bluuebunny/crossref_metadata_2025_split huggingface dataset:
ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation
Authors: Berhanu Aklile , King David S. , Mosier Stacie , Jordan Robert , Jones Kevin F. , Hruby Dennis E. , Grosenbach Douglas W. 
Published: September 2009

ABSTRACTOrthopoxvirusinfections, such as smallpox, can lead to severe systemic disease and result in considerable morbidity and mortality in immunologically naïve individuals. Treatment with ST-246, a small-molecule inhibitor of virus egress, has been shown to provide protection against severe disease and death induced by several members of the poxvirus family, including vaccinia, variola, and monkeypox viruses. Here, we show that ST-246 treatment not only results in the significant inhibition of vaccinia virus dissemination from the site of inoculation to distal organs, such as the spleen and liver, but also reduces the viral load in organs targeted by the dissemination. In mice intranasally infected with vaccinia virus, virus shedding from the nasal and lung mucosa was significantly lower (∼22- and 528-fold, respectively) upon ST-246 treatment. Consequently, virus dissemination from the nasal site of replication to the lung also was dramatically reduced, as evidenced by a 179-fold difference in virus levels in nasal versus bronchoalveolar lavage. Furthermore, in ACAM2000-immunized mice, vaccination site swabs showed that ST-246 treatment results in a major (∼3,900-fold by day 21) reduction in virus detected at the outside surfaces of lesions. Taken together, these data suggest that ST-246 would play a dual protective role if used during a smallpox bioterrorist attack. First, ST-246 would provide therapeutic benefit by reducing the disease burden and lethality in infected individuals. Second, by reducing virus shedding from those prophylactically immunized with a smallpox vaccine or harboring variola virus infection, ST-246 could reduce the risk of virus transmission to susceptible contacts.
High Level of Cross-Resistance between Kanamycin, Amikacin, and Capreomycin among
Mycobacterium tuberculosis
Isolates from Georgia and a Close Relation with Mutations in the
rrs
Gene
Authors: Jugheli Levan , Bzekalava Nino , de Rijk Pim , Fissette Krista , Portaels Françoise , Rigouts Leen 
Published: September 2009

ABSTRACT

The aminoglycosides kanamycin and amikacin and the macrocyclic peptide capreomycin are key drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB). The increasing rates of resistance to these drugs and the possible cross-resistance between them are concerns for MDR-TB therapy. Mutations in the 16S rRNA gene (
rrs
) have been associated with resistance to each of the drugs, and mutations of the
tlyA
gene, which encodes a putative rRNA methyltransferase, are thought to confer capreomycin resistance in
Mycobacterium tuberculosis
bacteria. Studies of possible cross-resistance have shown variable results. In this study, the MICs of these drugs for 145 clinical isolates from Georgia and the sequences of the
rrs
and
tlyA
genes of the isolates were determined. Of 78 kanamycin-resistant strains, 9 (11.5%) were susceptible to amikacin and 16 (20.5%) were susceptible to capreomycin. Four strains were resistant to capreomycin but were susceptible to the other drugs, whereas all amikacin-resistant isolates were resistant to kanamycin. Sequencing revealed six types of mutations in the
rrs
gene (A514C, C517T, A1401G, C1402T, C1443G, T1521C) but no mutations in the
tlyA
gene. The A514C, C517T, C1443G, and T1521C mutations showed no association with resistance to any of the drugs. The A1401G and C1402T mutations were observed in 65 kanamycin-resistant isolates and the 4 capreomycin-resistant isolates, respectively, whereas none of the susceptible isolates showed either of those mutations. The four mutants with the C1402T mutations showed high levels of resistance to capreomycin but no resistance to kanamycin and amikacin. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to kanamycin and amikacin, while the sensitivities reached 85.9% and 94.2%, respectively.
Surface-Exposed Histone-Like Protein A Modulates Adherence of
Streptococcus gallolyticus
to Colon Adenocarcinoma Cells
Authors: Boleij Annemarie , Schaeps Renée M. J. , de Kleijn Stan , Hermans Peter W. , Glaser Philippe , Pancholi Vijay , Swinkels Dorine W. , Tjalsma Harold 
Published: September 2009

