bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy is associated with unmet health care needs compared to the general population despite higher health resource utilization—A Canadian population‐based study
Authors: Reid Aylin Y. , Metcalfe Amy , Patten Scott B. , Wiebe Samuel , Macrodimitris Sophie , Jetté Nathalie
Published: January 2012

Purpose:  (1) To determine whether health resource utilization (HRU) and unmet health care needs differ for individuals with epilepsy compared to the general population or to those with another chronic condition (asthma, diabetes, migraine); and (2) to assess the association among epilepsy status, sociodemographic variables and HRU.

Methods:  Data on HRU were assessed using the 2001–2005 Canadian Community Health Surveys, a nationally representative population‐based survey. Weighted estimates of association were produced as adjusted odds ratio with 95% confidence intervals, and logistic regression was used to explore the association between sociodemographic variables and HRU in those with epilepsy. All data on disease status, HRU, and unmet health care needs were self‐reported.

Key Findings:  Individuals with epilepsy had the highest rate of hospitalizations and the highest mean number of consultations with physicians. Despite higher rates of consultation with psychologists and social workers compared to the general population, those with epilepsy were significantly more likely to say they had unmet mental health care needs. People with epilepsy were also less likely to use dental services compared to the general population. Epilepsy was a significant predictor of HRU in logistic regression models.

Significance:  Given the prevalence of psychiatric comorbidities in those with epilepsy, it is concerning that this group perceives unmet mental health care needs. It is also troublesome that there was decreased utilization of dental health care resources in those with epilepsy considering that these patients are more likely to have poor oral health. Although individuals with epilepsy use more health care services than the general population, this increase appears to be insufficient to address their health care needs.
Dose‐dependent functional benefit of human cardiosphere transplantation in mice with acute myocardial infarction
Authors: Shen Deliang , Cheng Ke , Marbán Eduardo
Published: January 2012

Despite mounting pre‐clinical and clinical evidence of the beneficial effects of cell‐based therapy, optimal cell dosing and delivery approaches have not been identified. Cardiospheres are self‐assembling three‐dimensional (3D) microtissues formed by cardiac stem cells and supporting cell types. The ability of cardiospheres to augment cardiac function has been demonstrated in animal models of ischemic cardiomyopathy. In this study, we studied the dose dependence of the benefits of human cardiospheres, delivered via intramyocardial injection, upon cardiac function and ventricular remodelling in SCID mice with acute myocardial infarction. Four doses of cardiospheres were used: 1 × 104, 5 × 104, 1 × 105 and 5 × 105 (expressed as number of plated cardiosphere‐forming cells). Acute (24 hr) cell retention rates in all groups were similar. Functional assessment and quantitative heart morphometry indicated benefit from higher cell doses (≥5 × 104) in terms of ejection fraction, infarct size and capillary density. Histological analysis indicated that the dose‐dependent benefit was primarily because of indirect effects of transplanted cells. The results provide scalable data on cardiosphere dosing for intramyocardial injection.
Raf‐1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis
Authors: Yotova Iveta , Quan Ping , Gaba Aulona , Leditznig Nadja , Pateisky Petra , Kurz Christine , Tschugguel Walter
Published: January 2012

Endometriosis is a disease characterized by the localization of endometrial tissue outside the uterine cavity. The differences observed in migration of human endometrial stromal cells (hESC) obtained from patients with endometriosis versus healthy controls were proposed to correlate with the abnormal activation of Raf‐1/ROCKII signalling pathway. To evaluate the mechanism by which Raf‐1 regulates cytoskeleton reorganization and motility, we used primary eutopic (Eu‐, n = 16) and ectopic (Ec‐, n = 8; isolated from ovarian cysts) hESC of patients with endometriosis and endometriosis‐free controls (Co‐hESC, n = 14). Raf‐1 siRNA knockdown in Co‐ and Eu‐hESC resulted in contraction and decreased migration versus siRNA controls. This phenotype was reversed following the re‐expression of Raf‐1 in these cells. Lowest Raf‐1 levels in Ec‐hESC were associated with hyperactivated ROCKII and ezrin/radixin/moesin (E/R/M), impaired migration and a contracted phenotype similar to Raf‐1 knockdown in Co‐ and Eu‐hESC. We further show that the mechanism by which Raf‐1 mediates migration in hESC includes direct myosin light chain phosphatase (MYPT1) phosphorylation and regulation of the levels of E/R/M, paxillin, MYPT1 and myosin light chain (MLC) phosphorylation indirectly via the hyperactivation of ROCKII kinase. Furthermore, we suggest that in contrast to Co‐and Eu‐hESC, where the cellular Raf‐1 levels regulate the rate of migration, the low cellular Raf‐1 content in Ec‐hESC, might ensure their restricted migration by preserving the contracted cellular phenotype. In conclusion, our findings suggest that cellular levels of Raf‐1 adjust the threshold of hESC migration in endometriosis.
Identification of two residues essential for the stringent substrate specificity and active site stability of the prokaryotic l‐arginine:glycine amidinotransferase CyrA
Authors: Muenchhoff Julia , Siddiqui Khawar S. , Neilan Brett A.
Published: January 2012

