bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefoxitin as an Alternative to Carbapenems in a Murine Model of Urinary Tract Infection Due to Escherichia coli Harboring CTX-M-15-Type Extended-Spectrum β-Lactamase
Authors: Lepeule Raphaël , Ruppé Etienne , Le Patrick , Massias Laurent , Chau Françoise , Nucci Amandine , Lefort Agnès , Fantin Bruno
Published: January 2012

We investigated the efficiency of the cephamycin cefoxitin as an alternative to carbapenems for the treatment of urinary tract infections (UTIs) due to
Escherichia coli
producing CTX-M-type extended-spectrum β-lactamases. The susceptible, UTI-inducing
E. coli
CFT073-RR strain and its transconjugant CFT073-RR Tc (p
bla
CTX-M-15
), harboring a
bla
CTX-M-15
carrying-plasmid, were used for all experiments. MICs of cefoxitin (FOX), ceftriaxone (CRO), imipenem (IMP), and ertapenem (ETP) for CFT073-RR and CFT073-RR Tc (p
bla
CTX-M-15
) were 4 and 4, 0.125 and 512, 0.5 and 0.5, and 0.016 and 0.032 μg/ml, respectively. Bactericidal activity was similarly achieved
in vitro
against the two strains after 3 h of exposure to concentrations of FOX, IMI, and ETP that were 2 times the MIC, whereas CRO was not bactericidal against CFT073-RR Tc (p
bla
CTX-M-15
). The frequencies of spontaneous mutants of the 2 strains were not higher for FOX than for IMP or ETP. In the murine model of UTIs, mice infected for 5 days were treated over 24 h. Therapeutic regimens in mice (200 mg/kg of body weight every 3 h or 4 h for FOX, 70 mg/kg every 6 h for CRO, 100 mg/kg every 2 h for IMP, and 100 mg/kg every 4 h for ETP) were chosen in order to reproduce the percentage of time that free-drug concentrations above the MIC are obtained in humans with standard regimens. All antibiotic regimens produced a significant reduction in bacterial counts (greater than 2 log
10
CFU) in kidneys and bladders for both strains (
P
< 0.001) without selecting resistant mutants
in vivo
, but the reduction obtained with CRO against CFT073-RR Tc (p
bla
CTX-M-15
) in kidneys was significantly lower than that obtained with FOX. In conclusion, FOX appears to be an effective therapeutic alternative to carbapenems for the treatment of UTIs due to CTX-M-producing
E. coli
.
Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress
Authors: Farshchi Andisi Vahid , Hinojosa Cecilia A. , de Jong Anne , Kuipers Oscar P. , Orihuela Carlos J. , Bijlsma Jetta J. E.
Published: January 2012

Streptococcus pneumoniae
is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle,
S. pneumoniae
is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H
2
O
2
) and from the host through the oxidative burst. How
S. pneumoniae
, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of
S. pneumoniae
against external oxidative stress, which plays an important role during invasive disease.
Conserved and Variant Epitopes of Plasmodium vivax Duffy Binding Protein as Targets of Inhibitory Monoclonal Antibodies
Authors: Ntumngia Francis B. , Schloegel Jesse , Barnes Samantha J. , McHenry Amy M. , Singh Sanjay , King Christopher L. , Adams John H.
Published: January 2012

The Duffy binding protein (DBP) is a vital ligand for
Plasmodium vivax
blood-stage merozoite invasion, making the molecule an attractive vaccine candidate against vivax malaria. Similar to other blood-stage vaccine candidates, DBP allelic variation eliciting a strain-specific immunity may be a major challenge for development of a broadly effective vaccine against vivax malaria. To understand whether conserved epitopes can be the target of neutralizing anti-DBP inhibition, we generated a set of monoclonal antibodies to DBP and functionally analyzed their reactivity to a panel of allelic variants. Quantitative analysis by enzyme-linked immunosorbent assay (ELISA) determined that some monoclonal antibodies reacted strongly with epitopes conserved on all DBP variants tested, while reactivity of others was allele specific. Qualitative analysis characterized by anti-DBP functional inhibition using an
in vitro
erythrocyte binding inhibition assay indicated that there was no consistent correlation between the endpoint titers and functional inhibition. Some monoclonal antibodies were broadly inhibitory while inhibition of others varied significantly by target allele. These data demonstrate a potential for vaccine-elicited immunization to target conserved epitopes but optimization of DBP epitope target specificity and immunogenicity may be necessary for protection against diverse
P. vivax
strains.
The Mycobacterium tuberculosis SecA2 System Subverts Phagosome Maturation To Promote Growth in Macrophages
Authors: Sullivan Jonathan Tabb , Young Ellen F. , McCann Jessica R. , Braunstein Miriam
Published: January 2012

