bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique and Highly Selective Anticytomegalovirus Activities of Artemisinin-Derived Dimer Diphenyl Phosphate Stem from Combination of Dimer Unit and a Diphenyl Phosphate Moiety
Authors: He Ran , Forman Michael , Mott Bryan T. , Venkatadri Rajkumar , Posner Gary H. , Arav-Boger Ravit
Published: June 2013

We report that the artemisinin-derived dimer diphenyl phosphate (DPP; dimer 838) is the most selective inhibitor of human cytomegalovirus (CMV) replication among a series of artemisinin-derived monomers and dimers. Dimer 838 was also unique in being an irreversible CMV inhibitor. The peroxide unit within artemisinins' chemical structures is critical to their activities, and its absence results in loss of anti-CMV activities. Surprisingly, the deoxy dimer of 838 retained modest anti-CMV activity, suggesting that the DPP moiety of dimer 838 contributes to its anti-CMV activities. DPP alone did not inhibit CMV replication, but triphenyl phosphate (TPP) had modest CMV inhibition, although its selectivity index was low. Artemisinin DPP derivatives dimer 838 and monomer diphenyl phosphate (compound 558) showed stronger CMV inhibition and a higher selectivity index than their analogs lacking the DPP unit. An add-on and removal assay revealed that removing DPP derivatives (compounds 558 and 838) but not the non-DPP backbones (artesunate and compound 606) at 24 h postinfection (hpi) already resulted in dominant CMV inhibition. CMV inhibition was fully irreversible with 838 and partially irreversible with 558, while non-DPP artemisinins were reversible inhibitors. While all artemisinin derivatives and TPP reduced the expression of the CMV immediate early 2 (IE2), UL44, and pp65 proteins at or after 48 hpi, only TPP inhibited the expression of both IE1 and IE2. Combination of a non-DPP dimer (compound 606) with TPP was synergistic in CMV inhibition, while ganciclovir and TPP were additive. Although TPP shared structural similarity with monomer DPP (compound 558) and dimer DPP (compound 838), its pattern of CMV inhibition was significantly different from the patterns of the artemisinins. These findings demonstrate that the DPP group contributes to the unique activities of compound 838.
Small-Molecule Inhibitors of Lethal Factor Protease Activity Protect against Anthrax Infection
Authors: Moayeri Mahtab , Crown Devorah , Jiao Guan-Sheng , Kim Seongjin , Johnson Alan , Leysath Clinton , Leppla Stephen H.
Published: June 2013

Bacillus anthracis
, the causative agent of anthrax, manifests its pathogenesis through the action of two secreted toxins. The bipartite lethal and edema toxins, a combination of lethal factor or edema factor with the protein protective antigen, are important virulence factors for this bacterium. We previously developed small-molecule inhibitors of lethal factor proteolytic activity (LFIs) and demonstrated their
in vivo
efficacy in a rat lethal toxin challenge model. In this work, we show that these LFIs protect against lethality caused by anthrax infection in mice when combined with subprotective doses of either antibiotics or neutralizing monoclonal antibodies that target edema factor. Significantly, these inhibitors provided protection against lethal infection when administered as a monotherapy. As little as two doses (10 mg/kg) administered at 2 h and 8 h after spore infection was sufficient to provide a significant survival benefit in infected mice. Administration of LFIs early in the infection was found to inhibit dissemination of vegetative bacteria to the organs in the first 32 h following infection. In addition, neutralizing antibodies against edema factor also inhibited bacterial dissemination with similar efficacy. Together, our findings confirm the important roles that both anthrax toxins play in establishing anthrax infection and demonstrate the potential for small-molecule therapeutics targeting these proteins.
A Colanic Acid Operon Deletion Mutation Enhances Induction of Early Antibody Responses by Live Attenuated Salmonella Vaccine Strains
Authors: Wang Shifeng , Shi Huoying , Li Yuhua , Shi Zhaoxing , Zhang Xin , Baek Chang-Ho , Mothershead Tabor , Curtiss Roy
Published: June 2013

Colanic acid (CA) is a common exopolysaccharide produced by many genera in theEnterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue bySalmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into twoSalmonellavaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophicSalmonellavaccine strain with the deletion mutation Δ(wza-wcaM)8developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. InSalmonellavaccine strains with RDAS, the strain with the Δ(wza-wcaM)8mutation resulted in higher levels of protective antigen production duringin vitrogrowth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 108and 109CFU. Thus, the mutation Δ(wza-wcaM)8will be included in various recombinant attenuatedSalmonellavaccine (RASV) strains with RDAS derived fromSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Typhi to induce protective immunity against bacterial pathogens.
Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells
Authors: Vu Kiem , Eigenheer Richard A. , Phinney Brett S. , Gelli Angie
Published: June 2013

