitis Giedrius , Balčiunas Tadas , Mücke Oliver D. , Pugzlys Audrius , Baltuška Andrius , Shim Bonggu , Schrauth Samuel E. , Gaeta Alexander , Hernández-García Carlos , Plaja Luis , Becker Andreas , Jaron-Becker Agnieszka , Murnane Margaret M. , Kapteyn Henry C.
Published: June 2012

From Long to Short

When you play a string instrument, you raise the frequency, or pitch, of the note by shortening the vibrating portion of the string: Drop the length in half, and you hear a harmonic at double the frequency. It is possible to do essentially the same thing with light waves by using selective excitation and relaxation processes of the electrons in crystals or high-pressure gases through which the beam of light is directed to produce light harmonics. Over the past decade, researchers have been optimizing the conversion of red light to the far edge of the ultraviolet, which corresponds to tens of harmonics.

Popmintchev
et al.

(p.
1287
) now show that mid-infrared light can undergo a process in high-pressure gas to generate ultrahigh harmonics up to orders greater than 5000 in the x-ray regime.
Titanium and Zinc Oxide Nanoparticles Are Proton-Coupled Electron Transfer Agents
Authors: Schrauben Joel N. , Hayoun Rebecca , Valdez Carolyn N. , Braten Miles , Fridley Lila , Mayer James M.
Published: June 2012

Pluses and Minuses

Because of their high surface area and tunable electronic structure, nanoparticles are of interest for next-generation photocatalysis and light-harvesting applications. Many of these applications involve electron transfer events at the particle surface after light absorption.

Schrauben
et al.

(p.
1298
) now show, through a series of radical trap kinetic studies, that proton transfer can concurrently accompany electron transfer at the solvent interfaces of two common nanoparticle formulations (oxides of titanium and of zinc). The results may help in the optimization of particle structure and energetics.
Interactions Between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis
Authors: Iliev Iliyan D. , Funari Vincent A. , Taylor Kent D. , Nguyen Quoclinh , Reyes Christopher N. , Strom Samuel P. , Brown Jordan , Becker Courtney A. , Fleshner Phillip R. , Dubinsky Marla , Rotter Jerome I. , Wang Hanlin L. , McGovern Dermot P. B. , Brown Gordon D. , Underhill David M.
Published: June 2012

The Mycobiome

In the past few years, much attention has been given to the trillions of bacterial inhabitants in our guts and the myriad of ways in which they influence our overall health. But what about fungi?

Iliev
et al.

(p.
1314
) now report that mice and humans, along with several other mammals, contain a resident intestinal population of fungi. Deletion of Dectin-1, which acts as a major innate immune sensor for fungi, led to enhanced susceptibility and worse pathology in a chemically induced model of colitis in mice. A polymorphism in the gene that encodes Dectin-1 has been observed in patients with ulcerative colitis, which hints that, besides the traditional bacterial microbiome, alterations in the “mycobiome” may also play a role in health and disease.
Viennese Memories, Art, and Freud
The Age of Insight
The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present

by Eric R. Kandel

Random House, New York, 2012. 655 pp. $40, C$46. ISBN 9781400068715.
Authors: Gross Charles
Published: June 2012

Beginning with a consideration of science and culture in early 20th-century Vienna, Kandel explores the interplay of neuroscience, psychology, and art.
Small But Extremely Tough
Authors: Tanner K. Elizabeth
Published: June 2012

The extreme strength and toughness of a natural material from a marine shrimp can be explained by its intricate layered structure.
Getting Established in Academia
A Guide to Academia
Getting Into and Surviving Grad School, Postdocs, and a Research Job

by Prosanta Chakrabarty

Wiley-Blackwell, Chichester, UK, 2012. 189 pp. Paper, $29.95, £20.50, €24.60. ISBN 9780470960417.
Authors: Kawahara Akito Y.
Published: June 2012

Chakrabarty's handbook for science students considering a future in academia aims to help them progress efficiently to tenure.
Oil Spill Researchers Lose Fight to Protect Documents
Authors: Kintisch Eli
Published: June 2012

