bluuebunny/crossref_metadata_2025 huggingface dataset:
The VP8* Domain of Neonatal Rotavirus Strain G10P[11] Binds to Type II Precursor Glycans
Authors: Ramani Sasirekha , Cortes-Penfield Nicolas W. , Hu Liya , Crawford Sue E. , Czako Rita , Smith David F. , Kang Gagandeep , Ramig Robert F. , Le Pendu Jacques , Prasad B. V. Venkataram , Estes Mary K.
Published: April 2013

Naturally occurring bovine-human reassortant rotaviruses with a P[11] VP4 genotype exhibit a tropism for neonates. Interaction of the VP8* domain of the spike protein VP4 with sialic acid was thought to be the key mediator for rotavirus infectivity. However, recent studies have indicated a role for nonsialylated glycoconjugates, including histo-blood group antigens (HBGAs), in the infectivity of human rotaviruses. We sought to determine if the bovine rotavirus-derived VP8* of a reassortant neonatal G10P[11] virus interacts with hitherto uncharacterized glycans. In an array screen of >600 glycans, VP8* P[11] showed specific binding to glycans with the Galβ1-4GlcNAc motif, which forms the core structure of type II glycans and is the precursor of H type II HBGA. The specificity of glycan binding was confirmed through hemagglutination assays; GST-VP8* P[11] hemagglutinates type O, A, and B red blood cells as well as pooled umbilical cord blood erythrocytes. Further, G10P[11] infectivity was significantly enhanced by the expression of H type II HBGA in CHO cells. The bovine-origin VP4 was confirmed to be essential for this increased infectivity, using laboratory-derived reassortant viruses generated from sialic acid binding rotavirus SA11-4F and a bovine G10P[11] rotavirus, B223. The binding to a core glycan unit has not been reported for any rotavirus VP4. Core glycan synthesis is constitutive in most cell types, and modification of these glycans is thought to be developmentally regulated. These studies provide the first molecular basis for understanding neonatal rotavirus infections, indicating that glycan modification during neonatal development may mediate the age-restricted infectivity of neonatal viruses.
Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study
Authors: Bugiardini Raffaele , Eskola Markku , Huhtala Heini , Niemelä Kari , Karhunen Pekka , Miglio Rossella , Manfrini Olivia , Pizzi Carmine , Nikus Kjell
Published: April 2013

Objectives

To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS).

Design

Propensity score-matched cohort study from the database of the Tampere ACS registry.

Setting

A single academic hospital in Finland.

Participants

1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias.

Primary and secondary outcome measures

The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up.

Results

Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, µmol/l: 114.9±70.7). They also showed the highest C reactive protein (7.3±9.5 mg/l) levels.

Conclusions

Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity.
Evaluating the construct of triage acuity against a set of reference vignettes developed via modified Delphi method
Authors: Twomey Michèle , Wallis Lee A , Myers Jonathan E
Published: April 2013

Objective

To evaluate the construct of triage acuity as measured by the South African Triage Scale (SATS) against a set of reference vignettes.

Methods

A modified Delphi method was used to develop a set of reference vignettes. Delphi participants completed a 2-round consensus-building process, and independently assigned triage acuity ratings to 100 written vignettes unaware of the ratings given by others. Triage acuity ratings were summarised for all vignettes, and only those that reached 80% consensus during round 2 were included in the reference set. Triage ratings for the reference vignettes given by two independent experts using the SATS were compared with the ratings given by the international Delphi panel. Measures of sensitivity, specificity, associated percentages for over-triage/under-triage were used to evaluate the construct of triage acuity (as measured by the SATS) by examining the association between the ratings by the two experts and the international panel.

Results

On completion of the Delphi process, 42 of the 100 vignettes reached 80% consensus on their acuity rating and made up the reference set. On average, over all acuity levels, sensitivity was 74% (CI 64% to 82%), specificity 92% (CI 87% to 94%), under-triage occurred 14% (CI 8% to 23%) and over-triage 12% (CI 8% to 23%) of the time.

Conclusions

The results of this study provide an alternative to evaluating triage scales against the construct of acuity as measured with the SATS. This method of using 80% consensus vignettes may, however, systematically bias the validity estimate towards better performance.
Effects of different protein and glycemic index diets on metabolic profiles and substrate partitioning in lean healthy males
Authors: Munsters Marjet J. , Geraedts Maartje C. , Saris Wim H.
Published: April 2013

