bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and Transcriptome Analysis of Mycobacterium tuberculosis Persisters
Authors: Keren Iris , Minami Shoko , Rubin Eric , Lewis Kim
Published: June 2011

Tuberculosis continues to be a major public health problem in many parts of the world. Significant obstacles in controlling the epidemic are the length of treatment and the large reservoir of latently infected people. Bacteria form dormant, drug-tolerant persister cells, which may be responsible for the difficulty in treating both acute and latent infections. We find that in
Mycobacterium  tuberculosis
, low numbers of drug-tolerant persisters are present in lag and early exponential phases, increasing sharply at late exponential and stationary phases to make up ~1% of the population. This suggests that persister formation is governed by both stochastic and deterministic mechanisms. In order to isolate persisters, an exponentially growing population was treated with
d
-cycloserine, and cells surviving lysis were collected by centrifugation. A transcriptome of persisters was obtained by using hybridization to an Affymetrix array. The transcriptome shows downregulation of metabolic and biosynthetic pathways, consistent with a certain degree of dormancy. A set of genes was upregulated in persisters, and these are likely involved in persister formation and maintenance. A comparison of the persister transcriptome with transcriptomes obtained for several
in vitro
dormancy models identified a small number of genes upregulated in all cases, which may represent a core dormancy response.

IMPORTANCE
It is estimated that every third person on the planet is infected with
Mycobacterium tuberculosis
. The two major problems in controlling
M. tuberculosis
are the length of the treatment and the large reservoir of latently infected people. Dormant persister cells may be responsible for both problems. We find that
M. tuberculosis
produces persisters
in vitro
in a growth phase-dependent manner. Persisters were isolated from an exponentially growing population, and their transcriptome shows a distinct pattern of dormancy. These results give the first insight into
M. tuberculosis
persisters and point to possible mechanisms responsible for their formation.
Molecular epidemiology of strangles outbreaks in the UK during 2010
Authors: Parkinson N. J. , Robin C. , Newton J. R. , Slater J. , Waller A. S.
Published: June 2011

The sequence of the Streptococcus equi subspecies equi (S equi) M‐like protein (SeM) gene was determined for 105 isolates of S equi from strangles outbreaks in the UK during 2010 and compared with previous data from 2007 to 2008. Twenty‐three distinct alleles were identified, including 11 novel alleles. One allele giving rise to a putative truncated M protein was identified from the guttural pouch of an asymptomatic carrier. Allele 9 was the most prevalent, comprising 57.7 per cent of isolates, followed by allele 6 (10.3 per cent). Significant changes in allele prevalence were found between 2007, 2008 and 2010, with an increasing prevalence in SeM‐9‐related alleles and a corresponding decreasing prevalence in SeM‐6‐related alleles observed over the period (P<0.001). Geographical proximity of outbreaks caused by some uncommon alleles was apparent between 2007, 2008 and 2010.
STATISTICAL TESTS FOR SERIAL DEPENDENCE AND LAMINARITY ON RECURRENCE PLOTS
Authors: HIRATA YOSHITO , AIHARA KAZUYUKI
Published: June 2011

Although recurrence quantification analysis provides useful information about underlying dynamics, it cannot be used to obtain significance levels on its own. Therefore, we propose methods to determine significance levels of serial dependence and laminarity from plotted patterns of recurrence plots. We evaluate the probability of two recurrences with an assumption that these recurrences are statistically independent. By modeling the number of simultaneous recurrences with a binomial distribution, we obtain the significance levels of serial dependence and laminarity without generating surrogate data. Further, we apply the proposed methods to a real wind dataset and find that it has serial dependence and laminarity.
IDENTIFYING SPATIAL PATTERNS AND DYNAMICS OF CLIMATE CHANGE USING RECURRENCE QUANTIFICATION ANALYSIS: A CASE STUDY OF QINGHAI–TIBET PLATEAU
Authors: ZHAO Z. Q. , LI S. C. , GAO J. B. , WANG Y. L.
Published: June 2011

The climate system is a prototypical nonlinear complex system exhibiting nonstationary temporal variation and complicated spatial patterns. One of the ideal locations for studying climate systems is the Qinghai–Tibet Plateau (QTP), which is considered an amplifier of global climate change. In this study, recurrence quantification analysis (RQA) was used to analyze the annual temperature series of 17 stations in different climate zones of the QTP, based on station observation data of daily temperature (minimum, maximum and mean) from 1961 to 2008. Spatial patterns and variation of RQA indices of Determinism (DET) and Kolmogorov (K2) entropy suggested that there are marked differences in temperature pattern in the QTP. Correlation analysis between RQA indices of temperature series and environmental factors, such as topographical variation and Normalized Difference Vegetation Index suggest that both the source and effect of climate complexity are nonlinear. Results of this study indicate that RQA measurement was indeed an efficient approach to analyze the dynamics of a climate system.
FILLING GAPS IN ECOLOGICAL TIME SERIES BY MEANS OF TWIN SURROGATES
Authors: FACCHINI ANGELO , MOCENNI CHIARA
Published: June 2011

This paper addresses the problem of reconstructing missing data in time series by the twin surrogates method. We consider a set of time series, collected by a sensor network, representing the same state variable measured at different locations of a spatially distributed system.