Thousands of internal e-mails and documents created by researchers attempting to determine the size of the 2010
Deepwater Horizon
oil spill have been handed over to BP as part of a massive lawsuit.
Validation of an Immunodiagnostic Assay for Detection of 13 Streptococcus pneumoniae Serotype-Specific Polysaccharides in Human Urine
Authors: Pride Michael W. , Huijts Susanne M. , Wu Kangjian , Souza Victor , Passador Sherry , Tinder Chunyan , Song Esther , Elfassy Arik , McNeil Lisa , Menton Ronald , French Roger , Callahan Janice , Webber Chris , Gruber William C. , Bonten Marc J. M. , Jansen Kathrin U.
Published: June 2012

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex
u
rinary
a
ntigen
d
etection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of
Streptococcus pneumoniae
by capturing serotype-specific
S. pneumoniae
polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified
Streptococcus pneumoniae
(13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults.
Abnormal Immune Responses in Persons with Previous Extrapulmonary Tuberculosis in anIn VitroModel That SimulatesIn VivoInfection with Mycobacterium tuberculosis
Authors: Fiske Christina T. , de Almeida Alexandre S. , Shintani Ayumi K. , Kalams Spyros A. , Sterling Timothy R.
Published: June 2012

Persons with previous extrapulmonary tuberculosis have reduced peripheral blood mononuclear cell cytokine production and CD4+lymphocytes compared to persons with previous pulmonary tuberculosis or latent tuberculosis infection, but specific defects related toMycobacterium tuberculosisinfection of macrophages have not been characterized. The objective of this study was to further characterize thein vitroimmune responses toM. tuberculosisinfection in HIV-seronegative persons with previous extrapulmonary tuberculosis. Peripheral blood mononuclear cells were isolated from HIV-seronegative persons with previous extrapulmonary tuberculosis (n= 11), previous pulmonary tuberculosis (n= 21), latentM. tuberculosisinfection (n= 19), and uninfected tuberculosis contacts (n= 20). Experimental conditions includedM. tuberculosis-infected macrophages cultured with and without monocyte-depleted peripheral blood mononuclear cells. Concentrations of interleukin 1β (IL-1β), IL-4, IL-6, CXCL8 (IL-8), IL-10, IL-12p70, IL-17, CCL2 (monocyte chemoattractant protein 1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by multiplex cytokine array. WhenM. tuberculosis-infected macrophages were cocultured with monocyte-depleted peripheral blood mononuclear cells, IFN-γ (P= 0.01), TNF-α (P= 0.04), IL-10 (P< 0.001), and IL-6 (P= 0.03) exhibited similar continua of responses, with uninfected persons producing the lowest levels, followed by extrapulmonary tuberculosis cases, pulmonary tuberculosis controls, and persons with latentM. tuberculosisinfection. A similar pattern was observed with CXCL8 (P= 0.04), IL-10 (P= 0.02), and CCL2 (P= 0.03) when monocyte-depleted peripheral blood mononuclear cells from the four groups were cultured alone. Persons with previous extrapulmonary tuberculosis had decreased production of several cytokines, both at rest and after stimulation withM. tuberculosis. Our results suggest that persons who develop extrapulmonary tuberculosis have a subtle global immune defect that affects their response toM. tuberculosisinfection.
Prosthetic Valve Endocarditis Due to Neisseria skkuensis, a Novel Neisseria Species
Authors: Park So Yeon , Kang Seung Ji , Joo Eun-Jeong , Ha Young Eun , Baek Jin Yang , Wi Yu Mi , Kang Cheol-In , Chung Doo Ryeon , Peck Kyong Ran , Lee Nam Young , Song Jae-Hoon
Published: June 2012

We describe the first reported case of endocarditis due to
Neisseria skkuensis
. The organism from the blood cultures taken on admission day was identified initially as unidentified Gram-negative cocci by Vitek2. Finally, it was identified as
Neisseria skkuensis
by 16 rRNA gene sequence analysis.
Duration of Hospital Admission and the Need for Empirical Antipseudomonal Therapy
Authors: Daneman N. , Elligsen M. , Walker S. A. N. , Simor A.
Published: June 2012

