bluuebunny/crossref_metadata_2025 huggingface dataset:
2H enrichment distribution of hepatic glycogen from2H2O reveals the contribution of dietary fructose to glycogen synthesis
Authors: Delgado Teresa C. , Martins Fátima O. , Carvalho Filipa , Gonçalves Ana , Scott Donald K. , O'Doherty Robert , Macedo M. Paula , Jones John G.
Published: December 2012

Dietary fructose can benefit or hinder glycemic control, depending on the quantity consumed, and these contrasting effects are reflected by alterations in postprandial hepatic glycogen synthesis. Recently, we showed that2H enrichment of glycogen positions 5 and 2 from deuterated water (2H2O) informs direct and indirect pathway contributions to glycogenesis in naturally feeding rats. Inclusion of position 6S2H enrichment data allows indirect pathway sources to be further resolved into triose phosphate and Krebs cycle precursors. This analysis was applied to six rats that had fed on standard chow (SC) and six rats that had fed on SC plus 35% sucrose in their drinking water (HS). After 2 wk, hepatic glycogenesis sources during overnight feeding were determined by2H2O administration and postmortem analysis of glycogen2H enrichment at the conclusion of the dark period. Net overnight hepatic glycogenesis was similar between SC and HS rodents. Whereas direct pathway contributions were similar (403 ± 71 μmol/g dry wt HS vs. 578 ± 76 μmol/g dry wt SC), triose phosphate contributions were significantly higher for HS compared with SC (382 ± 61 vs. 87 ± 24 μmol/g dry wt, P < 0.01) and Krebs cycle inputs lower for HS compared with SC (110 ± 9 vs. 197 ± 32 μmol/g dry wt, P < 0.05). Analysis of plasma glucose2H enrichments at the end of the feeding period also revealed a significantly higher fractional contribution of triose phosphate to plasma glucose levels in HS vs. SC. Hence, the2H enrichment distributions of hepatic glycogen and glucose from2H2O inform the contribution of dietary fructose to hepatic glycogen and glucose synthesis.
Neuropeptide Y and somatostatin inhibit insulin secretion through different mechanisms
Authors: Schwetz Tara A. , Ustione Alessandro , Piston David W.
Published: December 2012

Pancreatic β-cells regulate glucose homeostasis by secreting insulin in response to glucose elevation and G protein-coupled receptor (GPCR) activation. Neuropeptide Y (NPY) and somatostatin (SST) attenuate insulin secretion through Giactivation of Y1and SSTR1&5receptors, respectively. The downstream pathways altered by NPY and SST are poorly understood. Thus, we investigated these underlying mechanisms. NPY and SST increase cellular redox potential, suggesting that their inhibitory effect may not be mediated through metabolic inhibition. NPY does not affect intracellular calcium ([Ca2+]i) activity upon glucose stimulation, whereas SST alters this response. Gβγ-subunit inhibition by gallein attenuates insulin secretion but does not alter metabolism or [Ca2+]i. mSIRK-induced Gβγactivation does not modulate glucose metabolism but increases [Ca2+]iactivity and potentiates insulin release. Cotreatment with gallein and NPY or SST reduces insulin secretion to levels similar to that of gallein alone. mSIRK and NPY cotreatment potentiates insulin secretion similarly to mSIRK alone, whereas mSIRK and SST treatment decreases insulin release. The data support a model where SST attenuates secretion through Gβγinhibition of Ca2+activity, while NPY activates a Ca2+-independent pathway mediated by Gα. GPCR ligands signal through multiple pathways to inhibit insulin secretion, and determining these mechanisms could lead to novel diabetic therapies.
Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep
Authors: Gadhia Monika M. , Maliszewski Anne M. , O'Meara Meghan C. , Thorn Stephanie R. , Lavezzi Jinny R. , Limesand Sean W. , Hay William W. , Brown Laura D. , Rozance Paul J.
Published: December 2012

Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10–14 days during late gestation to target a 25–50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group ( P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) ( P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group ( P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing late-gestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell.
Nonequilibrium Gating of CFTR on an Equilibrium Theme
Authors: Jih Kang-Yang , Hwang Tzyh-Chang
Published: December 2012

Malfunction of cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC protein superfamily that functions as an ATP-gated chloride channel, causes the lethal genetic disease, cystic fibrosis. This review focuses on the most recent findings on the gating mechanism of CFTR. Potential clinical relevance and implications to ABC transporter function are also discussed.
Design of Wideband MIMO Car-to-Car Channel Models Based on the Geometrical Street Scattering Model
Authors: Avazov Nurilla , Pätzold Matthias
Published: December 2012