Assuming the presence of coherent dynamics among the available data, the method of twins is applied as an input–output model using the information provided by the complete time series for filling the incomplete recordings. The method is applied to the measurements of Dissolved Oxygen concentrations collected in the lagoon of Orbetello (Italy) and to time series obtained from the logistic chaotic map. Both cases show satisfactory performances in the reconstruction of missing data.
Molecular nanoarchitectures composed of porphyrins and carbon nanomaterials for light energy conversion
Authors: Hasobe Taku , Sakai Hayato
Published: June 2011

In this review, we report the recent advances in the construction of composite molecular nanoarchitectures of porphyrins and nanoscale carbon materials such carbon nanotubes (CNT), graphenes and polycyclic aromatic hydrocarbons (PAH) for photoinduced electron transfer and light energy conversion. First, we state novel single-wall carbon nanotubes (SWCNT)-driven aggregation of protonated porphyrins to produce supramolecular assemblies in the form of macroscopic bundles. Then, photoinduced electron transfer in self-assembled single-walled carbon nanotube (SWCNT)/zinc porphyrin (ZnP) hybrids utilizing (7,6)- and (6,5)-enriched SWCNTs having different band gaps is reported. Further, we discuss the structural and photoelectrochemical properties of porphyrin-based molecular assemblies of other carbon materials such as stacked-cup carbon nanotubes (SCCNT), carbon nanohorns (CNH) and graphenes. Finally, novel supramolecular patterning formation composed of triphenylene core-centered porphyrin hexamers for electronics is discussed.
GENERALIZED THERMOELASTIC WAVES IN MICROSTRETCH PLATES LOADED WITH FLUID OF VARYING TEMPERATURE
Authors: KUMAR S. , SHARMA J. N. , SHARMA Y. D.
Published: June 2011

In the present paper, the theory of generalized thermo-microstretch elasticity has been employed to study the propagation of straight and circular crested waves in microstretch thermoelastic plates bordered with inviscid liquid layers (or half-spaces), with varying temperature on both sides. The secular equations governing the wave motion in both rectangular and cylindrical plates have been investigated. The results in the case of thin (long wavelength) and thick (short wavelength) plates have also been obtained and discussed as special cases of this work. The secular equation in the case of microstretch coupled with thermoelastic, micropolar thermoelastic and thermoelastic plates can be obtained from the present analysis by an appropriate choice of relevant parameters. The results have been deduced and compared with the relevant publications available in the literature at the appropriate stages of this work. Finally, the analytical developments have been illustrated numerically for aluminum–epoxy-like material sandwiched in the inviscid liquid. The computer simulated results in respect of phase velocity, attenuation coefficient, specific loss factor of energy dissipation and relative frequency shift due to liquid layers on both sides of the plate are presented graphically.
STOCHASTIC STRUCTURAL MODAL ANALYSIS INVOLVING UNCERTAIN PARAMETERS USING GENERALIZED POLYNOMIAL CHAOS EXPANSION
Authors: SEPAHVAND K. , MARBURG S. , HARDTKE H.-J.
Published: June 2011

In this paper, the application of generalized polynomial chaos expansion in stochastic structural modal analysis including uncertain parameters is investigated. We review the theory of polynomial chaos and relating error analysis. A general formulation for the representation of modal problems by the polynomial chaos expansion is derived. It shows how the modal frequencies and modal shapes are influenced by the parameter uncertainties. The key issues that arise in the polynomial chaos simulation of modal analysis are discussed for two examples: a discrete 2-DOF system and continuous model of a microsensor. In both cases, the polynomial chaos expansion is used for the approximation of uncertain parameters, eigenfrequencies and eigenvectors. We emphasize the accuracy and time efficiency of the method in estimation of the stochastic modal responses in comparison with the sampling techniques, such as the Monte Carlo simulation.
Oceanic lithospheric mantle beneath the continental crust of the Chinese Altai
Authors: Yuan Chao , Sun Min , Xu Yigang , Zhao Guochun , Xiao Wenjiao , Long Xiaoping , Yin Jiyuan
Published: June 2011

Although subduction–accretion is proposed as a major regime in making new continental crust, how the lithospheric mantle forms remains unclear. Formed after the closure of the Palaeo-Asian Ocean, the Ashele basalt shows normal mid-ocean ridge basalt (N-MORB)-like characteristics with light REE-depleted patterns and extremely low contents of high field strength elements. The low Zr/Y and Nb/Y ratios of the basalt are significantly different from those of asthenosphere-derived melts, and the excess Eu and Sr suggest that the basalt was probably derived from accreted oceanic lithospheric mantle. The presence of the N-MORB-like terrestrial basalt implies that subduction–accretion is an effective mechanism in building the refractory lithospheric mantle of Phanerozoic continents.