To reduce selective pressure for antimicrobial resistance, empirical use of antipseudomonal antibiotics is often reserved for patients with late-onset hospital-acquired infections. We examined the likelihood of isolating
Pseudomonas aeruginosa
as a function of time from hospital admission. We conducted a retrospective cohort study of all positive bacterial cultures in a tertiary-care hospital between March 2010 and November 2011. The primary outcome was the proportion of positive cultures yielding
P. aeruginosa
. Multivariable logistic regression was employed to assess the impact of time from admission on the likelihood of isolating
P. aeruginosa
, after adjusting for other important risk factors. A total of 7,668 positive cultures were obtained from 4,108 unique patients during the study interval, including 633 (8.3%) yielding
P. aeruginosa
. The probability of isolating
P. aeruginosa
increased linearly from 79/2,044 (3.9%) positive cultures obtained on admission to 153/664 (23%) in the 10th week of admission or beyond. The unadjusted odds ratio was 1.002/day (95% confidence interval [CI], 1.0016 to 1.0028;
P
< 0.0001); the adjusted odds ratio (aOR) was 1.0007/day (95% CI, 1.0001 to 1.0013;
P
= 0.02). Other important predictors of
P. aeruginosa
isolation included respiratory specimen type (aOR, 13.8; 95% CI, 9.1 to 21.1), recent hospital admission (aOR,1.8; 95% CI, 1.4 to 2.3), prior
P. aeruginosa
isolation during current admission (aOR, 4.9; 95% CI, 3.7 to 6.4), and prior antipseudomonal (aOR, 1.9; 95% CI, 1.4 to 2.5) or nonantipseudomonal (aOR, 1.8; 95% CI, 1.4 to 2.4) antibiotic exposure. It was determined that as time from admission increases, there is a linear increase in the likelihood of
P. aeruginosa
isolation. Any guidelines which distinguish early from late hospital-acquired infection must consider the implications of time point selection on the likelihood of inadequate
P. aeruginosa
empirical coverage.
Clustered Tuberculosis in a Low-Burden Country: Nationwide Genotyping through 15 Years
Authors: Kamper-Jørgensen Z. , Andersen A. B. , Kok-Jensen A. , Bygbjerg I. C. , Andersen P. H. , Thomsen V. O. , Kamper-Jørgensen M. , Lillebaek T.
Published: June 2012

Molecular genotyping of
Mycobacterium tuberculosis
has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS
6110
restriction fragment length polymorphism (RFLP) genotyping of
M. tuberculosis
cases in Denmark, a country on the way toward tuberculosis elimination, we discuss
M. tuberculosis
transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (≥50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 enviornment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation.
Hepatitis D Virus Isolates with Low Replication and Epithelial-Mesenchymal Transition-Inducing Activity Are Associated with Disease Remission
Authors: Shih Hsuan Hui , Sheen I-Jane , Su Chien-Wei , Peng Wei-Li , Lin Ling-Hui , Wu Jaw-Ching
Published: June 2012

Clearance of hepatitis D virus (HDV) viremia leads to disease remission. Large hepatitis delta antigen (L-HDAg) has been reported to activate transforming growth factor β, which may induce epithelial-mesenchymal transition (EMT) and fibrogenesis. This study analyzed serum HDV RNA “quasispecies” in HDV-infected patients at two stages of infection: before and after alanine aminotransferase (ALT) elevations. Included in the study were four patients who went into remission after ALT elevation and three patients who did not go into remission and progressed to cirrhosis or hepatocellular carcinoma. Full-length HDV cDNA clones were obtained from the most abundant HDV RNA species at the pre- and post-ALT elevation stages. Using an
in vitro
model consisting of Huh-7 cells transfected with cloned HDV cDNAs, the pre- or post-ALT elevation dominant HDV RNA species were characterized for (i) their replication capacity by measuring HDV RNA and HDAg levels in transfected cells and (ii) their capacity to induce EMT by measuring the levels of the mesenchymal-cell-specific protein vimentin, the EMT regulators twist and snail, and the epithelial-cell-specific protein E-cadherin. Results show that in patients in remission, the post-ALT elevation dominant HDV RNA species had a lower replication capacity
in vitro
and lower EMT activity than their pre-ALT elevation counterparts. This was not true of patients who did not go into remission. The expression of L-HDAg, but not small HDAg, increased the expression of the EMT-related proteins. It is concluded that in chronically infected patients, HDV quasispecies with a low replication capacity and low EMT activity are associated with disease remission.
Hepatitis C Virus NS5A Disrupts STAT1 Phosphorylation and Suppresses Type I Interferon Signaling
Authors: Kumthip Kattareeya , Chusri Pattranuch , Jilg Nikolaus , Zhao Lei , Fusco Dahlene N. , Zhao Hong , Goto Kaku , Cheng Du , Schaefer Esperance A. , Zhang Leiliang , Pantip Chansom , Thongsawat Satawat , O'Brien Amornrat , Peng Lee F. , Maneekarn Niwat , Chung Raymond T. , Lin Wenyu
Published: June 2012