Dietary glycemic index (GI) and protein affects postprandial insulin responses and consequently 24 h glucose metabolism and therefore substrate partitioning. This study investigated the mechanistic effects of different protein and GI diets on 24 h profiles of metabolic markers and substrate partitioning. After 3 days of diet and physical activity standardization, 10 healthy male subjects (BMI: 22.5 ± 0.6 kg/m2) stayed in a respiration chamber 4 times for 36 h each time to measure substrate partitioning. All subjects randomly received four isoenergetic diets: a normal (15En%) dairy protein and low GI (<40 units) (NDP-LGI) diet; a high (25En%) dairy protein and low GI (HDP-LGI) diet; a normal vegetable protein and low GI (NVP-LGI) diet; or a normal dairy protein and high GI (>60 units) (NDP-HGI) diet. During the day, blood was sampled at fixed time points for the measurement of metabolic markers and satiety hormones. The HDP-LGI diet increased 24 h protein oxidation and sleeping metabolic rate (SMR) compared with the NDP-LGI diet (p < 0.002). No significant differences in 24 h carbohydrate and fat oxidation (day and night) were found between all intervention diets. Net incremental area under the curve (net iAUC) of 24 h plasma glucose decreased in the HDP-LGI diet compared with the NDP-LGI diet (p < 0.01), but no effect was observed on insulin levels. No difference in appetite profiles were observed between all intervention diets. The lower 24 h glycemic profile as a result of a high dairy protein diet did not lead to changes in 24 h substrate partitioning in lean healthy subjects with a normal insulin sensitivity.
A NEW LATTICE MODEL OF TWO-LANE TRAFFIC FLOW WITH THE CONSIDERATION OF MULTI-ANTICIPATION EFFECT
Authors: PENG GUANGHAN
Published: April 2013

In this paper, a new two-lane lattice model of traffic flow is proposed with the consideration of multi-anticipation effect. The linear stability condition of two-lane traffic is derived with the multi-anticipation effect term by linear stability analysis, which shows that the stable region enlarges with the number of multi-anticipation sites increasing. Nonlinear analysis near the critical point is carried out to obtain kink–antikink soliton solution of the mKdV equation with the multi-anticipation effect term. Numerical simulation also shows that the multi-anticipation effect can suppress the traffic jam efficiently with lane changing in two-lane system.
GRAVITY AND MIRROR GRAVITY IN PLEBANSKI FORMULATION
Authors: BENNETT D. L. , LAPERASHVILI L. V. , NIELSEN H. B. , TUREANU A.
Published: April 2013

We present several theories of four-dimensional gravity in the Plebanski formulation, in which the tetrads and the connections are the independent dynamical variables. We consider the relation between different versions of gravitational theories: Einsteinian, "topological," "mirror" gravities and gravity with torsion. We assume that our world, in which we live, is described by the self-dual left-handed gravity, and propose that if the Mirror World exists in Nature, then the "mirror gravity" is the right-handed antiself-dual gravity. In this connection, we give a brief review of gravi-weak unification models. In accordance with cosmological measurements, we consider the Universe with broken mirror parity. We also discuss the problems of cosmological constant and communication between visible and mirror worlds. Investigating a special version of the Riemann–Cartan space–time, which has torsion as an additional geometric property, we have shown that in the Plebanski formulation the ordinary and dual "topological" sectors of gravity, as well as the gravity with torsion, are equivalent. Equations of motion are obtained. In this context, we have also discussed a "pure connection gravity" — a diffeomorphism-invariant gauge theory of gravity. Loop Quantum Gravity is also briefly reviewed.
NATURALNESS IN A SIMPLE TWO HIGGS DOUBLET MODEL
Authors: JORA RENATA , NASRI SALAH , SCHECHTER JOSEPH
Published: April 2013

We study the implications of a criterion of naturalness for a simple two Higgs doublet model in the context of the discovery of a Higgs-like particle with a mass at 125 GeV. This condition which measures the amount of fine-tuning further limits the parameter space of this particular model and together with other phenomenological constraints lead to an allowed range of masses for the other neutral or charged Higgs bosons: H, a±, a0.
TOWARD A SUPERGRAVITY SPECTRAL ACTION
Authors: LÓPEZ J. L. , OBREGÓN O. , RYAN M. P. , SABIDO M.
Published: April 2013

A spectral action for a generalized bosonic sector corresponding to the Dirac operator of Euclidean supergravity is proposed. We calculate, up to a4, the Seeley–DeWitt coefficients in the expansion of the spectral action. It is in general not known how to construct a "matter fermionic" supersymmetric partner to the spectral action. The action we propose provides the effective action to be completed to get, at any order of the expansion, the corresponding supersymmetric action.
LINEAR TRANSFORMATIONS AND FLOQUET THEOREM FOR LINEAR IMPLICIT DYNAMIC EQUATIONS ON TIME SCALES
Authors: Du Nguyen Huu , Liem Nguyen Chi
Published: April 2013

This paper is concerned with Cauchy problem, Lyapunov transformations, Floquet and Lyapunov theorems for linear implicit dynamic equation AtxΔ= Btx with index-1 on time scales. The stability of this equation under the act of these Lyapunov transformations is also considered. The results are a unification and generalization of previous results for differential-algebraic equations and implicit difference systems.
FOURIER SINE AND COSINE TRANSFORMS ON BOEHMIAN SPACES
Authors: Roopkumar R. , Negrin E. R. , Ganesan C.
Published: April 2013

We construct suitable Boehmian spaces which are properly larger than [Formula: see text] and we extend the Fourier sine transform and the Fourier cosine transform more than one way. We prove that the extended Fourier sine and cosine transforms have expected properties like linear, continuous, one-to-one and onto from one Boehmian space onto another Boehmian space. We also establish that the well known connection among the Fourier transform, Fourier sine transform and Fourier cosine transform in the context of Boehmians. Finally, we compare the relations among the different Boehmian spaces discussed in this paper.
REGULAR ELEMENTS AND GREEN'S RELATIONS IN GENERALIZED TRANSFORMATION SEMIGROUPS
Authors: Mendes-Gonçalves Suzana , Sullivan R. P.
Published: April 2013