Cryptococcus
spp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. In order for
Cryptococcus neoformans
to invade the central nervous system (CNS), it must first penetrate the brain endothelium, also known as the blood-brain barrier (BBB). Despite the importance of the interrelation between
C. neoformans
and the brain endothelium in establishing CNS infection, very little is known about this microenvironment. Here we sought to resolve the cellular and molecular basis that defines the fungal-BBB interface during cryptococcal attachment to, and internalization by, the human brain endothelium. In order to accomplish this by a systems-wide approach, the proteomic profile of human brain endothelial cells challenged with
C. neoformans
was resolved using a label-free differential quantitative mass spectrometry method known as spectral counting (SC). Here, we demonstrate that as brain endothelial cells associate with, and internalize, cryptococci, they upregulate the expression of several proteins involved with cytoskeleton, metabolism, signaling, and inflammation, suggesting that they are actively signaling and undergoing cytoskeleton remodeling via annexin A2, S100A10, transgelin, and myosin. Transmission electronic microscopy (TEM) analysis demonstrates dramatic structural changes in nuclei, mitochondria, the endoplasmic reticulum (ER), and the plasma membrane that are indicative of cell stress and cell damage. The translocation of HMGB1, a marker of cell injury, the downregulation of proteins that function in transcription, energy production, protein processing, and the upregulation of cyclophilin A further support the notion that
C. neoformans
elicits changes in brain endothelial cells that facilitate the migration of cryptococci across the BBB and ultimately induce endothelial cell necrosis.
Intravitreal ranibizumab in the management of stage 2B Coats disease in a young adult Malay man
Authors: Teh Swee Sew , Ahem Amin , Bastion Mae-Lynn Catherine
Published: June 2013

This paper describes a rare case of Coats disease with late presentation in a young adult. The condition improved with a combination of focal photocoagulation, cryotherapy and intravitreal ranibizumab.
Diagnostic utility of androgen receptor expression in discriminating poorly differentiated urothelial and prostate carcinoma
Authors: Downes Michelle R , Torlakovic Emina E , Aldaoud Najla , Zlotta Alexandre R , Evans Andrew J , van der Kwast Theodorus H
Published: June 2013

Aims

Pathological separation of poorly differentiated urothelial and prostate carcinoma is difficult, but imperative because of the impact on patient management. Tumour morphology, in conjunction with a panel of immunohistochemistry (IHC), such as prostate-specific antigen (PSA), prostatic acid phosphatase (PSAP), CK7, CK20, p63 and high molecular weight keratins (HMWKs) are usually employed to resolve this issue. Androgen receptor (AR) expression is maintained in high-grade, undifferentiated prostate carcinoma, and thus, could be considered as a potentially useful adjunct to the conventional panel of markers.

Methods

We performed an institutional review of all cases from 2006 to 2012 in which AR IHC had been performed to determine its diagnostic utility in discriminating between poorly differentiated urothelial and prostate carcinoma. Of the eligible cases (n=40), there were 9 high-grade urothelial carcinomas, 27 prostate carcinomas and 4 with both prostate and bladder tumours. All diagnoses were made by integrating the clinical, radiological, morphological and IHC results.

Results

In all the prostate carcinomas, there was diffuse, intense nuclear staining for AR. The urothelial tumours were either negative, had cytoplasmic staining or showed occasionally weak nuclear staining. The difference was highly significant with p<0.0001 (Mann–Whitney U test).

Conclusions

We conclude that AR is an important marker as it is best able to distinguish between poorly differentiated urothelial and prostate carcinoma. AR appears superior to PSA and PSAP, which are not consistently expressed in high-grade prostate carcinoma. Also, high-grade urothelial carcinoma may be negative for CK20, p63/HMWK and occasionally CK7. We advocate the inclusion of AR in the panel of markers to differentiate these tumours.
Political and economic characteristics as moderators of the relationship between health services and infant mortality in less-developed countries
Authors: Chuang Kun-Yang , Sung Pei-Wei , Chang Chia-Jung , Chuang Ying-Chih
Published: June 2013

Background

Few studies have addressed how political and economic contexts shape the effects of health services and environment, such that a politically and economically unstable society, despite having sufficient health professionals and facilities, finds it difficult to transfer health resources into actual population health performance. We examined whether political and economic characteristics moderate the effects of health services on infant mortality rates (IMR) in less-developed countries.

Methods

This study used a longitudinal ecological study design and focused on 46 less-developed countries during the 30-year period from 1980 to 2009. Data were derived from World Development Indicators, the United Nations Commodity Trade Statistics Database and the Polity IV project. Lagged dependent variable panel regression models were used to increase the causal inferences. Random intercept models were used to accommodate the possible problem of a serial correlation of errors because of the repeated measurements.

Results

After controlling for baseline IMR and other socioeconomic variables, our study showed that democracy had a direct effect on IMR, and a moderating effect on the relationship between health services and IMR. The effects of health services on IMR were stronger for countries with a lower level of democracy than for countries with a higher level of democracy in the 10-year models. Compared with other trade-rated characteristics, democracy is a more robust predictor of long-term IMR in less-developed countries.