Supplementary material:

A photograph of the outcrop, and age and geochemical data are available at
http://www.geolsoc.org.uk/SUP18464
.
Widespread Cretaceous inversion event in northern Spain: evidence from subsurface and palaeomagnetic data
Authors: Soto Ruth , Casas-Sainz Antonio M. , Villalaín Juan J.
Published: June 2011

In this paper we present geological evidence of a mid-Cretaceous inversion event in the Polientes basin (northern Iberian plate) based on geological data. Analysis of seismic profiles across the basin indicates that this tectonic event resulted in the uplift of the basin depocentre and the formation of an upright gentle anticline before Cenomanian times. The presence of a pre-Alpine, syntectonic remagnetization in the Jurassic and Lower Cretaceous rocks of the Polientes basin allows us to define the geometry of the basin at the time between this early inversion event and the main Alpine compressional period. The early inversion in the Polientes basin is consistent with a transpressional tectonic setting, contemporaneous with the left-lateral strike-slip movement of Iberia with respect to Europe. This study shows the successful use of two approaches to unravel the geodynamic scenario of the northern Iberian plate during the Cretaceous, which was later obliterated during the Tertiary Pyrenean orogeny.
Structure and
40
Ar/
39
Ar thermochronology of an ultrahigh-pressure transition in western Norway
Authors: Young D.J. , Hacker B.R. , Andersen T.B. , Gans P.B.
Published: June 2011

The Nordfjord region of western Norway hosts an archetypal subducted crustal section, underpinned by ultrahigh-pressure (UHP) eclogite, overlain by Devonian sediments, and cored by a crustal-scale extensional shear zone. Structural mapping reveals two distinct displacement zones that played different roles during the formation and exhumation of this section: (1) the Sandane Shear Zone is a NW-dipping, amphibolite-facies, high-strain zone near the base of the eclogite-bearing crust that separates allochthonous units from underlying crystalline basement; it may have originated during early thrusting, but was overprinted by top-to-the-west extensional fabrics at lower crustal depths; (2) structurally above this, the Nordfjord–Sogn Detachment Zone is a top-to-the-west, amphibolite- to greenschist-facies detachment shear zone within allochthonous units that defines the upper boundary of the eclogitized crust and was responsible for exhumation through at least mid-crustal depths. Muscovite
40
Ar/
39
Ar ages suggest that amphibolite-facies deformation below the Nordfjord–Sogn Detachment was mostly finished by
c
. 397 Ma, whereas muscovite ages from the deeper parts of the UHP domain indicate that it cooled after 390 Ma. During exhumation through the middle crust, west-directed stretching was accompanied by north–south folding. Late sinistral transpressional faulting in the middle to upper crust truncated the earlier folds and shear zones.

Supplementary material:

Complete
40
Ar/
39
Ar data and a summary geological map of the Nordfjord region are available at
http://www.geolsoc.org.uk/SUP18460
.
The emplacement of the Palaeogene Mourne Granite Centres, Northern Ireland: new results from the Western Mourne Centre
Authors: Stevenson C.T.E. , Bennett N.
Published: June 2011

There is a basic assumption that the upper crustal point of magma emplacement overlies the point where magma was generated. This contribution discusses the concept of lateral magma movement in the upper crust based on the Mourne Granite Centres, Northern Ireland. We report anisotropy of magnetic susceptibility fabric data from the Western Mourne Centre that indicate SSW to NNE inflow in this centre, parallel to the Eastern Centre. This suggests that these two centres share a common feeder zone outside the Mourne area
c
. 20 km to the south, coincident with a
c
. 50 mGal gravity anomaly that may be caused by an unexposed mafic pluton. The links between mafic and felsic magmas in this region, and the coincidence of the projected Mourne granite feeder zone and the possible buried mafic pluton lead to a model in which the Mourne granites were emplaced in a NNE direction as two gently dipping sheets from this unexposed mafic body. From this we develop a model that incorporates existing geophysics and known tectonic framework and involves an interconnected upper crustal network of Early Palaeogene igneous intrusion pathways fed from a common tectonically controlled, and probably long-lived, deeply penetrating feeder zone.

