bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Hopanoid Biosynthesis Genes Involved in Polymyxin Resistance in Burkholderia multivorans
Authors: Malott Rebecca J. , Steen-Kinnaird Barbara R. , Lee Tracy D. , Speert David P. 
Published: October 2011

ABSTRACT

A major challenge to clinical therapy of
Burkholderia cepacia
complex (Bcc) pulmonary infections is their innate resistance to a broad range of antimicrobials, including polycationic agents such as aminoglycosides, polymyxins, and cationic peptides. To identify genetic loci associated with this phenotype, a transposon mutant library was constructed in
B. multivorans
ATCC 17616 and screened for increased susceptibility to polymyxin B. Compared to the parent strain, mutant 26D7 exhibited 8- and 16-fold increases in susceptibility to polymyxin B and colistin, respectively. Genetic analysis of mutant 26D7 indicated that the transposon inserted into open reading frame (ORF) Bmul_2133, part of a putative hopanoid biosynthesis gene cluster. A strain with a mutation in another ORF in this cluster, Bmul_2134, was constructed and named RMI19. Mutant RMI19 also had increased polymyxin susceptibility. Hopanoids are analogues of eukaryotic sterols involved in membrane stability and barrier function. Strains with mutations in Bmul_2133 and Bmul_2134 showed increased permeability to 1-
N
-phenylnaphthylamine in the presence of increasing concentrations of polymyxin, suggesting that the putative hopanoid biosynthesis genes are involved in stabilizing outer membrane permeability, contributing to polymyxin resistance. Results from a dansyl-polymyxin binding assay demonstrated that polymyxin B does not bind well to the parent or mutant strains, suggesting that Bmul_2133 and Bmul_2134 contribute to polymyxin B resistance by a mechanism that is independent of lipopolysaccharide (LPS) binding. Through this work, we propose a role for hopanoid biosynthesis as part of the multiple antimicrobial resistance phenotype in Bcc bacteria.
Synthesis of Artemiside and Its Effects in Combination with Conventional Drugs against Severe Murine Malaria
Authors: Guo Jin , Guiguemde Armand W. , Bentura-Marciano Annael , Clark Julie , Haynes Richard K. , Chan Wing-Chi , Wong Ho-Ning , Hunt Nicholas H. , Guy R. Kiplin , Golenser Jacob 
Published: October 2011

ABSTRACT

This research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both in
Plasmodium falciparum
culture and
in vivo
in a murine malaria model depicting cerebral malaria (CM).
In vitro
high-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM.
Resistance Emergence Mechanism and Mechanism of Resistance Suppression by Tobramycin for Cefepime for Pseudomonas aeruginosa
Authors: Drusano G. L. , Bonomo Robert A. , Bahniuk Nadzeya , Bulitta Juergen B. , VanScoy Brian , DeFiglio Holland , Fikes Steven , Brown David , Drawz Sarah M. , Kulawy Robert , Louie Arnold 
Published: October 2011

ABSTRACT

The panoply of resistance mechanisms in
Pseudomonas aeruginosa
makes resistance suppression difficult. Defining optimal regimens is critical. Cefepime is a cephalosporin whose 3′ side chain provides some stability against AmpC β-lactamases. We examined the activity of cefepime against
P. aeruginosa
wild-type strain PAO1 and its isogenic AmpC stably derepressed mutant in our hollow-fiber infection model. Dose-ranging studies demonstrated complete failure with resistance emergence (both isolates). Inoculum range studies demonstrated ultimate failure for all inocula. Lower inocula failed last (10 days to 2 weeks). Addition of a β-lactamase inhibitor suppressed resistance even with the stably derepressed isolate. Tobramycin combination studies demonstrated resistance suppression in both the wild-type and the stably derepressed isolates. Quantitating the RNA message by quantitative PCR demonstrated that tobramycin decreased the message relative to that in cefepime-alone experiments. Western blotting with AmpC-specific antibody for
P. aeruginosa
demonstrated decreased expression. We concluded that suppression of β-lactamase expression by tobramycin (a protein synthesis inhibitor) was at least part of the mechanism behind resistance suppression. Monte Carlo simulation demonstrated that a regimen of 2 g of cefepime every 8 h plus 7 mg/kg of body weight of tobramycin daily would provide robust resistance suppression for
Pseudomonas
isolates with cefepime MIC values up to 8 mg/liter and tobramycin MIC values up to 1 mg/liter. For
P. aeruginosa
resistance suppression, combination therapy is critical.
Fluoride Excess in Coccidioidomycosis Patients Receiving Long-Term Antifungal Therapy: an Assessment of Currently Available Triazoles
Authors: Thompson George R. , Bays Derek , Cohen Stuart H. , Pappagianis Demosthenes 
Published: October 2011