We propose a wideband multiple-input multiple-output (MIMO) car-to-car (C2C) channel model based on the geometrical street scattering model. Starting from the geometrical model, a MIMO reference channel model is derived under the assumption of single-bounce scattering in line-of-sight (LOS) and non-LOS (NLOS) propagation environments. The proposed channel model assumes an infinite number of scatterers, which are uniformly distributed in two rectangular areas located on both sides of the street. Analytical solutions are presented for the space-time-frequency cross-correlation function (STF-CCF), the two-dimensional (2D) space CCF, the time-frequency CCF (TF-CCF), the temporal autocorrelation function (ACF), and the frequency correlation function (FCF). An efficient sum-of-cisoids (SOCs) channel simulator is derived from the reference model. It is shown that the temporal ACF and the FCF of the SOC channel simulator fit very well to the corresponding correlation functions of the reference model. To validate the proposed channel model, the mean Doppler shift and the Doppler spread of the reference model have been matched to real-world measurement data. The comparison results demonstrate an excellent agreement between theory and measurements, which confirms the validity of the derived reference model. The proposed geometry-based channel simulator allows us to study the effect of nearby street scatterers on the performance of C2C communication systems.
Delayed Presentation of Traumatic Intraperitoneal Rupture of Urinary Bladder
Authors: Alhamzawi Hazim H. , Abdelrahman Husham M. , Abdelrahman Khalid M. , El-Menyar Ayman , Al-Thani Hassan , Latifi Rifat
Published: December 2012

Blunt injury of the urinary bladder is well known and usually associates pelvic fractures. Isolated bladder injury is a rare condition and on the other hand, delayed bladder perforation is an extremely rare entity. Herein, we described an unusual case of isolated delayed intraperitoneal bladder rupture that occurred on the third post injury day in a young male in the absence of free intraperitoneal fluid and pelvic fracture. The diagnostic workup, course and the need for surgical repair of the injury is presented.
Use of CAD/CAM in Esthetic Restoration of Badly Decayed Tooth
Authors: Haralur Satheesh B. , Al-Faifi Ali Hassan
Published: December 2012

Proper, intelligent use of materials and technology should be utilized for the benefit of the patient. This case report presents a patient with a badly broken premolar tooth demanding high esthetic all-ceramic restoration. Following multiple procedure tooth was restored with zirconia all ceramic restoration. Multiple procedures to save a tooth are a really worthy, in the interest of patients. Use of zirconia and CAD-CAM will help in saving many compromised tooth even in high-stress regions. This provides the patient a chance to have restorations, which are biomechanically superior in addition to being pleasing esthetically.
Trends in Ambulatory Prescribing of Antiplatelet Therapy among US Ischemic Stroke Patients: 2000–2007
Authors: Karve Sudeep , Levine Deborah , Seiber Eric , Nahata Milap , Balkrishnan Rajesh
Published: December 2012

Objective. Study objectives were to assess temporal trends and identify patient- and practice-level predictors of the prescription of antiplatelet medications in a national sample of ischemic stroke (IS) patients seeking ambulatory care.Methods. IS-related outpatient visits by adults were identified using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for the years 2000–2007. We assessed prescribing of antiplatelet medications using the generic drug code and drug entry codes in these data. Temporal trends in antiplatelet prescribing were assessed using the Cochran-Mantel-Haenszel test for trend.Results. We identified 9.5 million IS-related ambulatory visits. Antiplatelet medications were prescribed at 35.5% of visits. Physician office prescribing of the clopidogrel-aspirin combination increased significantly from 0.5% in 2000 to 22.0% in 2007 (P=0.05), whereas prescribing of aspirin decreased from 17.9% to 7.0% (P=0.50) during the same period.Conclusion. We observed a continued increase in prescription of the aspirin-clopidogrel combination from 2000 to 2007. Clinical trial evidence suggests that the aspirin-clopidogrel combination does not provide any additional benefit compared with clopidogrel alone; however, our study findings indicate that even with lack of adequate clinical evidence physician prescribing of this combination has increased in real-world community settings.
Spontaneous Resolution of Retinal Pigment Epithelial Detachments and Visual Improvement in Patient with MPGN II: A Case Report
Authors: Empeslidis T. , Imrani U. , Vardarinos A. , Menassa N. , Banerjee S.
Published: December 2012

A 31-year-old female suffering from membranoproliferative glomerulonephritis type II (MPGN II) presented to the Eye Casualty Department reporting a history of blurred and distorted vision. The patient appeared to have drusenoid retinal epithelial detachments and minimal intraretinal fluid. The subretinal deposits, basal lamina drusen, and pigment epithelial detachment appeared to resemble a “stars in the sky” picture with no symmetry between the eyes. The retinal pigment epithelial detachments improved and flattened over 18 month. and the best corrected visual acuity improved in the most affected eye. There was no evidence of neovascularization, and the intraretinal fluid disappeared spontaneously.
Using Mobile Health to Support the Chronic Care Model: Developing an Institutional Initiative
Authors: Nundy Shantanu , Dick Jonathan J. , Goddu Anna P. , Hogan Patrick , Lu Chen-Yuan E. , Solomon Marla C. , Bussie Arnell , Chin Marshall H. , Peek Monica E.
Published: December 2012