Supplementary material:

Anisotropy of magnetic susceptibility data, thermomagnetic analyses and a thin section showing magnetite in biotite cleavage are available at
http://www.geolsoc.org.uk/SUP18458
.
Insights of dyke emplacement mechanics from detailed 3D dyke thickness datasets
Authors: Kavanagh J.L. , Sparks R.Stephen J.
Published: June 2011

Dyke thickness datasets offer new insights into the detailed 3D geometry of dyke swarms and an exceptional opportunity to evaluate theoretical emplacement models. The Swartruggens kimberlite dyke swarm extends over 7 km along strike and intrudes a dolerite, quartzite, shale and andesitic lava succession. The Star kimberlite dykes cut shales and sandstones, intersect a large dolerite sill and extend 15 km along strike. Both dyke swarms comprise anastomosing en echelon segments, each several hundred metres long. In total 1532 Swartruggens dyke thickness measurements were taken, to 750 m below the surface over a 250 m depth range, and 3354 Star dyke thickness measurements were taken over a 520 m depth range. The Swartruggens dyke thicknesses are 0.05–1.95 m (mean 0.64 m), whereas the Star kimberlites range from <0.01 to 1.6 m thick (mean 0.40 m). Two-dimensional models of elastic cracks in a homogeneous, isotropic material subject to constant magmatic over-pressure poorly describe the dyke thickness variation, which is complex and varies along both breadth and length. The Swartruggens dyke segments thicken toward their terminations along strike, which represent regions where stresses were focused. Towards the surface, rock deformation is increasingly difficult to recover as inelastic processes such as host-rock brecciation, stoping, and magma solidification become important.
Mid- to Late Cambrian docking of the Río de la Plata craton to southwestern Gondwana: age constraints from U–Pb SHRIMP detrital zircon ages from Sierras de Ambato and Velasco (Sierras Pampeanas, Argentina)
Authors: Verdecchia Sebastián O. , Casquet Cesar , Baldo Edgardo G. , Pankhurst Robert J. , Rapela Carlos W. , Fanning Mark , Galindo Carmen
Published: June 2011

The Early Palaeozoic stratigraphy and tectonic history of the Eastern Sierras Pampeanas of central Argentina are complicated by metamorphism and deformation resulting from the Pampean (545–510 Ma) and Famatinian (490–440 Ma) orogenies. We report U–Pb sensitive high-resolution ion microprobe dating of detrital zircons in two metasedimentary successions exposed at Quebrada de La Cébila (
c
. 28°45'S, 66°25'W): the Ambato and the La Cébila metamorphic complexes. The Ambato zircons record age peaks corresponding to Pampean (530 ± 10 Ma), Brasiliano (
c
. 570 and
c
. 640 Ma), Grenville (
c
. 950 to
c
. 1025 Ma) and minor Neoarchaean ages. Similar peaks are also apparent in the La Cébila sample but it additionally contains Palaeoproterozoic zircons (
c
. 2.1 Ga) corresponding to the age of the Rio de la Plata craton, from which they are considered to have been sourced. Our interpretation is that the protolith of the Ambato complex was deposited prior to juxtaposition with the craton and is older than the Early Ordovician La Cébila metamorphic complex. We infer that the craton reached its current relative position in the Mid- to Late Cambrian, after the main Pampean tectonothermal event (530–520 Ma) and before deposition of the La Cébila protolith and the Achavil Formation (Sierra de Famatina), which contain comparable detrital zircon populations.
The growth of the Zimbabwe Craton during the late Archaean: an ion microprobe U–Pb zircon study
Authors: Rollinson Hugh R. , Whitehouse Martin
Published: June 2011

U–Pb zircon ages obtained by ion microprobe are presented for late Archaean granitoids from the Zimbabwe Craton and the North Marginal Zone of the Limpopo Belt. Similar ages of crust formation in the felsic gneisses of the Zimbabwe Craton and the felsic granulites of the North Marginal Zone support the view, previously argued on geological grounds, that they represent the middle and lower crustal layers respectively of the Zimbabwe Craton. Zircons from the southern margin of the Zimbabwe Craton and the northern part of the North Marginal Zone contain old cores, confirming the presence of an old (
c
. 3.5 Ga) nucleus to the Zimbabwe Craton and indicating that the areal extent of this old nucleus is greater than has been hitherto supposed. Thus late Archaean crustal growth involved both the reworking of and the addition of new magmas to this old crustal nucleus. At 2.7 Ga crustal growth was contemporaneous with plume volcanism in the greenstone belts. In contrast, crustal growth at 2.74, 2.67, 2.64 and ?2.62 Ga was focused at the margins of the ‘old craton' and may be related to Andean style continental margin magmatism. Lower crustal melting at 2.61–2.59 Ga led to the emplacement of granitoids in the upper crust.