The ability ofMycobacterium tuberculosisto grow in macrophages is critical to the virulence of this important pathogen. One wayM. tuberculosisis thought to maintain a hospitable niche in macrophages is by arresting the normal process of phagosomes maturing into acidified phagolysosomes. The process of phagosome maturation arrest byM. tuberculosisis not fully understood, and there has remained a need to firmly establish a requirement for phagosome maturation arrest forM. tuberculosisgrowth in macrophages. Other intracellular pathogens that control the phagosomal environment use specialized protein export systems to deliver effectors of phagosome trafficking to the host cell. InM. tuberculosis, the accessory SecA2 system is a specialized protein export system that is required for intracellular growth in macrophages. In studying the importance of the SecA2 system in macrophages, we discovered that SecA2 is required for phagosome maturation arrest. Shortly after infection, phagosomes containing a ΔsecA2mutant ofM. tuberculosiswere more acidified and showed greater association with markers of late endosomes than phagosomes containing wild-typeM. tuberculosis. We further showed that inhibitors of phagosome acidification rescued the intracellular growth defect of the ΔsecA2mutant, which demonstrated that the phagosome maturation arrest defect of the ΔsecA2mutant is responsible for the intracellular growth defect. This study demonstrates the importance of phagosome maturation arrest forM. tuberculosisgrowth in macrophages, and it suggests there are effectors of phagosome maturation that are exported into the host environment by the accessory SecA2 system.
Role of Francisella Lipid A Phosphate Modification in Virulence and Long-Term Protective Immune Responses
Authors: Kanistanon Duangjit , Powell Daniel A. , Hajjar Adeline M. , Pelletier Mark R. , Cohen Ilana E. , Way Sing Sing , Skerrett Shawn J. , Wang Xiaoyuan , Raetz Christian R. H. , Ernst Robert K.
Published: January 2012

Lipopolysaccharide (LPS) structural modifications have been shown to specifically affect the pathogenesis of many Gram-negative pathogens. InFrancisella, modification of the lipid A component of LPS resulted in a molecule with no to low endotoxic activity. The role of the terminal lipid A phosphates in host recognition and pathogenesis was determined using aFrancisella novicidamutant that lacked the 4′ phosphatase enzyme (LpxF). The lipid A of this strain retained the phosphate moiety at the 4′ position and the N-linked fatty acid at the 3′ position on the diglucosamine backbone. Studies were undertaken to determine the pathogenesis of this mutant strain via the pulmonary and subcutaneous routes of infection. Mice infected with thelpxF-nullF. novicidamutant by either route survived primary infection and subsequently developed protective immunity against a lethal wild-type (WT)F. novicidachallenge. To determine the mechanism(s) by which the host controlled primary infection by thelpxF-null mutant, the role of innate immune components, including Toll-like receptor 2 (TLR2), TLR4, caspase-1, MyD88, alpha interferon (IFN-α), and gamma interferon(IFN-γ), was examined using knockout mice. Interestingly, only the IFN-γ knockout mice succumbed to a primarylpxF-nullF. novicidamutant infection, highlighting the importance of IFN-γ production. To determine the role of components of the host adaptive immune system that elicit the long-term protective immune response, T- and B-cell deficient RAG1−/−mice were examined. All mice survived primary infection; however, RAG1−/−mice did not survive WT challenge, highlighting a role for T and B cells in the protective immune response.
Analysis of Global Transcriptional Profiles of Enterotoxigenic Escherichia coli Isolate E24377A
Authors: Sahl Jason W. , Rasko David A.
Published: January 2012

Enterotoxigenic
Escherichia coli
(ETEC) is an important pathogenic variant (pathovar) of
E. coli
in developing countries from a human health perspective, causing significant morbidity and mortality. Previous studies have examined specific regulatory networks in ETEC, although little is known about the global effects of inter- and intrakingdom signaling on the expression of virulence and colonization factors in ETEC. In this study, an
E. coli
/
Shigella
pan-genome microarray, combined with quantitative reverse transcriptase PCR (qRT-PCR) and RNA sequencing (RNA-seq), was used to quantify the expression of ETEC virulence and colonization factors. Biologically relevant chemical signals were combined with ETEC isolate E24377A during growth in either Luria broth (LB) or Dulbecco's modified Eagle medium (DMEM), and transcription was examined during different phases of the growth cycle; chemical signals examined included glucose, bile salts, and preconditioned media from
E. coli/Shigella
isolates. The results demonstrate that the presence of bile salts, which are found in the intestine and thought to be bactericidal, upregulates the expression of many ETEC virulence factors, including heat-stable (
estA
) and heat-labile (
eltA
) enterotoxin genes. In contrast, the ETEC colonization factors CS1 and CS3 were downregulated in the presence of bile, consistent with findings in studies of other enteric pathogens. RNA-seq analysis demonstrated that one of the most differentially expressed genes in the presence of bile is a unique plasmid-encoded AraC-like transcriptional regulator (
peaR
); other previously unknown genetic elements were found as well. These results provide transcriptional targets and putative mechanisms that should help improve understanding of the global regulatory networks and virulence expression in this important human pathogen.
A Single Chromosome Unexpectedly Links Highly Divergent Isolates of Toxoplasma gondii
Authors: Walzer Katelyn A. , Boyle Jon P.
Published: January 2012