ABSTRACT

Streptococcus gallolyticus
(formerly known as
Streptococcus bovis
biotype I) is a low-grade opportunistic pathogen which is considered to be associated with colon cancer. It is thought that colon polyps or tumors are the main portal of entry for this bacterium and that heparan sulfate proteoglycans (HSPGs) at the colon tumor cell surface are involved in bacterial adherence during the first stages of infection. In this study, we have shown that the histone-like protein A (HlpA) of
S. gallolyticus
is a genuine anchorless bacterial surface protein that binds to lipoteichoic acid (LTA) of the gram-positive cell wall in a growth phase-dependent manner. In addition, HlpA was shown to be one of the major heparin-binding proteins of
S. gallolyticus
able to bind to the HSPG-expressing colon tumor cell lines HCT116 and HT-29. Strikingly, although wild-type levels of HlpA appeared to contribute to adherence, coating of additional HlpA at the bacterial surface resulted in reduced binding to colon tumor cells. This may be explained by the fact that heparan sulfate and LTA compete for the same binding site in HlpA. Altogether, this study implies that HlpA serves as a fine-tuning factor for bacterial adherence.
Mycobacterium tuberculosis
Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to
Mycobacterium bovis
BCG-Primed Mice by Inhibiting Interleukin-4 Secretion
Authors: Fonseca Denise Morais da , Silva Celio Lopes , Wowk Pryscilla Fanini , Paula Marina Oliveira e , Ramos Simone Gusmão , Horn Cynthia , Marchal Gilles , Bonato Vânia Luiza Deperon 
Published: September 2009

ABSTRACT

Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine development. We previously showed that despite the high level of gamma interferon (IFN-γ) production elicited by homologous immunization with CFP plus CpG oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice were challenged with
Mycobacterium tuberculosis
. In order to use the IFN-γ-inducing ability of CFP antigens, in this study we evaluated a prime-boost heterologous immunization based on CFP/CpG to boost
Mycobacterium bovis
BCG vaccination in order to find an immunization schedule that could induce protection. Heterologous BCG-CFP/CpG immunization provided significant protection against experimental tuberculosis, and this protection was sustained during the late phase of infection and was even better than that conferred by a single BCG immunization. The protection was associated with high levels of antigen-specific IFN-γ and interleukin-17 (IL-17) and low IL-4 production. The deleterious role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed consistent protection similar to that elicited by BCG-CFP/CpG heterologous immunization. These findings show that a single dose of CFP/CpG can represent a new strategy to boost the protection conferred by BCG vaccination. Moreover, different immunological parameters, such as IFN-γ and IL-17 and tightly regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis vaccine.
Helminth Infection Can Reduce Insulitis and Type 1 Diabetes through CD25- and IL-10-Independent Mechanisms
Authors: Liu Qian , Sundar Krishnan , Mishra Pankaj K. , Mousavi Gity , Liu Zhugong , Gaydo Andrew , Alem Farhang , Lagunoff David , Bleich David , Gause William C. 
Published: September 2009

ABSTRACT

Parasitic helminth infection has been shown to modulate pathological inflammatory responses in allergy and autoimmune disease. The aim of this study was to examine the effects of infection with a helminth parasite,
Heligmosomoides polygyrus
, on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the mechanisms involved in this protection.
H. polygyrus
inoculation at 5 weeks of age protected NOD mice from T1D until 40 weeks of age and also inhibited the more aggressive cyclophosphamide-induced T1D. Moreover,
H. polygyrus
inoculation as late as 12 weeks of age reduced the onset of T1D in NOD mice. Following
H. polygyrus
inoculation of NOD mice, pancreatic insulitis was markedly inhibited. Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4
+
CD25
+
FoxP3
+
regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. Depletion of CD4
+
CD25
+
T cells in vivo did not abrogate
H. polygyrus
-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. These findings suggest that infection with
H. polygyrus
significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis.
Lung Cancer in Never Smokers: A Call to Action
Authors: Rudin Charles M. , Avila-Tang Erika , Samet Jonathan M. 
Published: September 2009