A novel prokaryotic l‐arginine:glycine amidinotransferase (CyrA; EC2.1.4.1) is involved in the biosynthesis of the polyketide‐derived cytotoxin cylindrospermopsin in the cyanobacterium Cylindrospermopsis raciborskii AWT250, and was previously characterized with regard to kinetic mechanism and substrate specificity [Muenchhoff J et al. (2010) FEBS J277, 3844–3860]. In order to elucidate the structure–function–stability relationship of this enzyme, two residues in its active site were replaced with the residues that occur in the human l‐arginine:glycine amidinotransferase (h‐AGAT) at the corresponding positions (F245N and S247M), and a double variant carrying both substitutions was also created. In h‐AGAT, both of these residues are critical for the function of this enzyme with regard to substrate binding, ligand‐induced structural changes, and stability of the active site. In this study, we demonstrated that both single residue replacements resulted in a dramatic broadening of substrate specificity, but did not affect the kinetic mechanism. Experiments with substrate analogues indicate that donor substrates require a carboxylate group for binding. Evidence from initial velocity studies suggests that CyrA undergoes ligand‐induced structural changes that involve Phe245. Stability parameters (Topt and Tmax) of the CyrA variants differed from those of wild‐type CyrA. Structural flexibilities of the wild type and all three variants were comparable on the basis of dynamic fluorescence quenching, indicating that changes in Topt are most likely attributable to localized effects within the active site. Overall, the results indicated that these two residues are essential for both stringent substrate specificity and the active site stability and flexibility of this unique cyanobacterial enzyme.
Different Potassium Channels are Involved in Relaxation of Rat Renal Artery Induced by P1075
Authors: Novakovic Aleksandra , Pavlovic Marija , Milojevic Predrag , Stojanovic Ivan , Nenezic Dragoslav , Jovic Miomir , Ugresic Nenad , Kanjuh Vladimir , Yang Qin , He Guo‐Wei
Published: January 2012

The ATP‐sensitive K+ channels opener (KATPCO), P1075 [N‐cyano‐N′‐(1,1‐dimethylpropyl)‐N″‐3‐pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP‐sensitive K+ (KATP) channels. In addition to the well‐known effect on the opening of KATP channels, it has been reported that vasorelaxation induced by some of the KATPCOs includes some other K+ channel subtypes. Given that there is still no information on other types of K+ channels possibly involved in the mechanism of relaxation induced by P1075, this study was designed to examine the effects of P1075 on the rat renal artery with endothelium and with denuded endothelium and to define the contribution of different K+ channel subtypes in the P1075 action on this blood vessel. Our results show that P1075 induced a concentration‐dependent relaxation of rat renal artery rings pre‐contracted by phenylephrine. Glibenclamide, a selective KATP channels inhibitor, partly antagonized the relaxation of rat renal artery induced by P1075. Tetraethylammonium (TEA), a non‐selective inhibitor of Ca2+‐activated K+ channels, as well as iberiotoxin, a most selective blocker of large‐conductance Ca2+‐activated K+ (BKCa) channels, did not abolish the effect of P1075 on rat renal artery. In contrast, a non‐selective blocker of voltage‐gated K+ (KV) channels, 4‐aminopyridine (4‐AP), as well as margatoxin, a potent inhibitor of KV1.3 channels, caused partial inhibition of the P1075‐induced relaxation of rat renal artery. In addition, in this study, P1075 relaxed contractions induced by 20 mM K+, but had no effect on contractions induced by 80 mM K+. Our results showed that P1075 induced strong endothelium‐independent relaxation of rat renal artery. It seems that KATP, 4‐AP‐ and margatoxin‐sensitive K+ channels located in vascular smooth muscle mediated the relaxation of rat renal artery induced by P1075.
Plant and Yeast NHX Antiporters: Roles in Membrane TraffickingF
Authors: Qiu Quan‐Sheng
Published: January 2012

The plant NHX gene family encodes Na+/H+ antiporters which are crucial for salt tolerance, potassium homeostasis and cellular pH regulation. Understanding the role of NHX antiporters in membrane trafficking is becoming an increasingly interesting subject of study. Membrane trafficking is a central cellular process during which proteins, lipids and polysaccharides are continuously exchanged among membrane compartments. Yeast ScNhx1p, a prevacuole/ vacuolar Na+/H+ antiporter, plays an important role in regulating pH to control trafficking out of the endosome. Evidence begins to accumulate that plant NHX antiporters might function in regulating membrane trafficking in plants.

image

[ Quan‐Sheng Qiu (Corresponding author)]
Expression of Mitochondrial Gene Fragments within the Tapetum Induce Male Sterility by Limiting the Biogenesis of the Respiratory Machinery in Transgenic TobaccoF
Authors: Shaya Felix , Gaiduk Svetlana , Keren Ido , Shevtsov Sofia , Zemah Hanita , Belausov Eduard , Evenor Dalia , Reuveni Moshe , Ostersetzer‐Biran Oren
Published: January 2012