Conclusions

Our study provides additional evidence that democracy has direct effects on IMR and further showed that democracy can modify the effects of health services on IMR.
Farmer attitudes to vaccination and culling of badgers in controlling bovine tuberculosis
Authors: Warren M. , Lobley M. , Winter M.
Published: June 2013

Controversy persists in England, Wales and Northern Ireland concerning methods of controlling the transmission of bovine tuberculosis (bTB) between badgers and cattle. The National Trust, a major land‐owning heritage organisation, in 2011, began a programme of vaccinating badgers against bTB on its Killerton Estate in Devon. Most of the estate is farmed by 18 tenant farmers, who thus have a strong interest in the Trust's approach, particularly as all have felt the effects of the disease. This article reports on a study of the attitudes to vaccination of badgers and to the alternative of a culling programme, using face‐to‐face interviews with 14 of the tenants. The results indicated first that the views of the respondents were more nuanced than the contemporary public debate about badger control would suggest. Secondly, the attitude of the interviewees to vaccination of badgers against bTB was generally one of resigned acceptance. Thirdly, most respondents would prefer a combination of an effective vaccination programme with an effective culling programme, the latter reducing population of density sufficiently (and preferably targeting the badgers most likely to be diseased) for vaccination to have a reasonable chance of success. While based on a small sample, these results will contribute to the vigorous debate concerning contrasting policy approaches to bTB control in England, Wales and Northern Ireland.
Experimental study on convection characteristics of crushed-rock layer
Authors: Qian Jin , Yu Qihao , Guo Lei , Hu Jun
Published: June 2013

Research on the measurement of micro wind-velocity and the airflow characteristics in the crushed-rock layer, which is caused by temperature difference, has long been problematic. For the first time, this study obtains the airflow characteristics in a crushed-rock layer by using high-precision micro wind-velocity detectors. Based on the experimental results, this study verifies the theory that the crushed-rock layer is available for convection heat exchange of porous media in a limited space. In boundary temperature fluctuations conditions, the cooling process is closely related to the natural convection process in the crushed-rock layer, and cooling occurs rapidly during the convection heat transfer process. The warming process, which occurs by heat conduction, happens gradually over a relatively long period of time, resulting in asymmetrical temperature change. The convection process exists only in the increasing and decreasing cooling stages of the entire cooling stage. The temperature difference between the top and the bottom in the crushed-rock layer is a key factor for the occurrence of convection and its intensity, although the air temperature changes also have an effect on the natural convection process in the increasing and decreasing cooling stages. Pore-air natural convection velocity increase is related to the increase in the temperature difference. Due to the different temperature and the penetration resistance of the crushed-rock layer, the velocity rapidly decreases in the depth direction, and there exits a delay phenomenon, so better cooling effect is in accordance with an optimal thickness of the crushed-rock layer.
Detecting landscape-level changes in tree biomass and biodiversity: methodological constraints and challenges of plot-based approaches
Authors: Salk Carl F. , Chazdon Robin L. , Andersson Krister P.
Published: June 2013

Understanding how human-impacted landscapes are changing is crucial for effective adaptive management and payment for ecosystem services programs. Landscape-level shifts in land use pose challenges not seen in typical ecological studies of well-protected forests. In human-modified landscapes, forests are often monitored using unique sets of randomized plots at each visit rather than re-censusing in the same permanent plots. We contrast field-based forest change monitoring using these two techniques and investigate whether sampling more plots or bigger plots better detects forest changes. Our empirical analysis employs long-term data sets from old-growth, second-growth, and managed tropical forests. We find that resampling in permanent plots reduces variation among subsequent censuses, but more importantly, it enables more powerful statistical tests. Increasing the number of plots improves detection of forest biomass changes more effectively than enlarging existing plot sizes, cost considerations being equal. This effect arises from more extensive capture of spatial heterogeneity by sampling in a greater number of locations. We further show that typical sampling techniques poorly assess the biodiversity of tropical forests and struggle to identify big changes in populations of common species. We conclude with practical suggestions for forest sampling in human-impacted tropical landscapes, including defining monitoring goals and delineating forests vs. entire landscapes as study areas.
INNER AMENABILITY OF LOCALLY COMPACT QUANTUM GROUPS
Authors: GHANEI MOHAMMAD REZA , NASR-ISFAHANI RASOUL
Published: June 2013

We initiate a study of inner amenability for a locally compact quantum group 𝔾 in the sense of Kustermans–Vaes. We show that all amenable and co-amenable locally compact quantum groups are inner amenable. We then show that inner amenability of 𝔾 is equivalent to the existence of certain functionals associated to characters on L1(𝔾). For co-amenable locally compact quantum groups, we introduce and study strict inner amenability and its relation to the extension of the co-unit ϵ from C0(𝔾) to L∞(𝔾). We then obtain a number of equivalent statements describing strict inner amenability of 𝔾 and the existence of certain means on subspaces of L∞(𝔾) such as LUC(𝔾), RUC(𝔾) and UC(𝔾). Finally, we offer a characterization of strict inner amenability in terms of a fixed point property for L1(𝔾)-modules.
AUXILIARY QUANTIZATION CONSTRAINTS ON THE VON ROOS ORDERING-AMBIGUITY AT ZERO BINDING ENERGIES; AZIMUTHALLY SYMMETRIZED CYLINDRICAL COORDINATES
Authors: MUSTAFA OMAR
Published: June 2013