Supplementary material:

A summary of previously published U–Pb zircon geochronology for the Zimbabwe Craton and the North Marginal Zone of the Limpopo Belt, field relationships and sample localities for the samples used in this study, and U–Th–Pb secondary ionization mass spectrometry data are available at
www.geolsoc.org.uk/SUP18466
.
Structural controls on mud volcano vent distributions: examples from Azerbaijan and Lusi, east Java
Authors: Roberts Katie S. , Davies Richard J. , Stewart Simon A. , Tingay Mark
Published: June 2011

Structural mapping, nearest neighbour and two-point azimuth statistical analysis of mud volcano vent distributions from nine examples in Azerbaijan and the Lusi mud volcano in east Java are described. Distributions are non-random, forming alignments subparallel to faults within anticlines, ring faults, conjugate faults and detachment faults; this finding confirms a spatial relationship and supports a model for subsurface flow along these features as well as showing fractionation at depth. As fracture and fault orientations are related to structures such as anticlines and the
in situ
stress state they are therefore predictable. We use vent distributions in Azerbaijan, where the structural geology is well constrained, to propose what controls the distribution of 169 vents at the Lusi mud volcano. This mud volcano system shows evidence for initial eruptions along a NE–SW trend, parallel to the Watukosek fault, changing to eruptions that follow east–west trends, subparallel to regional fold axes. Our analysis indicates that regions east and west of the Lusi mud volcano are more likely to be affected by new vents than those to the north and south, owing to probable onset of elongate caldera collapse within a 10 km diameter of the central vent.
Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat
Authors: Lin Yi , Wei Jie , Li Yuanyuan , Chen Jun , Zhou Zhao , Song Liqiong , Wei Zhengzheng , Lv Ziquan , Chen Xi , Xia Wei , Xu Shunqing
Published: June 2011

—Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg−1·day−1) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes.
Representation of comparison signals in cortical area MT during a delayed direction discrimination task
Authors: Lui Leo L. , Pasternak Tatiana
Published: June 2011

Visually guided behavior often involves decisions that are based on evaluating stimuli in the context of those observed previously. Such decisions are made by monkeys comparing two consecutive stimuli, sample and test, moving in the same or opposite directions. We examined whether responses in the motion processing area MT during the comparison phase of this task (test) are modulated by the direction of the preceding stimulus (sample). This modulation, termed comparison signal, was measured by comparing responses to identical test stimuli on trials when it was preceded by sample moving in the same direction (S-trials) with trials when it was preceded by sample moving in a different direction (D-trials). The test always appeared in the neuron's receptive field (RF), whereas sample could appear in the RF or in the contralateral visual field (remote sample). With sample in-RF, we found three types of modulation carried by different sets of neurons: early suppression on S-trials and late enhancement, one on S-trials, and the other on D-trials. Under these conditions, many neurons with and without comparison effects exhibited significant, choice-related activity. Response modulation was also present following the remote sample, even though the information about its direction could only reach MT indirectly via top-down influences. However, unlike on trials with in-RF sample, these signals were dominated by response suppression, shedding light on the contribution of top-down influences to the comparison effects. These results demonstrate that during the task requiring monkeys to compare two directions of motion, MT responses during the comparison phase of this task reflect similarities and differences between the two stimuli, suggesting participation in sensory comparisons. The nature of these signals provides insights into the operation of bottom-up and top-down influences involved in this process.
Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia
Authors: Scheff Jeremy D. , Mavroudis Panteleimon D. , Calvano Steven E. , Lowry Stephen F. , Androulakis Ioannis P.
Published: June 2011

Heart rate variability (HRV), the quantification of beat-to-beat variability, has been studied as a potential prognostic marker in inflammatory diseases such as sepsis. HRV normally reflects significant levels of variability in homeostasis, which can be lost under stress. Much effort has been placed in interpreting HRV from the perspective of quantitatively understanding how stressors alter HRV dynamics, but the molecular and cellular mechanisms that give rise to both homeostatic HRV and changes in HRV have received less focus. Here, we develop a mathematical model of human endotoxemia that incorporates the oscillatory signals giving rise to HRV and their signal transduction to the heart. Connections between processes at the cellular, molecular, and neural levels are quantitatively linked to HRV. Rhythmic signals representing autonomic oscillations and circadian rhythms converge to modulate the pattern of heartbeats, and the effects of these oscillators are diminished in the acute endotoxemia response. Based on the semimechanistic model developed herein, homeostatic and acute stress responses of HRV are studied in terms of these oscillatory signals. Understanding the loss of HRV in endotoxemia serves as a step toward understanding changes in HRV observed clinically through translational applications of systems biology based on the relationship between biological processes and clinical outcomes.
Glycemic index differences of high-fat diets modulate primarily lipid metabolism in murine adipose tissue
Authors: van Schothorst Evert M. , Bunschoten Annelies , Verlinde Eline , Schrauwen Patrick , Keijer Jaap
Published: June 2011