Plant mitochondrial genomes (mtDNAs) are large and undergo frequent recombination events. A common phenotype that emerges as a consequence of altered mtDNA structure is cytoplasmic‐male sterility (CMS). The molecular basis for CMS remains unclear, but it seems logical that altered respiration activities would result in reduced pollen production. Analysis of tobacco (Nicotiana tabacum) mtDNAs indicated that CMS‐associated loci often contain fragments of known organellar genes. These may assemble with organellar complexes and thereby interfere with normal respiratory functions. Here, we analyzed whether the expression of truncated fragments of mitochondrial genes (i.e. atp4, cox1 and rps3) may induce male sterility by limiting the biogenesis of the respiratory machinery. cDNA fragments corresponding to atp4f, cox1f and rps3f were cloned in‐frame to a mitochondrial localization signal and a C‐termini HA‐tag under a tapetum‐specific promoter and introduced to tobacco plants by Agrobacterium‐mediated transformation. The constructs were then analyzed for their effect on mitochondrial activity and pollen fertility. Atp4f, Cox1f and Rps3f plants demonstrated male sterility phenotypes, which were tightly correlated with the expression of the recombinant fragments in the floral meristem. Fractionation of native organellar extracts showed that the recombinant ATP4f‐HA, COX1f‐HA and RPS3f‐HA proteins are found in large membrane‐associated particles. Analysis of the respiratory activities and protein profiles indicated that organellar complex I was altered in Atp4f, Cox1f and Rps3f plants.
Low Molecular Weight Iron Dextran Increases Fibroblast Growth Factor‐23 Concentration, Together With Parathyroid Hormone Decrease in Hemodialyzed Patients
Authors: Hryszko Tomasz , Rydzewska‐Rosolowska Alicja , Brzosko Szymon , Koc‐Zorawska Ewa , Mysliwiec Michal
Published: January 2012

Fibroblast growth factor (FGF)‐23 inhibits PTH production. Elevated FGF‐23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF‐23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF‐23, PTH, degradation products of C‐terminal telopeptides of type I collagen (CTX) and procollagen I N‐terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF‐23 increased significantly from 453.4 (68.6–3971.5) pg/mL at baseline to 971.8 (779.5–3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4–1487.4) pg/mL at baseline to 315.7 (16.4–1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF‐23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation.
Effect of Heparin on Conformation of the β2‐Microglobulin Molecule
Authors: Uji Yoshinori , Motomiya Yoshihiro , Ando Yukio
Published: January 2012

Heparin, one of the essential molecules called glycosaminoglycans (GAGs), is the anticoagulant that is commonly used in regular hemodialysis, during which dialysis‐related amyloidosis (DRA) may develop. The pathogenic protein, i.e. precursor protein, in DRA is β2‐microglobulin (β2m). Recent studies defined amyloidosis as a protein misfolding disease of precursor proteins including β2m. Because the analytic technique capillary electrophoresis can identify molecular variants of the folded β2m, i.e. conformational variants, we utilized it to investigate the effect of heparin on β2m conformation and thus determined whether heparin can promote DRA development by inducing a conformational change in the amyloidogenic β2m molecule. Heparin had a slight but significant effect on intermediate β2m conformation but no effect on native β2m conformation and on conversion of native to intermediate β2m. Our findings thus suggest a possible association of β2m with GAGs containing a sulfate moiety, including heparin, in HD patients.
It Don't Come Easy: Overcoming Obstacles to Technology Use Within a Resistant Consumer Group
Authors: GILLY MARY C. , CELSI MARY WOLFINBARGER , SCHAU HOPE JENSEN
Published: January 2012

To identify ways in which resistance can be overcome and technology's potential realized, we study acceptance and use of a specific technology, the Internet, by a specific resistant group, older consumers. Using interviews and a survey of consumers who are over 65 years old, we discover that curiosity and proactive coping drive technology optimism, which then predicts adoption and heavier usage. Motivated seniors with technology discomfort get help to adopt and continued assistance to learn usage repertoires. Surprisingly, technology discomfort is positively rather than negatively related to usage enthusiasm. Implications are drawn for consumer groups resistant to technology.
Establishment of a Microplate‐Formatted Cell‐Based Immunoassay for Rapid Analysis of Nucleotide Excision Repair Ability in Human Primary Cells
Authors: Nishinaga Mari , Kurata Ryuichiro , Onishi Kazuyoshi , Kuriyama Kenichi , Wakasugi Mitsuo , Matsunaga Tsukasa
Published: January 2012

DNA photolesions induced by UV, cyclobutane pyrimidine dimer (CPD) and (6‐4) photoproduct (6‐4PP), are repaired by nucleotide excision repair (NER) in human cells. Various immunoassays using monoclonal antibodies specific for the photolesions have been developed and widely used for the analysis of cellular NER activity. In this study, we have newly developed a microplate‐formatted cell‐based immunoassay, based on indirect immunofluorescence staining with lesion‐specific antibodies combined with an infrared imaging system. Using this assay, we show the repair kinetics of CPD and 6‐4PP in various fibroblasts from newborn and adult donors with no age‐related difference. Furthermore, epidermal keratinocytes and melanocytes exhibit comparable NER activity, and calcium ion‐induced differentiation of keratinocytes has no significant impacts on their NER activity. We also evaluated the effects of a proteasome inhibitor, MG132, and a histone deacetylase inhibitor, sodium butyrate, on NER efficiency using this assay. All these results suggest that the new assay is highly useful for the rapid and quantitative analysis of NER activity in various primary cells with limited growth activity and is applicable to a screening system for drugs affecting NER efficiency.
Sources and Sinks of Phosphorus for a Perturbed Stream and the Effects of Mineral Deposits1
Authors: Effler Steven W. , Prestigiacomo Anthony R. , Matthews David A. , Peng Feng
Published: January 2012