Toxoplasma gondii
is an obligate intracellular parasite that can cause disease in all warm-blooded animals studied to date, including humans. Over a billion people have been infected with this parasite worldwide. In Europe and North America,
Toxoplasma
has a clonal population structure, where only three lineages are highly dominant (strain types I, II, and III). Khan et al. [

mBio
2(6)
: e00228-11, 2011

] have carried out phylogenetic analyses on a large number of diverse strains from outside of these lineages and found evidence for a significant split between the clonal North American/European lineages and those in South America. In contrast to most of the genome, nearly all North American/European strains sampled, and the majority of South American strains sampled, harbored at least portions of a monomorphic chromosome Ia (Ia*). In contrast to previous models, these data suggest that the monomorphic haplotype originated in South America and migrated to the North. These authors propose that South American haplotype 12 was a precursor to modern-day type II, while South American haplotypes 6 and 9 crossed with haplotype 12 to give rise to the type I and III lineages, respectively. However, the findings reported by Khan et al. complicate the origin of chromosome Ia, since there are members of haplotypes 9 and 12 with nearly complete versions of Ia* and members of haplotypes 6 and 12 with over 50% of Ia*. This unexpected finding raises exciting new questions about how an entire common chromosome can be found within strains that are highly divergent at most other genomic loci.
The ABC of handover: a qualitative study to develop a new tool for handover in the emergency department
Authors: Farhan Maisse , Brown Ruth , Woloshynowych Maria , Vincent Charles
Published: January 2012

Objectives

This study identifies best practice for shift handover and introduces a new tool used to hand over clinical and operational issues at the end of a shift in the emergency department (ED).

Methods

Literature review, semi-structured interviews and observations of handover were used to develop a standardised process for handover. Participants were ED middle grades, consultants and senior nurses. Interviews were used to identify agreed best practice and derive a tool to classify the information into relevant sections.

Results

Interviews identified a variety of perceived current deficits in handover including a lack of standardised practice and structure. Participants provided examples of poor handover that were thought to have led to adverse events; these included delay in investigations and treatment for patients who were handed over with brief or inaccurate information. There was wide variation in the understanding of the meaning and purpose of shift handover, and differences were apparent according to the level of experience of the middle grades interviewed. The experts' responses were used to reach a unifying ‘best practice’ for the content of handover. This was then grouped under ABCDE headings to develop the ABC of handover tool.

Conclusions

A simple tool was developed to provide the basis for medical shift handover, which includes clinical and operational information necessary for efficiency and organisation of the next shift. The ABC of handover classifies shift information to be handed over under the ABCDE headings, which are easy to remember and highly relevant to emergency medicine.
Management of subarachnoid hemorrhage with intracerebral hematoma: clipping and clot evacuation versus coil embolization followed by clot evacuation
Authors: Reyes Kenneth de los , Patel Aman , Bederson Joshua B , Frontera Jennifer A
Published: January 2012

Background

Aneurysmal subarachnoid hemorrhage (SAH) with associated intracerebral hemorrhage (ICH) is often treated with concomitant surgical clipping and ICH evacuation. The aim of this study was to determine if aneurysm coiling followed by ICH evacuation is a viable alternative treatment.

Methods

A retrospective review was conducted between July 2000 and March 2009 of patients with aneurysmal SAH plus ICH (>30 ml or with midline shift >5 mm) who underwent aneurysm repair (either coiling or clipping) and craniotomy for ICH evacuation. Demographic and radiographic criteria, time to aneurysm protection, length of stay (LOS), treatment complications, discharge disposition and 3 month functional outcome were compared between groups.

Results

Of 18 SAH+ICH patients, 10 underwent aneurysm coiling followed by ICH evacuation and eight underwent clipping with ICH evacuation. Compared with clipped patients, coiled patients had a lower Glasgow Coma Scale score (median 5.5 vs 7.5), higher ICH score (median 3 vs 2), worse modified Fisher score (median 4 vs 3) and higher rate of herniation at presentation (50% vs 25%). Median time to aneurysm protection was shorter in coiled patients (299 vs 885 min, p<0.001). Comparing coiled with clipped patients, rates of death (30% vs 25%), poor outcome (70% vs 50%), median ICU LOS (20 vs 22 days), median hospital LOS (27 vs 29 days) and total median direct costs ($64 537 vs $61 243) were similar, as were complication rates (all p>0.05).

Conclusions

Coiling followed by ICH evacuation is associated with faster time to aneurysm protection and similar outcome, LOS and cost as clipping and evacuation. This may be a viable alternative to clipping and ICH evacuation.
HPV-related information sharing and factors associated with US men's disclosure of an HPV test result to their female sexual partners
Authors: Marhefka Stephanie L , Daley Ellen M , Anstey Erica Hesch , Vamos Cheryl A , Buhi Eric R , Kolar Stephanie , Giuliano Anna R
Published: January 2012

Objectives

Prevalence of human papillomavirus (HPV) is high in both men and women, yet men have seldom been involved in HPV education/prevention programmes, and their disclosure of known HPV infection has rarely been studied. This analysis sought to determine factors associated with men's HPV test result disclosure and HPV-related information sharing with partners.

Methods

From 2007 to 2010, men enrolled in a psychosocial study of responses to HP testing who reported having a female main sexual partner (N=251) completed surveys including questions about HPV test results, disclosure of HPV test results to partner(s), relationship characteristics and stigma (for those who reported HPV-positive results) approximately 3 weeks after receiving an HPV test result. Logistic regression was conducted to determine factors associated with disclosure of HPV test results in cross-sectional analysis.

Results

Most men disclosed their test results to a main partner (82%). Self-reported HPV-negative test result, a high school education and a higher commitment to a sexual partner were significantly associated with increased disclosure in multivariable analysis. Men who disclosed (vs those who did not) were significantly more likely to provide their partners with HPV-related information. Among men who disclosed to their main partner, nearly half reported that partner asked them questions about HPV.