ABSTRACT
The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort.
Expansion of Paneth Cell Population in Response to Enteric Salmonella enterica Serovar Typhimurium Infection
Authors: Martinez Rodriguez Nadine R. , Eloi Marjannie D. , Huynh Alexandria , Dominguez Teresa , Lam Annie H. Cheung , Carcamo-Molina Dayana , Naser Zeina , Desharnais Robert , Salzman Nita H. , Porter Edith 
Published: October 2011

ABSTRACT

Paneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown that
Salmonella enterica
serovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with a
Salmonella
pathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.
New insights into the proximal tendons of adductor longus, adductor brevis and gracilis
Authors: Davis J A , Stringer M D , Woodley S J 
Published: October 2011

ObjectiveThe adductor muscles are implicated in the pathogenesis of groin strain, but the proximal morphology of this muscle group is poorly defined. The purpose of this study was to investigate the detailed anatomy of the entheses and proximal musculotendinous junctions (MTJs) of adductor longus (AL), adductor brevis (AB) and gracilis.MethodsThe adductors were dissected bilaterally in 10 embalmed cadavers (7 females, mean age at death 79 years (range 57–93 years)), focusing on the type of enthesis, and architecture of the proximal tendons and MTJs. Histology was used to determine if the entheses contained fibrocartilage and to semiquantitatively assess the vascularity of each proximal tendon.ResultsAll entheses were fibrocartilaginous. The proximal tendons of AB and gracilis were fused, forming a common tendinous insertion in all specimens. AL and AB both contained extensive intramuscular tendons of variable length (AL 11.1 ± 1.5 cm; AB 5.4 ± 1.1 cm); this has not been recorded previously. The vascularity of AL and AB tendons decreased significantly towards the enthesis (p < 0.05), and their entheses were significantly less vascular than that of gracilis (p < 0.05).ConclusionsThe proximal anatomy of AL, AB and gracilis is more complex than previously described. The arrangement and fusion of these muscles, their fibrocartilaginous entheses and differences in vascularity of their proximal tendons may be important anatomical considerations in the pathogenesis and pattern of adductor-related groin pain.
Effect of q-nonextensive distribution of electrons on dust acoustic shock waves in strongly coupled dusty plasmas
Authors: Pakzad Hamid Reza 
Published: October 2011

The reductive perturbation method is used to derive the Kordeweg – de Vries – Burgers equation in strongly coupled dusty plasmas containing Boltzmann distributed ions and q-nonextensive electrons. It is observed that the nonlinear propagation of the dust acoustic waves gives rise to shock structures when there is strong correlation among the dust grains. The effect of the q-nonextensive parameter on the shock waves is discussed.
Vision of the unseen
Authors: Rocha Anderson , Scheirer Walter , Boult Terrance , Goldenstein Siome 
Published: October 2011

Digital images are everywhere—from our cell phones to the pages of our online news sites. How we choose to use digital image processing raises a surprising host of legal and ethical questions that we must address. What are the ramifications of hiding data within an innocent image? Is this an intentional security practice when used legitimately, or intentional deception? Is tampering with an image appropriate in cases where the image might affect public behavior? Does an image represent a crime, or is it simply a representation of a scene that has never existed? Before action can even be taken on the basis of a questionable image, we must detect something about the image itself. Investigators from a diverse set of fields require the best possible tools to tackle the challenges presented by the malicious use of today's digital image processing techniques.
In this survey, we introduce the emerging field of digital image forensics, including the main topic areas of source camera identification, forgery detection, and steganalysis. In source camera identification, we seek to identify the particular model of a camera, or the exact camera, that produced an image. Forgery detection's goal is to establish the authenticity of an image, or to expose any potential tampering the image might have undergone. With steganalysis, the detection of hidden data within an image is performed, with a possible attempt to recover any detected data. Each of these components of digital image forensics is described in detail, along with a critical analysis of the state of the art, and recommendations for the direction of future research.
CATCH
Authors: Kleanthous Marios , Sazeides Yiannakis 
Published: October 2011