Abstract
The causative association between tobacco use and lung cancer is a well-established fact. However, lung cancer also occurs, at surprisingly high rates, in lifelong never smokers. In fact, lung cancer in never smokers is among the leading causes of cancer-related mortality. This CCR Focus summarizes recent data, identifies knowledge deficits, and suggests future research directions with regard to this critically important subset of lung cancer patients. (Clin Cancer Res 2009;15(18):5622–5)
A Duration-Dependent Account of Coarticulation for Hyper- and Hypoarticulation
Authors: Lindblom Björn , Sussman Harvey M. , Agwuele Augustine 
Published: September 2009

Abstract
Previous studies investigating anticipatory coarticulation in emphatically stressed CV sequences and during fast speaking rates reported that three factors contributed to the overall extent of the documented coarticulation. These factors were: (1) vowel identity, (2) vowel space expansion (emphasis) or reduction (fast rate), and a hypothesized (3) ‘deeper’ and ‘shallower’ stop closure contact in emphatic and faster speech, respectively. The objective of the current research was to conceptually and quantitatively unify these two studies. This was accomplished by showing that the opposite changes to frequency onsets of F2 transitions due to emphatic and rapid speech systematically vary as a function of the durational changes in the stop closure interval. Specifically, the decrease in coarticulation in emphatic speech is characterized by increases in F2 onsets and longer stop closures (relative to a normal baseline); the increase in coarticulation due to rapid speech shows concomitant decreases in F2 onsets coinciding with shorter stop closure intervals. Vocal tract area function simulations corresponding to emphatic and reduced speech implicitly support ‘deeper’ and ‘shallower’ closure contacts as a third factor contributing to the overall extent of anticipatory CV coarticulation.
Teenage Marriage in the Malay/Muslim Community of Singapore: Problems, Perceptions and Programmes
Authors: Rahman Noor Aisha Abdul 
Published: September 2009

AbstractTeenage marriage within the Malay community of Singapore was thrust under the national spotlight by the government in recent years. Though identified as one of the major social challenges confronting the Malay community, there is still at present, a gross lack of research necessary for an objective understanding of the phenomenon. The adverse implications of the lacunae are reinforced by instant solutions and prescriptions aimed at eradicating the problem. Utilising data obtained from interviews and responses to a survey administered to Malay teenage married couples, this paper examines dominant perceptions of teenage marriage in Singapore and their ramifications on policies and programmes. It is hoped that this paper can contribute towards a more objective understanding of the problem so vital for effective policy making.
What's so Special about Agglomeration? A Survival Analysis of Internet Consultancies in Australia
Authors: Mattar Yasser 
Published: September 2009

AbstractSince the 1970s, the Australian government has seen the information and communication technology industry as a viable industry for promotion and investment. This paper attempts to empirically evaluate policy initiatives geared towards geographical co-location through a survival analysis of Internet consultancy organisations that were in operation in New South Wales and the Australian Capital Territory between 1996 and 2003. This will be augmented by anecdotal evidence through interviews done with representatives of organisations sampled from the dataset. It will be shown that co-location in Australia does not offer the necessary resources for survival as predicted by locational economics. Rather, organisational networks that transcend physical displacements are of more importance in ensuring organisational survival.
The Freedom of Religion or Belief and the Freedom of Expression
Authors: Evans Malcolm 
Published: September 2009

AbstractThere is increasing scrutiny of the practice of states in relation to matters of religion or belief and whilst such practice takes place—and is subject to analysis—on many levels, one of the most important issues concerns the manner in which it bears upon the enjoyment of other fundamental rights. Given the importance placed upon the freedom of expression in the western liberal democratic tradition, it is easy to see why the relationship between religion, belief and expression has become so significant an issue and why the manner in which any tensions are addressed tends to assume something of a totemic significance in the eyes of some observers.
Natural Reason, Natural Rights, and Governmental Neutrality Toward Religion
Authors: Audi Robert 
Published: September 2009