If X and Y are sets, we let P(X, Y) denote the set of all partial transformations from X into Y (that is, all mappings whose domain and range are subsets of X and Y, respectively). If θ ∈ P(Y, X), then P(X, Y) is a so-called "generalized semigroup" of transformations under the "sandwich operation": α * β = α ◦ θ ◦ β, for each α, β ∈ P(X, Y). We denote this semigroup by P(X, Y, θ) and, in this paper, we characterize Green's relations on it: that is, we study equivalence relations which determine when principal left (or right, or 2-sided) ideals in P(X, Y, θ) are equal. This solves a problem raised by Magill and Subbiah in 1975. We also discuss the same idea for important subsemigroups of P(X, Y, θ) and characterize when these semigroups satisfy certain regularity conditions.
SPECIAL SEMIGROUP AMALGAMS OF QUASI UNITARY SUBSEMIGROUPS AND OF QUASI NORMAL BANDS
Authors: Alam Noor , Khan Noor Mohammad
Published: April 2013

We show that the special semigroup amalgam with core as a quasi-unitary subsemigroup is embedded in a semigroup. We also show that the special semigroup amalgam within the class of left [right] quasinormal bands is embeddable in a left [right] quasinormal band.
A METHOD TO CONSTRUCT COQUASITRIANGULAR HOPF GROUP ALGEBRAS
Authors: Guo Shuangjian
Published: April 2013

We study the notion of Radford biproduct Hopf algebras in the Zunino category. As an application, we describe coquasitriangular structures on the Radford biproduct Hopf group algebras.
EXTENDABILITY OF SEMI-METRICS TO COMPACTIFICATIONS
Authors: Ramkumar S. , Ganesa Moorthy C.
Published: April 2013

The extendability of a continuous semi-metric on a Tychonoff space to a compactification of the space is discussed. The extended semi-metrics are continuous on compactifications, constructed through an axiomatic approach.
Geochemical assessment of arsenic toxicity in mine site along the proposed Mineral Tramway Project, Camborne, Cornwall
Authors: Bowell R. J. , Rees S. B. , Barnes A. , Prestia A. , Warrender R. , Dey B. M.
Published: April 2013

Many abandoned mine sites in Cornwall, UK, are characterised by elevated concentrations of arsenic which can cause contamination of surrounding soil and water resources. Often these sites have important historical and cultural value that requires access to be maintained, despite the potential toxicity of As. In west Cornwall, the potential for As contamination has been recognized within the Industrial World Heritage site focused on the Mineral Tramway and mining sites mines in the Gwennap and Camborne mining districts. The major abandoned mine sites, arsenic calciner and milling sites along a proposed tourist route in this area have been assessed for As toxicity and bioavailability taking into account the proximity of footpaths to areas of potential contamination.

Arsenic concentrations up to 3.3% were found in soils along the proposed footpaths and exposed mine spoil, with 55% of all total As values above the UK criteria for contaminated industrial soil of 640 mg/kg in surface soil. Using a Physiologically Based Extraction Test (PBET), the maximum amount of As observed to be bioavailable varied from 4 mg/kg through to a maximum of 9,000 mg/kg with a positive correlation between total As concentrations and bioavailable As concentrations. Mineralogical and selective extraction evaluation identified that the PBET-released As is not so much associated with total As concentrations, but is positively correlated to As held within the weak ‘ionic-held’ As, strongly adsorbed As, As associated with amorphous iron and calcium oxide phases, and poorly crystallized As(V) salts. The data reported here have been used to develop a risk assessment of the sites and propose management strategies to mitigate these risks.
Limestone caves and the Quaternary record of terrestrial tetrapods on islands
Authors: McFarlane Donald A.
Published: April 2013

The potential for finding Quaternary tetrapod fossils on islands is governed by a combination of biodiversity, geology, fossil preservation, and time span of records. Islands with extensive limestone exposures are particularly well represented at low and middle latitudes, where biodiversity is potentially high, and the caves and karst fissures in these landscapes have proven to be rich reliquaries of the Quaternary fossil record. This is particularly apparent when we contrast limestone islands with volcanic islands in the Lesser Antilles; the latter present a serious deficiency in the fossil vertebrate record and an impediment to understanding the biogeography of the region. Caves and karst fissures are also ephemeral on geological time scales, and few tropical island sites are known that are older than the Last Interglacial. In Britain, important cave sites of Middle Pleistocene age are known, but are rare.
Large sulphur isotopic perturbations and oceanic changes during the Frasnian–Famennian transition of the Late Devonian
Authors: Chen Daizhao , Wang Jianguo , Racki Grzegorz , Li Hua , Wang Chengyuan , Ma Xueping , Whalen Michael T.
Published: April 2013