Cache-content-duplication (CCD) occurs when there is a miss for a block in a cache and the entire content of the missed block is already in the cache in a block with a different tag. Caches aware of content-duplication can have lower miss penalty by fetching, on a miss to a duplicate block, directly from the cache instead of accessing lower in the memory hierarchy, and can have lower miss rates by allowing only blocks with unique content to enter a cache.
This work examines the potential of CCD for instruction caches. We show that CCD is a frequent phenomenon and that an idealized duplication-detection mechanism for instruction caches has the potential to increase performance of an out-of-order processor, with a 16KB, 8-way, 8 instructions per block instruction cache, often by more than 10% and up to 36%.
This work also proposes CATCH, a hardware mechanism for dynamically detecting CCD for instruction caches. Experimental results for an out-of-order processor show that a duplication-detection mechanism with a 1.38KB cost captures on average 58% of the CCD's idealized potential.
Geographic Information Retrieval
Authors: Purves Ross , Jones Christopher 
Published: October 2011

This special issue of SIGSPATIAL Special presents a series of notes describing the state of the art in Geographic Information Retrieval. The notes are intended to provide a review of some of the challenges presented as key research areas in Geographic Information Retrieval [Larson, Jones and Purves], and reflect progress in the field in the intervening years. The challenges as originally set out in [2] were the following:
• detecting geographical references in the form of place names and associated spatial natural language qualifiers within text documents and in users' queries;
• disambiguating place names to determine which particular instance of a name is intended;
• geometric interpretation of the meaning of vague place names, such as the 'Midlands' and of vague spatial language such as 'near';
• indexing documents with respect to their geographic context as well as their non-spatial thematic content;
• ranking the relevance of documents with respect to geography as well as theme;
• developing effective user interfaces that help users to find what they want; and
• developing methods to evaluate the success of GIR.
Blockade of TGF-β Signaling by the TGFβR-I Kinase Inhibitor LY2109761 Enhances Radiation Response and Prolongs Survival in Glioblastoma
Authors: Zhang Mengxian , Kleber Susanne , Röhrich Manuel , Timke Carmen , Han Na , Tuettenberg Jochen , Martin-Villalba Ana , Debus Juergen , Peschke Peter , Wirkner Ute , Lahn Michael , Huber Peter E. 
Published: October 2011

Abstract
Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor that tends to be resistant to the ionizing radiotherapy used to treat it. Because TGF-β is a modifier of radiation responses, we conducted a preclinical study of the antitumor effects of the TGF-β receptor (TGFβR) I kinase inhibitor LY2109761 in combination with radiotherapy. LY2109761 reduced clonogenicity and increased radiosensitivity in GBM cell lines and cancer stem–like cells, augmenting the tumor growth delay produced by fractionated radiotherapy in a supra-additive manner in vivo. In an orthotopic intracranial model, LY2109761 significantly reduced tumor growth, prolonged survival, and extended the prolongation of survival induced by radiation treatment. Histologic analyses showed that LY2109761 inhibited tumor invasion promoted by radiation, reduced tumor microvessel density, and attenuated mesenchymal transition. Microarray-based gene expression analysis revealed signaling effects of the combinatorial treatments that supported an interpretation of their basis. Together, these results show that a selective inhibitor of the TGFβR-I kinase can potentiate radiation responses in glioblastoma by coordinately increasing apoptosis and cancer stem–like cells targeting while blocking DNA damage repair, invasion, mesenchymal transition, and angiogenesis. Our findings offer a sound rationale for positioning TGFβR kinase inhibitors as radiosensitizers to improve the treatment of glioblastoma. Cancer Res; 71(23); 7155–67. ©2011 AACR.
Should We Replace Disabled Newborn Infants?
Authors: Wilkinson Dominic 
Published: October 2011

AbstractIf a disabled newborn infant dies, her parents may be able to conceive another child without impairment. This is sometimes referred to as 'replacement'. Some philosophers have argued that replacement provides a strong reason for disabled newborns to be killed or allowed to die. In this paper I focus on the case for replacement as it relates to decisions about life support in newborn intensive care. I argue (following Jeff McMahan) that the impersonal reason to replace is weak and easily outweighed. I assess and reject several possible ways in which the impersonal reason to replace could be defended. I then address an alternative justification for replacement – as an individual-affecting benefit. The strongest justification for replacement may be the interests of parents. In the latter part of the paper I look at a related question. What role should replacement play in decisions about the funding of newborn intensive care?
Internal Market Preventive Controls of National Technical Standards and eir Impact on Environmental Measures
Authors: de Sadeleer Nicolas 
Published: October 2011