Responses to alpha interferon (IFN-α)-based treatment are dependent on both host and viral factors and vary markedly among patients infected with different hepatitis C virus (HCV) genotypes (GTs). Patients infected with GT3 viruses consistently respond better to IFN treatment than do patients infected with GT1 viruses. The mechanisms underlying this difference are not well understood. In this study, we sought to determine the effects of HCV NS5A proteins from different genotypes on IFN signaling. We found that the overexpression of either GT1 or GT3 NS5A proteins significantly inhibited IFN-induced IFN-stimulated response element (ISRE) signaling, phosphorylated STAT1 (P-STAT1) levels, and IFN-stimulated gene (ISG) expression compared to controls. GT1 NS5A protein expression exhibited stronger inhibitory effects on IFN signaling than did GT3 NS5A protein expression. Furthermore, GT1 NS5A bound to STAT1 with a higher affinity than did GT3 NS5A. Domain mapping revealed that the C-terminal region of NS5A conferred these inhibitory effects on IFN signaling. The overexpression of HCV NS5A increased HCV replication levels in JFH1-infected cells through the further reduction of levels of P-STAT1, ISRE signaling, and downstream ISG responses. We demonstrated that the overexpression of GT1 NS5A proteins resulted in less IFN responsiveness than did the expression of GT3 NS5A proteins through stronger binding to STAT1. We confirmed that GT1 NS5A proteins exerted stronger IFN signaling inhibition than did GT3 NS5A proteins in an infectious recombinant JFH1 virus. The potent antiviral NS5A inhibitor BMS-790052 did not block NS5A-mediated IFN signaling suppression in an overexpression model, suggesting that NS5A's contributions to replication are independent of its subversive action on IFN. We propose a model in which the binding of the C-terminal region of NS5A to STAT1 leads to decreased levels of P-STAT1, ISRE signaling, and ISG transcription and, ultimately, to preferential GT1 resistance to IFN treatment.
Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B
Authors: Tamura Tomokazu , Sakoda Yoshihiro , Yoshino Fumi , Nomura Takushi , Yamamoto Naoki , Sato Yuka , Okamatsu Masatoshi , Ruggli Nicolas , Kida Hiroshi
Published: June 2012

Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE
−
was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE
−
vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE
−
/P-11 virus isolated from the tonsils after the 11th passage
in vivo
had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies
in vitro
indicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency
in vitro
and pathogenicity in pigs.
Hepatitis C Virus Upregulates Beclin1 for Induction of Autophagy and Activates mTOR Signaling
Authors: Shrivastava Shubham , Bhanja Chowdhury Joydip , Steele Robert , Ray Ranjit , Ray Ratna B.
Published: June 2012

Hepatitis C virus (HCV) induces autophagosome formation in infected human hepatocytes. We have previously reported that HCV exploits autophagic machinery in favor of virus growth and survival in host cells (S. Shrivastava et al., Hepatology
53:
406–414, 2011); however, the mechanisms for autophagy induction is poorly understood. In the present study, we observed that HCV infection transcriptionally upregulates Beclin1, which forms complex with Vps34, the class III phosphatidylinositol 3-kinase, as a first step for autophagy initiation. Although Bcl-2 has an anti-autophagy effect by its association with Beclin1 in nutrient-deprived cells, our studies revealed that HCV-mediated autophagy occurs independent of Beclin1–Bcl-2 dissociation. Mammalian target of rapamycin (mTOR) is a positive regulator of cell growth and is recognized as an inhibitor of autophagy induction. Our results demonstrated that HCV infection enhances phospho-mTOR expression and its downstream target 4EBP1 activation, suggesting that mTOR is not a negative regulator of HCV-induced autophagy. On the other hand, HCV infection in autophagy-impaired cells reduced phospho-mTOR, mTOR, and phospho-4EBP1 expression. Together, these results suggested that HCV induces autophagy by upregulating Beclin1 and activates mTOR signaling pathway, which in turn may promote hepatocyte growth.
Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T Cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice
Authors: Joeckel Lars T. , Wallich Reinhard , Metkar Sunil S. , Froelich Christopher J. , Simon Markus M. , Borner Christoph
Published: June 2012