Conclusions

Results from this study highlight the critical role that men who are symptomatic for, who are tested for or who are vaccinated against HPV can play in educating their sexual partners, independent of whether they actually disclose their test results.
NUCLEAR REACTIONS IN HOT ASTROPHYSICAL PLASMAS WITH T > 1010 K
Authors: KAFEXHIU ERVIN , AHARONIAN FELIX , VILA GABRIELA S.
Published: January 2012

The importance of nuclear reactions in low-density astrophysical plasmas with ion temperatures T ≥1010 K has been recognized for more than thirty years. However, the lack of comprehensive data banks of relevant nuclear reactions and the limited computational power have not previously allowed detailed theoretical studies. Recent developments in these areas make it timely to conduct comprehensive studies on the nuclear properties of very hot plasmas formed around compact relativistic objects such as black holes and neutron stars. Such studies are of great interest in the context of scientific programs of future low-energy cosmic γ-ray spectrometry. In this work, using the publicly available code TALYS, we have built a large nuclear network relevant for temperatures exceeding 1010 K. We have studied the evolution of the chemical composition and accompanying prompt gamma-ray emission of such high-temperature plasmas. We present the results on the abundances of light elements D, T, 3 He , 4 He , 6 Li , 7 Li , 9 Be , 10 B , 11 B , and briefly discuss their implications on the astrophysical abundances of these elements.
FUNCTIONAL-INTEGRAL SOLUTION FOR THE SCHRÖDINGER EQUATION WITH POLYNOMIAL POTENTIAL: A WHITE NOISE APPROACH
Authors: MAZZUCCHI SONIA
Published: January 2012

A functional integral representation for the weak solution of the Schrödinger equation with polynomially growing potentials is proposed in terms of a white noise functional.
DOMINATION IN THE TOTAL GRAPH ON ℤn
Authors: CHELVAM T. TAMIZH , ASIR T.
Published: January 2012

For a commutative ring R, let Z(R) be its set of zero-divisors. The total graph of R, denoted by TΓ(R), is the undirected graph with vertex set R, and for distinct x, y ∈ R, the vertices x and y are adjacent if and only if x + y ∈ Z(R). Tamizh Chelvam and Asir studied about the domination in the total graph of a commutative ring R. In particular, it was proved that the domination number γ(TΓ(ℤn)) = p1 where p1 is the smallest prime divisor of n. In this paper, we characterize all the γ-sets in TΓ(ℤn). Also, we obtain the values of other domination parameters like independent, total and perfect domination numbers of the total graph on ℤn.
A RANDOMIZED ALGORITHM FOR WEIGHTED APPROXIMATION OF POINTS BY A STEP FUNCTION
Authors: LIU JIN-YI
Published: January 2012

The problem considered in this paper is: Given an integer k > 0 and a set P of n points in the plane each with a corresponding nonnegative weight, find a step function f with k steps that minimize the maximum weighted vertical distance between f and all the points in P. We present a randomized algorithm to solve the problem in O(n log n) expected running time. The bound is obviously optimal for the unsorted input. The previously best known algorithm runs in O(n log 2 n) worst-case time. Another merit of the algorithm is its simplicity. The algorithm is just a randomized implementation of Frederickson and Johnson's matrix searching technique, and it only exploits a simple data structure.
CYCLIC CONNECTIVITY OF STAR GRAPH
Authors: LIU QINGHAI , ZHANG ZHAO , YU ZHIHUA
Published: January 2012

For a connected graph G, a vertex subset F ⊂ V(G) is a cyclic vertex-cut of G if G - F is disconnected and at least two of its components contain cycles. The cardinality of a minimum cyclic vertex-cut of G, denoted by κc(G), is the cyclic vertex-connectivity of G. In this paper, we show that for any integer n ≥ 4, the n-dimensional star graph SGnhas κc(SGn) = 6(n - 3).
TIME OPTIMAL ALGORITHMS FOR BLACK HOLE SEARCH IN RINGS
Authors: BALAMOHAN B. , FLOCCHINI P. , MIRI A. , SANTORO N.
Published: January 2012

In a network environment supporting mobile entities (called robots or agents), a black hole is a harmful site that destroys any incoming entity without leaving any visible trace. The black-hole search problit is the task of a team of k > 1 mobile entities, starting from the same safe location and executing the same algorithm, to determine within finite time the location of the black hole. In this paper, we consider the black hole search problit in asynchronous ring networks of n nodes, and focus on time complexity. It is known that any algorithm for black-hole search in a ring requires at least 2(n - 2) time in the worst case. The best known algorithm achieves this bound with a team of n - 1 agents with an average time cost of 2(n - 2), equal to the worst case. In this paper, we first show how the same number of agents using 2 extra time units in the worst case, can solve the problit in only [Formula: see text] time on the average. We then prove that the optimal average case complexity of [Formula: see text] can be achieved without increasing the worst case using 2(n - 1) agents. Finally, we design an algorithm that achieves asymptotically optimal both worst and average case time complexities itploying an optimal team of k = 2 agents, thus improving on the earlier results that required O(n) agents.
ON THE STEINER RATIO IN $\mathcal{R}_{n}$
Authors: DU HAI , WU WEILI , LU ZAIXIN , XU YINFENG
Published: January 2012