Background. Self-management support and team-based care are essential elements of the Chronic Care Model but are often limited by staff availability and reimbursement. Mobile phones are a promising platform for improving chronic care but there are few examples of successful health system implementation.Program Development. An iterative process of program design was built upon a pilot study and engaged multiple institutional stakeholders. Patients identified having a “human face” to the pilot program as essential. Stakeholders recognized the need to integrate the program with primary and specialty care but voiced concerns about competing demands on clinician time.Program Description. Nurse administrators at a university-affiliated health plan use automated text messaging to provide personalized self-management support for member patients with diabetes and facilitate care coordination with the primary care team. For example, when a patient texts a request to meet with a dietitian, a nurse-administrator coordinates with the primary care team to provide a referral.Conclusion. Our innovative program enables the existing health system to support ade novocare management program by leveraging mobile technology. The program supports self-management and team-based care in a way that we believe engages patients yet meets the limited availability of providers and needs of health plan administrators.
An Iterative Method for Problems with Multiscale Conductivity
Authors: Kim Hyea Hyun , Minhas Atul S. , Woo Eung Je
Published: December 2012

A model with its conductivity varying highly across a very thin layer will be considered. It is related to a stable phantom model, which is invented to generate a certain apparent conductivity inside a region surrounded by a thin cylinder with holes. The thin cylinder is an insulator and both inside and outside the thin cylinderare filled with the same saline. The injected current can enter only through the holes adopted to the thin cylinder. The model has a high contrast of conductivity discontinuity across the thin cylinder and the thickness of the layer and the size of holes are very small compared to the domain of the model problem. Numerical methods for such a model require a very fine mesh near the thin layer to resolve the conductivity discontinuity. In this work, an efficient numerical method for such a model problem is proposed by employing a uniform mesh, which need not resolve the conductivity discontinuity. The discrete problem is then solved by an iterative method, where the solution is improved by solving a simple discrete problem with a uniform conductivity. At each iteration, the right-hand side is updated by integrating the previous iterate over the thin cylinder. This process results in a certain smoothing effect on microscopic structures and our discrete model can provide a more practical tool for simulating the apparent conductivity. The convergence of the iterative method is analyzed regarding the contrast in the conductivity and the relative thickness of the layer. In numerical experiments, solutions of our method are compared to reference solutions obtained from COMSOL, where very fine meshes are used to resolve the conductivity discontinuity in the model. Errors of the voltage inL2norm followO(h)asymptotically and the current density matches quitewell those from the reference solution for a sufficiently small mesh sizeh. The experimental results present a promising feature of our approach for simulating the apparent conductivity related to changes in microscopic cellular structures.
Mesenchymal Hamartoma: Prenatal and Postnatal Diagnosis by Imaging
Authors: Martínez-Varea Alicia , Vila-Vives Jose María , Hidalgo-Mora Juan José , Abad-Carrascosa Antonio , Llorens-Salvador Roberto , Perales-Marín Alfredo
Published: December 2012

We present a case of a twin pregnancy in which one fetus developed a rapidly growing unilateral intrathoracic tumor. While a cystic adenomatoid malformation was suspected in the ultrasound scan, the magnetic resonance scan suggested a pulmonary blastoma or a bronchioalveolar carcinoma. Postnatal chest radiography and contrast-enhanced computed tomography of the affected newborn were performed, and it was ruled out the possibility of malignant origin. Finally, the anatomopathologic exam revealed the presence of a mesenchymal hamartoma in the chest wall. Nevertheless, parents refused any treatment for the newborn.
Regioselective Syntheses of 3-Benzyl-Substituted 7H-Thiazolo[3,2-a]pyrimidine-7-ones through Palladium-Catalyzed Heteroannulation of Acetylenic Compounds
Authors: Bakherad Mohammad , Gholipoor Farzaneh
Published: December 2012

An efficient synthesis of 3-benzyl-substituted 7H-thiazolo[3,2-a]pyrimine-7-ones in acetonitrile is accomplished via Pd- and Cu-catalyzed reaction of 2-mercaptopropargylpyrimidone with various aryl iodides in the presence of triethylamine as the base.
Molecular Networks Involved in the Immune Control of BK Polyomavirus
Authors: Girmanova Eva , Brabcova Irena , Klema Jiri , Hribova Petra , Wohlfartova Mariana , Skibova Jelena , Viklicky Ondrej
Published: December 2012

BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%–80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%–10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n=11), infected asymptomatic patients (n=9), and patients with BK virus nephropathy (n=10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E,CD68,CCR2,ICAM-1, andSKI) (P<0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g.,CD40/CD40L;P<0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.
Relativistic Corrections for Calculating Ionization Energies of One- to Five-Electron Isoelectronic Atomic Ions
Authors: Lang Peter F. , Smith Barry C.
Published: December 2012

We have previously proposed a simple empirical equation to reproduce the literature values of the ionization energies of one-electron to four-electron atomic ions with very good agreement. However, we used a potential energy approach in our equation, which has no theoretical basis. This paper discusses an alternative kinetic energy expression for one to five electrons with simple corrections for relativistic and Lamb shift effects and for two- to-five electron ions additional effects including electron relaxation and residual interactions. For calculated values of one-electron (hydrogen-like) and two electron (helium like) atomic ions, the difference with the literature values is typically 0.001% or less. Agreement with the literature values for three-, four-, and five-electron ions is 99% or better. First electron affinities calculated by our expression also agree fairly well with generally recommended values. These results show that there is strong evidence that our methodology can be developed to reliably predict, with fairly good accuracy, ionization energies of multielectron atomic ions that have not been measured.
Development and Kinematic Verification of a Finite Element Model for the Lumbar Spine: Application to Disc Degeneration
Authors: Ibarz Elena , Herrera Antonio , Más Yolanda , Rodríguez-Vela Javier , Cegoñino José , Puértolas Sergio , Gracia Luis
Published: December 2012

The knowledge of the lumbar spine biomechanics is essential for clinical applications. Due to the difficulties to experiment on living people and the irregular results published, simulation based on finite elements (FE) has been developed, making it possible to adequately reproduce the biomechanics of the lumbar spine. A 3D FE model of the complete lumbar spine (vertebrae, discs, and ligaments) has been developed. To verify the model, radiological images (X-rays) were taken over a group of 25 healthy, male individuals with average age of 27.4 and average weight of 78.6 kg with the corresponding informed consent. A maximum angle of 34.40° is achieved in flexion and of 35.58° in extension with a flexion-extension angle of 69.98°. The radiological measurements were 33.94 ± 4.91°, 38.73 ± 4.29°, and 72.67°, respectively. In lateral bending, the maximum angles were 19.33° and 23.40 ± 2.39, respectively. In rotation a maximum angle of 9.96° was obtained. The model incorporates a precise geometrical characterization of several elements (vertebrae, discs, and ligaments), respecting anatomical features and being capable of reproducing a wide range of physiological movements. Application to disc degeneration (L5-S1) allows predicting the affection in the mobility of the different lumbar segments, by means of parametric studies for different ranges of degeneration.
Pressure–Diameter Relationship in Human Coronary Arteries
Authors: Muller Olivier , Pyxaras Stylianos A. , Trana Catalina , Mangiacapra Fabio , Barbato Emanuele , Wijns William , Taylor Charles A. , De Bruyne Bernard
Published: December 2012

Background—

To quantify the changes in arterial dimensions after the acute changes in pressure associated with percutaneous coronary intervention (PCI).

Methods and Results—

Forty-eight patients with one angiographically moderate-to-severe stenosis were included in the study. The pressure proximal and distal to the stenosis and the arterial diameter proximal and distal to the stenosis were measured at baseline, after intracoronary nitrates, and after stent PCI. In addition, in 8 patients distal pressure and coronary diameter were assessed while graded, controlled stenoses were created in the stented segment by progressive inflation of a balloon catheter. The mean diameter of the proximal coronary segment was 2.75±0.08 mm, 2.92±0.08 mm (+7.4%), and 3.10±0.07 mm (+14.7%) at baseline, after nitrates and after PCI, respectively (
P
<0.001). The mean diameter of the distal coronary segment was 2.07±0.09 mm, 2.23±0.09 mm (+9.7%), and 2.5±0.07 mm (+28.4%) at baseline, after nitrates and after PCI, respectively (
P
<0.001). The increase in distal diameter correlated significantly with the increase in distal pressure after PCI (
r
2
=0.57;
P
<0.001). When graded stenoses were created, a decrease in diameter of 18±4% was observed with a pressure drop of 43±5 mm Hg.

Conclusions—

The diameter of coronary arteries markedly varies with their distending pressure. After re-establishment of a normal distending pressure by stenting of severe coronary stenoses, a proportional increase in vessel diameter is observed. This should be taken into account when choosing the stent diameter and is an argument to discourage direct stenting.
Selecting Antiplatelet Therapy at the Time of Percutaneous Intervention for an Acute Coronary Syndrome
Authors: Salisbury Adam C. , Wang Kaijun , Cohen David J. , Li Yan , Jones Philip G. , Spertus John A.
Published: December 2012

Background—

On average, acute coronary syndrome patients treated with prasugrel experience fewer ischemic complications, but more bleeding, than those receiving clopidogrel. However, heterogeneity in treatment effects can alter the likelihood of benefits and risks of an individual patient. We developed predictive models of the benefits (reduced ischemic events) and risks (increased bleeding) to support targeting prasugrel to those who benefit most from treatment.