The Frasnian–Famennian transition of the Late Devonian was one of the most critical intervals in the Phanerozoic. Sulphur isotopic pairs of carbonate-associated sulphate and pyrite sulphide from coeval sections in South China and Poland reveal frequent perturbations of sulphur cycling during this time interval. These data suggest a sudden oceanic overturn during a rapid sea-level fall probably induced by jerky block tilting in the latest Frasnian. This event was followed by long-lasting photic-zone euxinia during a rapid sea-level rise in the earliest Famennian. Large increases in continental nutrient fluxes, and subsequent primary productivity and organic burial, could have greatly enhanced bacterial sulphate reduction, producing excessive sulphide through the water columns owing to iron depletion. Subsequently, rapid ventilation of oceanic basins occurred, during which direct aerobic oxidation of sulphide into sulphate predominated in bottom waters and even surface sediments with minimal fractionation. This oxygenation was probably induced by intensive climatic cooling and/or large-scale sea-level fall. The temporal coincidence of two extinction phases with the oceanic overturn and succeeding photic-zone euxinia suggests that these extreme oceanic events played an important role in the severe biotic crisis. Furthermore, photic-zone euxinia coupled with subsequent climatic cooling may have delayed post-extinction recovery of some taxa.

Supplementary materials:

Two supplementary tables (S1 and S2) indicating pyrite and CAS contents and sulphur isotopic results (δ
34
S
CAS
, δ
34
S
py
and Δ
34
S) across the F-F boundary at Fuhe, South China and Kowala, Poland, respectively, and a supplementary figure showing systematic sulphur isotopic variations across the F-F boundary and their correlations between the two studied sections are available at
www.geolsoc.org.uk/SUP18593
.
Climatic oscillations stall vegetation recovery from K/Pg event devastation
Authors: Jolley D. W. , Daly R. , Gilmour I. , Kelley S.P.
Published: April 2013

Sedimentary rocks filling the Boltysh meteorite crater preserve an expanded record of post Cretaceous–Palaeogene (K/Pg) event vegetation destruction and subsequent floral recolonization. A post-destruction barren zone is succeeded by a fern spore spike recording the initial recovery vegetation. The Boltysh fern spore spike is divisible into two phases. Phase 1 is characterized by low abundances of fern spores, whereas the overlying Phase 2 has high fern spore abundances and contains common palm pollen. Comparison of the Boltysh Phase 2 fern spore spike with other palynological records shows strong similarities to the immediately post K/Pg boundary record of the Western Interior, North America. Variation in the composition of the Boltysh palynofloras has been used to define four moisture availability cycles between the K/Pg boundary and the Dan-C2 negative carbon isotope excursion, a period of some 300 kyr. Early post K/Pg event vegetation community recovery followed a common seral successional pathway at rates seen in large igneous provinces, although enhanced by high moisture availability. Continued succession to the first true swamp community was at a considerably slower tempo. The post K/Pg event vegetation recovery was therefore retarded by lack of moisture availability, extending the apparent period of recovery.
Tectonosedimentary evidence in the Tunisian Atlas, Bou Arada Trough: insights for the geodynamic evolution and Africa–Eurasia plate convergence
Authors: Ben Chelbi Mohamed , Kamel Samir , Harrab Salah , Rebaï Noemen , Melki Fetheddine , Meghraoui Mustapha , Zargouni Fouad
Published: April 2013

The Bou Arada Trough is an east–west-oriented structure located 80 km SW of Tunis, characterizing the central Tunisian Atlas. This trough is filled by a thick Quaternary sand and clay series and is bordered by complex systems of folds generally trending NE–SW. Contacts between the Bou Arada Trough and the neighbouring folds are accommodated by NE–SW- and NW–SE-oriented faults. In contrast to the other troughs of the Tunisian Atlas, which are related to the Pliocene–Quaternary orogenic period, the geodynamic evolution of the Bou Arada Trough began in the Maastrichtian and has continued until the present day. Structural, tectonosedimentary and seismic data analyses are undertaken in the study area to better understand the evolutionary scenario of this trough. The results obtained show that the Bou Arada Trough is fragmented into three NW–SE-oriented sub-basins and records a continuous history of downthrow. Indeed, during extensional to transtensional regimes, this trough has evolved in response to the two networks of perpendicular fractures whereas during compressive to transpressive periods, the collapse of the Bou Arada Trough has been induced by a pull-apart mechanism using the same network of faults but with a strike-slip movement. The Bou Arada Trough thus preserves a record of the convergence between the European and African plates since the Maastrichtian.
An emerging palaeoceanographic ‘missing link’: multidisciplinary study of rarely recovered parts of deep-sea Santonian–Campanian transition from Shatsky Rise
Authors: Ando A. , Woodard S. C. , Evans H. F. , Littler K. , Herrmann S. , Macleod K. G. , Kim S. , Khim B.-K. , Robinson S. A. , Huber B. T.
Published: April 2013

The Cretaceous deep-sea record of the Santonian–Campanian transition is commonly interrupted by an extensive unconformity (representing <10 Myr of hiatus). The resultant palaeoceanographic gap can now be partly bridged by a recent short core of pelagic ooze from Shatsky Rise (Integrated Ocean Drilling Program (IODP) Site U1348), with precise multidisciplinary age constraints developed herein. New oxygen isotope data from very well-preserved benthic foraminifera, together with accurately compiled comparable benthic data from previous Pacific deep-sea sections, exhibit a large (
c
. +1‰) early Campanian shift. We propose the Santonian–Campanian climatic transition was not gradual but was the first major cooling step after sustained mid-Cretaceous hothouse conditions.