Using azimuthally symmetrized cylindrical coordinates, we report the consequences of zero-energy quantal states on the von Roos Hamiltonian. A position-dependent mass (PDM) M(ρ, φ, z) = bzjρ2υ+1/2 is used. We show that the zero-energy setting not only offers an additional degree of freedom toward feasible separability for the von Roos Hamiltonian, but also manifestly yields auxiliary quantized ambiguity parametric constraints (i.e. the ambiguity parameters are given in terms of quantum numbers).
ORBITAL SELECTIVE PHASE TRANSITION
Authors: YAO YAO , ZHANG YU-ZHONG , LEE HUNPYO , JESCHKE HARALD O. , VALENTÍ ROSER , LIN HAI-QING , WU CHANG-QIN
Published: June 2013

In this paper, we review theoretical investigations on the origin of the orbital selective phase where localized and itinerant electrons coexist in the d shell at intermediate strength of the on-site Coulomb interactions between electrons. In particular, the effect of spatial fluctuations on the phase diagram of the two-orbital Hubbard model with unequal bandwidths is discussed. And different band dispersions in different orbitals as well as different magnetically ordered states in different orbitals which are responsible for orbital selective phase transitions are emphasized. This is due to the fact that these two mechanisms are independent of the Hund's rule coupling, and are completely distinct from other well-known mechanisms like orbitals of unequal bandwidths and orbitals with different degeneracies. Moreover, crystal field splitting is not required in these two recently proposed mechanisms.
ENTROPY OF SOME CK METRICS TO ASSESS OBJECT-ORIENTED SOFTWARE QUALITY
Authors: TURNU IVANA , CONCAS GIULIO , MARCHESI MICHELE , TONELLI ROBERTO
Published: June 2013

The term "software entropy" refers to the tendency for software, over time, to become difficult and costly to maintain. A software system that undergoes continuous change, such as having new functionality added to its original design, will eventually become more complex and can become disorganized as it grows, losing its original design structure.

A recent study show that software degradation may be measured using the WMC expressed in terms of Shannon entropy. In this paper we extended the empirical analyses also to RFC and CBO since these CK metrics have been shown to be correlated with fault-proneness of OO classes.

We analyzed various releases of the publicly available Eclipse and Netbeans software systems, calculating the entropy of some CK metrics for every release analyzed. The validity is shown through a direct measure of software quality such as the number of detected defects. Our results display a very good correlation between the entropy of CBO and RFC and the number of bugs for Eclipse and Netbeans.

Complexity and quality metrics are in general computed on every system module while the entropy is just a scalar number that characterizes a whole system, this result suggests that the entropy of some CK metrics could be considered as a global quality metric for large software systems. Our results need, however, to be confirmed for other large software systems.
ON NEGATIVE MASS
Authors: BELLETÊTE JONATHAN , PARANJAPE M. B.
Published: June 2013

The Schwarzschild solution to the matter free, spherically symmetric Einstein equations has one free parameter, the mass. But the mass can be of any sign. What is the meaning of the negative mass solutions? The answer to this question for the case of a pure Schwarzschild negative mass black solution is still elusive, however, in this essay, we will consider negative mass solutions within a Schwarzschild–de Sitter geometry. We show that there exist reasonable configurations of matter, bubbles of distributions of matter, that satisfy the dominant energy condition everywhere, that are nonsingular and well behaved everywhere, but correspond to the negative mass Schwarzschild–de Sitter geometry outside the matter distribution. These negative mass bubbles could occur as the end state of a quantum tunneling transition.
PREFACE
Authors: WIMBERGER SANDRO , MANNELLA RICCARDO
Published: June 2013

We give a brief sketch of the interdisciplinary field of noisy systems, classical as well as quantum ones, with great perspectives toward many-body systems and the engineering of their dynamics by the noise. A tiny cross section of the vast field is introduced along the lines of the research papers contained in this special issue.
TWO-DOF COUPLED AND SELF-ADAPTIVE (COSA) FINGER: A NOVEL UNDER-ACTUATED MECHANISM
Authors: ZHANG WENZENG , ZHAO DEYANG , ZHOU HAIPENG , SUN ZHENGUO , DU DONG , CHEN QIANG
Published: June 2013

A large amount of effort has been devoted to design better under-actuated robot hands. The most widely adopted approaches include rigid coupled hands and self-adaptive hands. The objective of this research is to design a robot finger which combines advantages of both ways and overcomes their disadvantages. The concept of coupling and self-adaptation (COSA) was introduced. A linkage-based two-DOF (degree of freedom) COSA robot finger was designed, optimized and studied in this paper. The theoretical analysis and the experiments on the finger show that it is able to execute human-like motion and adaptive grasps in multiple patterns. The research exposes a promising novel under-actuated mechanism for hands design with wide applications.
VOLUME SEGMENTATION BY POST-PROCESSING DATA FROM SIMULATION OF SOLIDIFICATION IN THE METAL CASTING PROCESS
Authors: JACOB ELIZABETH , MANOJ M. , SASIKUMAR ROSCHEN
Published: June 2013