The Steiner minimum tree and the minimum spanning tree are two important problems in combinatorial optimization. Let P denote a finite set of points, called terminals, in the Euclidean space. A Steiner minimum tree of P, denoted by SMT(P), is a network with minimum length to interconnect all terminals, and a minimum spanning tree of P, denoted by MST(P), is also a minimum network interconnecting all the points in P, however, subject to the constraint that all the line segments in it have to terminate at terminals. Therefore, SMT(P) may contain points not in P, but MST(P) cannot contain such kind of points. Let [Formula: see text] denote the n-dimensional Euclidean space. The Steiner ratio in [Formula: see text] is defined to be [Formula: see text], where Ls(P) and Lm(P), respectively, denote lengths of a Steiner minimum tree and a minimum spanning tree of P. The best previously known lower bound for [Formula: see text] in the literature is 0.615. In this paper, we show that [Formula: see text] for any n ≥ 2.
A DIVIDE-AND-CONQUER ALGORITHM FOR FINDING A MOST RELIABLE SOURCE ON A RING-EMBEDDED TREE NETWORK WITH UNRELIABLE EDGES
Authors: DING WEI , XUE GUOLIANG
Published: January 2012

Given an unreliable communication network, we seek a most reliable source (MRS) of the network, which maximizes the expected number of nodes that are reachable from it. The problem of computing an MRS in general graphs is #P-hard. However, this problem in tree networks has been solved in a linear time. A tree network has a weakness of low capability of failure tolerance. Embedding rings into it by adding some additional certain edges to it can enhance its failure tolerance, resulting in another class of sparse networks, called the ring-tree networks. This class of network also has an underlying tree-like topology, leading to its advantage of being easily administrated. This paper concerns with an important case whose underlying topology is a strip graph, called λ–rings network, and focuses on an unreliable λ–rings network where each link has an independent operational probability while all nodes are immune to failures. We apply the Divide-and-Conquer approach to design a fast algorithm for computing an MRS, and employ a binary division tree (BDT) to analyze its time complexity to be [Formula: see text].
BOUNDS FOR NONADAPTIVE GROUP TESTS TO ESTIMATE THE AMOUNT OF DEFECTIVES
Authors: DAMASCHKE PETER , MUHAMMAD AZAM SHEIKH
Published: January 2012

Group testing is the problem of finding d defectives in a set of n elements, by asking carefully chosen subsets (pools) whether they contain defectives. Strategies are preferred that use both a small number of tests close to the information-theoretic lower bound d log 2 n, and a small constant number of stages, where tests in every stage are done in parallel, in order to save time. They should even work if d is not known in advance. In fact, one can succeed with O(d log n) queries in two stages, if certain tests are randomized and a constant failure probability is allowed. An essential ingredient of such strategies is to get an estimate of d within a constant factor. This problem is also interesting in its own right. It can be solved with O( log n) randomized group tests of a certain type. We prove that Ω( log n) tests are also necessary, if elements for the pools are chosen independently. The proof builds upon an analysis of the influence of tests on the searcher's ability to distinguish between any two candidate numbers with a constant ratio. The next challenge is to get optimal constant factors in the O( log n) test number, depending on the prescribed error probability and the accuracy of d. We give practical methods to derive upper bound tradeoffs and conjecture that they are already close to optimal. One of them uses a linear programming formulation.
FUZZY UNIVERSAL HASHING AND APPROXIMATE AUTHENTICATION
Authors: SAFAVI-NAINI REIHANEH , TONIEN DONGVU
Published: January 2012

Traditional data authentication systems are sensitive to single bit changes and so are unsuitable for message spaces that are naturally "fuzzy" where "similar" messages are considered "the same" or indistinguishable. In this paper, we study unconditionally secure approximate authentication. We generalize traditional universal hashing to fuzzy universal hashing and use it to construct secure approximate authentication for multiple messages.
FoxO1 as a double-edged sword in the pancreas: analysis of pancreas- and β-cell-specific FoxO1 knockout mice
Authors: Kobayashi Masaki , Kikuchi Osamu , Sasaki Tsutomu , Kim Hye-Jin , Yokota-Hashimoto Hiromi , Lee Yong-Soo , Amano Kosuke , Kitazumi Tomoya , Susanti Vina Yanti , Kitamura Yukari Ido , Kitamura Tadahiro
Published: January 2012

Diabetes is characterized by an absolute or relative deficiency of pancreatic β-cells. New strategies to accelerate β-cell neogenesis or maintain existing β-cells are desired for future therapies against diabetes. We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. P-FoxO1-KO, but not β-FoxO1-KO, showed improved glucose tolerance with HFHSD. Immunohistochemical analysis revealed that P-FoxO1-KO had increased β-cell mass due to increased islet number rather than islet size, indicating accelerated β-cell neogenesis. Furthermore, insulin-positive pancreatic duct cells were increased in P-FoxO1-KO but not β-FoxO1-KO. In contrast, db/db mice crossed with P-FoxO1-KO or β-FoxO1-KO showed more severe glucose intolerance than control db/db mice due to decreased glucose-responsive insulin secretion. Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress.
The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury
Authors: Kriegel Alison J. , Liu Yong , Fang Yi , Ding Xiaoqiang , Liang Mingyu
Published: January 2012