The T cell granule exocytosis pathway is essential to control hepatotropic lymphocytic choriomeningitis virus strain WE (LCMV-WE) but also contributes to the observed pathology in mice. Although effective antiviral T cell immunity and development of viral hepatitis are strictly dependent on perforin and granzymes, the molecular basis underlying induction of functionally competent virus-immune T cells, including participation of the innate immune system, is far from being resolved. We demonstrate here that LCMV-immune T cells of interleukin-1 receptor (IL-1R)-deficient mice readily express transcripts for perforin and granzymes but only translate perforin, resulting in the lack of proapoptotic potentialin vitro. LCMV is not cleared in IL-1R-deficient mice, and yet the infected mice develop neither splenomegaly nor hepatitis. These results demonstrate that IL-1R signaling is central to the induction of proapoptotic CD8 T cell immunity, including viral clearance and associated tissue injuries in LCMV infection.
Structural Properties of the C Terminus of Vesicular Stomatitis Virus N Protein Dictate N-RNA Complex Assembly, Encapsidation, and RNA Synthesis
Authors: Heinrich Bianca S. , Morin Benjamin , Rahmeh Amal A. , Whelan Sean P. J.
Published: June 2012

The vesicular stomatitis virus (VSV) nucleoprotein (N) associates tightly with the viral genomic RNA. This N-RNA complex constitutes the template for the RNA-dependent RNA polymerase L, which engages the nucleocapsid via its phosphoprotein cofactor P. While N and P proteins play important roles in regulating viral gene expression, the molecular basis of this regulation remains incompletely understood. Here we show that mutations in the extreme C terminus of N cause defects in viral gene expression. To determine the underlying cause of such defects, we examined the effects of the mutations separately on encapsidation and RNA synthesis. Expression of N together with P in
Escherichia coli
results predominantly in the formation of decameric N-RNA rings. In contrast, nucleocapsid complexes containing the substitution N
Y415A
or N
K417A
were more loosely coiled, as revealed by electron microscopy (EM). In addition, the N
EF419/420AA
mutant was unable to encapsidate RNA. To further characterize these mutants, we engineered an infectious cDNA clone of VSV and employed N-RNA templates from those viruses to reconstitute RNA synthesis
in vitro
. The transcription assays revealed specific defects in polymerase utilization of the template that result in overall decreased RNA quantities, including reduced amounts of leader RNA. Passage of the recombinant viruses in cell culture led to the accumulation of compensatory second-site mutations in close proximity to the original mutations, underscoring the critical role of structural features within the C terminus in regulating N function.
Cytotoxic T-Lymphocyte Escape Mutations Identified by HLA Association Favor Those Which Escape and Revert Rapidly
Authors: Fryer Helen R. , Frater John , Duda Anna , Palmer Duncan , Phillips Rodney E. , McLean Angela R.
Published: June 2012

Identifying human immunodeficiency virus (HIV) immune escape mutations has implications for understanding the impact of host immunity on pathogen evolution and guiding the choice of vaccine antigens. One means of identifying cytotoxic-T-lymphocyte (CTL) escape mutations is to search for statistical associations between mutations and host human leukocyte antigen (HLA) class I alleles at the population level. The impact of evolutionary rates on the strength of such associations is not well defined. Here, we address this topic using a mathematical model of within-host evolution and between-host transmission of CTL escape mutants that predicts the prevalence of escape mutants at the population level. We ask how the rates at which an escape mutation emerges in a host who bears the restricting HLA and reverts when transmitted to a host who does not bear the HLA affect the strength of an association. We consider the impact of these factors when using a standard statistical method to test for an association and when using an adaptation of that method that corrects for phylogenetic relationships. We show that with both methods, the average sample size required to identify an escape mutation is smaller if the mutation escapes and reverts quickly. Thus, escape mutations identified as HLA associated systematically favor those that escape and revert rapidly. We also present expressions that can be used to infer escape and reversion rates from cross-sectional escape prevalence data.
A pilot study of rapid benchtop sequencing ofStaphylococcus aureusandClostridium difficilefor outbreak detection and surveillance
Authors: Eyre David W , Golubchik Tanya , Gordon N Claire , Bowden Rory , Piazza Paolo , Batty Elizabeth M , Ip Camilla L C , Wilson Daniel J , Didelot Xavier , O'Connor Lily , Lay Rochelle , Buck David , Kearns Angela M , Shaw Angela , Paul John , Wilcox Mark H , Donnelly Peter J , Peto Tim E A , Walker A Sarah , Crook Derrick W
Published: June 2012

Objectives

To investigate the prospects of newly available benchtop sequencers to provide rapid whole-genome data in routine clinical practice. Next-generation sequencing has the potential to resolve uncertainties surrounding the route and timing of person-to-person transmission of healthcare-associated infection, which has been a major impediment to optimal management.