A low vs. high glycemic index of a high-fat (HF) diet (LGI and HGI, respectively) significantly retarded adverse health effects in adult male C57BL/6J mice, as shown recently (Van Schothorst EM, Bunschoten A, Schrauwen P, Mensink RP, Keijer J. FASEB J 23: 1092–1101, 2009). The LGI diet enhanced whole body insulin sensitivity and repressed HF diet-induced body and white adipose tissue (WAT) weight gain, resulting in significantly reduced serum leptin and resistin levels and increased adiponectin levels. We questioned how WAT is modulated and characterized the molecular mechanisms underlying the glycemic index-mediated effects using whole genome microarrays. This showed that the LGI diet mainly exerts its beneficial effects via substrate metabolism, especially fatty acid metabolism. In addition, cell adhesion and cytoskeleton remodeling showed reduced expression, in line with lower WAT mass. An important transcription factor showing enhanced expression is PPAR-γ. Furthermore, serum levels of triglycerides, total cholesterol, and HDL- and LDL-cholesterol were all significantly reduced by LGI diet, and simultaneously muscle insulin sensitivity was significantly increased as analyzed by protein kinase B/Akt phosphorylation. Cumulatively, even though these mice were fed an HF diet, the LGI diet induced significantly favorable changes in metabolism in WAT. These effects suggest a partial overlap with pharmacological approaches by thiazolidinediones to treat insulin resistance and statins for hypercholesterolemia. It is therefore tempting to speculate that such a dietary approach might beneficially support pharmacological treatment of insulin resistance or hypercholesterolemia in humans.
Emerging Vaccine Informatics
Authors: He Yongqun , Rappuoli Rino , De Groot Anne S. , Chen Robert T.
Published: June 2011

Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictablein silicofrom genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protectionin vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning.
The Strategy of Combining Antidepressants in the Treatment of Major Depression: Clinical Experience in Spanish Outpatients
Authors: Martín-López Luis M. , Rojo Jose E. , Gibert Karina , Martín Juan Carlos , Sperry Lyli , Duñó Lurdes , Bulbena Antonio , Vallejo Julio
Published: June 2011

Introduction. The combination of antidepressants is a useful tool in the treatment of major depression, especially in cases where there is a partial response to antidepressant monotherapy. However, the use of this strategy is a matter of controversy, and its frequency of use in clinical practice is not clear. The aim of our study is to assess the use of antidepressants combination in Spain by reviewing three databases used between 1997 and 2001.Methods. Databases pertain to patients who are study subjects of major depression treatment. These databases are a result of studies performed in Spain and in which 550 psychiatrists participated. The total studied sample was comprised ofN=2,842patients, aged over 18, fitting DSM-IV criteria for Major Depressive Episode. The percentage of patients who received more than one antidepressant and the types of combinations used was described. Subsequently, a comparative study between the group which received a combination of antidepressants (N=64) and the group which received antidepressant monotherapy (N=775) was performed.Results. 27.1% of patients were on antidepressive monotherapy treatment, and 2.2% were on combination therapy. In the comparison of patients on combination therapy and monotherapy, there were significant differences only in episode duration (P=0.001). The most frequent combinations are SSRIs and tricyclic antidepressants. The active principle most widely combined is fluoxetine.Conclusions. The prevalence of use of antidepressant combination therapy is 2.2% of the global sample and 8.3% of treated patients. Other than duration of the depressive episode, no clinical characteristics exclusive to patients who received combination rather than monotherapy were found. Our study found that the most frequent combination is SSRIs + TCAs, also being the most studied.
Cecal Schwannoma: A Rare Cause of Gastrointestinal Bleeding in a Young Woman with Review of Literature
Authors: Kanneganti Kalyan , Patel Harish , Niazi Masooma , Kumbum Kavitha , Balar Bhavna
Published: June 2011

Schwannomas are rare mesenchymal tumors of the gastrointestinal tract. Occurrence of these tumors is more common in the stomach than in the large intestine. These tumors usually present as polypoidal intraluminal lesions and based on their location can present with rectal bleeding, colonic obstruction, and abdominal pain or defecation disorders. We present a case of a thirty-five-year-old woman who presented with abdominal pain and melena. Patient was diagnosed with a nonobstructing superficially ulcerated mass in the cecum on colonoscopy and required right hemicolectomy. A very rare pathological diagnosis of cecal schwannoma was made postoperatively.
An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines
Authors: Salvador Aiala , Igartua Manoli , Hernández Rosa Maria , Pedraz José Luis
Published: June 2011

The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune systemin vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.
Pregnancy and Delivery in Ehlers-Danlos Syndrome (Hypermobility Type): Review of the Literature
Authors: Dutta Indranil , Wilson Helen , Oteri Odiri
Published: June 2011

Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders which are divided into various distinguishable phenotypes. The type of EDS determines the potential obstetric complications. Due to the spectrum of clinical manifestation and overlap between phenotypes, there are no standardised obstetric management guidelines. Existing literature illustrates different obstetric management in hypermobility type of EDS, including uneventful term vaginal deliveries as well as preterm cesarean section deliveries. This paper discusses obstetric management of a woman with EDS hypermobility type. Cesarean section was deemed the most appropriate delivery method in this patient due to the possible complications including risk of joint dislocation and pain morbidity. No obstetric complications were experienced, and good maternal and neonatal outcomes were achieved.
Smoking and Pulmonary Fibrosis: Novel Insights
Authors: Samara Katerina D. , Margaritopoulos George , Wells Athol U. , Siafakas Nikolaos M. , Antoniou Katerina M.
Published: June 2011

The relationship between smoking and pulmonary fibrosis is under debate and intense investigation. The aim of this paper is to review the existing literature and identify further areas of research interest. Recently the negative influence of cigarette smoking on IPF outcome was highlighted, as non-smokers exhibit a better survival than ex-smokers and combined current- and ex-smokers. In patients with non-specific interstitial pneumonia (NSIP), a high prevalence of emphysema was recently demonstrated, providing an indirect support for a smoking pathogenetic hypothesis in NSIP. The coexistence of pulmonary fibrosis and emphysema has been extensively described in a syndrome termed combined pulmonary fibrosis and emphysema (CPFE). Connective tissue disorders (CTDs) are a group of autoimmune diseases which affect the lung, as one of the most common and severe manifestations. However, the relationship between smoking and autoimmune disorders is still conflicting. Rheumatoid arthritis results from the interaction between genetic and environmental factors, while the best established environmental factor is tobacco smoking. Smoking has also a negative impact on the response of the RA patients to treatment. The aforementioned smoking-related implications give rise to further research questions and certainly provide one more important reason for physicians to advocate smoking cessation and smoke-free environment.
Electronic Waste: A Growing Concern in Today′s Environment
Authors: Bhutta M. Khurrum S. , Omar Adnan , Yang Xiaozhe
Published: June 2011

Over the recent past, the global market of electrical and electronic equipment (EEE) has grown exponentially, while the lifespan of these products has become increasingly shorter. More of these products are ending up in rubbish dumps and recycling centers, posing a new challenge to policy makers. The purpose of this paper is to provide a review of the e‐Waste problem and to put forward an estimation technique to calculate the growth of e‐Waste.
Prognostic Factors for the Development of Biochemical Recurrence after Radical Prostatectomy
Authors: Kotb Ahmed F. , Elabbady Ahmed A.
Published: June 2011

Prostate cancer is one of the most common cancers in Western countries and is associated with a considerable risk of mortality. Biochemical recurrence following radical prostatectomy is a relatively common finding, affecting approximately 25% of cases. The aim of our paper was to identify factors that can predict the occurrence of biochemical recurrence, so the patient can be properly counselled pre- and postoperatively. Medline review of the literatures was done followed by a group discussion on the chosen publications and their valuable influence. Preoperative serum total PSA and clinical stage, together with prostatectomy Gleason grade, tumour volume, and perineural and vascular invasions, were the most important variables found to influence outcome.
Functional Diversity of the Schistosoma mansoni Tyrosine Kinases
Authors: Avelar Lívia G. A. , Nahum Laila A. , Andrade Luiza F. , Oliveira Guilherme
Published: June 2011

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs.
The Use of Telehealth Technology in Assessing the Accuracy of Self-Reported Weight and the Impact of a Daily Immediate-Feedback Intervention among Obese Employees
Authors: Pronk Nicolaas P. , Crain A. Lauren , VanWormer Jeffrey J. , Martinson Brian C. , Boucher Jackie L. , Cosentino Daniel L.
Published: June 2011

Objective.To determine the accuracy of self-reported body weight prior to and following a weight loss intervention including daily self-weighing among obese employees.Methods.As part of a 6-month randomized controlled trial including a no-treatment control group, an intervention group received a series of coaching calls, daily self-weighing, and interactive telemonitoring. The primary outcome variable was the absolute discrepancy between self-reported and measured body weight at baseline and at 6 months. We used general linear mixed model regression to estimate changes and differences between study groups over time.Results.At baseline, study participants underreported their weight by an average of 2.06 (se=0.33) lbs. The intervention group self-reported a smaller absolute body weight discrepancy at followup than the control group.Conclusions.The discrepancy between self-reported and measured body weight appears to be relatively small, may be improved through daily self-monitoring using immediate-feedback telehealth technology, and negligibly impacts change in body weight.
A Top-Down Clustering and Cluster-Tree-Based Routing Scheme for Wireless Sensor Networks
Authors: Bandara H. M. N. Dilum , Jayasumana Anura P. , Illangasekare Tissa H.
Published: June 2011

