bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations within a Conserved Region of the Hepatitis C Virus E2 Glycoprotein That Influence Virus-Receptor Interactions and Sensitivity to Neutralizing Antibodies
Authors: Dhillon Simrat , Witteveldt Jeroen , Gatherer Derek , Owsianka Ania M. , Zeisel Mirjam B. , Zahid Muhammad N. , Rychłowska Małgorzata , Foung Steven K. H. , Baumert Thomas F. , Angus Allan G. N. , Patel Arvind H.
Published: March 2010

Cell culture-adaptive mutations within the hepatitis C virus (HCV) E2 glycoprotein have been widely reported. We identify here a single mutation (N415D) in E2 that arose during long-term passaging of HCV strain JFH1-infected cells. This mutation was located within E2 residues 412 to 423, a highly conserved region that is recognized by several broadly neutralizing antibodies, including the mouse monoclonal antibody (MAb) AP33. Introduction of N415D into the wild-type (WT) JFH1 genome increased the affinity of E2 to the CD81 receptor and made the virus less sensitive to neutralization by an antiserum to another essential entry factor, SR-BI. Unlike JFH1
WT
, the JFH1
N415D
was not neutralized by AP33. In contrast, it was highly sensitive to neutralization by patient-derived antibodies, suggesting an increased availability of other neutralizing epitopes on the virus particle. We included in this analysis viruses carrying four other single mutations located within this conserved E2 region: T416A, N417S, and I422L were cell culture-adaptive mutations reported previously, while G418D was generated here by growing JFH1
WT
under MAb AP33 selective pressure. MAb AP33 neutralized JFH1
T416A
and JFH1
I422L
more efficiently than the WT virus, while neutralization of JFH1
N417S
and JFH1
G418D
was abrogated. The properties of all of these viruses in terms of receptor reactivity and neutralization by human antibodies were similar to JFH1
N415D
, highlighting the importance of the E2 412-423 region in virus entry.
Evaluating the Substrate-Envelope Hypothesis: Structural Analysis of Novel HIV-1 Protease Inhibitors Designed To Be Robust against Drug Resistance
Authors: Nalam Madhavi N. L. , Ali Akbar , Altman Michael D. , Reddy G. S. Kiran Kumar , Chellappan Sripriya , Kairys Visvaldas , Özen Ayşegül , Cao Hong , Gilson Michael K. , Tidor Bruce , Rana Tariq M. , Schiffer Celia A.
Published: March 2010

Drug resistance mutations in HIV-1 protease selectively alter inhibitor binding without significantly affecting substrate recognition and cleavage. This alteration in molecular recognition led us to develop the substrate-envelope hypothesis which predicts that HIV-1 protease inhibitors that fit within the overlapping consensus volume of the substrates are less likely to be susceptible to drug-resistant mutations, as a mutation impacting such inhibitors would simultaneously impact the processing of substrates. To evaluate this hypothesis, over 130 HIV-1 protease inhibitors were designed and synthesized using three different approaches with and without substrate-envelope constraints. A subset of 16 representative inhibitors with binding affinities to wild-type protease ranging from 58 nM to 0.8 pM was chosen for crystallographic analysis. The inhibitor-protease complexes revealed that tightly binding inhibitors (at the picomolar level of affinity) appear to “lock” into the protease active site by forming hydrogen bonds to particular active-site residues. Both this hydrogen bonding pattern and subtle variations in protein-ligand van der Waals interactions distinguish nanomolar from picomolar inhibitors. In general, inhibitors that fit within the substrate envelope, regardless of whether they are picomolar or nanomolar, have flatter profiles with respect to drug-resistant protease variants than inhibitors that protrude beyond the substrate envelope; this provides a strong rationale for incorporating substrate-envelope constraints into structure-based design strategies to develop new HIV-1 protease inhibitors.
Mortality in ulcerative colitis—what should we tell our patients? Three year mortality following admission for the treatment of ulcerative colitis: a 6 year retrospective case review
Authors: Falvey J , Greenwood R , Creed T J , Smithson J , Sylvester P , Fraser A , Probert C S
Published: March 2010

Objectives

To determine the 3 year mortality of patients admitted to hospital for the treatment of ulcerative colitis (UC).

Design

Retrospective case note review of all patients admitted to hospital for treatment of active UC over a 6 year period from 1 January 2000.

Setting

Teaching hospital with a tertiary referral practice for the management of infiammatory bowel disease.

Patients

106 patients (134 admissions) met the inclusion criteria.

Interventions

Elective and emergency colectomy was undertaken in 16 and 26 patients, respectively.

Main outcome measures

Mortality at 3 years.