Supplementary material:

Detailed analytical methods including biostratigraphic notes and Sr isotopic chronology, supplementary figures (locality map; additional geochemical, isotopic and micropalaeontological results; palaeomagnetic results; global Sr isotope compilation and age model; benthic foraminiferal stable isotope compilation), tables of microfossil occurrences and numerical data are available at
http://www.geolsoc.org.uk/SUP18598
.
Using 3D seismic data to map shallow-marine geohazards: a case study from the Santos Basin, Brazil
Authors: Sharp Andy , Badalini Gianluca
Published: April 2013

This paper documents a study that used high quality, conventionally processed, speculative 3D seismic data for two specific purposes: first, to identify and avoid any health, safety, security and environmental (HSSE) issues regarding the water bottom and, secondly, to avoid shallow (<1 s below the mud line) geohazards when drilling the wells. The study integrated existing legacy well data, new 3D data from the BM-S-52 concession and a targeted programme of water-bottom grab samples from the BM-S-52 concession, Santos Basin, offshore Brazil. Two aspects of the analysis are described: the first addresses the problem and solution adopted for characterizing the water-bottom environment in this area; the second addresses the interpretation of the data for shallow geohazards.

The results of this case study have been accepted by the regulatory authorities as representing sufficient evidence of risk evaluation that no further dedicated site-survey data acquisition is required. This has led to savings in time and in costs which would otherwise have been expended on deep-water site-survey campaigns. Furthermore, the use of 3D seismic data for well-location planning brings benefits in improved imaging of the near-mud-line geology, full coverage over the whole concession, operational flexibility for changing well location and timely availability of data. The analysis workflow may also be applicable in other, similar deep-water areas.
Aspects of water well design and construction in confined Chalk overlain by Basal Sands in the London Basin with particular reference to sand ingress
Authors: Charalambous A. N. , Burnet B. R. , Jones M. A.
Published: April 2013

The Palaeocene Basal Sands of the London Basin are usually in hydraulic continuity with the underlying Cretaceous Chalk aquifer. They are a minor aquifer rarely utilized for water supply. Instead, production wells are completed in the Chalk aquifer, which provides the bulk of the water. The conventional well design is for cemented casing to extend into the top few metres of the Chalk, with the rest of the Chalk section below left unlined (open hole). Although this has generally proved to be successful, there have been occasions where failures have occurred owing to sand entering the wells from the Basal Sands. The pathways are not always evident, but can include fractures in the Chalk, damaged casings or poor grout seals. Setting casings deep into the Chalk does reduce the risk of sand ingress, but yields may be diminished. In some cases, screening of the Basal Sands and the very top part of the Chalk has been used as an alternative. Detailed data from geological and geophysical logs can greatly assist in the design process, and the risk of sand ingress can be reduced by following good drilling and construction practice and ensuring that casings have been properly grouted. In this paper the terms wells, production wells, boreholes and water supply boreholes are used interchangeably.
Reflections on the residual strength of clay soils, with special reference to bedding-controlled landslides
Authors: Bromhead Edward Nicholas
Published: April 2013

This Glossop Lecture is about landslides and their slip surfaces at residual strength in clays. Particularly in southern England, but also elsewhere, landslides in infrastructure cuttings and many natural slopes are commonly found to be slowly moving compound landslides with a component of their basal shear surfaces following a particular bed (or ‘slide-prone horizon’). A selection of both historical and modern case records of this type of landslide are presented briefly. The geotechnical conditions that give rise to this occurrence are discussed, and the dominant factor relates to the dip of the strata, which must be of low inclination for the landslide mass to remain in place over the critical clay bed in the geological sequence after sliding has been initiated. Observations of the slip surfaces in the field lead to the conclusion that the bedding-controlled elements of this type of landslide develop along thin,
slide-prone
or
slide-susceptible
, horizons in the bedding. The question of what caused the formation of those horizons in the first place is answered by putting forward two hypotheses to explain why bedding-controlled slip surfaces form where they do, and considering the evidence for or against each of them. The conclusion is reached that despite the attractiveness of the concept that these slip surfaces form by a progressive failure mechanism at the junction of two materials with dissimilar properties, the alternative concept that they occur where there is a bed of slightly enhanced smectite content better fits the observations. The mechanisms for such local changes in clay mineralogy are linked to inputs of volcanic ash at the time of deposition. Definitive proof of concept is, however, lacking, but taking into account how clay sediments are deposited in sedimentary basins, this paper makes suggestions for future lines of enquiry. Even now, nearly a half-century after Skempton’s seminal Rankine Lecture that introduced the concept of residual strength of clays to the wider geotechnical profession, the corpus of data is rather limited. Some of the datasets are shown to exhibit remarkable similarities, and the implications of this tend to support the preferred explanation of the origin of slide-prone horizons.
Relative contributions of the thalamus and the paraventricular nucleus of the hypothalamus to the cardiac sympathetic afferent reflex
Authors: Xu Bo , Zheng Hong , Patel Kaushik P.
Published: April 2013