In the process of interpreting simulation results, new post-processing techniques are developed. This work presents a post-processing method that analyzes the solidification pattern formed by simulation of the solidification process of molten metal in a mold to produce shaped castings. Simulations generally involve numerical solutions of differential equations which are discretized by dividing the three-dimensional computational domain into small finite volume elements using a 3D grid. The locations of the grid points and values of the solidification time at these locations are used to divide the spatial data into 3D sections such that starting from a hotspot location within the section that has high solidification time, there is a gradient outwards with lower values of solidification time. Each section is assumed to be fed by one or more feeders that must freeze only after the section has solidified completely. The volume of a feeder can be determined from the volume of the section it is supposed to feed. The volume and surface area of sections are determined approximately to calculate feeder size and dimensions. The post-processing algorithm is a simulation-based quantitative approach to feeder design which in conventional foundry practice has been more of an art than science. It is also general enough for use in other 3D segmentation applications.
Use of multiple oxygen isotope proxies for elucidating Arctic Cretaceous palaeo-hydrology
Authors: Suarez Celina A. , Ludvigson G. A. , Gonzalez L. A. , Fiorillo A. R. , Flaig P. P. , McCarthy P. J.
Published: June 2013

Stable oxygen isotope analysis of siderite and dinosaur tooth enamel phosphate from the Campanian–Maastrichtian Prince Creek Formation, Alaska, USA, are analysed to determine the palaeohydrology of the ancient Colville Basin north of the Ancestral Brooks Range. δ
18
O of freshwater siderites relative to V-PDB ranges between −14.86 and −16.21‰. Dinosaur tooth enamel δ
18
O from three different sites (Kikak–Tegoseak, Pediomys Point, Liscomb) range between +3.9‰ and +10.2.0‰. δ
18
O
meteoric water
are calculated from δ
18
O
siderite
that formed at seasonal temperatures ranging from −2 to 14.5 °C, with a mean annual temperature of 6.3 °C. At 6.3 °C, the δ
18
O
w
calculated from siderite ranged between −22.23 and −20.89‰ V-SMOW. Ingested water compositions are estimated from dinosaur teeth assuming body temperatures of 37 °C and local relative humidity of 77.5%, resulting in values ranging from −28.7 to −20.4‰ V-SMOW, suggesting consumption of meteoric water and orographically depleted runoff from the Brooks Range. The ranges in calculated δ
18
O
meteoric water
are compatible between the two proxies, and are mutually corroborating evidence of extremely
18
O-depleted precipitation at high latitudes during the Late Cretaceous relative to those generated using general circulation models. This depletion is proposed to result from increased rainout effects from an intensified hydrological cycle, which probably played a role in sustaining polar warmth.

Supplementary material:

Parameters used for generation of equations compared to Kohn (1996) can be found at
http://www.geolsoc.org.uk/SUP18642
Using Generalized Annotated Programs to Solve Social Network Diffusion Optimization Problems
Authors: Shakarian Paulo , Broecheler Matthias , Subrahmanian V. S. , Molinaro Cristian
Published: June 2013

There has been extensive work in many different fields on how phenomena of interest (e.g., diseases, innovation, product adoption) “diffuse” through a social network. As social networks increasingly become a fabric of society, there is a need to make “optimal” decisions with respect to an observed model of diffusion. For example, in epidemiology, officials want to find a set of
k
individuals in a social network which, if treated, would minimize spread of a disease. In marketing, campaign managers try to identify a set of
k
customers that, if given a free sample, would generate maximal “buzz” about the product. In this article, we first show that the well-known Generalized Annotated Program (GAP) paradigm can be used to express many existing diffusion models. We then define a class of problems called
Social Network Diffusion Optimization Problems
(SNDOPs). SNDOPs have four parts: (i) a diffusion model expressed as a GAP, (ii) an objective function we want to optimize with respect to a given diffusion model, (iii) an integer
k
 > 0 describing resources (e.g., medication) that can be placed at nodes, (iv) a logical condition
VC
that governs which nodes can have a resource (e.g., only children above the age of 5 can be treated with a given medication). We study the computational complexity of SNDOPs and show both NP-completeness results as well as results on complexity of approximation. We then develop an exact and a heuristic algorithm to solve a large class of SNDOPproblems and show that our GREEDY-SNDOPs algorithm achieves the best possible approximation ratio that a polynomial algorithm can achieve (unless
P
 = 
NP
). We conclude with a prototype experimental implementation to solve SNDOPs that looks at a real-world Wikipedia dataset consisting of over 103,000 edges.
Ph.D. students must break away from undergraduate mentality
Authors: Hong Jason
Published: June 2013

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Jason Hong considers how students working on their doctorates in computer science must adapt and evolve to succeed.
Backing creativity
Authors: Savage Neil
Published: June 2013

Hacker spaces are spreading around the world, though some government funding is raising questions.
Network-wide energy optimization for adaptive embedded systems
Authors: Heinrich Patrick , Prehofer Christian
Published: June 2013

This paper discusses network-wide energy optimization of embedded systems which can adapt by switching configurations. We model applications and their task chains in a network of embedded devices, including sleep modes and change of configuration, which provides a basic adaptation mechanism. We present a formal model of the energy consumption for such systems and apply it to automotive embedded systems. In particular, we develop new potential for network-wide energy savings as well as optimizations for adaptive systems. For instance, we show that non-optimal configurations may lead to a globally optimal system setup, if a system adapts regularly.
Clinical Significance and Prognostic Value of CA72‐4 Compared with CEA and CA19‐9 in Patients with Gastric Cancer
Authors: Ychou M. , Duffour J. , Kramar A. , Gourgou S. , Grenier J.
Published: June 2013