Methods and Results—

Using 12 579 patients from Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38), we fit risk models for ischemic events (cardiovascular death, spontaneous myocardial infarction, stroke) and bleeding (TIMI major/minor) over a 14.8-month follow-up and then calculated each patient’s predicted risk for major ischemia and bleeding with both prasugrel and clopidogrel. We found substantial heterogeneity of the treatment effect of prasugrel (mean absolute reduction in the ischemia risk with prasugrel=1.5±3.0%, ranging from an 8.4% increased risk to a 31.2% reduction in risk for ischemia compared with clopidogrel). The mean absolute increase in the bleeding risk with prasugrel versus clopidogrel was 1.3±1.4% and ranged from a 7.9% lower risk to an 11.2% higher risk with prasugrel. The ratio of the difference in predicted ischemia risk/difference in predicted bleeding risk between prasugrel and clopidogrel was calculated for each patient to identify the proportion likely to benefit from prasugrel. Considering both ischemia and bleeding risk, a large proportion of TRITON participants (42%) were predicted to experience net benefit with prasugrel, a rate that increased if patients more strongly preferred avoiding ischemic events than bleeding.

Conclusions—

The expected benefits and risks of prasugrel versus clopidogrel depend highly on patient characteristics. The use of risk models could support individualized thienopyridine selection to maximize the benefits and safety of these drugs.
Inactive Period of Western North Pacific Tropical Cyclone Activity in 1998–2011
Authors: Liu Kin Sik , Chan Johnny C. L.
Published: December 2012

Tropical cyclone (TC) activity over the western North Pacific (WNP) exhibits a significant interdecadal variation during 1960–2011, with two distinct active and inactive periods each. This study examines changes in TC activity and atmospheric conditions in the recent inactive period (1998–2011). The overall TC activity shows a significant decrease, which is partly related to the decadal variation of TC genesis frequency in the southeastern part of the WNP and the downward trend of TC genesis frequency in the main development region.

The investigation on the factors responsible for the low TC activity mainly focuses on the effect of vertical wind shear and subtropical high on multidecadal time scales. A vertical wind shear index, defined as the mean magnitude of the difference of the 200- and 850-hPa horizontal zonal winds (10°–17.5°N, 150°E–180°) averaged between June and October, is highly correlated with the annual TC number and shows a significant interdecadal variation. Positive anomalies of vertical wind shear are generally found in the eastern part of the tropical WNP during this inactive period. A subtropical high area index, calculated as the area enclosed by the 5880-gpm line of the June–October 500-hPa geopotential height (0°–40°N, 100°E–180°), shows a significant upward trend. A high correlation is also found between this index and the annual TC number, and a stronger-than-normal subtropical high is generally observed during this inactive period. The strong vertical wind shear and strong subtropical high observed during 1998–2011 together apparently lead to unfavorable atmospheric conditions for TC genesis and hence the low TC activity during the period.
Self consistency grouping: a stringent clustering method
Authors: Kim Bong-Hyun , Chitturi Bhadrachalam , Grishin Nick V
Published: December 2012

Background

Numerous types of clustering like single linkage and K-means have been widely studied and applied to a variety of scientific problems. However, the existing methods are not readily applicable for the problems that demand high stringency.

Methods

Our method, self consistency grouping, i.e. SCG, yields clusters whose members are closer in rank to each other than to any member outside the cluster. We do not define a distance metric; we use the best known distance metric and presume that it measures the correct distance. SCG does not impose any restriction on the size or the number of the clusters that it finds. The boundaries of clusters are determined by the inconsistencies in the ranks. In addition to the direct implementation that finds the complete structure of the (sub)clusters we implemented two faster versions. The fastest version is guaranteed to find only the clusters that are not subclusters of any other clusters and the other version yields the same output as the direct implementation but does so more efficiently.

Results

Our tests have demonstrated that SCG yields very few false positives. This was accomplished by introducing errors in the distance measurement. Clustering of protein domain representatives by structural similarity showed that SCG could recover homologous groups with high precision.

Conclusions

SCG has potential for finding biological relationships under stringent conditions.
Inference of gene regulatory subnetworks from time course gene expression data
Authors: Liang Xi-Jun , Xia Zhonghang , Zhang Li-Wei , Wu Fang-Xiang
Published: December 2012

Background

Identifying gene regulatory network (GRN) from time course gene expression data has attracted more and more attentions. Due to the computational complexity, most approaches for GRN reconstruction are limited on a small number of genes and low connectivity of the underlying networks. These approaches can only identify a single network for a given set of genes. However, for a large-scale gene network, there might exist multiple potential sub-networks, in which genes are only functionally related to others in the sub-networks.