Design

The authors used Illumina MiSeq benchtop sequencing to undertake case studies investigating potential outbreaks of methicillin-resistantStaphylococcus aureus(MRSA) andClostridium difficile.

Setting

Isolates were obtained from potential outbreaks associated with three UK hospitals.

Participants

Isolates were sequenced from a cluster of eight MRSA carriers and an associated bacteraemia case in an intensive care unit, another MRSA cluster of six cases and two clusters ofC difficile. Additionally, allC difficileisolates from cases over 6 weeks in a single hospital were rapidly sequenced and compared with local strain sequences obtained in the preceding 3 years.

Main outcome measure

Whole-genome genetic relatedness of the isolates within each epidemiological cluster.

Results

Twenty-six MRSA and 15 C difficileisolates were successfully sequenced and analysed within 5 days of culture. Both MRSA clusters were identified as outbreaks, with most sequences in each cluster indistinguishable and all within three single nucleotide variants (SNVs). Epidemiologically unrelated isolates of the samespa-type were genetically distinct (≥21 SNVs). In bothC difficileclusters, closely epidemiologically linked cases (in one case sharing the same strain type) were shown to be genetically distinct (≥144 SNVs). A reconstruction applying rapid sequencing inC difficilesurveillance provided early outbreak detection and identified previously undetected probable community transmission.

Conclusions

This benchtop sequencing technology is widely generalisable to human bacterial pathogens. The findings provide several good examples of how rapid and precise sequencing could transform identification of transmission of healthcare-associated infection and therefore improve hospital infection control and patient outcomes in routine clinical practice.
A stochastic programming standard response model for wildfire initial attack planning
Authors: Ntaimo Lewis , Arrubla Julián A. Gallego , Stripling Curt , Young Joshua , Spencer Thomas
Published: June 2012

Wildfires are responsible for several civilians deaths and millions of dollars in property losses every year, on average. Wildfire containment is the result of an effectively performed initial attack. We formulate a two-stage stochastic integer programming standard response model for initial attack. The model assumes a known standard response needed to contain a fire of given size. The goal of the model is to contain as many fires as possible while minimizing the fixed rental and travel costs and the expected future operational costs. We report on a study based on district TX12, which is one of the fire planning units of the Texas Forest Service (TFS) in East Texas, involving seven operations bases and up to 28 dozers. We use our methodology to position the dozers based on 30- and 60-min maximum travel time restrictions and evaluate each deployment in terms of the number of fire-fighting resources positioned at each operations base and the expected number of escaped (contained) fires. We also consider deploying additional resources to operations bases that need them the most. The deployments made by our methodology provide several insights and show that the original distribution of resources in TX12 at the time of this study was not optimal. For example, more dozers were initially located at operations bases in areas of low density of fires while fewer dozers were located at bases in areas of high density of fires.
Optimize landscape fuel treatment locations to create control opportunities for future fires
Authors: Wei Yu
Published: June 2012

Fuel treatment can improve the efficiency of controlling future catastrophic fires. Selecting optimal fuel treatment locations across a landscape is a challenging strategic planning problem in wildland fire management. This research develops a new fuel treatment optimization model by extending a fire suppression model to simultaneously consider many future fires. Fire is ignited from every grid cell in a landscape and modeled for various durations in a mixed integer programming model. Fuel treatment in a cell decreases its fire intensity and makes future fire control effective in it. This model allocates fuel treatments to minimize the total landscape future fire loss. It was first tested on several artificial landscapes for model validation. Results show that it tends to allocate fuel treatments in contiguous areas following regular and intuitive spatial patterns. Spatial fuel treatment layouts vary according to the change of fire ignition probability distribution, the distribution of value to be protected from fire, and fire duration assumptions. Trade-off between protecting different parts of a landscape is a major driver in designing fuel treatment layouts. A test case in the Sequoia and Kings Canyon national parks demonstrates how this model assembles spatial information and helps study the effects of fuel treatments in a heterogeneous landscape. This model allows managers to assemble information from many possible future fires to make informative strategic-level fuel treatment decisions. A potential model extension and the limitations of this model are also discussed.
Do chestnut, northern red, and white oak germinant seedlings respond similarly to light treatments? II. Gas exchange and chlorophyll responses
Authors: Rebbeck Joanne , Scherzer Amy , Gottschalk Kurt
Published: June 2012