Carcinoembryonic antigen (CEA) and CA 19‐9 are both widely used in the follow up of patients with gastrointestinal cancer. More recently another tumor marker, named CA 72‐4 has been identified and characterized using two different monoclonal antibodies B72.3 and CC49. Several reports evaluated CA 72‐4 as a serum tumor marker for gastric cancer and compared its clinical utility with that of CEA or CA 19‐9; few reports concerned its prognostic value. In the present study, CA 72‐4 is evaluated and compared with CEA and CA 19‐9 in various populations of patients with gastric cancer and benign disease; for 52 patients with gastric adenocarcinoma and 57 patients without neoplastic disease CEA, CA 19‐9 and CA 72‐4 were evaluated before treatment. Sensitivity of the tumor markers CA 72‐4, CA 19‐9 and CEA at the recommended cut‐off level in all 52 patients were 58%, 50% the sensitivity increased to 75%. of these markers, for non metastatic patients, multivariate analyses indicated that none of the markers were significant, when adjusted for gender and age (which were indicators of poor prognosis); patients with abnormal values of CA72‐4 tended to have shorter survival than patients with normal values (p < 0.07). In the metastatic population, only high values of CA19‐9 (p < 0.02) and gender (women) (p < 0.03) were indicators of poor prognosis in univariate analysis; multivariate analysis revealed that both CA72‐4 (p = 0.034) and CA19‐9 p = 0.009), adjusted for gender were independent prognostic factors. However, CA72‐4 lost significance (p = 0.41) when adjusted for CA19‐9 and gender, indicating that CA19‐9 provides more prognostic information than CA72‐4.

When limited to the metastatic male population with normal values of CA 19‐9 and CEA, CA 72‐4 pretherapeutic positive levels were associated with a worse prognosis (p < 0.005).

In conclusion, this study suggests that the addition of CA 72‐4 to CEA and/or CA 19‐9 could improve sensitivity in gastric cancer. The prognostic role of this marker is not yet clearly demonstrated but its usefulness in the monitoring of gastric cancer should be taken into account.
Human Surfactant Protein – A Gene Locus for Genetic Studies in the Finnish Population
Authors: Rämet Mika , Haataja Ritva , Marttila Riitta , Häamäaläainen Anu-Maaria , Knip Mikael , Hallman Mikko
Published: June 2013

Lung surfactant lowers the surface tension but surfactant proteins also have other functions. Surfactant protein A (SP‐A) has a well‐defined role in innate immunity. The gene locus for human SP‐A genes is in chromosome 10q21 through q24 and consists of two highly homologous functional SP‐A genes (SP‐A1 and SP‐A2) and a pseudogene. Several alleles that differ by a single amino acid have been identified for both SP‐A genes. The SP‐A gene locus has been shown to be sufficiently polymorphic for genetic studies in the American population. In this study, we analysed the SP‐A allele frequencies in a Finnish population (n = 790) and found them to differ from the frequencies observed in US. Furthermore, we describe several new alleles for both SP‐A genes. The heterozygosity indices and polymorphism information content values ranged between 0.50–0.62 indicating that SP‐A gene locus is polymorphic enough for studies associating the locus with pulmonary diseases.
Searching for Pharmacogenomic Markers: The Synergy between Omic and Hypothesis‐Driven Research
Authors: Weinstein John N.
Published: June 2013

With 35,000 genes and hundreds of thousands of protein states to identify, correlate, and understand, it no longer suffices to rely on studies of one gene, gene product, or process at a time. We have entered the “omic” era in biology. But large‐scale omic studies of cellular molecules in aggregate rarely can answer interesting questions without the assistance of information from traditional hypothesis‐driven research. The two types of science are synergistic. A case in point is the set of pharmacogenomic studies that we and our collaborators have done with the 60 human cancer cell lines of the National Cancer Institute’s drug discovery program. Those cells (the NCI‐60) have been characterized pharmacologically with respect to their sensitivity to > 70,000 chemical compounds. We are further characterizing them at the DNA, RNA, protein, and functional levels. Our major aim is to identify pharmacogenomic markers that can aid in drug discovery and design, as well as in individualization of cancer therapy. The bioinformatic and chemoinformatic challenges of this study have demanded novel methods for analysis and visualization of high‐dimensional data. Included are the color‐coded “clustered image map” and also the MedMiner program package, which captures and organizes the biomedical literature on gene‐gene and gene‐drug relationships. Microarray transcript expression studies of the 60 cell lines reveal, for example, a gene‐drug correlation with potential clinical implications – that between the asparagine synthetase gene and the enzyme‐drug L‐asparaginase in ovarian cancer cells.
Speech Recognition of Arabic Spoken Digits
Authors: Allosh Anas , Zlitni Nura , Ganoun Ali
Published: June 2013