Effler, Steven W., Anthony R. Prestigiacomo, David A. Matthews, and Feng Peng, 2012. Sources and Sinks of Phosphorus for a Perturbed Stream and the Effects of Mineral Deposits. Journal of the American Water Resources Association (JAWRA) 48(2): 321‐335. DOI: 10.1111/j.1752‐1688.2011.00617.x

Abstract:  Patterns of concentrations and loading rates of multiple forms of phosphorus (P) are resolved and analyzed along Ninemile Creek, New York, a stream perturbed by a domestic waste discharge and residual effects of a closed industry. This analysis is based on biweekly monitoring of total, dissolved, and soluble reactive P (SRP) for 19 months at four sites that bracket each of these effects, and 15 years of biweekly measurements at the two sites that bound industrial deposits. The minerogenic particle populations of the stream and the surficial sediments along the reach with extensive CaCO3 and clay mineral deposits are characterized with an individual particle analysis technique. Mass balance analyses depict: (1) increasing nonpoint inputs of particulate and dissolved organic P along the stream length; (2) input of P from a domestic waste facility, almost entirely in the form of SRP; and (3) a compensating downstream loss of SRP over the reach with the extensive industrial deposits of CaCO3. The downstream sink process for SRP is attributed to sorption processes with minerogenic deposits. The domestic waste‐based source and the compensating industrial waste‐based sink are noteworthy fluxes relative to other prevailing loads received by downstream Onondaga Lake, for which a major rehabilitation program targeting cultural eutrophication is underway. The P source/sink conditions of this stream are considered in the context of this rehabilitation program.
A Sampler for Measuring Deposited Fine Sediments in Streams1
Authors: Turner Andy W. , Hillis Jeff J. , Rabeni Charles F.
Published: January 2012

Turner, Andy W., Jeff J. Hillis, and Charles F. Rabeni, 2012. A Sampler for Measuring Deposited Fine Sediments in Streams. Journal of the American Water Resources Association (JAWRA) 48(2): 366‐378. DOI: 10.1111/j.1752‐1688.2011.00618.x

Abstract:  Improvements and standardization of methodologies to quickly and accurately quantify deposited sediment in streams will allow advances in our understanding of biological effects of sedimentation. Most methods used to evaluate streambed conditions as part of biological monitoring or assessment programs are selected for ease of use, but can be subjective, inappropriate, and often of unknown accuracy. We developed a portable, light‐weight device to quantify deposited unconsolidated sediment (particles <2 mm) in wadeable streams. This deposited sediment sampler is a hand‐held unit that circumscribes an area of the streambed and through suction creates a force that suspends unconsolidated materials into a collector. Laboratory evaluations determined the efficiency (percent of available deposited sediment recovered) of the sampler to collect different sizes and concentrations of deposited sediment under differing streambed conditions, which allowed appropriate correction factors to be applied to each of four categories of streambed particle size. Field trials comparing our sampler to other methods commonly used by many state and federal agencies showed high comparability. The sampler can be constructed in just a few hours from inexpensive, easily obtained materials.
Design of an Extra-Tall Mast Above Blade-Tip Heights for Wind Resource Assessments Across Complex Terrain Regions
Authors: Womeldorf Carole A.
Published: January 2012

Wind energy predictions for many rural, complex terrain regions are based solely on large-scale meteorological models that may poorly characterize the local resource. Changes in government policies, energy economics, and wind technologies suggest that the best wind resources across such a complex terrain region in southeast Ohio may be economically viable. The wind energy and assessment visualization (WEAV) assessment approach is a meso-scale strategy to locate the best resource in a marginal wind region. The measurement component is described here. Wind characteristics measurements on a communications tower at six heights up to 240 m, are being acquired. This data will be input into a complex-terrain wind simulator with terrain information to model the wind resource across approximately 2000 square miles (5200 km2). Advantages of the WEAV assessment strategy include explicit measurement of wind shear and velocities, long-term characterization of the free stream velocity field, and evaluation of a much larger assessment region. Included is a description of, the motivation for and advantages of this approach, details of the design, installation, and challenges of an extra-tall tower wind measurements, and a discussion of the economics of both Class 2 wind (∼250 W/m2) and the WEAV assessment approach compared with conventional wind assessments.
Experimental and Numerical Investigations on Nonlinear Aeroelasticity of Forward-Swept, Compliant Wings
Authors: Thwapiah Ghalib Y. , Campanile L. Flavio
Published: January 2012

At the beginning of aviation history, aeroelastic static instabilities represented a problem in operating monoplane aircraft. After being discovered, they were systematically avoided, since they would have led to large deformations and structural failure. A new idea (active aeroelasticity) reverts this approach and utilizes static instabilities to realize wing morphing instead of avoiding them. Another innovative idea (compliant systems) deals with structures designed to achieve large deformations within the elastic range of the material. Joining those two ideas leads to a novel class of airfoil structures (active aeroelastic, compliant airfoils) which enable operation at and beyond aeroelastic instabilities. Such structures need a new modeling approach, which includes nonlinearities of structural and aerodynamic kinds. In this paper, a non linear analysis of aeroelastic bending divergence (a phenomenon which concerns forward-swept wings) is presented, initially based on so-called low-fidelity models. Such models are, to some extent, inaccurate but allow a good insight into the physical behavior of the phenomenon and are very useful in preliminary design. The results of wind-tunnel tests follow, which were performed to investigate the aeroelastic response of a compliant airfoil model near divergence. Finally, high fidelity simulation results based on state-of-the-art methods (finite element method and fluid-structure-interaction) are shown and discussed. Those tools allow the prediction of the system response more accurately and are therefore well suited to the detailed design of active aeroelastic, compliant airfoils.
Modeling of Cross-Coupling Responses on Hingeless Helicopters via Gyroscopic Effect
Authors: Lau Tak Kit , Liu Yun-hui
Published: January 2012