Cluster-based organization of large sensor networks is the basis for many techniques aimed at enhancing power conservation and network management. A backbone network in the form of a cluster tree further enhances routing, broadcasting, and in-network processing. We propose a configurable top-down cluster and cluster-tree formation algorithm, a cluster-tree self-optimization phase, a hierarchical cluster addressing scheme, and a routing scheme. Such self-organization makes it possible to effectively deliver messages to a sink as well as within the network. For example, a circular sensor field with a sink in the center can establish cross-links and circular-paths within the cluster tree to deliver messages through shorter routes while reducing hotspots and consequently increasing network lifetime. Cluster and cluster-tree formation algorithm is independent of physical topology, and does not require a priori neighborhood information, location awareness, or time synchronization. Algorithm parameters allow for formation of cluster trees with desirable properties such as controlled breadth/depth, uniform cluster size, and circular clusters. Characteristics of clusters, cluster tree, and routing are used to demonstrate the effectiveness of the schemes over existing techniques.
Truncated ErbB2 Expressed in Tumor Cell Nuclei Contributes to Acquired Therapeutic Resistance to ErbB2 Kinase Inhibitors
Authors: Xia Wenle , Liu Zuguo , Zong Rongrong , Liu Leihua , Zhao Sumin , Bacus Sarah S. , Mao Yubin , He Jia , Wulfkuhle Julia D. , Petricoin Emanuel F. , Osada Takuya , Yang Xiao-Yi , Hartman Zachary C. , Clay Timothy M. , Blackwell Kimberly L. , Lyerly Herbert K. , Spector Neil L.
Published: June 2011

ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185ErbB2). In addition to p185ErbB2, truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumors. The contribution of these truncated forms, specifically those expressed in tumor cell nuclei, to the development of therapeutic resistance to ErbB2 TKIs has not been previously shown. Here, we show that expression of a 95-kDa tyrosine phosphorylated form of ErbB2, herein referred to as p95L (lapatinib-induced p95) was increased in ErbB2+ breast cancer cells treated with potent ErbB2 TKIs (lapatinib, GW2974). Expressed in tumor cell nuclei, tyrosine phosphorylation of p95L was resistant to inhibition by ErbB2 TKIs. Furthermore, the expression of p95L was increased in ErbB2+ breast cancer models of acquired therapeutic resistance to lapatinib that mimic the clinical setting. Pretreatment with proteasome inhibitors blocked p95L induction in response to ErbB2 TKIs, implicating the role of the proteasome in the regulation of p95L expression. In addition, tyrosine phosphorylated C-terminal fragments of ErbB2, generated by alternate initiation of translation and similar in molecular weight to p95L, were expressed in tumor cell nuclei, where they too were resistant to inhibition by ErbB2 TKIs. When expressed in the nuclei of lapatinib-sensitive ErbB2+ breast cancer cells, truncated ErbB2 rendered cells resistant to lapatinib-induced apoptosis. Elucidating the function of nuclear, truncated forms of ErbB2, and developing therapeutic strategies to block their expression and/or activation may enhance the clinical efficacy of ErbB2 TKIs. Mol Cancer Ther; 10(8); 1367–74. ©2011 AACR.
Osteopontin Stimulates Preneoplastic Cellular Proliferation Through Activation of the MAPK Pathway
Authors: Luo Xianmin , Ruhland Megan K. , Pazolli Ermira , Lind Anne C. , Stewart Sheila A.
Published: June 2011

Alterations in the microenvironment collaborate with cell autonomous mutations during the transformation process. Indeed, cancer-associated fibroblasts and senescent fibroblasts stimulate tumorigenesis in xenograft models. Because senescent fibroblasts accumulate with age, these findings suggest that they contribute to age-related increases in tumorigenesis. Previously we showed that senescence-associated stromal-derived osteopontin contributes to preneoplastic cell growth in vitro and in xenografts, suggesting that it impacts neoplastic progression. Analysis of fibroblasts within premalignant and malignant skin lesions ranging from solar/actinic keratosis to squamous cell carcinoma revealed they express osteopontin. Given the stromal expression of osteopontin, we investigated how osteopontin impacts preneoplastic cell growth. We show that osteopontin promotes preneoplastic keratinocyte cellular proliferation and cell survival through the CD44 cell receptor and activation of the MAPK pathway. These data suggest that stromal-derived osteopontin impacts tumorigenesis by stimulating preneoplastic cell proliferation thus allowing expansion of initiated cells in early lesions. Mol Cancer Res; 9(8); 1018–29. ©2011 AACR.