The cardiac sympathetic afferent reflex (CSAR) is induced by stimulating the cardiac sympathetic afferents, which evokes increases in sympathetic outflow and arterial pressure. In the present study, we attempted to identify the contribution of thalamic and hypothalamic nuclei involved in the CSAR. First, we observed that there was an increase in the number of c-Fos-labeled cells in the paraventricular nucleus (PVN) (190 ± 18 vs. 101 ± 15; P < 0.05), the paraventricular nucleus of the thalamus (PVT) (239 ± 23 vs. 151 ± 15; P < 0.05), and the mediodorsal thalamic nucleus (MD) (92 ± 9 vs. 63 ± 6; P < 0.05) following epicardial application of bradykinin (BK) compared with the control group ( P < 0.05). Second, using extracellular single-unit recording, we found 25% of spontaneously active neurons in the thalamus were stimulated by epicardial application of BK or capsaicin in intact rats. However, 24% of spontaneously active neurons in the thalamus were still stimulated by epicardial application of BK or capsaicin despite vagotomy and sinoaortic denervation. None of the neurons in the thalamus responded to baroreflex changes in arterial pressure, induced by intravenous injection of phenylephrine or sodium nitroprusside. The CSAR was inhibited by microinjection of muscimol or lidocaine into the PVN. However, it was not inhibited or blocked by microinjection of muscimol or lidocaine into the thalamus. Taken together, these data suggest that the thalamus, while activated, is not critical for autonomic adjustments in response to activation of the CSAR. On the other hand, the PVN is critically involved in the central pathway of the CSAR.
Perinatal taurine exposure affects adult oxidative stress
Authors: Lerdweeraphon Wichaporn , Wyss James Michael , Boonmars Thidarut , Roysommuti Sanya
Published: April 2013

Perinatal exposure to taurine (a β-amino acid) can alter adult physiological functions, including arterial pressure, hormonal and renal functions. Whereas perinatal taurine supplementation appears to have only minor effects on adult physiology, perinatal taurine depletion is associated with multiple adverse health effects, especially in animals postnatally exposed to other insults. New studies indicate that the mechanism for many of the physiological effects of taurine is related to the antioxidant activity of taurine. Thus the perinatal taurine depletion leads to oxidative stress in adult animals. It is likely that perinatal taurine depletion increases oxidative stress throughout life and that the early life taurine depletion leads to perinatal, epigenetic programming that impacts adult physiological function.
Impaired foot-force direction regulation during postural loaded locomotion in individuals poststroke
Authors: Liang Jing Nong , Brown David A.
Published: April 2013

Following stroke, hemiparesis results in impaired motor control. Specifically, inappropriate direction of foot-forces during locomotion has been reported. In our previous study ( Liang and Brown 2011 ) that examined poststroke foot-force direction during a seated, supported locomotor task, we observed that foot-force control capabilities were preserved poststroke. In this current study, we sought to better understand the mechanisms underlying the interaction of locomotor and postural control as an interactive mechanism that might interfere, poststroke, with appropriate foot-force generation. We designed an experiment in which participants performed biomechanically controlled locomotor tasks, under posturally challenged pedaling conditions while they generated mechanical output that was comparable to pedaling conditions without postural challenge, thus allowing us to monitor the strategies that the nervous system adopts when postural conditions were manipulated. We hypothesized that, with postural influence, individuals poststroke would generate inappropriate shear forces accompanied by inappropriate changes to muscle activity patterns when performing a mechanically controlled locomotor task, and would be exaggerated with increased postural loading. Sixteen individuals with chronic poststroke hemiparesis and 14 age-similar nonimpaired controls pedaled on a cycle ergometer under 1) seated supported and 2) nonseated postural loaded pedaling conditions, generating matched pedal force outputs of two effort levels. When we compared postural influence with seated pedaling, we observed increased magnitudes of forward-directed shear forces in the paretic legs associated with increased magnitude of leg extensor muscle activity, but not in controls. These findings provide evidence to support a model that describes independent controllers for posture and locomotion, but that the interaction between the two controllers is impaired poststroke.
Extensive excitatory network interactions shape temporal processing of communication signals in a model sensory system
Authors: Ma Xiaofeng , Kohashi Tsunehiko , Carlson Bruce A.
Published: April 2013