The perplexing cross-coupled responses between the control axes on hingeless helicopters have puzzled researchers for years. Unlike previous studies, which introduced a physically meaningless phase-lag to account for the cross-couplings, this paper proposes a new method to relate both on-axis and off-axis responses by the gyroscopic moments through the actuation mechanism of hingeless helicopters. This new method allows investigators to directly and analytically quantify the debatable cross-coupling due to the complex actuation of the rotor. This method is based on the fact that when the angular momentum of the spinning rotor is disturbed by an incremental lift along the main blades due to the varying cyclic pitch angle controlled by the servo mechanisms, off-axis moments are induced to counteract the changes in angular momentum according to the principles of the gyroscope, and hence these gyroscopic moments directly exhibit on-axis responses. This new method yields a parametric framework for examining the previously unexplained cross-coupled responses of hingeless helicopters and demonstrates that, in addition to aerodynamics, intricate dynamic nonlinearities also occur due to non-intuitive actuation mechanisms on the rotor of hingeless helicopters. Finally, simulations and experiments were performed to validate the proposed modeling method.
Fabrication of stable and reproducible submicron tunnel junctions
Authors: Pop I. M. , Fournier T. , Crozes T. , Lecocq F. , Matei I. , Pannetier B. , Buisson O. , Guichard W.
Published: January 2012

The authors have performed a detailed study of the time stability and reproducibility of submicron Al/AlOx/Al tunnel junctions, fabricated using standard double angle shadow evaporations. The authors have found that by aggressively cleaning the substrate before the evaporations; thus preventing any contamination of the junction, they obtained perfectly stable oxide barriers. The authors also present measurements on large ensembles of junctions which prove the reproducibility of the fabrication process. The measured tunnel resistance variance in large ensembles of identically fabricated junctions is in the range of only a few percent. Finally, the authors have studied the effect of different thermal treatments on the junction barrier. This is especially important for multiple step fabrication processes which imply annealing the junction.
Activation-Induced B Cell Fates Are Selected by Intracellular Stochastic Competition
Authors: Duffy Ken R. , Wellard Cameron J. , Markham John F. , Zhou Jie H. S. , Holmberg Ross , Hawkins Edwin D. , Hasbold Jhagvaral , Dowling Mark R. , Hodgkin Philip D.
Published: January 2012

Stochastic or Asymmetric Fate Determination?

During an adaptive immune response, B lymphocytes rapidly divide and differentiate into effector cell populations, including antibody-secreting plasmablasts and memory B cells. Many also change the class of antibody they secrete, through a process called isotype switching. During this process, some cells die. Whether cells acquire these different fates in a stochastic or programmed manner, however, is unclear.

Duffy
et al.

(p.
338
, published online 5 January) used single-cell tracking to determine the times to division, differentiation into a plasmablast, isotype switching, and death of stimulated B lymphocytes. Statistical analysis and mathematical modeling revealed that these cell-fate decisions appear to be the result of random clocks: Which clock went off first (division, differentiation, or death), determined the fate of the cell.

Barnett
et al.

(p.
342
, published online 15 December) sought to determine whether asymmetrical cell division, which is thought to contribute to effector cell-fate decisions in T cells, may be at work in B lymphocytes. Indeed, factors important for the initiation and maintenance of germinal center B lymphocyte identity, along with an ancestral polarity protein, were asymmetrically distributed and maintained their asymmetry during cell division.
Dystroglycan Function Requires Xylosyl- and Glucuronyltransferase Activities of LARGE
Authors: Inamori Kei-ichiro , Yoshida-Moriguchi Takako , Hara Yuji , Anderson Mary E. , Yu Liping , Campbell Kevin P.
Published: January 2012

Going LARGE

Dystroglycan (DG) is a highly glycosylated extracellular matrix (ECM) receptor involved in a variety of physiological processes, including maintenance of skeletal muscle membrane integrity and the structure and function of the central nervous system. The like-acetylglucosaminyltransferase (LARGE) is responsible for posttranslational modifications of alpha-dystroglycan (α-DG) required for its function. Now,

Inamori
et al.

(p.
93
) demonstrate that LARGE is a bifunctional glycosyltransferase able to transfer xylose and glucuronic acid. These modifications allow α-DG to bind the laminin-G domain–containing ECM ligands: laminin, agrin, and neurexin.
Comment on “Nonreciprocal Light Propagation in a Silicon Photonic Circuit”
Authors: Fan Shanhui , Baets Roel , Petrov Alexander , Yu Zongfu , Joannopoulos John D. , Freude Wolfgang , Melloni Andrea , Popović Miloš , Vanwolleghem Mathias , Jalas Dirk , Eich Manfred , Krause Michael , Renner Hagen , Brinkmeyer Ernst , Doerr Christopher R.
Published: January 2012

We show that the structure demonstrated by Feng
et al
. (Reports, 5 August 2011, p. 729) cannot enable optical isolation because it possesses a symmetric scattering matrix. Moreover, one cannot construct an optical isolator by incorporating this structure into any system as long as the system is linear and time-independent and is described by materials with a scalar dielectric function.
Variable Outcome of Mutations
Authors: Deplancke Bart , Verstrepen Kevin J.
Published: January 2012