Results

There were six deaths after 3 years. Case fatality at 30 days, 1, 2 and 3 years was 1.0% (95% CI 0.2 to 5.1), 1.9% (95% CI 0.2 to 6.6), 2.9% (95% CI 5.9 to 8.0) and 5.7% (95% CI 2.1 to 11.9), respectively. There were no deaths in either surgical group. One patient (89 years, female) died while awaiting emergency colectomy. Patients who died were significantly older at the time of admission (79 years (95% CI 71 to 88 years) vs 41.2 years (95% CI 38 to 45 years)) and were more likely to have comorbid illness (p<0.001). Severity of disease, prior immunosuppressive use, first presentation and smoking status were not associated with increased mortality.

Conclusions

Three year mortality following admission for treatment of UC was 5.7% (95% CI 2.1 to 11.9), significantly lower than that reported previously. Mortality was significantly associated with increasing age and the presence of comorbid disease. Disease specific factors such as severity, extent and first presentation were associated with emergency colectomy but not mortality.
The characteristics of an excellent endoscopy trainer
Authors: Wells Christopher
Published: March 2010

A description of the characteristics of an excellent endoscopy trainer is provided. These characteristics are presented in an accessible format for endoscopy trainers to use to develop their endoscopy teaching. Excellent endoscopy teaching is a fundamental part of providing a high quality, motivated endoscopy workforce.
MODELING THE EVOLUTION OF COMPLEX NETWORKS THROUGH THE PATH-STAR TRANSFORMATION AND OPTIMAL MULTIVARIATE METHODS
Authors: DA F. COSTA L. , RODRIGUES F. A. , VILLAS BOAS P. R.
Published: March 2010

The topology of real-world complex networks, such as in transportation and communication, is always changing with time. Such changes can arise not only as a natural consequence of their growth, but also due to major modifications in their intrinsic organization. For instance, the network of transportation routes between cities and towns (hence locations) of a given country undergo a major change with the progressive implementation of commercial air transportation. While the locations could be originally interconnected through highways (paths, giving rise to geographical networks), transportation between those sites progressively shifted or was complemented by air transportation, with scale free characteristics. In the present work we introduce the path-star transformation (in its uniform and preferential versions) as a means to model such network transformations where paths give rise to stars of connectivity. It is also shown, through optimal multivariate statistical methods (i.e. canonical projections and maximum likelihood classification) that while the US highways network adheres closely to a geographical network model, its path-star transformation yields a network whose topological properties closely resembles those of the respective airport transportation network.
ENTRAINMENT COMPETITION IN COMPLEX NETWORKS
Authors: LEYVA I. , SENDIÑA-NADAL I. , ALMENDRAL J. A. , BULDÚ J. M. , LI D. , HAVLIN S. , BOCCALETTI S.
Published: March 2010

The response of a random and modular network to the simultaneous presence of two frequencies is considered. The competition for controlling the dynamics of the network results in different behaviors, such as frequency changes or permanent synchronization frustration, which can be directly related to the network structure. From these observations, we propose a new method for detecting overlapping communities in structured networks.
EVOLUTION OF HETEROGENEOUS NETWORKS UNDER PREFERENTIAL ATTACHMENT
Authors: SANTIAGO ANTONIO , BENITO ROSA M.
Published: March 2010

In this paper, we present results concerning a natural extension of the class of heterogeneous preferential attachment models, a generalization of the Barabási–Albert model to heterogeneous networks. In this extended class, the network nodes enjoy a nonzero attractiveness even when their connectivity degrees are zero. We analytically show that the degree densities of models in the extended class exhibit a richer scaling behavior than their homogeneous counterparts, and that power-law scaling in their degree distribution is robust in the presence of the offset in the attachment kernel.
NANOSCALE VOID GROWTH IN MAGNESIUM: A MOLECULAR DYNAMICS STUDY
Authors: GROH SEBASTIEN , MARIN ESTEBAN B. , HORSTEMEYER M. F.
Published: March 2010

Molecular dynamics calculations were carried out in single crystal magnesium specimens to reveal the dependence of strain rate, temperature, and orientation of the crystal on damage evolution as defined by pore growth. Two specific crystallographic orientations [0001] and [Formula: see text] were examined. During a [0001] tensile test, twin boundaries developed at the void surface leading to a constraint on the [Formula: see text] crystallographic orientation. On the other hand, during the [Formula: see text] tensile deformation, emission of shear loops in the prismatic slip planes arose when void growth initiated. Furthermore, analysis of the damage components (nucleation, growth and coalescence) revealed that a large number of small voids nucleated that rapidly grew and fractured the specimens independent of the temperature and the strain rate.
A DIFFERENTIAL QUADRATURE FINITE ELEMENT METHOD
Authors: XING YUFENG , LIU BO , LIU GUANG
Published: March 2010