Understanding differences in physiological and growth strategies in low-light environments among upland oak species may help managers address the challenges of oaks’ poor regeneration. Gas exchange and chlorophyll content were measured for northern red oak ( Quercus rubra L.), chestnut oak ( Quercus prinus L.), and white oak ( Quercus alba L.) germinants grown at 25%, 18%, and 6% of full sun in one of two native forest soil mixes for two summers. Northern red and chestnut oak photosynthesis at saturating light (Amax, mass) increased by 23%–36% as light levels increased from 6% to 25% of full sun, while white oak Amax, massdeclined by 20% and plateaued at 18% of full sun. White oak light compensation point is representative of deep shade (7.2 µmol·m–2·s–1), while northern red and chestnut oak averaged 17.8 µmol·m–2·s–1. Total chlorophyll content increased as light levels decreased for all species. Of the three species, the slow-growing white oak seedlings appeared to be more efficient in utilizing light than northern red or chestnut oak seedlings. This suggests no additional benefits to increasing light above that typically found in a light shelterwood cut; however, it is crucial to control faster-growing competing vegetation.
Distinguishing isolates of Deladenus siricidicola, a biological control agent of Sirex noctilio, from North America and the Southern Hemisphere using PCR–RFLP
Authors: Leal I. , Foord B. , Davis C. , de Groot P. , Mlonyeni X.O. , Slippers B.
Published: June 2012

The woodwasp Sirex noctilio Fabricius, along with its obligate symbiotic fungus Amylostereum areolatum (Chaillet ex Fr.) Boidin, is amongst the most damaging invasive species to many commercial pine plantations. The most effective biocontrol agent for management of this woodwasp has been the nematode Deladenus siricidicola Bedding. Before this agent can be used in North America, answering key questions about its interaction with native siricids and other strains of the nematode is essential, as would be the need to track its spread after release. The aim of this study was to develop tools to differentiate between the North American D. siricidicola isolates and the Southern Hemisphere Kamona strain of this species. We sequenced a region from ribosomal DNA and the cytochrome oxidase subunit 1 and developed a PCR–RFLP method based on a single nucleotide polymorphism flanking a microsatellite sequence. These markers will be useful for science-based operational biocontrol of S. noctilio.
Route selection for best distances in road databases based on drivers’ and customers’ preferences
Authors: Flisberg P. , Lidén B. , Rönnqvist M. , Selander J.
Published: June 2012

The importance of road databases for distance calculations and route selection is increasing. One reason is that payments and invoicing are often based on the distance driven. However, it can be hard to agree on a “best” distance because of drivers’ preferences. These preferences can be described by road features such as road length, quality, width, speed limits, etc. Moreover, a pure standard “shortest path”, which is often used in road databases, can result in a route that is considerably shorter than a preferred and agreed distance. Consequently, there is a need to find suitable weights for the features of the roads that provide fair and agreed distances at the same time for all users. We propose an approach to find values of such weights for the features. The optimization model to find weights is an inverse shortest path problem formulated in a mixed integer programming model. The approach is tested for the Swedish Forestry National Road database. Since 2010, it has been in daily use to establish distances and is available for all forestry companies and haulers in Sweden through an online system.
An assessment of seedling damage by wild house mice (Mus musculus) and wild deer mice (Peromyscus spp.)
Authors: Witmer Gary W. , Snow Nathan P. , Moulton Rachael S. , Swartz Jenna L.
Published: June 2012