Environmental stress and stochastic differences in the expression of protective genes influence the effect of mutations.
Lloyd J. Old (1933–2011)
Authors: Sharma Padmanee , Allison James P.
Published: January 2012

An immunologist devoted his life's work to understanding how the immune system fights cancer.
In the Eye of the Storm, Two Rivals, Two Strategies
Authors: Enserink Martin
Published: January 2012

The two influenza researchers whose work has triggered a far-reaching debate on the limits of scientific freedom could hardly have handled their publicity more differently.
Unraveling the Obesity-Cancer Connection
Authors: Taubes Gary
Published: January 2012

A growing body of research shows that insulin and a related hormone play a key role in fueling tumors. They also may be a link between obesity, diabetes, and cancer.
Evaluation of a Recombinant Multiepitope Peptide for Serodiagnosis of Toxoplasma gondii Infection
Authors: Dai Jianfang , Jiang Min , Wang Yanyun , Qu Lili , Gong Rujun , Si Jin
Published: January 2012

Detection ofToxoplasma gondiiinfection with sensitive and specific methods is a key step in the prevention and treatment of toxoplasmosis. Among the available diagnostic tests, serology is commonly used. Although serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. There is therefore a real need to acquire specific and effective recombinant antigens for the serodiagnosis ofT. gondiiinfection. In this study, a multiepitope peptide was designed and successfully expressed inEscherichia coli, and then IgG and IgM enzyme-linked immunosorbent assays (ELISAs) were developed and evaluated. Our results showed that the new multiepitope antigen is one of the most promising recombinant antigens which could be used in routine screening of human toxoplasmosis.
Multisite Reproducibility of the Broth Microdilution Method for Susceptibility Testing of Nocardia Species
Authors: Conville Patricia S. , Brown-Elliott Barbara A. , Wallace Richard J. , Witebsky Frank G. , Koziol Deloris , Hall Geraldine S. , Killian Scott B. , Knapp Cindy C. , Warshauer David , Van Tam , Wengenack Nancy L. , Deml Sharon , Woods Gail L.
Published: January 2012

Antimicrobial susceptibility testing (AST) of clinical isolates of
Nocardia
is recommended to detect resistance to commonly used antimicrobial agents; such testing is complicated by difficulties in inoculum preparation and test interpretation. In this study, six laboratories performed repetitive broth microdilution testing on single strains of
Nocardia brasiliensis
,
Nocardia cyriacigeorgica
,
Nocardia farcinica
,
Nocardia nova
, and
Nocardia wallacei
. For each isolate, a total of 30 microdilution panels from three different lots were tested at most sites. The goal of the study was to determine the inter- and intralaboratory reproducibility of susceptibility testing of this group of isolates. Acceptable agreement (>90% agreement at ±1 dilution of the MIC mode) was found for amikacin, ciprofloxacin, clarithromycin, and moxifloxacin. After eliminating MIC values from single laboratories whose results showed the greatest deviation from those of the remaining laboratories, acceptable agreement was also found for amoxicillin-clavulanic acid, linezolid, minocycline, and tobramycin. Results showed unsatisfactory reproducibility of broth microdilution testing of ceftriaxone with
N. cyriacigeorgica
and
N. wallacei
, tigecycline with
N. brasiliensis
and
N. cyriacigeorgica
, and sulfonamides with
N. farcinica
and
N. wallacei. N. nova
ATCC BAA-2227 is proposed as a quality control organism for AST of
Nocardia
sp., and the use of a disk diffusion test for sulfisoxazole is proposed as a check of the adequacy of the inoculum and to confirm sulfonamide MIC results.
Risk factors for ischaemic heart disease mortality among men with different occupational physical demands. A 30-year prospective cohort study
Authors: Holtermann Andreas , Mortensen Ole Steen , Søgaard Karen , Gyntelberg Finn , Suadicani Poul
Published: January 2012

Objectives

Men with high physical work demands have elevated cardiovascular strain, which may lead to enhanced atherosclerosis. Theoretically, the impact of risk factors for ischaemic heart disease (IHD) may thus depend on physical work demands. The authors investigated this hypothesis.

Design

Prospective 30-year follow-up.

Setting

The Copenhagen Male Study.

Participants

5249 gainfully employed men aged 40–59 years; 311 men with cardiovascular disease/diabetes were excluded.

Primary and secondary outcome measures

IHD and all-cause mortality.

Results

579 men (11.8%) died due to IHD and 2628 (53.7%) from all-cause mortality. Similarities and differences in risk predictors were found between men with low (n=1219), medium (n=2636) and high (n=846) physical work demands. After control for potential confounders, high physical fitness conferred a reduced risk of IHD mortality only among men with high physical work demands (HR: 0.48, 95% CI 0.24 to 0.96), a moderate/high level of leisure-time physical activity was associated with reduced risk of IHD mortality only among men with moderate and high physical work demands. High systolic blood pressure and smoking were risk factors in all groups. Similar, but less pronounced differences in risk factors for all-cause mortality between groups were found.