This paper studies the differential quadrature finite element method (DQFEM) systematically, as a combination of differential quadrature method (DQM) and standard finite element method (FEM), and formulates one- to three-dimensional (1-D to 3-D) element matrices of DQFEM. It is shown that the mass matrices of C 0 finite element in DQFEM are diagonal, which can reduce the computational cost for dynamic problems. The Lagrange polynomials are used as the trial functions for both C 0 and C 1 differential quadrature finite elements (DQFE) with regular and/or irregular shapes, this unifies the selection of trial functions of FEM. The DQFE matrices are simply computed by algebraic operations of the given weighting coefficient matrices of the differential quadrature (DQ) rules and Gauss-Lobatto quadrature rules, which greatly simplifies the constructions of higher order finite elements. The inter-element compatibility requirements for problems with C 1 continuity are implemented through modifying the nodal parameters using DQ rules. The reformulated DQ rules for curvilinear quadrilateral domain and its implementation are also presented due to the requirements of application. Numerical comparison studies of 2-D and 3-D static and dynamic problems demonstrate the high accuracy and rapid convergence of the DQFEM.
MECHANICAL BEHAVIOUR OF TRANSVERSELY ISOTROPIC POROUS NEO-HOOKEAN SOLIDS
Authors: GUO ZAOYANG , CANER FERHUN C.
Published: March 2010

In this paper, the mechanical responses of a recently developed hyperelastic model for the neo-Hookean solids with aligned continuous cylindrical pores under finite homogeneous deformation that can capture the anisotropic compressibility as well as the coupling between the volumetric and deviatoric behaviours are examined. To this end, the strain energy function of this hyperelastic compressible transversely isotropic model contains terms for the coupling of volumetric and deviatoric behaviours. It is shown that, the asymptotic response of this anisotropic compressible model under extreme loading situations is considerably different from that of incompressible models. The unstable behaviour of the porous solid under hydrostatic stress/strain loadings is discussed in detail. When a general simple 2D shear deformation is applied to this porous solid in i1 – i2 plane, the normal stress in the third axial direction (i3) is nonzero. The loss of monotonicity of the stress tensor under off-axis simple 2D shear loading is demonstrated as well.
REFINED BEAM THEORIES BASED ON A UNIFIED FORMULATION
Authors: CARRERA ERASMO , GIUNTA GAETANO
Published: March 2010

This paper proposes several axiomatic refined theories for the linear static analysis of beams made of isotropic materials. A hierarchical scheme is obtained by extending plates and shells Carrera's Unified Formulation (CUF) to beam structures. An N-order approximation via Mac Laurin's polynomials is assumed on the cross-section for the displacement unknown variables. N is a free parameter of the formulation. Classical beam theories, such as Euler-Bernoulli's and Timoshenko's, are obtained as particular cases. According to CUF, the governing differential equations and the boundary conditions are derived in terms of a fundamental nucleo that does not depend upon the approximation order. The governing differential equations are solved via the Navier type, closed form solution. Rectangular and I-shaped cross-sections are accounted for. Beams undergo bending and torsional loadings. Several values of the span-to-height ratio are considered. Slender as well as deep beams are analysed. Comparisons with reference solutions and three-dimensional FEM models are given. The numerical investigation has shown that the proposed unified formulation yields the complete three-dimensional displacement and stress fields for each cross-section as long as the appropriate approximation order is considered. The accuracy of the solution depends upon the geometrical parameters of the beam and loading conditions.
Effect of osmotic shock and urea on phosphatidylserine scrambling in thrombocyte cell membranes
Authors: Gatidis Sergios , Borst Oliver , Föller Michael , Lang Florian
Published: March 2010

Blood passing the renal medulla enters a strongly hypertonic environment challenging functional properties and survival of blood cells. In erythrocytes, exposure to hyperosmotic shock stimulates Ca2+ entry and ceramide formation with subsequent cell membrane scrambling, an effect partially reversed by high concentrations of Cl− or urea. Cell membrane scrambling with phosphatidylserine exposure is part of the procoagulant phenotype of platelets. Coagulation in the hypertonic renal medulla would jeopardize blood flow in the vasa recta. The present study thus explored whether hypertonic environment and urea modify phosphatidylserine exposure of human platelets. FACS analysis was employed to estimate cytosolic Ca2+ activity with Fluo3 fluorescence, ceramide formation, P-selectin, and glycoprotein IIb/IIIa activation with fluorescent antibodies and phosphatidylserine exposure with annexin V-binding. The spontaneous platelet aggregation was measured by impedance aggregometry. Hyperosmotic shock (addition of 500 mM sucrose or 250 mM NaCl) significantly enhanced cytosolic Ca2+ activity, ceramide formation, phosphatidylserine exposure, platelet degranulation, and aggregability. Addition of 500 mM urea to isotonic saline did not significantly modify cytosolic Ca2+ activity, ceramide abundance, or annexin V-binding but significantly blunted the respective effects of hypertonic shock following addition of 500 mM sucrose. In isotonic solutions, both ceramide (20 μM) and Ca2+ ionophore ionomycin (0.5 μM) increased annexin V-binding, effects again significantly blunted by 500 mM urea. Moreover, oxidative stress by addition of 0.5 mM peroxynitrite increased cytosolic Ca2+ activity and triggered annexin V-binding, effects again blunted in the presence of 500 mM urea. The observations reveal that hyperosmotic shock and oxidative stress trigger a procoagulant platelet phenotype, an effect blunted by the presence of high urea concentrations.
Decreased phospho-Akt signaling in a mouse model of total parenteral nutrition: a potential mechanism for the development of intestinal mucosal atrophy
Authors: Feng Yongjia , McDunn Jonathan E. , Teitelbaum Daniel H.
Published: March 2010