With the widespread growth in the use of digital computers, there has been an increasing need to be able to communicate with machines in a simple manner. One of the main tasks that simplify the communication with machines is the speech recognition. Speech recognition is the translation of spoken words into text. However, speech recognition is a very complex problem. This paper is related to the recognition of spoken Arabic digits. Two recognition techniques have been implemented and tested: Pitch Detection Algorithm (PDA) and Cepstrum Correlation Algorithm (CCA). In order to analyze the recognition accuracy of the selected techniques, a database of spoken Arabic digits has been created. The performance of the two techniques has been analyzed based on the created database.
Removal of Lead (II) Ions from Aqueous Solutions onto Activated Carbon Derived from Waste Biomass
Authors: Erdem Murat , Ucar Suat , Karagöz Selhan , Tay Turgay
Published: June 2013

The removal of lead (II) ions from aqueous solutions was carried out using an activated carbon prepared from a waste biomass. The effects of various parameters such as pH, contact time, initial concentration of lead (II) ions, and temperature on the adsorption process were investigated. Energy Dispersive X‐Ray Spectroscopy (EDS) analysis after adsorption reveals the accumulation of lead (II) ions onto activated carbon. The Langmuir and Freundlich isotherm models were applied to analyze equilibrium data. The maximum monolayer adsorption capacity of activated carbon was found to be 476.2 mg g−1. The kinetic data were evaluated and the pseudo‐second‐order equation provided the best correlation. Thermodynamic parameters suggest that the adsorption process is endothermic and spontaneous.
Solutions and Thermodynamics of Charged Rotating Black Holes in a Fuzzy Space
Authors: El Boukili Abderrahman , Nach Mourad , Chaqsare Hamid , Aouragh Moulay Driss , Sedra Moulay Brahim
Published: June 2013

We investigate the effect of fuzzy space on black hole and its thermodynamic Properties;
we also present our results in different types of black holes according to the parameters and representing electric and magnetic charges.
Graptopetalum paraguayenseAmeliorates Airway Inflammation and Allergy in Ovalbumin- (OVA-) Sensitized BALB/C Mice by Inhibiting Th2 Signal
Authors: Lee Bao-Hong , Cheng Yu-Hsiang , Wu She-Ching
Published: June 2013

Role of inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airways diseases has received increasing attention in recent years. Nuclear factor erythroid 2-related factor 2 is the primary transcription factor that regulates the expression of antioxidant and detoxifying enzymes.Graptopetalum paraguayenseE. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury through elevating antioxidation. Recently, we found that gallic acid is an active compound ofGraptopetalum paraguayenseE. Walther, which has been reported to inhibit T-helper 2 cytokines. Currently, we assumed thatGraptopetalum paraguayenseE. Walther may potentially protect against ovalbumin-induced allergy and airway inflammation. Results demonstrated thatGraptopetalum paraguayenseE. Walther ethanolic extracts (GPE) clearly inhibited airway inflammation, mucus cell hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, GPE also prevented T-cell infiltration and Th2 cytokines, including interleukin- (IL-)4, IL-5, and IL-13 generations in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1 and VCAM-1 were substantially reduced by GPE treatment mediated by Nrf2 activation. Moreover, GPE attenuated GATA3 expression and inhibited Th2 signals of the T cells. These findings suggested that GPE ameliorated the development of airway inflammation through immune regulation.
Demonstration of Hepatitis C Virus RNA withIn SituHybridization Employing a Locked Nucleic Acid Probe in Humanized Liver of Infected Chimeric Mice and in Needle-Biopsied Human Liver
Authors: Shiogama Kazuya , Inada Ken-ichi , Kohara Michinori , Teramoto Hidemi , Mizutani Yasuyoshi , Onouchi Takanori , Tsutsumi Yutaka
Published: June 2013

Background.In situhybridization (ISH) with high sensitivity has been requested to demonstrate hepatitis C virus (HCV) RNA in formalin-fixed, paraffin-embedded (FFPE) sections of the liver.Methods. ISH employing a locked-nucleic-acid- (LNA-)modified oligonucleotide probe and biotin-free catalyzed signal amplification system (CSAII) was applied to HCV-RNA detection in the liver tissue. Nested reverse-transcription polymerase chain reaction (RT-PCR) was performed for HCV genotyping using total RNA extracted from FFPE sections. The target tissues included FFPE tissue sections of humanized livers in HCV-infected chimeric mice (HCV genotypes 1a, 1b, and 2a and noninfected) and of needle-biopsied livers from HCV-infected patients.Results. HCV-RNA was demonstrated with the ISH technique in HCV-infected liver tissues from both chimeric mice and 9 (82%) of 11 patients with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR confirmed the genotype in 8 (73%) of 11 livers (type 1b: 6 lesions and type 2a: 2 lesions). HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver, autoimmune hepatitis, and hepatocellular carcinoma.Conclusion. ISH using the LNA-modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in routinely prepared FFPE liver specimens.
Short-Term Stability of Biomarkers of Oxidative Stress and Antioxidant Status in Human Serum
Authors: Jansen Eugène H. J. M. , Beekhof Piet K. , Cremers Johannes W. J. M. , Viezeliene Dale , Muzakova Vladimira , Skalicky Jiri
Published: June 2013