AbstractWith a view to overcoming the shortcomings of “negative harmonisation”, the EU lawmaker has been adopting different directives requiring the Member States to notify to the Commission their draft regulations setting technical standards before their enactment. The aim of this article is to shed the light on two internal market preventive procedures: Directive 98/34 on the provision of information in the field of technical standards and regulation and Regulation 764/2008/EC relating to the application of certain national technical rules to products lawfully marketed in another Member State. In particular, the paper assesses the manner in which the directive and the regulation are likely to impinge on the enactment of national environmental measures.
Xenotransplantation: Consent, Public Health and Charter Issues
Authors: Caulfield T.A. , Robertson G.B. 
Published: October 2011

There is a growing body of literature and commentary analyzing the ethical and public policy concerns associated with xenotransplantation. While this technology holds great promise to provide an almost limitless supply of organs for transplantation, there remains grave concern about possible public health ramifications. As a result, it has been recommended that patients who undergo xenotransplantations will need to agree, inter alia, to a lifetime of close health monitoring, participation in an international database and autopsy upon death. It has been suggested that this agreement would transform the nature of informed consent into a “binding contract.” Though such draconian measures are understandable given the magnitude of the risks involved, would existing common law and legislation allow their implementation? This paper analyzes relevant Canadian consent and public health law in the context of the xenotransplantation. Canada is a country with a particularly rich body of informed consent jurisprudence—jurisprudence firmly rooted (rightly or not) in the ethical principle of autonomy. In this climate, many of the suggested monitoring strategies would find little support from Canadian law. Before xenotransplantations proceed, policy makers must be sensitive to the legal barriers which exist to the implementation effective public health measures. Effective surveillance programs will require novel approaches to consent and the enactment of specific public health laws.
Constitutionalising Equality in the European Union: A Children's Rights Perspective
Authors: Stalford Helen 
Published: October 2011

The concept of equality has been central to the development of the European Union social agenda to such an extent that it is now universally acknowledged as a constitutionally-embedded norm. This paper discusses how equality has driven important legislative, judicial and institutional change in the EU, particularly for women, and how the success of the gender campaign has inspired important changes in respect of other marginalised groups. The paper focuses, in particular, on how the concept of equality offers an appropriate, meaningful and effective basis on which to enhance the status of children in the EU. Following a formal analysis of how children fit within the equality/nondiscrimination paradigm at EU constitutional level, the paper moves on to discuss more critically how these provisions are transposed into tangible entitlement for this category of citizens. It explores mainstreaming as a potential mechanism for achieving substantive equality for children, again alluding to the successes of the gender campaign in this respect. The paper concludes by speculating on how a mainstreaming strategy might be adapted and applied in favour of children and discusses the advancements that have already been made in this regard.
Screening and identification of seed-specific genes using digital differential display tools combined with microarray data from common wheat
Authors: Yang Xinglu , Xu Hongliang , Li Wenhui , Li Le , Sun Jinyue , Li Yaxuan , Yan Yueming , Hu Yingkao 
Published: October 2011

Abstract

Background
Wheat is one of the most important cereal crops for human beings, with seeds being the tissue of highly economic value. Various morphogenetic and metabolic processes are exclusively associated with seed maturation. The goal of this study was to screen and identify genes specifically expressed in the developing seed of wheat with an integrative utilization of digital differential display (DDD) and available online microarray databases.

Results
A total of 201 unigenes were identified as the results of DDD screening and microarray database searching. The expressions of 6 of these were shown to be seed-specific by qRT-PCR analysis. Further GO enrichment analysis indicated that seed-specific genes were mainly associated with defense response, response to stress, multi-organism process, pathogenesis, extracellular region, nutrient reservoir activity, enzyme inhibitor activity, antioxidant activity and oxidoreductase activity. A comparison of this set of genes with the rice (Oryza sativa) genome was also performed and approximately three-fifths of them have rice counterparts. Between the counterparts, around 63% showed similar expression patterns according to the microarray data.

Conclusions
In conclusion, the DDD screening combined with microarray data analysis is an effective strategy for the identification of seed-specific expressed genes in wheat. These seed-specific genes screened during this study will provide valuable information for further studies about the functions of these genes in wheat.