Total parenteral nutrition (TPN) leads to a decline in phosphatidylinositol 3-kinase (PI3K)/phospho-Akt (p-Akt) activity, affecting downstream signaling, reducing epithelial cell (EC) proliferation, and contributing to intestinal mucosal atrophy. We hypothesized that promoting Akt activity would prevent these changes. We used a novel Akt-activating peptide, TCL1 (a head-to-tail dimer of the Akt-binding domain of T-cell lymphoma-1), or an inactive mutant sequence TCL1G conjugated to a transactivator of transcription peptide sequence to promote intracellular uptake. Four groups of mice were studied, enteral nutrition group (control), control mice given a functioning TCL1 (control + TCL1), TPN mice given TCL1G (control peptide, TPN + TCL1G); and TPN mice given TCL1. TPN mice given TCL1G showed a significant decrease in jejunal EC p-Akt (Ser473 and Thr308) abundance, whereas TPN + TCL1 mice showed increased p-Akt (Ser473) abundance. Phosphorylation of β-catenin and glycogen synthase kinase-3β (downstream targets of Akt signaling) were also decreased in the TPN + TCL1G group and completely prevented in the TPN + TCL1 group. Use of TCL1 nearly completely prevented the decline in EC proliferation seen in the TPN + TCL1G group, as well as partly returned EC apoptosis levels close to controls. The mammalian target of rapamycin pathway demonstrated a similar reduction in activity in the TPN + TCL1G group that was significantly prevented in the TPN + TCL1 group. These results support a significant loss of PI3K/p-Akt signaling upon replacing enteral nutrition with TPN, and prevention of this loss demonstrates the key importance of PI3K/p-Akt signaling in maintaining gut integrity including EC proliferation and reduction in apoptosis.
Suppression of nephrin expression by TNF-α via interfering with the cAMP-retinoic acid receptor pathway
Authors: Saito Yukinori , Okamura Maro , Nakajima Shotaro , Hayakawa Kunihiro , Huang Tao , Yao Jian , Kitamura Masanori
Published: March 2010

Nephrin, a crucial component of the slit diaphragm, is downregulated in proteinuric glomerular diseases including glomerulonephritis. We previously reported that 1) expression of nephrin in cultured podocytes is reinforced by retinoic acid (RA) and 1,25-dihydroxyvitamin D3, 2) these effects are mediated by retinoic acid receptor (RAR) and vitamin D receptor (VDR), and 3) basal and inducible expression of nephrin is downregulated by TNF-α. In the present investigation, we identified that TNF-α selectively represses activity of RAR but not VDR. To elucidate mechanisms underlying this observation, we tested involvement of downstream targets for TNF-α: nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases, phosphatidylinositol 3-kinase (PI3K)-Akt, and cAMP-protein kinase A (PKA). TNF-α caused activation of NF-κB, MAP kinases, and PI3K-Akt in podocytes, whereas blockade of these molecules did not affect inhibition of RAR by TNF-α. In contrast, TNF-α depressed activity of cAMP-PKA, and blockade of PKA inhibited basal and RA-induced activation of RAR. Furthermore, activity of RAR was significantly upregulated by cAMP, and the suppressive effect of TNF-α on RAR was reversed by cAMP-elevating agents. These results suggest that 1) expression of nephrin in podocytes is regulated by the cAMP-RAR pathway and 2) suppression of nephrin by TNF-α is caused, at least in part, through selective inhibition of this pathway.
Changes in Spinal Reflex Excitability Associated With Motor Sequence Learning
Authors: Lungu Ovidiu , Frigon Alain , Piché Mathieu , Rainville Pierre , Rossignol Serge , Doyon Julien
Published: March 2010