AbstractThis article explores the normative basis of church-state separation and of some separationist principles that apply to the conduct of individual citizens. It states institutional principles for the guidance of governmental policy toward religious institutions; it articulates citizenship standards for political conduct on the part of individuals; and it explores the case for affirming these two kinds of standards on the basis of what, historically, has been called natural reason. A major question for the article is whether natural reason may be properly considered to be secular, in a sense that implies normative authority that is not dependent on religion or theology and is also sufficient to justify affirming natural rights, such as rights to freedom of action, religious liberty, and equal treatment under the law. The article argues that natural reason may be viewed as secular in this sense and that, as has not been generally noticed, this poses a challenge to liberal political theory. On the plausible assumption that democracies may not properly assume that natural reason cannot—independently of religious premises—establish theism, they lack an adequate basis for a robust separation of church and state and cannot justify the far-reaching governmental neutrality toward religion endorsed by liberal political theory. The article assesses this challenge to liberal political theory, sketches a kind of governmental neutrality consistent with a strong conception of natural reason, and proposes a principle of toleration that supports both a desirable balance between an appropriate secularity in government and a high degree of religious liberty in society.
Initial Development and Genesis of Hurricane Dolly (2008)
Authors: Fang Juan , Zhang Fuqing 
Published: September 2009

AbstractBased on a successful cloud-resolving simulation with the Weather Research and Forecasting Model, this study examines key processes that led to the early development of Hurricane Dolly (2008). The initial development of Dolly consisted of three stages: (i) an initial burst of convection; (ii) stratiform development, dry intrusion, and thermodynamic recovery; and (iii) reinvigoration of moist convection and rapid intensification. Advanced diagnosis of the simulation—including the use of vorticity budget analysis, contour frequency analysis diagrams, and two-dimensional spectral decomposition and filtering—suggests that the genesis of Dolly is essentially a “bottom-up” process. The enhancement of the low-level vorticity is mainly ascribed to the stretching effect, which converges the ambient vorticity through stretching enhanced by moist convection. In the rapid intensification stage, smaller-scale positive vorticity anomalies resulting from moist convection are wrapped into the storm center area under the influence of background convergent flow. The convergence and accompanying aggregation of vorticity anomalies project the vorticity into larger scales and finally lead to the spinup of the system-scale vortex. On the other hand, although there is apparent stratiform development in the inner-core areas of incipient storm after the initial burst of convection, little evidence is found to support the genesis of Dolly through downward extension of the midlevel vorticity, a key process in the “top-down” thinking.
A Last Saturation Analysis of ENSO Humidity Variability in the Subtropical Pacific
Authors: Hurley John V. , Galewsky Joseph 
Published: September 2009

Abstract
Water vapor tracers of last saturation were used in an atmospheric tracer transport model to evaluate ENSO variability in the generation of the dry air that defines the subtropical middle troposphere over the North Pacific. Fifteen Northern Hemisphere winters, including El Niño, La Niña, and ENSO-neutral seasons, were evaluated using both Northern Hemisphere and global last saturation water vapor tracer configurations. During El Niño northern winter, the free troposphere over the subtropical North Pacific is both drier and warmer than during La Niña.
The probability distributions of the last saturation position for the dry air in the middle troposphere were evaluated over the subtropical North Pacific and were found to be further poleward, at a higher altitude, and more westerly in their components during the warm phase compared to the cold phase. During warm phase (cold phase) northern winter, 57% (49%) of the air at 20°N and 633 hPa over the North Pacific was last saturated poleward of 20°N and above 500 hPa. Coherency was demonstrated between tropical sea surface temperatures, extratropical atmospheric saturation, and subtropical aridity of the middle troposphere. The stronger westerly component of last saturation during the warm phase ties ENSO-variable subtropical aridity to midlatitude westerlies when there is enhanced baroclinicity and an equatorward migration of the Pacific storm track.
Humidity reconstructions from the water vapor tracers capture observed ENSO humidity variability and demonstrate that it can be explained in terms of changes in the location of last saturation, and not by changes in the temperature field. This study shows how teleconnections between the tropical ocean and the extratropical upper troposphere can impact the humidity of the middle troposphere of the subtropical dry regions.
Jet Formation and Evolution in Baroclinic Turbulence with Simple Topography
Authors: Thompson Andrew F. 
Published: September 2009