Results

We propose the network and community identification (NCI) method for identifying multiple subnetworks from gene expression data by incorporating community structure information into GRN inference. The proposed algorithm iteratively solves two optimization problems, and can promisingly be applied to large-scale GRNs. Furthermore, we present the efficient Block PCA method for searching communities in GRNs.

Conclusions

The NCI method is effective in identifying multiple subnetworks in a large-scale GRN. With the splitting algorithm, the Block PCA method shows a promosing attempt for exploring communities in a large-scale GRN.
A systematic model of the LC-MS proteomics pipeline
Authors: Sun Youting , Braga-Neto Ulisses , Dougherty Edward R
Published: December 2012

Motivation

Mass spectrometry is a complex technique used for large-scale protein profiling with clinical and pharmaceutical applications. While individual components in the system have been studied extensively, little work has been done to integrate various modules and evaluate them from a systems point of view.

Results

In this work, we investigate this problem by putting together the different modules in a typical proteomics work flow, in order to capture and analyze key factors that impact the number of identified peptides and quantified proteins, protein quantification error, differential expression results, and classification performance. The proposed proteomics pipeline model can be used to optimize the work flow as well as to pinpoint critical bottlenecks worth investing time and resources into for improving performance. Using the model-based approach proposed here, one can study systematically the critical problem of proteomic biomarker discovery, by means of simulation using ground-truthed synthetic MS data.
Minocycline reduces reactive gliosis in the rat model of hydrocephalus
Authors: Xu Hao , Tan Guowei , Zhang Shaolin , Zhu Hongwei , Liu Feng , Huang Caiquan , Zhang Feifei , Wang Zhanxiang
Published: December 2012

Background

Reactive gliosis had been implicated in injury and recovery patterns associated with hydrocephalus. Our aim is to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce reactive gliosis and inhibit the development of hydrocephalus.

Results

The ventricular dilatation were evaluated by MRI at 1-week post drugs treated, while GFAP and Iba-1were detected by RT-PCR, Immunohistochemistry and Western blot. The expression of GFAP and Iba-1 was significantly higher in hydrocephalic group compared with saline control group (p < 0.05). Minocycline treatment of hydrocephalic animals reduced the expression of GFAP and Iba-1 significantly (p < 0.05). Likewise, the severity of ventricular dilatation is lower in minocycline treated hydrocephalic animals compared with the no minocycline group (p < 0.05).

Conclusion

Minocycline treatment is effective in reducing the gliosis and delaying the development of hydrocephalus with prospective to be the auxiliary therapeutic method of hydrocephalus.
MC1R variants predisposing to concomitant primary cutaneous melanoma in a monozygotic twin pair
Authors: Pellegrini Cristina , Fargnoli Maria Concetta , Suppa Mariano , Peris Ketty
Published: December 2012

Background

Concomitant primary cutaneous melanoma in monozygotic twins has been reported in only two pairs but in neither of them genetic analysis was performed. Two high-penetrance susceptibility genes,CDKN2AandCDK4and one low-penetrance gene,MC1R,are well-defined genetic risk factors for melanoma.MITFhas been recently identified as a novel intermediate risk melanoma-predisposing gene.

Case presentation

We describe the extraordinary occurrence of a primary cutaneous invasive melanoma in two 44-year-old identical, female twins, on the same body site within 30 days of each other and report for the first time the genetic analysis of melanoma susceptibility genes in both twins. Data on characteristics of the twins were collected through a standardized questionnaire and skin examination. Exons 1α, 1β, 2 and 3 ofCDKN2A, exon 2 ofCDK4, the entire open reading frame ofMC1Rand the recently describedMITFc.952 G > A (p.Glu318Lys) variant were investigated by direct sequencing. Sequencing analysis of the high-penetrance susceptibility genes showed no changes inCDKN2Aand in exon 2 of theCDK4gene. Both patients were heterozygous for the sameCDKN2AUTR c.*29C > G variant. Interestingly, the same two heterozygous variants of theMC1Rwere identified in both twins: the c.451C > T (p.Arg151Cys) and the c.456C > A (p.Tyr152*) variants. Neither patient showed the c.952 G > A (p.Glu318Lys) substitution in theMITFgene.