Conclusions

The risk factors for IHD and all-cause mortality, low physical fitness and low leisure-time physical activity are not identical for men with different physical work demands. Preventive initiatives for IHD should be tailored to the physical work demands.
Breast cancer survival and season of surgery: an ecological open cohort study
Authors: Teilum Dorthe , Bjerre Karsten D , Tjønneland Anne M , Kroman Niels
Published: January 2012

Background

Vitamin D has been suggested to influence the incidence and prognosis of breast cancer, and studies have found better overall survival (OS) after diagnosis for breast cancer in summer–autumn, where the vitamin D level are expected to be highest.

Objective

To compare the prognostic outcome for early breast cancer patients operated at different seasons of the year.

Design

Open population-based cohort study.

Setting

Danish women operated 1978–2010.

Cases

79 658 adjusted for age at surgery, period of surgery, tumour size, axillary lymph node status and hormone receptor status.

Statistical analysis

The association between OS and season of surgery was analysed by Cox proportional hazards regression models, at survival periods 0–1, 0–2, 0–5 and 0–10 years after surgery. A two-sided p value <0.05 was considered statistical significant.

Results

Only after adjustment for prognostic factors that may be influenced by vitamin D, 1-year survival was close to significantly associated season of surgery. 2, 5 and 10 years after surgery, the association between OS and season of surgery was not significant.

Limitations

Season is a surrogate measure of vitamin D.

Conclusions

The authors found no evidence of a seasonal variation in the survival after surgery for early breast cancer. Lack of seasonal variation in this study does not necessarily mean that vitamin D is of no importance for the outcome for breast cancer patients.
Hearing in 44–45 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study
Authors: Rahman Shamima , Ecob Russell , Costello Harry , Sweeney Mary G , Duncan Andrew J , Pearce Kerra , Strachan David , Forge Andrew , Davis Adrian , Bitner-Glindzicz Maria
Published: January 2012

Background

The mitochondrial DNA mutation m.1555A>G predisposes to permanent idiosyncratic aminoglycoside-induced deafness that is independent of dose. Research suggests that in some families, m.1555A>G may cause non-syndromic deafness, without aminoglycoside exposure, as well as reduced hearing thresholds with age (age-related hearing loss).

Objectives

To determine whether adults with m.1555A>G have impaired hearing, a factor that would inform the cost–benefit argument for genetic testing prior to aminoglycoside administration.

Design

Population-based cohort study.

Setting

UK.

Participants

Individuals from the British 1958 birth cohort.

Measurements

Hearing thresholds at 1 and 4 kHz at age 44–45 years; m.1555A>G genotyping.

Results

19 of 7350 individuals successfully genotyped had the m.1555A>G mutation, giving a prevalence of 0.26% (95% CI 0.14% to 0.38%) or 1 in 385 (95% CI 1 in 714 to 1 in 263). There was no significant difference in hearing thresholds between those with and without the mutation. Single-nucleotide polymorphism analysis indicated that the mutation has arisen on a number of different mitochondrial haplogroups.

Limitations

No data were collected on aminoglycoside exposure. For three subjects, hearing thresholds could not be predicted because information required for modelling was missing.

Conclusions

In this cohort, hearing in those with m.1555A>G is not significantly different from the general population and appears to be preserved at least until 44–45 years of age. Unbiased ascertainment of mutation carriers provides no evidence that this mutation alone causes non-syndromic hearing impairment in the UK. The findings lend weight to arguments for genetic testing for this mutation prior to aminoglycoside administration, as hearing in susceptible individuals is expected to be preserved well into adult life. Since global use of aminoglycosides is likely to increase, development of a rapid test is a priority.
Effect of vitamin A supplementation in women of reproductive age on cause-specific early and late infant mortality in rural Ghana: ObaapaVitA double-blind, cluster-randomised, placebo-controlled trial
Authors: Edmond Karen , Hurt Lisa , Fenty Justin , Amenga-Etego Seeba , Zandoh Charles , Hurt Chris , Danso Samuel , Tawiah Charlotte , Hill Zelee , ten Asbroek Augustinus H A , Owusu-Agyei Seth , Campbell Oona , Kirkwood Betty R
Published: January 2012

Objectives

To assess the effect of vitamin A supplementation in women of reproductive age in Ghana on cause- and age-specific infant mortality. In addition, because of recently published studies from Guinea Bissau, effects on infant mortality by sex and season were assessed.

Design

Double-blind, cluster-randomised, placebo-controlled trial.

Setting

7 contiguous districts in the Brong Ahafo region of Ghana.

Participants

All women of reproductive age (15–45 years) resident in the study area randomised by cluster of residence. All live born infants from 1 June 2003 to 30 September 2008 followed up through 4-weekly home visits.

Intervention

Weekly low-dose (25 000 IU) vitamin A.

Main outcome measures

Early infant mortality (1–5 months); late infant mortality (6–11 months); infection-specific infant mortality (0–11 months).

Results

1086 clusters, 62 662 live births, 52 574 infant-years and 3268 deaths yielded HRs (95% CIs) comparing weekly vitamin A with placebo: 1.04 (0.88 to 1.05) early infant mortality; 0.99 (0.84 to 1.18) late infant mortality; 1.03 (0.92 to 1.16) infection-specific infant mortality. There was no evidence of modification of the effect of vitamin A supplementation on infant mortality by sex (Wald statistic =0.07, p=0.80) or season (Wald statistic =0.03, p=0.86).