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: “sequence”–externally triggered, repeating and sequential movements, “random”–similar movements, but performed in an arbitrary order, and “simple”– involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 ± 1.47%. mean ± SE) compared with the random (38.2 ± 1.60%) and simple (31.5 ± 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.
In Vivo Bioassay of Recombinant Human Growth Hormone Synthesized inB. moriPupae
Authors: Lan Hanglian , Nie Zuoming , Liu Yue , Lv Zhengbing , Liu Yingshuo , Quan Yanping , Chen Jianqing , Zhen Qingliang , Chen Qin , Wang Dan , Sheng Qing , Yu Wei , Chen Jian , Wu Xiangfu , Zhang Yaozhou
Published: March 2010

The human growth hormone (hGH) has been expressed in prokaryotic expression system with low bioactivity previously. Then the effectiveB. moribaculovirus system was employed to express hGH identical to mature hGH successfully in larvae, but the expression level was still limited. In this work, the hGH was expressed inB. moripupae by baculovirus system. Quantification of recombinant hGH protein (BmrhGH) showed that the expression of BmrhGH reached the level of approximately 890 μg/mL pupae supernatant solution, which was five times more than the level using larvae. Furthermore, Animals were gavaged with BmrhGH at the dose of 4.5 mg/rat.day, and the body weight gain (BWG) of treated group had a significant difference (P<.01) compared with the control group. The other two parameters of liver weight and epiphyseal width were also found to be different between the two groups (P<.05). The results suggested that BmrhGH might be used as a protein drug by oral administration.
Nonlinear Circuit Analysis via Perturbation Methods and Hardware Prototyping
Authors: Odame K. , Hasler P. E.
Published: March 2010

Nonlinear signal processing is necessary in many emerging applications where form factor and power are at a premium. In order to make such complex computation feasible under these constraints, it is necessary to implement the signal processors as analog circuits. Since analog circuit design is largely based on a linear systems perspective, new tools are being introduced to circuit designers that allow them to understand and exploit circuit nonlinearity for useful processing. This paper discusses two such tools, which represent nonlinear circuit behavior in a graphical way, making it easy to develop a qualitative appreciation for the circuits under study.
Global Dissipativity on Uncertain Discrete‐Time Neural Networks with Time‐Varying Delays
Authors: Song Qiankun , Cao Jinde
Published: March 2010

The problems on global dissipativity and global exponential dissipativity are investigated for
uncertain discrete‐time neural networks with time‐varying delays and general activation functions. By constructing
appropriate Lyapunov‐Krasovskii functionals and employing linear matrix inequality technique, several new delay‐dependent
criteria for checking the global dissipativity and global exponential dissipativity of the addressed neural
networks are established in linear matrix inequality (LMI), which can be checked numerically using the effective
LMI toolbox in MATLAB. Illustrated examples are given to show the effectiveness of the proposed criteria. It is
noteworthy that because neither model transformation nor free‐weighting matrices are employed to deal with cross
terms in the derivation of the dissipativity criteria, the obtained results are less conservative and more computationally
efficient.
Chronic Sleep Disturbance Impairs Glucose Homeostasis in Rats
Authors: Barf R. Paulien , Meerlo Peter , Scheurink Anton J. W.
Published: March 2010

Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control.
Immunotherapy Responsive Autoimmune Subacute Encephalitis: A Report of Two Cases
Authors: Mittal Manoj , Hammond Nancy , G. Lynch Sharon
Published: March 2010

Objective.To describe the clinical characteristics and radiological findings in two patients with subacute encephalitis associated with elevated serum voltage-gated potassium channel antibody (VGKCAb) and antithyroperoxidase (TPO) antibody.Case Reports.Case 1: 63-year-old woman was admitted for altered mental status and possible seizure activity. MRI brain showed hyperintensity in the bilateral hippocampal areas. She was positive for VGKCAb and anti-TPO antibodies. She was treated with steroids, IVIG, plasma exchange and azathioprine. After 8 months, she had marked improvement in her memory and seizures. Case 2: 61-year-old woman was admitted for video EEG monitoring of unclassified seizure and cognitive function decline. MRI of the brain showed mild hyperintensity in bilateral hippocampal areas and significant atrophy in the frontotemporal lesion. Anti-TPO antibody and VGKCAb were positive. She was treated with steroids, plasma exchange and azathioprine. After 9 months, she had marked improvement in her memory and seizures.Conclusion.Autoimmune subacute encephalitis appears to be an underdiagnosed entity. It is important to screen patients with subacute encephalitis for anti-TPO antibody and VGKCAb, particularly in the presence of seizures. Immunosuppressive therapy appears to be effective in treating this entity.
Identification of an MSI-H Tumor-Specific Cytotoxic T Cell Epitope Generated by the (−1) Frame ofU79260(FTO)
Authors: Linnebacher Michael , Wienck Anne , Boeck Inga , Klar Ernst
Published: March 2010

Microsatellite instability (MSI-H) induced by defects of the DNA mismatch repair system results in insertion or deletion of single nucleotides at short repetitive DNA sequences. About 15% of sporadic and approximately 90% of hereditary nonpolyposis colorectal cancers display MSI-H. When affecting coding regions, MSI-H results in frameshift mutations and expression of corresponding frameshift peptides (FSPs). Functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by MSI-H. Contrary, immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers. Here, we provide conclusive data that the (−1) frame ofU79260(FTO)encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV). T cells specific for FSP11 efficiently recognized HLA-A0201(pos)tumor cells harboring the mutated reading frame. Considering the exceptionally high mutation rate ofU79260(FTO)in MSI-H colorectal carcinoma (81.8%), this recommends that FSP11 be a component of future vaccines.
Induced Opening of the Gastroesophageal Junction Occurs at a Lower Gastric Pressure in Gerd Patients and in Hiatal Hernia Subjects than in Normal Control Subjects
Authors: Vegesna Anil , Besetty Ramashesai , Kalra Amit , Farooq Umar , Korimilli Annapurna , Chuang Keng yu , Fisher Robert , Parkman Henry , Miller Larry
Published: March 2010

Purpose. To determine intragastric pressure threshold for inducing gastroesophageal junction (GEJ) opening in normal control subjects with and without hiatal hernia, and in patients with gastroesophageal reflux disease.Methods. This study was performed in 13 normal volunteers, 5 volunteers with hiatal hernia, and 3 patients with gastroesophageal reflux disease. During endoscopy a pressure transducer was used to measure baseline gastric pressures. The pressure in the stomach was measured while air was insufflated into the stomach until the gastroesophageal junction opened on endoscopic view.Results. There were two patterns of GEJ opening in normal volunteers. The mean opening pressure for Gastroesophageal junction in normal pattern-I, normal pattern-II, hiatal hernia, and Gastroesophageal reflux patients was 11.5, 12.6, 3.4, and 1.3 mmHg, respectively.Conclusions. GEJ opening is induced at a significantly lower pressure in subjects with hiatal hernia and in patients with gastroesophageal reflux disease than in normal volunteers.
Best Proximity Points of Cyclic "Equation missing" -Contractions on Reflexive Banach Spaces
Authors: Rezapour Sh , Derafshpour M , Shahzad N
Published: March 2010

We provide a positive answer to a question raised by Al-Thagafi and Shahzad (Nonlinear Analysis, 70 (2009), 3665-3671) about best proximity points of cyclic "Equation missing"-contractions on reflexive Banach spaces.
Neuropsychobiological Aspects, Comorbidity Patterns and Dimensional Models in Borderline Personality Disorder
Authors: Dell’Osso Bernardo , Berlin Heather A. , Serati Marta , Altamura Alfredo Carlo
Published: March 2010

Borderline personality disorder (BPD) is a comorbid and disabling condition with high prevalence in psychiatric settings. The pathogenesis of BPD involves complex interactions among genetic, neurobiological and environmental factors, resulting in multiple core symptom domains such as emotional dysregulation, impulse dyscontrol, aggression, cognitive dysfunctions and dissociative states. Neurobiological studies show that symptoms and behaviors of BPD are partly associated with alterations in glutamatergic, dopaminergic and serotonergic systems. In addition, neuroimaging studies in BPD patients indicate differences in the volume and activity of specific brain regions related to emotion and impulse control, such as the prefrontal and cingulate cortex, amygdala and hippocampus. Neurobiological alterations are related to cognitive disturbances in patients with BPD and neuropsychological tests have shown abnormalities of memory, attention, language, and executive functions. The aim of the present review is to provide an updated overview of the main neuropsychobiological aspects of BPD and their relation to clinical symptoms, comorbidity patterns and dimensional models.
The Bern Psychopathology Scale for the Assessment of System-Specific Psychotic Symptoms
Authors: Strik Werner , Wopfner Alexander , Horn Helge , Koschorke Philipp , Razavi Nadja , Walther Sebastian , Wirtz Gustav
Published: March 2010

The translation from psychiatric core symptoms to brain functions and vice versa is a largely unresolved issue. In particular, the search for disorders of single brain regions explaining classical symptoms has not yielded the expected results. Based on the assumption that the psychopathology of psychosis is related to a functional imbalance of higher-order brain systems, the authors focused on three specific candidate brain circuitries, namely the language, and limbic and motor systems. These domains are of particular interest for understanding the disastrous communication breakdown during psychotic disorders. Core symptoms of psychosis were mapped on these domains by shaping their definitions in order to match the related brain functions. The resulting psychopathological assessment scale was tested for interrater reliability and internal consistency in a group of 168 psychotic patients. The items of the scale were reliable and a principal component analysis (PCA) was best explained by a solution resembling the three candidate systems. Based on the results, the scale was optimized as an instrument to identify patient subgroups characterized by a prevailing dysfunction of one or more of these systems. In conclusion, the scale is apt to distinguish symptom domains related to the activity of defined brain systems. PCA showed a certain degree of independence of the system-specific symptom clusters within the patient group, indicating relative subgroups of psychosis. The scale is understood as a research instrument to investigate psychoses based on a system-oriented approach. Possible immediate advantages in the clinical application of the understanding of psychoses related to system-specific symptom domains are also discussed.
Longitudinal Examination of Obesity and Cognitive Function: Results from the Baltimore Longitudinal Study of Aging
Authors: Gunstad John , Lhotsky April , Wendell Carrington Rice , Ferrucci Luigi , Zonderman Alan B.
Published: March 2010

Background: Obesity indices (i.e. BMI, waist-to-hip ratio) show differential relationships to other health outcomes, though their association to neurocognitive outcome is unclear. Methods: We examined whether central obesity would be more closely associated with cognitive function in 1,703 participants from the Baltimore Longitudinal Study of Aging. Results: Longitudinal mixed-effects regression models showed multiple obesity indices were associated with poorer performance in a variety of cognitive domains, including global screening measures, memory, and verbal fluency tasks. Obesity was associated with better performance on tests of attention and visuospatial ability. An obesity index by age interaction emerged in multiple domains, including memory and attention/executive function. Conclusion: Obesity indices showed similar associations to cognitive function, and further work is needed to clarify the physiological mechanisms that link obesity to poor neurocognitive outcome.
Development of Digestive Enzymes in the Piglet from Birth to 8 Weeks
Authors: Aumaitre A. , Corring T.
Published: March 2010

The changes with age of intestinal mucosa, protein, lactase, maltase and sucrase were followed in the piglet between day 105 of gestation and 8 weeks after birth. Lactase and maltase activities appeared during fetal life in the whole of the small intestine. Activity of sucrase was recorded after the 1st postnatal week. Lactase activity was high at birth and reached a maximum at 1 week (× 2.5); maltase activity which was low at birth increased to the 8th week (× 143). Activities of all enzymes were low in the duodenum; lactase was most active in the jejunum. Similar activities of maltase and sucrase were found in the two distal parts of the small intestine. Specific activity (related to protein content) of lactase reached a maximum at the end of the 1st week after birth and decreased afterwards. Specific maltase and sucrase activities were higher in the 2nd week, decreased between the 2nd and 4th week and increased afterwards (maltase) or decreased to the 6th-8fh week (sucrase).
Epicardial–Myocardial Signaling Directing Coronary Vasculogenesis
Authors: Olivey Harold E. , Svensson Eric C.
Published: March 2010

Abstract
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The establishment of the coronary circulation is critical for the development of the embryonic heart. Over the last several years, there has been tremendous progress in elucidating the pathways that control coronary development. Interestingly, many of the pathways that regulate the development of the coronary vasculature are distinct from those governing vasculogenesis in the rest of the embryo. It is becoming increasingly clear that coronary development depends on a complex communication between the epicardium, the subepicardial mesenchyme, and the myocardium mediated in part by secreted growth factors. This communication coordinates the growth of the myocardium with the formation of the coronary vasculature. This review summarizes our present understanding of the role of these growth factors in the regulation of coronary development. Continued progress in this field holds the potential to lead to novel therapeutics for the treatment of patients with coronary artery disease.
Holy Praiseco: Negotiating Sacred and Popular Music and Dance in African Pentecostalism
Authors: Kalu Ogbu U.
Published: March 2010

In post-colonial Africa, Pentecostal-Charismatic Christianity has slowly emerged as an influential shaper of culture and identity through its use of music, media, and dance. This article gives an overview of the transitions that have occurred in African politics, identity awareness, and culture, especially as it relates to the indigenous village public and it’s interface with the external Western public, and how the emergent cultural public has become the most influential player in shaping the African moral universe. Pentecostal-Charismatic Christianity has navigated the shift from a missionary-driven avoidance of indigenous music and dance to the incorporation of indigenous elements, leading in turn to the popularization of Pentecostal music and dance that blends indigenous forms and concepts, Christian symbolism, and popular cultural expressions. The resulting forms have not only shaped Christianity, but also the surrounding culture and its political environment.
Adolescence in the Atlantic: Charity Boys as Seamen in the Spanish Maritime World
Authors: Tikoff Valentina K.
Published: March 2010