Many sensory brain regions are characterized by extensive local network interactions. However, we know relatively little about the contribution of this microcircuitry to sensory coding. Detailed analyses of neuronal microcircuitry are usually performed in vitro, whereas sensory processing is typically studied by recording from individual neurons in vivo. The electrosensory pathway of mormyrid fish provides a unique opportunity to link in vitro studies of synaptic physiology with in vivo studies of sensory processing. These fish communicate by actively varying the intervals between pulses of electricity. Within the midbrain posterior exterolateral nucleus (ELp), the temporal filtering of afferent spike trains establishes interval tuning by single neurons. We characterized pairwise neuronal connectivity among ELp neurons with dual whole cell recording in an in vitro whole brain preparation. We found a densely connected network in which single neurons influenced the responses of other neurons throughout the network. Similarly tuned neurons were more likely to share an excitatory synaptic connection than differently tuned neurons, and synaptic connections between similarly tuned neurons were stronger than connections between differently tuned neurons. We propose a general model for excitatory network interactions in which strong excitatory connections both reinforce and adjust tuning and weak excitatory connections make smaller modifications to tuning. The diversity of interval tuning observed among this population of neurons can be explained, in part, by each individual neuron receiving a different complement of local excitatory inputs.
Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors
Authors: Morris Erick J. , Jha Sharda , Restaino Clifford R. , Dayananth Priya , Zhu Hugh , Cooper Alan , Carr Donna , Deng Yongi , Jin Weihong , Black Stuart , Long Brian , Liu Jenny , DiNunzio Edward , Windsor William , Zhang Rumin , Zhao Shuxia , Angagaw Minilik H. , Pinheiro Elaine M. , Desai Jagdish , Xiao Li , Shipps Gerald , Hruza Alan , Wang James , Kelly Joe , Paliwal Sunil , Gao Xiaolei , Babu Boga Sobhana , Zhu Liang , Daublain Pierre , Zhang Ling , Lutterbach Bart A. , Pelletier Marc R. , Philippar Ulrike , Siliphaivanh Phieng , Witter David , Kirschmeier Paul , Bishop W. Robert , Hicklin Daniel , Gilliland D. Gary , Jayaraman Lata , Zawel Leigh , Fawell Stephen , Samatar Ahmed A.
Published: April 2013

The high frequency of activating RAS or BRAF mutations in cancer provides strong rationale for targeting the mitogen-activated protein kinase (MAPK) pathway. Selective BRAF and MAP-ERK kinase (MEK) inhibitors have shown clinical efficacy in patients with melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the extracellular signal-regulated kinase (ERK) signaling pathway. Here, we describe the identification and characterization of SCH772984, a novel and selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors. SCH772984 has nanomolar cellular potency in tumor cells with mutations in BRAF, NRAS, or KRAS and induces tumor regressions in xenograft models at tolerated doses. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in BRAF or MEK inhibitor–resistant models as well as in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. These data support the clinical development of ERK inhibitors for tumors refractory to MAPK inhibitors.

Significance: BRAF and MEK inhibitors have activity in MAPK-dependent cancers with BRAF or RAS mutations. However, resistance is associated with pathway alterations resulting in phospho-ERK reactivation. Here, we describe a novel ERK1/2 kinase inhibitor that has antitumor activity in MAPK inhibitor-naïve and MAPK inhibitor-resistant cells containing BRAF or RAS mutations. Cancer Discov; 3(7); 742–50. ©2013 AACR.

See related commentary by Nissan et al., p. 719

This article is highlighted in the In This Issue feature, p. 705
Liquid-Based Fine Needle Aspiration Biopsy of Papillary Thyroid Carcinoma: Logistic Regression Analysis with Conventional and New Cytomorphologic Features
Authors: Lee Jae Seok , Choi Hee-Seung , Park In Ae , Ryu Han Suk
Published: April 2013

Objective: The morphological interpretation of liquid-based preparation (LBP) remains a diagnostic challenge due to altered cytomorphology with technical reason. Only a few published accounts of the cytopathological features needed for diagnosis of papillary thyroid carcinoma (PTC) on an LBP exist. We utilized the SurePath LBP system to evaluate conventional and newly recognized cytomorphologic features on histologically confirmed PTC to identify their potent diagnostic significance compared to benign follicular neoplasm (BFN). Study Design: One-hundred and three cases of PTC and 84 BFNs were collected using preoperative fine needle aspiration biopsies. We evaluated and compared 16 cytomorphologic findings in PTC and BFN using an LBP. Results: Among the conventional criteria, papillary structures, fewer background colloids and macrophages, hobnail patterns (54.4% in PTC vs. 10.7% in BFN; p < 0.001) and swirling architecture (14.6% in PTC vs. 0% in BFN; p < 0.001; positive predictive value 100.0%) were significant diagnostic findings for PTC compared to BFN. The hobnail pattern was shown as a newly recognized strong diagnostic parameter for PTC (odds ratio 50.157, p < 0.001). Conclusion: The identified distinctive cytological criteria may be helpful in cases where conventional criteria for PTC are insufficient. Furthermore, application of these findings, along with classical criteria, may enhance the diagnostic accuracy of PTC by fine needle aspiration biopsy.
The Second Deletion Mutation in Exon 8 of EDA Gene in an XLHED Pedigree
Authors: Yin Wei , Ye Xiaoqian , Bian Zhuan
Published: April 2013

Background: X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by hypodontia, hypohidrosis, sparse hair and characteristic facial features and is caused by mutation in the ectodysplasin A (EDA) gene. Objective: In this study we report on a large Chinese XLHED family and investigate the molecular genetics of the defect. Methods: All individuals of the family were examined by clinical and radiographic examinations. The EDA gene was sequenced in the whole family and in 150 controls. Results: Three male patients had classic XLHED phenotype. A novel one-nucleotide deletion mutation (c.855delG) in exon 8 which caused premature termination of the polypeptide at amino acid 307 was confirmed. The mutant lost parts of the TNF domain may prevent transmission of the intracellular downstream signal. This was the second deletion mutation in exon 8 that was reported in a Chinese individual. Conclusions: Our findings suggested deletion mutations in exon 8 might be specific to the Chinese population.
Serous Cystadenoma of the Pancreas with Endoscopic Ultrasound Fine Needle Aspiration Biopsy and Surgical Correlation
Authors: Collins Brian T.
Published: April 2013