The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. miR-29s are encoded by two gene clusters. Binding sites for several transcriptional factors have been identified in the promoter regions of miR-29 genes. The miR-29 family members share a common seed region sequence and are predicted to target largely overlapping sets of genes. However, the miR-29 family members exhibit differential regulation in several cases and different subcellular distribution, suggesting their functional relevance may not be identical. miR-29s directly target at least 16 extracellular matrix genes, providing a dramatic example of a single microRNA targeting a large group of functionally related genes. Strong antifibrotic effects of miR-29s have been demonstrated in heart, kidney, and other organs. miR-29s have also been shown to be proapoptotic and involved in the regulation of cell differentiation. It remains to be explored how various cellular effects of miR-29s determine functional relevance of miR-29s to specific diseases and how the miR-29 family members may function cooperatively or separately.
Boundedness of Weighted Hardy Operator and Its Adjoint on Triebel-Lizorkin-Type Spaces
Authors: Tang Canqin , Zhou Ruohong
Published: January 2012

Letp∈[1,∞],q∈[1,∞),τ∈(0,∞), andα∈(0,1)such thatτ>1/p-1/qandα≤n(1/p-τ), letUψbe the weighted Hardy operator andVψits adjoint operator with respect to the weight functionψ. In this paper, the authors establish a sufficient and necessary condition on weight functionψto ensure the boundedness ofUψandVψon the Triebel-Lizorkin-type spacesḞp,qα,τ(ℝn)and their predual spaces, Triebel-Lizorkin-Hausdorff spaces, which unify and generalize the known results onQ-type spaces.
Preventing Cancer with Vaccines: Progress in the Global Control of Cancer
Authors: Kane Mark A.
Published: January 2012

The cancer control community is largely unaware of great advances in the control of major human cancers with vaccines, including the dramatic control of hepatocellular (liver) cancer with hepatitis B virus (HBV) vaccine, now used routinely in more than 90% of countries. The biotechnology revolution has given us a new generation of highly effective vaccines against major global killers, global funding for immunization is orders of magnitude higher than ever before, and the vaccine delivery infrastructure has improved very significantly even in the poorest countries. Liver cancer is the greatest cause of cancer deaths in men of sub-Saharan Africa and much of Asia. Even in highly endemic countries such as China, the prevalence of HB surface antigen carriers has fallen from 10% to 1%–2% in immunized cohorts of children, and liver cancer has already fallen dramatically in Taiwanese children. The Global Alliance for Vaccines and Immunization (now called the GAVI Alliance) has greatly expedited this success by providing HBV vaccine free for five years in most of the world's 72 poorest countries. HBV vaccination can serve as a model for the global control of human papillomavirus (HPV)–related cervical and other cancers with HPV vaccines. Cervical cancer is the greatest cause of cancer death in women in many developing countries; HPV vaccines are highly effective in preventing HPV infection and precancerous lesions in women, and the quadrivalent vaccine also prevents genital warts in men and women and precancerous anal lesions in men. HPV is causing a growing proportion of oropharyngeal cancers, and HPV-related noncervical cancers (penile, anal, and oropharyngeal) may exceed the incidence of cervical cancer within a decade in industrial countries, where cervical screening is effective, causing reevaluation of male HPV immunization. In developing countries, few women are screened for cervical precancerous lesions, making immunization even more important. Currently, 26 primarily industrial countries routinely immunize girls with HPV vaccine, and GAVI will begin to accept applications in 2012 to fund vaccine in developing countries that can deliver the vaccine and if GAVI can negotiate an acceptable price (one manufacturer has already offered a price of $5 per dose). Cancer Prev Res; 5(1); 24–29. ©2012 AACR.
Does Dialysis Modality Influence the Oxidative Stress of Uremic Patients?
Authors: Capusa Cristina , Stoian Irina , Rus Elvira , Lixandru Dana , Barbulescu Carmen , Mircescu Gabriel
Published: January 2012

Background/Aims: Since peritoneal membrane is more compatible and residual renal function better preserved during peritoneal dialysis, we questioned whether the oxidative burden in chronic kidney disease (CKD) is influenced by dialysis modality. Methods: 49 stable CKD patients, 17 on continuous ambulatory peritoneal dialysis (CAPD), 16 on hemodialysis (HD), and 16 non-dialyzed, and 13 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS; nmol/g protein), serum total antioxidant activity (TAA), total plasma-free thiols (Pt-SH; µmol/g protein), albumin and uric acid were measured by spectrophotometry. Serum residual antioxidant activity (RAA) was calculated. Results: TBARS were higher in HD (78.3 ± 20.3) versus both non-dialyzed (53.1 ± 27.9, p = 0.007) and CAPD groups (58.3 ± 19.8, p = 0.008). Pt-SH was reduced in CKD patients, but showed comparable values between dialysis groups. TAA and RAA were similarly increased in HD and CAPD patients than in the other two groups. Conclusion: Oxidative stress occurs in all CKD patients and worsens as renal function declines. Lipid peroxidation seems more augmented during chronic HD as compared to CAPD, but the plasma antioxidant status did not differ between the investigated dialysis methods. Therefore, dialysis modality appears to influence lipid peroxidation without changing the extracellular antioxidant defense of CKD patients.
Placental Chorangiosis: The Association with Oxidative Stress and Angiogenesis
Authors: Barut Aykut , Barut Figen , Kandemir Nilufer Onak , Aktunc Erol , Arikan Ilker , Harma Muge , Harma Mehmet Ibrahim , Gun Banu Dogan
Published: January 2012