Abstract
Satellite altimetry and high-resolution ocean models indicate that the Southern Ocean comprises an intricate web of narrow, meandering jets that undergo spontaneous formation, merger, and splitting events, as well as rapid latitude shifts over periods of weeks to months. The role of topography in controlling jet variability is explored using over 100 simulations from a doubly periodic, forced-dissipative, two-layer quasigeostrophic model. The system is forced by a baroclinically unstable, vertically sheared mean flow in a domain that is large enough to accommodate multiple jets. The dependence of (i) meridional jet spacing, (ii) jet variability, and (iii) domain-averaged meridional transport on changes in the length scale and steepness of simple sinusoidal topographical features is analyzed.
The Rhines scale, ℓβ = 2πVe/β, where Ve is an eddy velocity scale and β is the barotropic potential vorticity gradient, measures the meridional extent of eddy mixing by a single jet. The ratio ℓβ /ℓT, where ℓT is the topographic length scale, governs jet behavior. Multiple, steady jets with fixed meridional spacing are observed when ℓβ ≫ ℓT or when ℓβ ≈ ℓT. When ℓβ &lt; ℓT, a pattern of perpetual jet formation and jet merger dominates the time evolution of the system. Zonal ridges systematically reduce the domain-averaged meridional transport, while two-dimensional, sinusoidal bumps can increase transport by an order of magnitude or more. For certain parameters, bumpy topography gives rise to periodic oscillations in the jet structure between purely zonal and topographically steered states. In these cases, transport is dominated by bursts of mixing associated with the transition between the two regimes. Topography modifies local potential vorticity (PV) gradients and mean flows; this can generate asymmetric Reynolds stresses about the jet core and can feed back on the conversion of potential energy to kinetic energy through baroclinic instability. Both processes contribute to unsteady jet behavior. It is likely that these processes play a role in the dynamic nature of Southern Ocean jets.
Southern Ocean Response to Relative Velocity Wind Stress Forcing
Authors: Hutchinson David K. , Hogg Andrew Mc C. , Blundell Jeffrey R. 
Published: September 2009

Abstract
An eddy-resolving quasigeostrophic model of the Southern Ocean coupled to a dynamic atmospheric mixed layer is used to compare the performance of two different wind stress parameterization schemes. The first is the standard quadratic drag law, based on atmospheric velocity alone, whereas the second (more exact) formulation is based on the difference between ocean and atmosphere velocities. The two different schemes give very similar magnitudes of mean stress; however, the relative velocity scheme has substantially lower power input, resulting in a weaker eddy field, and consequently, greater circumpolar transport. These results are explored in terms of the existing theories of the Antarctic Circumpolar Current (including eddy saturation and eddy damping) and the implications for modeling the Southern Ocean are discussed.
Measurement of Whole Body Cellular and Collagen Nitrogen, Potassium, and Other Elements by Neutron Activation and Whole Body Counting
Authors: James H.M. , Fabricius P.J. , Dykes P.W. 
Published: September 2009

Whole body nitrogen can be measured by neutron activation analysis with an acceptable radiation dose; it is an index of body protein which, in normal subjects, is 65% cellular protein and 35% extracellular connective collagen. Whole body potassium can be measured by whole body counting without irradiating the subject; it is an index of body cell mass.We measured whole body nitrogen, potassium, extracellular water, intracellular water, and fat‐folds. The differences between 37 malnourished patients and five normal subjects suggested that the patients had 9 kg less cell mass than normal, but no difference in extracellular mass. Measurements were made on eight patients before and after 14 days of total parenteral nutrition; balance of nitrogen intake and excretion also was measured. The changes were consistent with mean increases of 3 kg of cellular mass and 3 kg of fat with no change of extracellular mass.The accuracy and sensitivity of the whole body measurements need further confirmation for use in patients with changing body composition. Where tissue wasting is largely from the cellular compartment, potassium could be a more sensitive index of wasting than nitrogen. Multielement analysis of nitrogen, potassium, chlorine, and carbon will probably be valuable in elucidating body composition in malnutrition. (Journal of Parenteral and Enteral Nutrition11:48S‐50S, 1987)