Although it is known that voles will damage seedlings, we do not know the extent to which deer mice (Peromyscus spp.) and house mice (Mus musculus Linnaeus, 1758) damage seedlings. Knowing this information can assist resource managers in better targeting problem species and implementing appropriate management actions. We planted and monitored ponderosa pine (Pinus ponderosa Douglas ex Lawson & C. Lawson) and narrow-leaf cottonwood (Populus angustifolia E. James) seedlings in metal stock tanks occupied by deer mice or house mice to assess the potential for damage by these rodents. Both species damaged leaves and stems of cottonwood seedlings, but house mice did more damage. House mouse damage resulted in mortality of over half of the cottonwood seedlings, whereas deer mice caused a much lower level of seedling mortality. Only slight damage was done by either species to pine seedlings. Neither species damaged the roots of seedlings, despite the extensive burrowing by house mice. Although voles are often considered to be the primary rodent species causing seedling damage, we have shown that deer mice and especially house mice could also cause substantial damage to deciduous seedlings. However, our work suggests that rodent control to prevent damage to conifer seedlings might not be warranted in general unless there are extenuating circumstances and the species causing the damage are identified to assist with targeting control methods more precisely.
Relationships between growth, quality, and stocking within managed old-growth northern hardwoods
Authors: Gronewold Chris , D’Amato Anthony W. , Palik Brian J.
Published: June 2012

An understanding of long-term growth dynamics is central to the development of sustainable uneven-aged silvicultural systems for northern hardwood forests in eastern North America. Of particular importance are quantitative assessments of the relationships between stocking control and long-term growth and quality development. This study examined these relationships in a long-term silviculture experiment established in northern hardwood stands in the Upper Peninsula of Michigan, USA. Stands were old growth at the onset of the experiment and were maintained at three residual stocking levels (11.5, 16.1, and 20.7 m2·ha–1) over a 57-year period. Several aspects of long-term stocking control were evaluated, including the effects of residual stocking on tree quality development and the relationships between stand stocking and individual tree growth and stand-level production. Results suggest that residual stocking had little impact on quality development, likely due to the initial old-growth condition of the stands examined. In contrast, our results indicate that a range of stand densities will maintain acceptable rates of stand-level production in selection systems and that growth can be shifted between diameter classes depending on desired future stand conditions.
Changes in faunal and vegetation communities along a soil calcium gradient in northern hardwood forests
Authors: Beier Colin M. , Woods Anne M. , Hotopp Kenneth P. , Gibbs James P. , Mitchell Myron J. , Dovčiak Martin , Leopold Donald J. , Lawrence Gregory B. , Page Blair D.
Published: June 2012

Depletion of Ca from forest soils due to acidic deposition has had potentially pervasive effects on forest communities, but these impacts remain largely unknown. Because snails, salamanders, and plants play essential roles in the Ca cycle of northern hardwood forests, we hypothesized that their community diversity, abundance, and structure would vary with differences in biotic Ca availability. To test this hypothesis, we sampled 12 upland hardwood forests representing a soil Ca gradient in the Adirondack Mountains, New York (USA), where chronic deposition has resulted in acidified soils but where areas of well-buffered soils remain Ca rich due to parent materials. Along the gradient of increasing soil [Ca2+], we observed increasing trends in snail community richness and abundance, live biomass of redback salamanders ( Plethodon cinereus (Green, 1818)), and canopy tree basal area. Salamander communities were dominated by mountain dusky salamanders ( Desmognathus ochrophaeus Cope, 1859) at Ca-poor sites and changed continuously along the Ca gradient to become dominated by redback salamanders at the Ca-rich sites. Several known calciphilic species of snails and plants were found only at the highest-Ca sites. Our results indicated that Ca availability, which is shaped by geology and acidic deposition inputs, influences northern hardwood forest ecosystems at multiple trophic levels, although the underlying mechanisms require further study.
NON-BEITER TERNARY CYCLOTOMIC POLYNOMIALS WITH AN OPTIMALLY LARGE SET OF COEFFICIENTS
Authors: MOREE PIETER , ROŞU EUGENIA
Published: June 2012

Let l ≥ 1 be an arbitrary odd integer and p, q and r be primes. We show that there exist infinitely many ternary cyclotomic polynomials Φpqr(x) with l2 + 3l + 5 ≤ p < q < r such that the set of coefficients of each of them consists of the p integers in the interval [-(p - l - 2)/2, (p + l + 2)/2]. It is known that no larger coefficient range is possible. The Beiter conjecture states that the cyclotomic coefficients apqr(k) of Φpqr satisfy |apqr(k)| ≤ (p + 1)/2 and thus the above family contradicts the Beiter conjecture. The two already known families of ternary cyclotomic polynomials with an optimally large set of coefficients (found by G. Bachman) satisfy the Beiter conjecture.