Conclusions

Identification of two high-riskMC1Rvariants in our identical twins in the absence ofCDKN2AandCDK4mutations highlights the contribution of low penetrance genes, such asMC1R, in melanoma susceptibility.
MRI findings are often missed in the diagnosis of Creutzfeldt-Jakob disease
Authors: Carswell Christopher , Thompson Andrew , Lukic Ana , Stevens John , Rudge Peter , Mead Simon , Collinge John , Hyare Harpreet
Published: December 2012

Background

Establishing a confident clinical diagnosis before an advanced stage of illness can be difficult in Creutzfeldt-Jakob disease (CJD) but unlike common causes of dementia, prion diseases can often be diagnosed by identifying characteristic MRI signal changes. However, it is not known how often CJD-associated MRI changes are identified at the initial imaging report, whether the most sensitive sequences are used, and what impact MRI-diagnosis has on prompt referral to clinical trial-like studies.

Methods

We reviewed the MRI scans of 103 patients with CJD referred to the National Prion Clinic since 2007 and reviewed the presence of CJD-associated changes, compared these findings with the formal report from the referring centre and reviewed the types of sequence performed.

Results

In sCJD we found CJD-associated MRI changes in 83 of 91 cases (91% sensitivity). However, the referring centres documented CJD-associated MRI changes in 43 of the sCJD cases (47% sensitivity). The most common region not documented by referring centres was the cortex (23 of 68 sCJD cases), but there was a statistically significant discrepancy in all regions (p<0.0001). Patients in whom MRI abnormalities were missed by the referring hospital were more advanced at the time of recruitment to a clinical trial-like study (p=0.03).

Conclusions

CJD-associated MRI changes are often not documented on the formal investigation report at the referring centre. This is important as delay makes enrolment to clinical trials futile because of highly advanced disease. If a diagnosis of CJD is suspected, even if the initial imaging is reported as normal, a specialist MRI review either by an experienced neuroradiologist or by a prion disease specialist unit could facilitate earlier diagnosis.
Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment
Authors: Heuvers Marlies E , Aerts Joachim G , Cornelissen Robin , Groen Harry , Hoogsteden Henk C , Hegmans Joost P
Published: December 2012

Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recently it was often thought that tumors are more or less undetected or tolerated by the patient’s immune system causing the neoplastic cells to divide and spread without resistance. However, it is without any doubt that the tumor environment contains a wide variety of recruited host immune cells. These tumor infiltrating immune cells influence anti-tumor responses in opposing ways and emerges as a critical regulator of tumor growth. Here we provide a summary of the relevant immunological cell types and their complex and dynamic roles within an established tumor microenvironment. For this, we focus on both the systemic compartment as well as the local presence within the tumor microenvironment of late-stage non-small cell lung cancer (NSCLC), admitting that this multifaceted cellular composition will be different from earlier stages of the disease, between NSCLC patients. Understanding the paradoxical role that the immune system plays in cancer and increasing options for their modulation may alter the odds in favor of a more effective anti-tumor immune response. We predict that the future standard of care of lung cancer will involve patient-tailor-made combination therapies that associate (traditional) chemotherapeutic drugs and biologicals with immune modulating agents and in this way complement the therapeutic armamentarium for this disease.
Idiopathic pleuroparenchymal fibroelastosis: consideration of a clinicopathological entity in a series of Japanese patients
Authors: Kusagaya Hideki , Nakamura Yutaro , Kono Masato , Kaida Yusuke , Kuroishi Shigeki , Enomoto Noriyuki , Fujisawa Tomoyuki , Koshimizu Naoki , Yokomura Koshi , Inui Naoki , Suda Takafumi , Colby Thomas V , Chida Kingo
Published: December 2012

Background

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported group of disorders characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes. We report five Japanese cases fulfilling the criteria of IPPFE and address whether it should be considered a separate clinicopathologic entity. And this study was an attempt to identify features in common between IPPFE and previously described idiopathic upper lobe fibrosis (IPUF), allowing IPPFE to be considered as a distinct entity in our Japanese series.

Methods

Five consecutive cases of idiopathic interstitial lung disease confirmed as IPPFE by surgical lung biopsy were studied.

Results

There were four males and one female, aged 70±2.76 yr. No associated disorder or presumed cause was found in any case. Lung function tests found a restrictive ventilatory defect (4/5) and/or impairment of DLco (4/5). Chest X-ray showed marked apical pleural thickening in all cases. Computed tomography of the chest in all cases mainly showed intense pleural thickening and volume loss associated with evidence of fibrosis, predominantly in the upper lobes. In all cases in this study, markedly thickened visceral pleura and prominent subpleural fibrosis characterized by both elastic tissue and dense collagen were clearly shown. All cases were alive at the last follow-up, 17.6±13.59 months after diagnosis; however, all had deteriorated both clinically and radiologically.