The oxidation and antioxidant status of serum are often determined in serum samples which have been frozen for some time. The oxidative stress process is prone to fast alterations in the sample because of the possible instability of the reactants. Here one oxidation assay (ROM) and three antioxidant assays (FRAP, TAS, and BAP) have been tested on their performance and stability at short-time storage. The most commonly used temperatures for storage and handling of serum samples (+4 and +20°C) were selected. In three short-term studies in which the storage time varied between 3 and 48 hrs the performance of these assays were tested on human serum samples. The general conclusion is that most assays performed well and gave stable results during 2 days of storage of the samples at both temperatures. Only the FRAP and TAS assays showed a small deviation at some storage conditions.
In conclusion, handling of serum samples at +4 and +20°C during short-time periods did not affect the quality and performance of the oxidation and antioxidant assays during day-to-day analyses.
Synergy in B-Cell Activation between Toll-Like Receptor 9 and Transmembrane Activator and Calcium-Modulating Cyclophilin Ligand Interactor (TACI) in A181E/C104R Compound Heterozygous Siblings
Authors: van de Ven Annick A. J. M. , Janssen Willemijn J. M. , van de Corput Lisette , Bloem Andries C. , van Montfrans Joris M. , Boes Marianne
Published: June 2013

Purpose. Approximately 9% of common variable immunodeficiency (CVID) patients harbor variants in the transmembrane activator and CAML interactor gene, TACI, which contribute to CVID development. We found identical compound heterozygous TACI variants (C104R and A181E) in kindred of which one sibling had severe CVID with refractory auto immunity, and a second sibling remained asymptomatic. This study investigated possible differences in B-cell phenotype and function that could explain this divergent clinical expression. Methods. C104R and A181E TACI variants were identified through Sanger sequencing. Phenotypic evaluation of the lymphocyte compartment was performed by flow cytometry analyses. Lymphoblastoid cell lines (LCL) from the index patient, asymptomatic sibling, and controls were generated. Intracellular TACI expression was determined, and activation-associated calcium flux capacity was measured. In vitro stimulation assays and RT PCR were performed. Results. Both intracellular levels and surface expressed TACI protein were higher in the asymptomatic sibling than the CVID patient as were TACI-triggering-induced mRNA expression AID and production of Ig class-switched antibodies. In analogy, the asymptomatic sibling displayed enhanced Toll-like receptor 9 expression and signaling, suggesting a compensatory immune mechanism. Conclusions. Posttranscriptional regulation of TACI protein and cross-talk with TLR9 signaling may contribute to phenotypic diversity between individuals with TACI variants.
Effect ofPiper betleandBrucea javanicaon the Differential Expression of Hyphal Wall Protein (HWP1) in Non-Candida albicans Candida(NCAC) Species
Authors: Wan Harun Wan Himratul Aznita , Jamil Nur Alyaa , Jamaludin Nor Hazwani , Nordin Mohd-Al-Faisal
Published: June 2013

The study aimed to identify theHWP1gene in non-Candida albicans Candidaspecies and the differential expression ofHWP1following treatment withPiper betleandBrucea javanicaaqueous extracts. All candidal suspensions were standardized to1×106 cells/mL. The suspension was incubated overnight at 37 °C (C. parapsilosis, 35°C). Candidal cells were treated with each respective extract at 1, 3, and 6 mg/mL for 24 h. The total RNA was extracted and reverse transcription-polymerase chain reaction was carried out with a specific primer ofHWP1.HWP1mRNAs were only detected inC. albicans,C. parapsilosis, andC. tropicalis. Exposing the cells to the aqueous extracts has affected the expression ofHWP1transcripts.C. albicans,C. parapsilosis, andC. tropicalishave demonstrated different intensity of mRNA. Compared toP. betle,B. javanicademonstrated a higher suppression on the transcript levels ofHWP1in all samples.HWP1was not detected inC. albicansfollowing the treatment ofB. javanicaat 1 mg/mL. In contrast,C. parapsilosisandC. tropicaliswere shown to haveHWP1regulation. However, the expression levels were reduced upon the addition of higher concentration ofB. javanicaextract.P. betleandB. javanicahave potential to be developed as oral health product.
Orthodontic Wire Ingestion during Treatment: Reporting a Case and Review the Management of Foreign Body Ingestion or Aspiration (Emergencies)
Authors: Hoseini Mohammad , Mostafavi Seyed Morteza Saadat , Rezaei Navid , Boluri Ehsan Javadzadeh
Published: June 2013

Today orthodontic treatment is in growing demand and is not limited to a specific age or social group. The nature of orthodontic treatment is such that the orthodontic wires and appliances, which are used to apply force and move the teeth, are exposed to the oral cavity. Shaping and replacing these wires in oral cavity are the major assignments of orthodontist on appointments. Therefore, we can say that orthodontic treatment requires working with dangerous tools in a sensitive place like oral cavity which is the entrance of respiratory and digestive systems. In this paper, a case of ingesting a broken orthodontic wire during eating is reported, and also necessary remedial measures at the time of encountering foreign body ingestion or aspiration are provided.
Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus Erythematosus
Authors: Kaleta Beata , Bogaczewicz Jarosław , Robak Ewa , Sysa-Jędrzejowska Anna , Wrzosek Małgorzata , Szubierajska Weronika , Mróz Piotr , Łukaszkiewicz Jacek , Woźniacka Anna
Published: June 2013

The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (r=0.438; P=0.002). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy.