bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance features of primary central nervous system lymphoma in the immunocompetent patient: A pictorial essay
Authors: Yap Kelvin K , Sutherland Tom , Liew Elaine , Tartaglia Con J , Pang Mei , Trost Nick
Published: March 2012

Primary central nervous system lymphoma (PCNSL) is an uncommon but important variant of non‐Hodgkin lymphoma and represents up to 6% of all primary central nervous system (CNS) malignancies. Recognition of this entity by radiologist on MRI may avoid unnecessary neurosurgical resection and redirect to biopsy. The pretreatment MRI of patients with biopsy proven PCNSL from the last 5 years at our institution was reviewed. Selected examples were used to construct a pictorial essay to illustrate some of the typical and atypical MR features of PCNSL. MRI of other CNS conditions with imaging similarities to PCNSL was included to demonstrate possible mimics. The typical features of PCNSL lymphoma are intra‐axial homogenous single or multiple contrast enhancing lesions, with marked surrounding oedema and restricted diffusion, usually contacting a cerebrospinal fluid (CSF) surface. Necrosis, peripheral enhancement, haemorrhage or calcification are unusual and other diagnoses should be considered if any of these features are present. Potential mimics include high grade glioma, infarcts, metastatic disease, demyelination, abscess and secondary lymphoma. Careful assessment of the MR features and correlation with the clinical findings should enable the radiologists to raise the possibility of PCNSL and minimise the risk of unnecessary resection.
DNA barcoding in native plants of the Labiatae (Lamiaceae) family from Chios Island (Greece) and the adjacent Çeşme‐Karaburun Peninsula (Turkey)
Authors: THEODORIDIS SPYROS , STEFANAKI ANASTASIA , TEZCAN MELTEM , AKI CUNEYT , KOKKINI STELLA , VLACHONASIOS KONSTANTINOS E.
Published: March 2012

The plant family Labiatae (Lamiaceae) is known for its fine medicinal and aromatic herbs like lavender, mint, oregano, sage and thyme and is a rich source of essential oils for the food, pharmaceutical and cosmetic industry. Besides its great economic importance, the Labiatae family contributes significantly to the endemic flora of Greece and Turkey. Owing to its economic and biological significance and to the difficult identification based on morphological characters of several of its taxa, the Labiatae family is an ideal case for developing DNA barcodes. The purpose of this study is to evaluate the utility of DNA barcoding on a local scale in discriminating Labiatae species in Chios Island (Greece) and the adjacent Çeşme‐Karaburun Peninsula (Turkey). We chose three cpDNA regions (matK, rbcL, trnH‐psbA) that were proposed by previous studies and tested them either as single region or as multiregion barcodes based on the criteria determined by Consortium for the Barcode of Life (CBOL). Our results show that matK and trnH‐psbA taken as useful in discriminating species of the Labiatae, for the species we examined, as any multiregion combination. matK and trnH‐psbA could serve as single‐region barcodes for Labiatae species contributing to the conservation and the trade control of valuable plant resources.
Comparison of the metabolic profiling of hepatitis B virus‐infected cirrhosis and alcoholic cirrhosis patients by using 1H NMR‐based metabonomics
Authors: Qi Suwen , Tu Zhiguang , Ouyang Xin , Wang Linxian , Peng Wujian , Cai Anji , Dai Yong
Published: March 2012

Aim:  The aims of the present study were to depict the serum metabolic characteristics of hepatitis B virus (HBV)‐infected cirrhosis and alcoholic cirrhosis patients, and to find the specific serum biomarkers associated with the diseases.

Methods:  A pilot metabolic profiling study was conducted using three groups: HBV‐infected cirrhosis patients (n = 21), alcoholic cirrhosis patients (n = 20) and healthy controls (n = 20). 1H nuclear magnetic resonance (NMR)‐based metabonomics was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least‐squares‐discriminant analysis (OPLS‐DA). The discriminatory metabolites between HBV‐infected cirrhosis and alcoholic cirrhosis were further validated by classical biochemical assays.

Results:  The OPLS‐DA model was capable of distinguishing between HBV‐infected and alcoholic cirrhosis patients. Five metabolites, creatine, acetoacetate, isobutyrate, glutamine and glutamate, were identified as the most influential factors to compare HBV‐infected cirrhosis and alcoholic cirrhosis. The validation tests showed that the changes of the five metabolites were well coincident with the results of NMR.

Conclusion:  NMR spectra combined with pattern recognition analysis techniques may provide a new way to explore the pathogenesis of HBV‐infected and alcoholic cirrhosis patients.
Oxidative stress and liver disease
Authors: Zhu Runzhi , Wang Yajing , Zhang Liangqing , Guo Qinglong
Published: March 2012

In humans, oxidative stress and antioxidant defenses are the sum of a complicated network of enzymatic and non‐enzymatic processes. Depending on the stage and severity of diseases, a patient's antioxidant armamentarium may increase as an appropriate response to an oxidant challenge, whereas others may decrease as an indication of unbalanced consumption. In some cases, the formation of reactive oxygen species is a requisite and healthy event. In fact, free radicals can affect intracellular signal transduction and gene regulation, resulting in cytokine production essential to the inflammatory process. In many other cases, especially liver diseases, excessive oxidative stress undoubtedly contributes to the progression and pathological findings of disease and serves as a prognostic indicator. Reactive oxygen species are highly reactive molecules that are naturally generated in small amounts through metabolism and could damage cellular molecules such as lipids, proteins or DNA. Oxidative stress plays a major role in many liver diseases. In this review, we summarize the biological character of free radicals and some antioxidants, and the related methods of analysis. Then, we discusses the association of oxidative stress to many types of liver diseases.
Magnetic Resonance Imaging for the Differentiation of Neoplastic, Inflammatory, and Cerebrovascular Brain Disease in Dogs
Authors: Wolff C.A. , Holmes S.P. , Young B.D. , Chen A.V. , Kent M. , Platt S.R. , Savage M.Y. , Schatzberg S.J. , Fosgate G.T. , Levine J.M.
Published: March 2012

Background

The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown.

Objectives

To estimate sensitivity, specificity, and inter‐rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs.

Animals

One hundred and twenty‐one client‐owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44).

Methods

Retrospective, multi‐institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter‐rater agreement were calculated to estimate diagnostic performance.

Results

MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter‐rater agreement was very good for overall detection of structural brain lesions (κ = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (κ = 0.299, 95% CI = 0, 0.761, P = .21).

Conclusions and Clinical Importance

MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.
Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation
Authors: NíÓgáin Orla , Tajber Lidia , Corrigan Owen I , Healy Anne Marie
Published: March 2012

Objectives

The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation.

Methods

Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed.

Key findings

The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs.

Conclusions

NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin.
What would Batman eat?: priming children to make healthier fast food choices
Authors: Wansink B. , Shimizu M. , Camps G.
Published: March 2012

Background

Fast food patronage is a frequent reality for many children and their parents. Although there are increasingly healthier alternatives for popular menu items (apple slices instead of French fries), they are infrequently selected.

Objectives

We investigated whether either of two priming tactics – the priming of a role model's food choices or the priming of healthy foods – could influence children to make healthier fast food choices.

Methods

In the priming model condition, 22 children (ranging in age from 6 to 12 years) were presented with 12 photos of 6 admirable and 6 less admirable models and asked, ‘Would this person order apple fries or French fries?’ In the health prime condition, the same children were shown 12 photos of 6 healthy foods and 6 less healthy foods and asked to indicate if each food was healthy or unhealthy.

Results

When children were asked what various admirable people – such as Batman or Spiderman – would eat, 45% chose apple slices over French fries, which was higher than the health prime (P < 0.001) or the control condition (P < 0.001).

Conclusions

Advising a parent to ask their child ‘What would Batman (or another admired character or person) eat?’ might be an easy step to take in what could be a healthier fast food world.
Re-Engineering Heavy Haul Turnouts for Passenger Higher Speed Rail Operations
Authors: Peterson Blaine O.
Published: March 2012

With the recent renewed interest in higher speed passenger rail (“HrSR”) in North America, there will be increased pressure on freight railroads to collaborate with public transportation agencies in the establishment of “shared use” tracks. Track infrastructure in these corridors must be robust enough to support the heavy axle loading associated with conventional North American freight traffic while accommodating FRA Class 6-7 passenger operating speeds in excess of 100 mph. Turnouts which permit higher diverging route speeds will become increasingly important as service-sensitive passenger operations look to reduce transit times and freights grapple with capacity concerns. Innovative approaches to the design, manufacture and construction of turnouts are called for. Critical design elements for a new generation of “shared use” turnouts will include: a) Tangential and compound geometries to optimize ride quality and safety; b) Respecting the spatial constraints of existing infrastructure (opposing signal locations) while maximizing diverging route permissible speeds; c) Kinematic gauge optimization through switches to enhance ride quality and increase component life; d) Premium frog designs to minimize running surface discontinuities; e) Cross tie housed rodding and position detection systems to facilitate continuous maintenance surfacing; f) Integrated switch drive, detection and monitoring systems to facilitate proactive intervention by maintenance forces.
Real‐time scintillation array dosimetry for radiotherapy: The advantages of photomultiplier detectors
Authors: Liu Paul Z. Y. , Suchowerska Natalka , Abolfathi Peter , McKenzie David R.
Published: March 2012

Purpose:

In this paper, a photomultiplier tube (PMT) array dosimetry system has been developed and tested for the real‐time readout of multiple scintillation signals from fiber optic dosimeters. It provides array dosimetry with the advantages in sensitivity provided by a PMT, but without the need for a separate PMT for each detector element.

Methods:

The PMT array system consisted of a multianode PMT, a multichannel data acquisition system, housing and optic fiber connections suitable for clinical use. The reproducibility, channel uniformity, channel crosstalk, acquisition speed, and sensitivity of the PMT array were quantified using a constant light source. Its performance was compared to other readout systems used in scintillation dosimetry. Anin vivo HDR brachytherapy treatment was used as an example of a clinical application of the dosimetry system to the measurement of dose at multiple sites in the rectum. The PMT array system was also tested in the pulsed beam of a linear accelerator to test its response speed and its application with two separate methods of Cerenkov background removal.

Results:

The PMT array dosimetry system was highly reproducible with a measurement uncertainty of 0.13% for a 10 s acquisition period. Optical crosstalk between neighboring channels was accounted for by omitting every second channel. A mathematical procedure was used to account for the crosstalk in next‐neighbor channels. The speed and sensitivity of the PMT array system were found be superior to CCD cameras, allowing for measurement of more rapid changes in dose rate. This was further demonstrated by measuring the dose delivered by individual photon pulses of a linear accelerator beam.

Conclusions:

The PMT array system has advantages over CCD camera‐based systems for the readout of scintillation light. It provided a more sensitive, more accurate, and faster response to meet the demands of future developments in treatment delivery.
An Impactor Origin for Lunar Magnetic Anomalies
Authors: Wieczorek Mark A. , Weiss Benjamin P. , Stewart Sarah T.
Published: March 2012

Bringing Magnetic Materials to the Moon

The Apollo missions to the Moon revealed that portions of the lunar crust are strongly magnetized. Lunar rocks are poor at recording the magnetic field, thus these magnetic anomalies have been difficult to explain. Based on numerical simulations of large-scale impacts,

Wieczorek
et al.

(p.
1212
; see the Perspective by

Collins

) show that the vast majority of lunar magnetic anomalies can be explained by highly magnetic materials that originated outside the Moon and were delivered by the asteroid that hit the Moon and formed the South Pole–Aitken basin, the largest impact basin in the solar system.
Designing Responsive Buckled Surfaces by Halftone Gel Lithography
Authors: Kim Jungwook , Hanna James A. , Byun Myunghwan , Santangelo Christian D. , Hayward Ryan C.
Published: March 2012

Smooth Operator

When thin sheets are compressed they can buckle and wrinkle, such as when the edges of a sheet of paper, or two areas of skin, are pushed together. Variations in local thickness and stiffness will alter the buckling patterns, but controlling this in a simple and predictable way is difficult.

Kim
et al.

(p.
1201
; see the Perspective by

Sharon

) used halftone lithography with two photomasks to create highly cross-linked dots embedded in a lightly cross-linked matrix of a swellable polymer. This material could generate “smooth” swelling profiles on thin sheets with arbitrary two-dimensional geometries so that complex three-dimensional structures could be produced.
The Economic Logic of U.S. Science

How Economics Shapes Science
by Paula Stephan

Harvard University Press, Cambridge, MA, 2012. 383 pp. $45, £33.95, €40.50. ISBN 9780674049710.
Authors: Feldman Maryann
Published: March 2012

Examining university science as an economic enterprise, Stephan explores what it costs, who pays for it, and who benefits.
Pictures of Remembering
Memory
Fragments of a Modern History

by Alison Winter

University of Chicago Press, Chicago, 2011. 329 pp. $30, £19.95. ISBN 9780226902586.
Authors: Johnston Elizabeth
Published: March 2012

Winter traces scientific and cultural aspects of our understanding of memory through the 20th century.
Embryonic Clutch Control
Authors: Razzell William , Martin Paul
Published: March 2012

A molecular clutch couples actin-based contractions to changes in cell shape that drive morphogenesis.
Surprising Twist in Debate Over Lab-Made H5N1
Authors: Cohen Jon
Published: March 2012

A researcher who created one of the H5N1 mutants believed to be capable of triggering an influenza pandemic and a leading U.S. health official are offering clarifications and "new data" to better gauge the risk it presents.
A Bumper Year for Chinese Science
Authors: Hvistendahl Mara
Published: March 2012

In a draft budget, China has earmarked 32.45 billion yuan ($5.14 billion) for basic research in 2012—up 26% from last year's appropriation.
The Quest for Transplantation Tolerance: Have We Finally Sipped from the Cup?
Authors: Markmann James F. , Kawai Tatsuo
Published: March 2012

New advances in achieving hematopoietic chimerism may facilitate immunological tolerance to kidney transplants.
Cytomegalovirus-Induced Effector T Cells Cause Endothelial Cell Damage
Authors: van de Berg Pablo J. E. J. , Yong Si-La , Remmerswaal Ester B. M. , van Lier René A. W. , ten Berge Ineke J. M.
Published: March 2012

Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial cell damage, but definitive proof for a direct cytopathic effect of CMV in these diseases is lacking. CMV infection is associated with a strong increase in both CD4+and CD8+T cells with constitutive effector functions that can perpetuate systemic inflammation. We investigated whether CMV-induced immune responses could lead to endothelial damage in humans. We found that terminally differentiated effector CD4+and CD8+T cells, formed during primary CMV infection and maintained throughout latency, express high levels of CX3CR1 and CXCR3. The ligands of these receptors, fractalkine and IP-10, respectively, are expressed by activated endothelial cells. Peripheral blood mononuclear cells (PBMC) stimulated with CMV antigen produced soluble factors that stimulated endothelial cells to produce both chemokines. Finally, effector cells migrated in a fractalkine- and IP-10-dependent fashion to activated endothelial cells and induced apoptosis in endothelial cells that were stimulated by supernatant from CMV-activated PBMC. Our findings offer an explanation for the accumulation of highly differentiated T cells near to the endothelium in CMV-infected individuals that may result in endothelial damage.
New Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against Hepatitis Delta Virus Using a Hepatitis Delta Antigen Derived from a Taiwanese Clone and Comparison to the Abbott Radioimmunoassay
Authors: Kuo Yung-Bin , Chao Mei , Lee Yi-Hsuan , Yeh Chau-Ting , Chan Err-Cheng
Published: March 2012

An anti-hepatitis delta (HD) enzyme-linked immunosorbent assay (ELISA) using a specific recombinant hepatitis delta antigen derived from a local dominant hepatitis delta virus (hepatitis D virus; HDV) strain in Taiwan has been established. The detection efficiency of this assay was comparable to that of the commercially available Abbott anti-HD radioimmunoassay (RIA) and could be useful in routine laboratory diagnoses of HDV infection.
Molecular Fingerprinting of Mycobacterium abscessus Strains in a Cohort of Pediatric Cystic Fibrosis Patients
Authors: Harris Kathryn A. , Kenna Dervla T. D. , Blauwendraat Cornelis , Hartley John C. , Turton Jane F. , Aurora Paul , Dixon Garth L. J.
Published: March 2012

Forty-one
Mycobacterium abscessus
complex isolates from 17 pediatric cystic fibrosis (CF) patients were typed using a novel variable-number tandem repeat (VNTR) scheme and an automated repetitive-PCR (rep-PCR) system. Both VNTR and rep-PCR typing methods differentiate between members of the
M. abscessus
complex. The isolates from individual patients are indistinguishable, and the data strongly suggest that individual CF patients are persistently infected with one strain and also suggests that different CF patients can harbor the same strain.
A New and Frequent Human T-Cell Leukemia Virus Indeterminate Western Blot Pattern: Epidemiological Determinants and PCR Results in Central African Inhabitants
Authors: Filippone Claudia , Bassot Sylviane , Betsem Edouard , Tortevoye Patricia , Guillotte Micheline , Mercereau-Puijalon Odile , Plancoulaine Sabine , Calattini Sara , Gessain Antoine
Published: March 2012

Human T-cell leukemia virus (HTLV) indeterminate Western blot (WB) serological patterns are frequently observed in plasma/serum from persons living in intertropical areas. In the framework of ongoing projects on HTLV-1/2 and related viruses in Central Africa, we systematically analyzed plasma from villagers living in South Cameroon by WB. The group included 1,968 individuals (mean age, 44 years; age range, 5 to 90 years; 978 women/990 men), both Bantus (1,165) and Pygmies (803). Plasma samples were tested by WB analysis (MPD HTLV Blot 2.4) and interpreted according to the manufacturer's instructions. Only clear bands were considered in the analysis. Among the 1,968 plasma samples, 38 (1.93%) were HTLV-1, 13 (0.66%) were HTLV-2, and 6 (0.3%) were HTLV WB seropositive. Furthermore, 1,292 (65.65%) samples were WB sero-indeterminate, including 104 (5.28%) with an HTLV-1 Gag-indeterminate pattern (HGIP) and 68 (3.45%) with a peculiar yet unreported pattern exhibiting mostly a strong shifted GD21 and a p28. The other 619 (31.45%) samples were either WB negative or exhibited other patterns, mostly with unique p19 or p24 bands. DNA, extracted from peripheral blood buffy coat, was subjected to PCR using several primer pairs known to detect HTLV-1/2/3/4. Most DNAs from HTLV-1- and HTLV-seropositive individuals were PCR positive. In contrast, all the others, from persons with HTLV-2, HGIP, new WB, and other indeterminate patterns, were PCR negative. Epidemiological determinant analysis of the persons with this new peculiar WB pattern revealed that seroprevalence was independent from age, sex, or ethnicity, thus resembling the indeterminate profile HGIP rather than HTLV-1. Moreover, this new pattern persists over time.
Adaptation of a Genotype 3 Hepatitis E Virus to Efficient Growth in Cell Culture Depends on an Inserted Human Gene Segment Acquired by Recombination
Authors: Shukla P. , Nguyen H. T. , Faulk K. , Mather K. , Torian U. , Engle R. E. , Emerson S. U.
Published: March 2012

An infectious cDNA clone of a genotype 3 strain of hepatitis E virus adapted to growth in HepG2/C3A human hepatoma cells was constructed. This virus was unusual in that the hypervariable region of the adapted virus contained a 171-nucleotide insertion that encoded 58 amino acids of human S17 ribosomal protein. Analyses of virus from six serial passages indicated that genomes with this insert, although initially rare, were selected during the first passage, suggesting it conferred a significant growth advantage. RNA transcripts from this cDNA and the viruses encoded by them were infectious for cells of both human and swine origin, the major host species for this zoonotic virus. Mutagenesis studies demonstrated that the S17 insert was a major factor in cell culture adaptation. Introduction of 54 synonymous mutations into the insert had no detectable effect, thus implicating protein, rather than RNA, as the important component. Truncation of the insert by 50% decreased the levels of successful transfection by ∼3-fold. Substitution of the S17 sequence by a different ribosomal protein sequence or by GTPase-activating protein sequence resulted in a partial enhancement of transfection levels, whereas substitution with 58 amino acids of green fluorescent protein had no effect. Therefore, both the sequence length and the amino acid composition of the insert were important. The S17 sequence did not affect transfection of human hepatoma cells when inserted into the hypervariable region of a genotype 1 strain, but this chimeric genome acquired a dramatic ability to replicate in hamster cells.
Attenuated Influenza Virus Construct with Enhanced Hemagglutinin Protein Expression
Authors: Maamary Jad , Pica Natalie , Belicha-Villanueva Alan , Chou Yi-ying , Krammer Florian , Gao Qinshan , García-Sastre Adolfo , Palese Peter
Published: March 2012

Influenza A viruses encoding an altered viral NS1 protein have emerged as promising live attenuated vaccine platforms. A carboxy-terminal truncation in the NS1 protein compromises its interferon antagonism activity, making these viruses attenuated in the host yet still able to induce protection from challenge with wild-type viruses. However, specific viral protein expression by NS1-truncated viruses is known to be decreased in infected cells. In this report, we show that recombinant H5N1 and H1N1 influenza viruses encoding a truncated NS1 protein expressed lower levels of hemagglutinin (HA) protein in infected cells than did wild-type viruses. This reduction in HA protein expression correlated with a reduction in HA mRNA levels in infected cells. NS1 truncation affected the expression of HA protein but not that of the nucleoprotein (NP). This segment specificity was mapped to the terminal sequences of their specific viral RNAs. Since the HA protein is the major immunogenic component in influenza virus vaccines, we sought to restore its expression levels in NS1-truncated viruses in order to improve their vaccine efficacy. For this purpose, we generated an NS1-truncated recombinant influenza A/Puerto Rico/8/34 (rPR8) virus carrying the G3A C8U “superpromoter” mutations in the HA genomic RNA segment. This strategy retained the attenuation properties of the recombinant virus but enhanced the expression level of HA protein in infected cells. Finally, mice immunized with rPR8 viruses encoding a truncated NS1 protein and carrying the G3A C8U mutations in the HA segment demonstrated enhanced protection from wild-type virus challenge over that for mice vaccinated with an rPR8 virus encoding the truncated NS1 protein alone.
Shelterin Dysfunction and p16
INK4a
-Mediated Growth Inhibition in HIV-1-Specific CD8 T Cells
Authors: Lichterfeld Mathias , Cung Thai , Seiss Katherine , Rosenberg Eric S. , Pereyra Florencia , Yu Xu G.
Published: March 2012

HIV-1-specific cytotoxic T cell responses are expanded during advanced HIV-1 infection but seem unable to effectively protect the host against disease progression. These cells are able to produce gamma interferon and remain metabolically active but have defective proliferative activities, shortened telomeric DNA, and other signs of accelerated aging. To investigate the molecular mechanisms underlying the premature senescence of HIV-1-specific T cells, we focused here on the expression and function of a group of six nucleoproteins that are responsible for protecting and maintaining the structural integrity of telomeric DNA and are commonly referred to as “shelterin.” We show that in progressive HIV-1 infection, the two major shelterin components TRF2 and TPP1 are selectively reduced in HIV-1-specific CD8 T cells, but not in T cells recognizing alternative viral species. This coincided with increased recruitment of 53BP1, a prominent DNA damage response factor, to telomeric DNA sites and was associated with elevated expression of the tumor suppressor p16
INK4a
, which causes cellular growth inhibition in response to structural DNA damage. Notably, defective shelterin function and upregulation of p16
INK4a
remained unaffected by experimental blockade of PD-1, indicating a possibly irreversible structural defect in HIV-1-specific CD8 T cells in progressors that cannot be overcome by manipulation of inhibitory cell-signaling pathways. These data suggest that shelterin dysfunction and ensuing upregulation of the tumor suppressor p16
INK4a
promote accelerated aging of HIV-1-specific T cells during progressive HIV-1 infection.
Vaccinia Virus A6 Is Essential for Virion Membrane Biogenesis and Localization of Virion Membrane Proteins to Sites of Virion Assembly
Authors: Meng Xiangzhi , Embry Addie , Rose Lloyd , Yan Bo , Xu Chungui , Xiang Yan
Published: March 2012