Conclusions

IPPFE deserves to be defined as a separate, original clinicopathologic entity owing to its uniformity and IPPFE has some features in common with previously described idiopathic upper lobe fibrosis (IPUF). Our limited experience with a cohort of 5 subjects suggests that IPPFE can be rapidly progressive.
Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan
Authors: Shah Syed Muhammad Mukarram , Ullah Farhat , Shah Syed Muhammad Hassan , Zahoor Mohammad , Sadiq Abdul
Published: December 2012

Background

Medicinal plants are used for the treatment of different diseases in almost all cultures. Teucrium species grow wildly at different geographical locations around the world. Teucrium stocksianum is used in folk medicine for the treatment of diarrhea, cough, jaundice and abdominal pain. Scientific study on Teucrium stocksianum shows that it possesses anthelmintic, cytotoxic and antispasmodic activity. The aim of our present study is to identify the chemical composition and antinociceptive potential of the essential oil extracted from Teucrium stocksianum bioss.

Method

Essential oil (EO) from the aerial parts of Teucrium stocksianum were extracted by hydrodistillation process. The qualitative and quantitative composition of essential oil was determined with Gas chromatography/Mass spectrometer. Antinociceptive activity was determined by acetic acid induced writhing method. Percent inhibition of writhes of the test concentration was determined by comparing it with that of control. Tween-80 emulsion 2.5% (5 ml/kg b.w) was used as a control while Diclofenic sodium 50 mg/kg (b.w) was used as a standard drug.

Results

The chromatogram of the essential oil of Teucrium stocksianum shows differences both qualitatively and quantatively from essential oil composition reported in other countries. Hydrodistillation of Teucrium stocksianum yielded 0.4% (v/w), pale yellowish oil on dry basis. A total of 26 chemicals were identified by GC-MS accounting for 90.28% of the oil. The major components of essential oil were δ-cadinene (12.92%), α-pinene (10.3%), myrcene (8.64%), β-caryophyllene (8.23%), germacrene D (5.18%) and limonene (2.36%). Essential oil of Teucrium stocksianum has shown outstanding antinociceptive activity. It has been observed that increase in percent writhe inhibition (PWI) occurred from 20-80 mg/kg (b.w) and maximum writhe inhibition has been noted at a concentration of 80 mg/kg (b.w), but PWI decreased at 160 mg/kg, which may be due to some toxic effect of higher dose. ED50 value for Teucrium stocksianum was calculated as 31.5 ± 1.72415 mg/kg (b.w).

Conclusion

Our results indicate that there is a lot of variation in the composition of essential oil of Teucrium stocksianum boiss, which may be due to different climatic and experimental conditions. Secondly, the essential oil possesses strong antinociceptive activity and could be used in analgesic preparations especially for topical use.
Expenditure and resource utilisation for cervical screening in Australia
Authors: Lew Jie-Bin , Howard Kirsten , Gertig Dorota , Smith Megan , Clements Mark , Nickson Carolyn , Shi Ju-Fang , Dyer Suzanne , Lord Sarah , Creighton Prudence , Kang Yoon-Jung , Tan Jeffrey , Canfell Karen
Published: December 2012

Background

The National Cervical Screening Program in Australia currently recommends that women aged 18–69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010.

Methods

A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination.

Results

The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities.

Conclusions

Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia.
GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle
Authors: Aerni-Flessner Lauren , Abi-Jaoude Melissa , Koenig Amanda , Payne Maria , Hruz Paul W
Published: December 2012

Background

The heart derives energy from a wide variety of substrates including fatty acids, carbohydrates, ketones, and amino acids. The healthy heart generates up to 30% of its ATP from glucose. Under conditions of cardiac injury or stress, the heart relies even more heavily on glucose as a source of fuel. Glucose is transported into the heart by members of the family of facilitative glucose transporters (GLUTs). While research examining the transport of glucose into the heart has primarily focused on the roles of the classical glucose transporters GLUT1 and GLUT4, little is known about the functions of more newly identified GLUT isoforms in the myocardium.

Methods

In this study the presence and relative RNA message abundance of each of the known GLUT isoforms was determined in left ventricular tissue from two commonly used inbred laboratory mouse strains (C57BL/6J and FVB/NJ) by quantitative real time PCR. Relative message abundance was also determined in GLUT4 null mice and in murine models of dilated and hypertrophic cardiomyopathy.

Results

GLUT4, GLUT1, and GLUT8 were found to be the most abundant GLUT transcripts in the normal heart, while GLUT3, GLUT10, and GLUT12 are present at relatively lower levels. Assessment of relative GLUT expression in left ventricular myocardium from mice with dilated cardiomyopathy revealed increased expression of GLUT1 with reduced levels of GLUT4, GLUT8, and GLUT12. Compensatory increase in the expression of GLUT12 was observed in genetically altered mice lacking GLUT4.

Conclusions

Glucose transporter expression varies significantly among murine models of cardiac dysfunction and involves several of the class III GLUT isoforms. Understanding how these more newly identified GLUT isoforms contribute to regulating myocardial glucose transport will enhance our comprehension of the normal physiology and pathophysiology of the heart.