Conclusions

This is the largest analysis of cause of infant deaths from Africa to date. Weekly vitamin A supplementation in women of reproductive age has no beneficial or deleterious effect on the causes of infant death to age 6 or 12 months in rural Ghana.

Trial registration number

http://ClinicalTrials.gov:NCT00211341.
Gonorrhoea or chlamydia in a US military HIV-positive cohort
Authors: Spaulding Alicen B , Lifson Alan R , Iverson Erik R , Ganesan Anuradha , Landrum Michael L , Weintrob Amy C , Agan Brian K , Bavaro Mary F , O'Connell Robert J , Macalino Grace E ,   the Infectious Disease Clinical Research Program HIV Working Group
Published: January 2012

Objectives

To investigate the epidemiology and risk factors of gonorrhoea (GC) or chlamydia (CT) coinfection in an HIV-positive US military cohort, focusing on the time after participants' knowledge of HIV diagnosis.

Methods

The authors analysed data from 4461 participants enrolled in the US Military Natural History Study cohort for GC or CT infection ≥6 months after their HIV-positive test.

Results

During a mean follow-up of 7.08 years, 482 (11%) participants acquired a GC or CT infection. Of these, 283 (6%) acquired a GC infection, 278 (6%) acquired a CT infection and 123 (3%) had multiple GC or CT infections during follow-up. Risk of GC or CT infection was significantly greater in those younger, male, African–American and with a history of GC or CT infection.

Conclusions

Frequent GC and CT diagnoses observed among members of this HIV-positive cohort indicate substantial ongoing risk behaviours that raise concerns for HIV transmission and underscore the need for continued screening to help identify and treat these sexually transmitted infections in this population.
Advertisements promoting human papillomavirus vaccine for adolescent boys: does source matter?: Figure 1
Authors: Pepper Jessica K , Reiter Paul L , McRee Annie-Laurie , Brewer Noel T
Published: January 2012

Objectives

Many parents recall hearing of human papillomavirus (HPV) vaccine through drug company advertisements. This study sought to examine whether parents accurately recall the source (ie, sponsor) of advertisements promoting HPV vaccine and the impact of drug company advertisements.

Methods

A US national sample of 544 parents of adolescent boys aged 11–17 participated in an online between-subjects experiment. Parents viewed an advertisement encouraging HPV vaccination for boys with a logo from a randomly assigned source. Parents rated trust, likability and motivation for vaccination while viewing the advertisement and later indicated who they believed sponsored it.

Results

Nearly half (43%) of parents who viewed a hypothetical advertisement containing a logo incorrectly identified the advertisement source. More parents correctly identified the source of drug company advertisements than advertisement from other sources (62% vs 25%, OR 4.93, 95% CI 3.26 to 7.46). The majority of parents who saw a logo-free advertisement believed a drug company created it (60%). Among parents who correctly identified the advertisement source, drug company advertisements decreased motivation to vaccinate their sons, an association mediated by reduced liking of and trust in the advertisements.

Conclusions

Parents were more accurate in identifying drug company advertisements, primarily because they tended to assume any advertisement was from a drug company. Public health organisations may need to take special measures to ensure their messages are not perceived as sponsored by drug companies.
ANISOTROPIC POWER-LAW INFLATION FROM ROLLING TACHYONS
Authors: BHOWMICK SAMRAT , MUKHERJI SUDIPTA
Published: January 2012

We provide an explicit solution representing an anisotropic power-law inflation within the framework of rolling tachyon model. This is generated by allowing a non-minimal coupling between the tachyon and the world-volume gauge field on non-BPS D3 brane. We also show that this solution is perturbatively stable.
APPLYING k-SEPARABILITY TO COLLABORATIVE RECOMMENDER SYSTEMS
Authors: ALEXANDRIDIS GEORGIOS , SIOLAS GEORGIOS , STAFYLOPATIS ANDREAS
Published: January 2012

Most recommender systems have too many items to propose to too many users based on limited information. This problem is formally known as the sparsity of the ratings' matrix, because this is the structure that holds user preferences. This paper outlines a Collaborative Filtering Recommender System that tries to amend this situation. After applying Singular Value Decomposition to reduce the dimensionality of the data, our system makes use of a dynamic Artificial Neural Network architecture with boosted learning to predict user ratings. Furthermore we use the concept of k-separability to deal with the resulting noisy data, a methodology not yet tested in Recommender Systems. The combination of these techniques applied to the MovieLens datasets seems to yield promising results.
THE DESIGN OF A PROACTIVE PERSONAL AGENT FOR TASK MANAGEMENT
Authors: YORKE-SMITH NEIL , SAADATI SHAHIN , MYERS KAREN L. , MORLEY DAVID N.
Published: January 2012

Personal assistant agents capable of proactively offering assistance can be more helpful to their users through their ability to perform tasks that otherwise would require user involvement. This article characterizes the properties desired of proactive behavior by a personal assistant agent in the realm of task management and develops an operational framework to implement such capabilities. We present an extended agent architectural model that features a meta-level layer charged with identifying potentially helpful actions and determining when it is appropriate to perform them. The reasoning that answers these questions draws on a theory of proactivity that describes user desires and a model of helpfulness. Operationally, assistance patterns represent a compiled form of this knowledge, instantiating meta-reasoning over the agent's beliefs about its user's activities as well as over world state. The resulting generic framework for proactive goal generation and deliberation has been implemented as part of a personal assistant agent in the computer desktop domain.