Poxvirus acquires its primary envelope through a process that is distinct from those of other enveloped viruses. The molecular mechanism of this process is poorly understood, but several poxvirus proteins essential for the process have been identified in studies of vaccinia virus (VACV), the prototypical poxvirus. Previously, we identified VACV A6 as an essential factor for virion morphogenesis by studying a temperature-sensitive mutant with a lesion in A6. Here, we further studied A6 by constructing and characterizing an inducible virus (iA6) that could more stringently repress A6 expression. When A6 expression was induced by the inducer isopropyl-β-
d
-thiogalactoside (IPTG), iA6 replicated normally, and membrane proteins of mature virions (MVs) predominantly localized in viral factories where virions were assembled. However, when A6 expression was repressed, electron microscopy of infected cells showed the accumulation of large viroplasm inclusions containing virion core proteins but no viral membranes. Immunofluorescence and cell fractionation studies showed that the major MV membrane proteins A13, A14, D8, and H3 did not localize to viral factories but instead accumulated in the secretory compartments, including the endoplasmic reticulum. Overall, our results show that A6 is an additional VACV protein that participates in an early step of virion membrane biogenesis. Furthermore, A6 is required for MV membrane protein localization to sites of virion assembly, suggesting that MV membrane proteins or precursors of MV membranes are trafficked to sites of virion assembly through an active, virus-mediated process that requires A6.
TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core
Authors: Valle-Casuso Jose Carlos , Di Nunzio Francesca , Yang Yang , Reszka Natalia , Lienlaf Maritza , Arhel Nathalie , Perez Patricio , Brass Abraham L. , Diaz-Griffero Felipe
Published: March 2012

TNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to integration. To investigate the mechanistic requirement of TNPO3 in HIV-1 infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3 binds to the HIV-1 core. Overall, this work suggests that TNPO3 interacts with the incoming HIV-1 core in the cytoplasm to assist a process that is important for HIV-1 infection after nuclear import.
Structure of the Fab-Labeled “Breathing” State of Native Poliovirus
Authors: Lin Jun , Lee Lily Y. , Roivainen Merja , Filman David J. , Hogle James M. , Belnap David M.
Published: March 2012

At 37°C, the structure of poliovirus is dynamic, and internal polypeptides VP4 and N terminus of VP1 (residues 1 to 53) externalize reversibly. An Fab fragment of a monospecific antibody, which binds to residues 39 to 55 of VP1, was utilized to locate the N termini of VP1 in native (160S) particles in this “breathing” state. Fab and virus were mixed and imaged via cryogenic electron microscopy. The resulting reconstruction showed the capsid expands similarly to the irreversibly altered cell entry intermediate (135S) particle, but the N terminus of VP1 is located near the 2-fold axes, instead of the “propeller tip” as in 135S particles.
Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrP
C
to PrP
Sc
in Prion-Infected Neuroblastoma Cells
Authors: Hara Hideyuki , Okemoto-Nakamura Yuko , Shinkai-Ouchi Fumiko , Hanada Kentaro , Yamakawa Yoshio , Hagiwara Ken'ichi
Published: March 2012

Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrP
Sc
; PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrP
C
) to PrP
Sc
and the subsequent conversion of PrP
C
to PrP
Sc
. We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrP
C
and PrP
Sc
. Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrP
Sc
state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrP
Sc
and interfered with the conversion of endogenous MoPrP
C
. The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrP
Sc
. Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrP
C
reduced the accumulation of PrP
Sc
after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrP
C
plays a key role in conversion after binding to MoPrP
Sc
.
Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate Pseudomonas aeruginosa in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
Authors: Alemayehu Debebe , Casey Pat G. , McAuliffe Olivia , Guinane Caitriona M. , Martin James G. , Shanahan Fergus , Coffey Aidan , Ross R. Paul , Hill Colin
Published: March 2012

Pseudomonas aeruginosa
is a common cause of infection in the lungs of patients with cystic fibrosis (CF). In addition, biofilm formation and antibiotic resistance of
Pseudomonas
are major problems that can complicate antibiotic therapy. We evaluated the efficacy of using bacteriophages to kill the pathogen in both biofilms and in the murine lung. We isolated and characterized two phages from a local wastewater treatment plant, a myovirus (ϕNH-4) and a podovirus (ϕMR299-2). Both phages were active against clinical isolates of
P. aeruginosa
. Together, the two phages killed all 9 clinical isolate strains tested, including both mucoid and nonmucoid strains. An equal mixture of the two phages was effective in killing
P. aeruginosa
NH57388A (mucoid) and
P. aeruginosa
MR299 (nonmucoid) strains when growing as a biofilm on a cystic fibrosis bronchial epithelial CFBE41o- cell line. Phage titers increased almost 100-fold over a 24-h period, confirming replication of the phage. Furthermore, the phage mix was also effective in killing the pathogen in murine lungs containing 1 × 10
7
to 2 × 10
7
P. aeruginosa
.
Pseudomonas
was effectively cleared (reduced by a magnitude of at least 3 to 4 log units) from murine lungs in 6 h. Our study demonstrates the efficacy of these two phages in killing clinical
Pseudomonas
isolates in the murine lung or as a biofilm on a pulmonary cell line and supports the growing interest in using phage therapy for the control and treatment of multidrug-resistant
Pseudomonas
lung infections in CF patients.

IMPORTANCE
Given the rise in antibiotic resistance, nonantibiotic therapies are required for the treatment of infection. This is particularly true for the treatment of
Pseudomonas
infection in patients with cystic fibrosis. We have identified two bacterial viruses (bacteriophages) that can kill
Pseudomonas
growing on human lung cells and in an animal model of lung infection. The use of bacteriophages is particularly appropriate because the killing agent can replicate on the target cell, generating fresh copies of the bacteriophage. Thus, in the presence of a target, the killing agent multiplies. By using two bacteriophages we can reduce the risk of resistant colonies developing at the site of infection. Bacteriophage therapy is an exciting field, and this study represents an important demonstration of efficacy in validated infection models.
Decreased length of stay after addition of healthcare provider in emergency department triage: a comparison between computer-simulated and real-world interventions
Authors: Day Theodore Eugene , Al-Roubaie Abdul Rahim , Goldlust Eric Jonathan
Published: March 2012

Objective

(1) To determine the effects of adding a provider in triage on average length of stay (LOS) and proportion of patients with >6 h LOS. (2) To assess the accuracy of computer simulation in predicting the magnitude of such effects on these metrics.

Methods

A group-level quasi-experimental trial comparing the St. Louis Veterans Affairs Medical Center emergency department (1) before intervention, (2) after institution of provider in triage, and discrete event simulation (DES) models of similar (3) ‘before’ and (4) ‘after’ conditions. The outcome measures were daily mean LOS and percentage of patients with LOS >6 h.

Results

The DES-modelled intervention predicted a decrease in the %6-hour LOS from 19.0% to 13.1%, and a drop in the daily mean LOS from 249 to 200 min (p<0.0001). Following (actual) intervention, the number of patients with LOS >6 h decreased from 19.9% to 14.3% (p<0.0001), with the daily mean LOS decreasing from 247 to 210 min (p<0.0001).

Conclusion

Physician and mid-level provider coverage at triage significantly reduced emergency department LOS in this setting. DES accurately predicted the magnitude of this effect. These results suggest further work in the generalisability of triage providers and in the utility of DES for predicting quantitative effects of process changes.
Analysis of genetic diversity inElytrigia repensgermplasm using intersimple sequence repeat (ISSR) markers
Authors: Meng Lin , Zhang Xiaoyan , Mao Peichun , Tian Xiaoxia
Published: March 2012

The genetic diversity among 30 accessions of Elytrigia repens (L.) Nevski was analyzed using 100 intersimple sequence repeat (ISSR) primers, 12 of which generated distinct amplification products. Out of the 132 repeatable bands detected, 100 bands were polymorphic. The percentage of polymorphic bands was 70.66%, with a mean of 8.33 percentage of polymorphic bands per primer. The ISSR-based genetic similarity coefficients among the 30 accessions ranged from 0.509 to 0.873, revealing high genetic diversity. The 30 E. repens accessions were divided into eight groups based on an unweighted pair-group method with arithmetic mean cluster analysis and a principal components analysis. We found that genetic distance is correlated with geographical distance among the 30 E. repens accessions studied (r = 0.812, p < 0.05) using Mantel’s test. Our results confirm the potential value of genetic diversity preservation for future breeding programs.
SEPARATION OF COUPLED SYSTEMS OF SCHRODINGER EQUATIONS BY DARBOUX TRANSFORMATIONS
Authors: HUMI MAYER
Published: March 2012

Darboux transformations in one independent variable have found numerous applications in various field of mathematics and physics. In this paper, we introduce a novel application of these transformations in two dimensions to decouple systems of Schrodinger equations. We derive explicit representation for three classes of such systems which can be decoupled by such transformations. We also show that there is an elegant relationship between these transformations and analytic complex matrix functions.
2 MeV-PIXE TECHNIQUE FOR COASTAL MATERIAL ANALYSIS
Authors: MANIKANDAN E. , PRITHIVIRAJ BHARATH , KAVITHA G. , MAGUDAPATHY P. , RAJAMANNAN B.
Published: March 2012

Ion beam analysis (IBA) is a group of PIXE (particle induced X-ray emission) techniques dedicated to the analysis of material for geological sample of coastal sediment samples. Coastal/Beach samples collected from South East Coast of Tamilnadu were analyzed by PIXE technique and obtain the elemental composition of coastal sediments. The PIXE analysis was carried out using 1.7 MV Tandem accelerators with the energy of 2 MeV protons at Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Tamilnadu, India. The data analysis is normally done in an interactive mode of GUPIX analytical software computer code. The identified elements are present in the fingerprint X-ray spectrum in the range of ppm to ppb level. Therefore in this paper, introductory results concerning determination of concentration of chosen elements such as K , P , Ca , Ti , Fe , Cr , Co , Zn , Mn , Ni , Cu , Rb , Sr , As , Zr , Hf , Pb and Hg of coastal sediment samples from the east coast of Tamilnadu, India are presented. The validation of the technique is assessed using standard reference material (SRM) NIST 1646a estuarine sediment and the result shows the good agreement with the certified one. The results were used to assess environmental toxicity of heavy metals and radiation hazard in the study area.
PIXE ANALYSIS OF A MURINE FIBROSARCOMA TUMOR TREATED WITH A VASCULAR DISRUPTING AGENT AVE8062
Authors: TERAKAWA A. , ISHII K. , MATSUYAMA S. , KIKUCHI Y. , YASUNAGA S. , ITO Y. , TAGAWA A. , KAWAMURA T. , TAKAHASHI Y. , HATORI Y. , HAMADA N. , FUJIKI K. , MIURA Y. , YAMAZAKI H. , FUNAKI Y. , FURUMOTO S. , ITO N. , WADA S. , SERA K.
Published: March 2012

Spatial distributions of principal elements in a NFSa fibrosarcoma tumor treated with a vascular disruption agent, AVE8062 (a derivative of combretastatin A-4) at a single dose of 40 mg/kg were evaluated on the basis of particle-induced X-ray emission (PIXE) analysis using a submillimeter-sized proton beam. We found not only potassium and sulfur concentrations at the periphery of the treated tumor but also a ring-shaped calcium distribution in the area between the inner necrotic region and the periphery. These observations were supported by results for quantitative evaluation of elemental concentrations in the tumor samples obtained from conventional PIXE analysis based on the internal standard method. It is suggested that the potassium and sulfur concentrations are related to residual viable cells at the tumor periphery which are commonly observed in VDA treatments whereas the ring of calcium concentration just inside the tumor periphery is possibly derived from hypoxia-induced response.
ELEMENTAL ACCUMULATION PATTERNS OF THE LICHEN SPECIES PHYSCIA TRIBACOIDES NYL., HETERODERMIA DISSECTA AND BACIDIA BECKHAUSII KÖRBER FROM THE WALAYAR RF REGION, TAMIL NADU, INDIA
Authors: PRITHIVIRAJ BHARATH , MANIKANDAN E. , HARIHARAN G. N. , NAIR K. G. M.
Published: March 2012

Lichens have been used extensively as biomonitors of air quality (Richardson 1992; Seaward 1995, 2005). Lichen thalli lack a protective layer and hence accumulate airborne pollutants and particulate matter from the environment by wet and dry deposition (Nash 1996). The elements accumulated on lichen thalli can be quantitatively analysed using techniques such as Proton Induced X-ray Emission (PIXE) and Electron probe microanalysis. These techniques yield two-dimensional, quantitative element information with micron-level spatial resolution. This study used Scanning Electron Microscopy-Energy Dispersive X-ray (SEM-EDX) and PIXE to quantify elements accumulated on lichen thalli of selected species collected from polluted and unpolluted areas of the Madukkarai – Walayar forests. Thalli of selected lichen species from the study site (polluted and unpolluted) were irradiated using 1.7 MV tandem accelerator with Proton beam energy of 2 MeV. The ion induced X-rays were detected by Si ( Li ) semiconductor detector. The morphological analysis and localization of elements accumulated on these lichen samples were also carried out with the use of a SEM-EDX microanalysis using environmental scanning electron microscopy (ESEM) as supporting evidence. PIXE spectral elemental output revealed the presence of elements such as As , Ba , Br , Ca , Cu , Fe , K , Mn , Zn , Cl , Ti , Cr and Pd with the incidence of increased Calcium levels. IAEA 336 lichen reference material was used for standardization.
ENTROPY IN QUANTUM CHROMODYNAMICS
Authors: CORNWALL JOHN M.
Published: March 2012

We review the role of zero-temperature entropy in several closely-related contexts in QCD. The first is entropy associated with disordered condensates, including [Formula: see text]. The second is effective vacuum entropy arising from QCD solitons such as center vortices, yielding confinement and chiral symmetry breaking. The third is entanglement entropy, which is entropy associated with a pure state, such as the QCD vacuum, when the state is partially unobserved and unknown. Typically, entanglement entropy of an unobserved three-volume scales not with the volume but with the area of its bounding surface. The fourth manifestation of entropy in QCD is the configurational entropy of light-particle world-lines and flux tubes; we argue that this entropy is critical for understanding how confinement produces chiral symmetry breakdown, as manifested by a dynamically-massive quark, a massless pion, and a [Formula: see text] condensate.
MASS SPECTRUM FROM STOCHASTIC LÉVY-SCHRÖDINGER RELATIVISTIC EQUATIONS: POSSIBLE QUALITATIVE PREDICTIONS IN QCD
Authors: PETRONI NICOLA CUFARO , PUSTERLA MODESTO
Published: March 2012

Starting from the relation between the kinetic energy of a free Lévy–Schrödinger particle and the logarithmic characteristic of the underlying stochastic process, we show that it is possible to get a precise relation between renormalizable field theories and a specific Lévy process. This subsequently leads to a particular cutoff in the perturbative diagrams and can produce a phenomenological mass spectrum that allows an interpretation of quarks and leptons distributed in the three families of the standard model.
OPTICAL INTERSUBBAND TRANSITIONS AND BINDING ENERGIES OF DONOR IMPURITIES IN Ga1-xInxNyAs1-y/GaAs/Al0.3Ga0.7As QUANTUM WELL UNDER THE ELECTRIC FIELD
Authors: UNGAN F. , YESILGUL U. , KASAPOGLU E. , SARI H. , SOKMEN I.
Published: March 2012

The effects of nitrogen and indium mole concentration on the intersubband optical absorption for (1–2) transition and the binding energy of the shallow-donor impurities in a Ga 1-x In x N y As 1-y/ GaAs / Al 0.3 Ga 0.7 As quantum well under the electric field is theoretically calculated within the framework of the effective-mass approximation. Results are obtained for several concentrations of nitrogen and indium, and the applied electric field. The numerical results show that the intersubband transitions and the impurity binding energy strongly depend on the nitrogen and indium concentrations.