Background/Aims: Chorangiosis is considered to be strongly associated with fetal, maternal, and placental disorders, and has been found to be correlated with increased fetal morbidity and mortality. In this study, it is aimed to investigate the association of angiogenesis and oxidative stress with the pathogenesis of chorangiosis. Methods: Expressions of heat shock protein 70 (HSP70), vascular endothelial growth factor-A (VEGF-A) and basic fibroblast growth factor (b-FGF), which are investigated with avidin-biotin-peroxidase method in formalin-fixed, paraffin-embedded sections from placental tissues diagnosed as no chorangiosis (n = 18) and chorangiosis (n = 18), have been evaluated in a semiquantitative manner. Results: There were significant differences between chorangiosis and no chorangiosis cases with respect to birth weight, birth length, and Apgar scores (p < 0.001). Statistically significant (p < 0.001), diffuse and strong expressions with HSP70, VEGF-A and b-FGF were observed in the villous tissue of placental chorangiosis cases when compared with no chorangiosis cases. Conclusion: The majority of the chorangiosis cases had an accompanying poor perinatal outcome, and also those with accompanying angiogenesis and increased oxidative stress demonstrated diffuse and strong expressions of HSP70, VEGF-A and b-FGF. The interaction of maternal, placental, and fetal factors with increased oxidative stress and angiogenesis may possibly contribute to this arising pathologic change.
When Is the Best Moment to Assess the Ankle Brachial Index: Pre- or Post-Hemodialysis?
Authors: Jimenez Zaida Noemy Cabrera , de Castro Isac , Pereira Benedito Jorge , de Oliveira Rodrigo Bueno , Romão, Jr. João Egidio , Elias Rosilene Motta
Published: January 2012

Background: Cardiovascular disease is an important cause of death in patients on dialysis. Peripheral arterial disease (PAD) is a prognostic factor for cardiovascular disease. The ankle brachial index (ABI) is a noninvasive method used for the diagnosis of PAD. The difference between ABI pre- and post-dialysis had not yet been formally tested, and it was the main objective of this study. Methods: The ABI was assessed using an automated oscillometric device in incident patients on hemodialysis. All blood pressure readings were taken in triplicate pre- and post-dialysis in three consecutive dialysis sessions (times 1, 2, and 3). Results: One hundred and twenty-three patients (85 men) aged 53 ± 19 years were enrolled. We found no difference in ABI pre- and post-dialysis on the right or left side, and there was no difference in times 1, 2, and 3. In patients with a history of PAD, the ABI pre- versus post-dialysis were of borderline significance on the right side (p = 0.088). Conclusion: ABI measured pre- and post-dialysis presented low variability. The ABI in patients with a history of PAD should be evaluated with caution. The applicability of the current method in predicting mortality among patients on hemodialysis therefore needs further investigation.
C-Reactive Protein Induces Interleukin-6 and Thrombospondin-1 Protein and mRNA Expression through Activation of Nuclear Factor-ĸB in HK-2 Cells
Authors: Wang Hai-rong , Chen De-liang , Zhao Mingming , Shu Shao-wu , Xiong Shi-xi , Gan Xue-dong , Chao Sheng-ping , Cao Jian-lei
Published: January 2012

Background: Although C-reactive protein (CRP) is significantly increased in patients with diabetic nephropathy, whether CRP exerts direct proinflammatory effects on human renal tubular epithelial cells (HK-2 cells) is still unclear. Methods: HK-2 cells were incubated with purified CRP at clinically relevant concentrations (0, 5, 10, 20 and 40 µg/ml). The protein and transcript levels of thrombospondin-1 (TSP-1) and interleukin-6 (IL-6) were determined by ELISA and RT-PCR. Phosphorylation of p38MAPK was investigated through Western blot analysis in HK-2 cells induced by CRP. The activation of nuclear factor-kappa B (NF-ĸB) was studied via EMSA. A specific p38MAPK inhibitor (SB203580) and an NF-ĸB inhibitor (PDTC; pyrrolidine dithiocarbamate) were used to analyze the signal transduction in CRP induction. To explore the direct or indirect role of CRP in HK-2 cells, IL-6 or TSP-1 antibodies were used. The expression of IL-6, TSP-1 and transforming growth factor-β1 (TGF-β1) were determined through Western blot analysis in HK-2 cells. Results: In HK-2 cells, purified CRP significantly induced protein release and mRNA expression of IL-6 and TSP-1 in a dose- and time-dependent manner. TGF-β1 protein was overexpressed in HK-2 cells induced by CRP, which cannot be inhibited by IL-6 or TSP-1 antibodies. CRP triggered phosphorylation of p38MAPK and activation of NF-ĸB-mediated signal transduction. SB203580 (5 µM) and PDTC (50 µM) efficiently suppressed those effects of CRP in HK-2 cells. Conclusions: CRP induces IL-6 and TSP-1 protein release and mRNA expression from HK-2 cells via activation of the p38MAPK and NF-ĸB signaling pathways and TGF-β1 was highly expressed in HK-2 cells, suggesting that CRP plays an important role in the propagation and prolongation of inflammation in renal fibrosis.
Staphylococcus aureus Secretes Coagulase and von Willebrand Factor Binding Protein to Modify the Coagulation Cascade and Establish Host Infections
Authors: McAdow Molly , Missiakas Dominique M. , Schneewind Olaf
Published: January 2012