Objectives: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsies are commonly used to diagnose tumors of the pancreas. Serous cystadenoma (SCA) is a benign neoplasm that is uncommon and accounts for 1-2% of all pancreatic neoplasms. Study Design: Surgically excised SCAs with preoperative EUS FNA biopsy over a 10-year span were identified. Clinical data were collected, and cytomorphologic features reviewed retrospectively and correlated with surgical excision data. Original cytopathologic diagnoses and retrospectively reviewed cytomorphology features were recorded. Results: Seventeen patients were identified. Original EUS FNA interpretation included 1 ‘unsatisfactory', 9 ‘negative for malignancy' and 7 ‘atypical' or greater; however, all cases were categorized as benign/negative or nondiagnostic on retrospective review. The cases were hypocellular and possessed variable (rare to few-moderate) groups of bland cuboidal epithelial cells embedded in granular debris. Mucosal sampling was present (7/17) and cell blocks were acellular (5/17). Conclusion: This is a large series of pancreas SCAs subjected exclusively to EUS FNA biopsy where all cases had surgical excision confirmation. The 17 cases had hypocellular aspirate smears with the majority showing few bland epithelial cells; however, this can limit definitive diagnosis based on the cytomorphologic evaluation alone. The aspirate smear pattern of EUS FNA of SCAs of the pancreas supports a benign/negative or nondiagnostic categorization.
Remineralization of Artificial Enamel Lesions by Theobromine
Authors: Amaechi B.T. , Porteous N. , Ramalingam K. , Mensinkai P.K. , Ccahuana Vasquez R.A. , Sadeghpour A. , Nakamoto T.
Published: April 2013

Objective: This study investigated the remineralization potential of theobromine in comparison to a standard NaF dentifrice. Methods: Three tooth blocks were produced from each of 30 teeth. Caries-like lesion was created on each block using acidified gel. A smaller block was cut from each block for baseline scanning electron microscopy imaging and electron-dispersive spectroscopy (EDS) analysis for surface Ca level. A tooth slice was cut from each lesion-bearing block for transverse microradiography (TMR) quantification of baseline mineral loss (Δz) and lesion depth (LD). Then baseline surface microhardness (SMH) of each lesion was measured. The three blocks from each tooth were assigned to three remineralizing agents: (1) artificial saliva; (2) artificial saliva with theobromine (0.0011 mol/l), and (3) NaF toothpaste slurry (0.0789 mol/l F). Remineralization was conducted using a pH cycling model with storage in artificial saliva. After a 28-day cycle, samples were analyzed using EDS, TMR, and SMH. Intragroup comparison of pre- and posttest data was performed using t tests (p < 0.05). Intergroup comparisons were performed by post hoc multistep comparisons (Tukey). Results: SMH indicated significant (p < 0.01) remineralization only with theobromine (38 ± 32%) and toothpaste (29 ± 16%). With TMR (Δz/lD), theobromine and toothpaste exhibited significantly (p < 0.01) higher mineral gain relative to artificial saliva. With SMH and TMR, remineralization produced by theobromine and toothpaste was not significantly different. With EDS, calcium deposition was significant in all groups, but not significantly different among the groups (theobromine 13 ± 8%, toothpaste 10 ± 5%, and artificial saliva 6 ± 8%). Conclusion: The present study demonstrated that theobromine in an apatite-forming medium can enhance the remineralization potential of the medium.
Qualitative and Quantitative Issues of Lymph Nodes as Prognostic Factor in Colon Cancer
Authors: Veen Torhild , Nedrebø Bjørn S. , Stormark Kjartan , Søreide Jon Arne , Kørner Hartwig , Søreide Kjetil
Published: April 2013

For patients undergoing curative resections for colon cancer, the nodal status represents the strongest prognostic factor, yet at the same time the most disputed issue as well. Consequently, the qualitative and quantitative aspects of lymph node evaluation are thus being scrutinized beyond the blunt distinction between ‘node positive' (pN+) and ‘node negative' (pN0) disease. Controversy ranges from a minimal or ‘least-unit' strategy as exemplified by the ‘sentinel node' to a maximally invasive or ‘all inclusive' approach by extensive surgery. Ranging between these two extremes of node sampling strategies are factors of quantitative and qualitative value, which may be subject to modification. Qualitative issues may include aspects of lymph node harvest reflected by surgeon, pathologist and even hospital performance, which all may be subject to modification. However, patient's age, gender and genotype may be non-modifiable, yet influence node sample. Quantitative issues may reflect the balance between absolute numbers and models investigating the relationships of positive to negative nodes (lymph node ratio; log odds of positive lymph nodes). This review provides an updated overview of the current controversies and a state-of-the-art perspective on the qualitative and quantitative aspects of using lymph nodes as a prognostic marker in colon cancer.