Clinical isolates of Staphylococcus aureus secrete coagulases, polypeptides that bind to and activate prothrombin, thereby converting fibrinogen to fibrin and promoting the clotting of plasma or blood. Two staphylococcal products, the canonical coagulase (Coa) as well as the recently identified von Willebrand factor binding protein (vWbp), promote similar modifications of the coagulation cascade during host infection. Staphylococcal binding to fibrinogen or fibrin is an important attribute of disease pathogenesis, which leads to the formation of abscesses and bacterial persistence in host tissues and also enables the pathogen to cause lethal sepsis. Circumstantial evidence suggests that the product of coagulase activity, staphylococci captured within a fibrin meshwork, enable this pathogen to disseminate as thromboembolic lesions and to resist opsonophagocytic clearance by host immune cells. In addition, the coagulation products of staphylococci appear to display discrete differences when compared to those of thrombin-mediated coagulation, the latter representing a key innate defense mechanism against many invading pathogens. Preclinical evidence suggests that inactivation or neutralization of coagulases may prevent the pathogenesis of staphylococcal infections, a strategy that could be used to combat the current epidemic of hospital-acquired infections with drug-resistant S. aureus isolates.
Antiangiogenic-Induced Hypertension: The Molecular Basis of Signaling Network
Authors: Nagai Akira , Sado Toshiyuki , Naruse Katsuhiko , Noguchi Taketoshi , Haruta Shoji , Yoshida Shozo , Tanase Yasuhito , Tsunemi Taihei , Kobayashi Hiroshi
Published: January 2012

Problem: Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal death globally. Angiogenic factors including vascular endothelial growth factor (VEGF) are involved in the formation of new blood vessels required for placental development and function. The hallmark of preeclampsia is similar to the toxicities related to antiangiogenesis therapy. VEGF inhibitors or antagonists promote vasoconstriction, hypertension and proteinuria. VEGF plays a role in attenuating hypertension and improving kidney damage in an animal model; however, the mechanisms underlying this effect remain poorly defined. The aim of this paper is to summarize recent advances in VEGF-mediated signaling and the target molecules, and provide new insights into treatment strategies for preeclampsia. Method of Study: This article reviews the English-language literature for pathogenesis of preeclampsia based on VEGF signaling and hypertension. Results: VEGF activates downstream signaling molecules, including Ca2+/CAMKK, Rac1/NOX, ROS/ERK, Ezrin/Calpain/PI3K/Akt, PLCγ/PKC and Src/HSP90. Among these signalings, important pathways for receptor-triggered intracellular signaling are (1) the PI3K/Akt-dependent, (2) the PLCγ-dependent and (3) the ERK/Egr-1-dependent pathway. VEGF is closely involved in receptor-activated signaling events, leading to eNOS-dependent NO synthesis and eNOS-independent endothelial cell proliferation, respectively, and thus modulates vasoactive function and angiogenic response. Conclusion: This review highlights the potential role of NO in vasodilation, while stress-related ERK activation might act to strengthen angiogenesis, migration and proliferation. We discuss the similarity between preeclampsia and VEGF-targeted therapy-induced hypertension.
Lack of Association of Mouse Mammary Tumor Virus-Like Sequences in Iranian Breast Cancer Patients
Authors: Motamedifar Mohmmad , Saki Morteza , Ghaderi Abbas
Published: January 2012

Objective: The present study aimed to detect mouse mammary tumor virus (MMTV)-like sequences in Iranian breast cancer patients in the city of Shiraz, located in southwest Iran. Subjects and Methods: We searched for two MMTV genetic regions in the peripheral blood leukocytes of 300 women with breast cancer, 300 age-matched healthy control subjects, and 50 breast tumor tissues. Two regions of MMTV, 660 bp and 250 bp, were searched by nested polymerase chain reactions. Results: None of the above two regions were detected. There were no differences between the control group and the breast cancer group. Conclusion: Our findings did not show any association of MMTV-like sequences with breast cancer development in Iranian patients in Shiraz.
Distribution of Risk Factors in Patients with Premature Coronary, Supra-Aortic Branches and Peripheral Atherosclerotic Disease
Authors: Radak Djordje , Babic Srdjan , Peric Miodrag , Popov Petar , Tanaskovic Slobodan , Babic Dusan , Jocic Dario , Otasevic Petar
Published: January 2012

Objective: The aim of this study was to determine the distribution of major risk factors among patients with atherosclerotic disease aged ≤50 years. Subjects and Methods: The study population comprised 944 patients aged ≤50 years with clinically significant manifestations of atherosclerotic disease compared with 350 consecutive (control) older patients (age >50 years). Results: The most significant risk factors for atherosclerotic disease of the supra-aortic branches were: smoking (87.5%, p < 0.001), family history of atherosclerosis (52.3%, p < 0.001), diabetes mellitus (28.5%) and being male (56.9%) (p < 0.05 for both). In patients with coronary artery disease, there was considerable disparity in the prevalence of smoking (85.4%), hyperlipoproteinemia (67.4%), and family history of atherosclerosis (68%) (p < 0.001). For peripheral artery disease, the most significant risk factors were smoking (97%, p < 0.001), hyperlipidemia (p < 0.01), and family history of atherosclerotic disease (p < 0.01). When compared to controls, patients with premature atherosclerosis smoked more frequently, had hyperlipidemia, had a family history of atherosclerosis, and were more frequently of male sex. Conclusion: Premature atherosclerosis was most frequently associated with smoking, hyperlipidemia, family history of atherosclerotic disease, and male sex.