This article examines life at a maritime orphanage and at sea for wards of the Royal School of San Telmo in Seville, which operated between 1681 and 1847. At its heart is a microhistorical analysis of Francisco de Cáceres Martínez, a ward whose life is traced from the time he entered the orphanage as a twelve-year-old in 1788 until he became an assistant pilot in 1802. This examination of the lives of Cáceres and other adolescent wards of the San Telmo orphanage sheds light on the experiences of young sailors and charity wards dispatched to sea, both of which were common in early modern maritime fleets but about whom details are often scarce. It also shows connections between their lives on land and at sea. The case of Cáceres and other San Telmo wards illuminates interactions among these youths, orphanage administrators, and Spanish naval officials, especially in the late eighteenth century. These interactions reveal that the same society and culture that tapped orphaned boys to meet Spanish maritime demands also afforded a measure of maneuverability to at least some of them, as wards used the language and institutions of a patriarchal system to navigate the eighteenth-century maritime world.
Education and Development: Why are Koreans Obsessed with Learning?
Authors: Oh Ingyu
Published: March 2010

The Korean learning pattern during the developmental period is typified by high levels of individual educational achievements despite extreme poverty in society. At the moment, the Korean proportion of private educational spending to GDP is the largest among OECD countries. I argue that the ongoing Korean educational frenzy is a result of a traditional subculture that emphasizes social success through education and individual educational choices, made by parents on behalf of their children based on psychological mechanisms of fear and han (or emotional enmity). The benefit of education in terms of economic development and political democracy continues to reinforce parents to be obsessive about children’s education even during the post-developmental stage. Yet, it is now obvious to Korean policymakers and parents alike that educational obsession is hampering both democracy and economic development.
Activism Gone Shopping: An Empirical Exploration of Individual-Level Determinants of Political Consumerism and Donating
Authors: Sandovici Maria Elena , Davis Terri
Published: March 2010

Using data collected from the European Social Survey (made available by the Norwegian Social Science Data Services), we compare the political acts of buycotting, boycotting, and direct monetary donation and examine the different individual-level attributes that determine people to engage in these political acts. Specifically, we examine the individual attributes that best indicate an individual’s propensity to engage in these activities. Our main findings are that women and young people participate in political consumerism more than men and older people. We also find that donors differ substantially from buycotters and boycotters, which leads us to conclude that donating is a different, more traditional type of participation than is political consumerism. This sets the stage for studying nontraditional realms of political expression and in particular indicates a need for future studies on political actors most likely to engage in political consumerism.
Standards of Good Practice in Qualitative Comparative Analysis (QCA) and Fuzzy-Sets
Authors: Schneider Carsten Q. , Wagemann Claudius
Published: March 2010

As a relatively new methodological tool, QCA is still a work in progress. Standards of good practice are needed in order to enhance the quality of its applications. We present a list from A to Z of twenty-six proposals regarding what a “good” QCA-based research entails, both with regard to QCA as a research approach and as an analytical technique. Our suggestions are subdivided into three categories: criteria referring to the research stages before, during, and after the analytical moment of data analysis. This listing can be read as a guideline for authors, reviewers, and readers of QCA.
Overcoming the Nagorno-Karabakh Stalemate
Authors: Hopmann P. Terrence , Zartman I. William
Published: March 2010

Six authors of the younger generation ‐ three from Armenia and three from Azerbaijan ‐ examine the conflict over Nagorno-Karabakh in a joint effort to overcome their heritage of stereotypes and hostility. While their proposals vary, there is some creative overlap, and all of them recognize the obstacles as four standard characteristics of intractable conflicts: no salient solution, no ripeness, profitability, and no Zone of Possible Agreement (ZOPA). From these obstacles stem some ideas for creative progress, if not immediate solutions.
Mountainous Karabakh: New Paradigms for Peace and Development in the 21st Century
Authors: Huseynov Tabib
Published: March 2010

This article analyzes the Karabakh conflict’s peace process and suggests a set of approaches to guide future progress. Proceeding from an interest-based framework, the research examines ways to reconcile the power, rights and interests of the conflicting parties. It is argued that a serious shift in the approaches and policies of both the conflicting parties and also the mediators is needed to achieve a breakthrough in the talks. In broader and long-term perspective, stable and sustainable conflict resolution requires the establishment of a power-sharing arrangement that would be based on equal and horizontal relationships between Armenians and Azeris at both sub-national (Mountainous Karabakh), and national (Azerbaijan) levels, and combines this power-sharing arrangement with regional integration.
Empowering and Engaging Civil Society in Conflict Resolution: The Case of Nagorno-Karabakh
Authors: Ghaplanyan Irina
Published: March 2010

Civil societies in Armenia, Azerbaijan and Nagorno-Karabakh have become alienated from the actual process of conflict resolution and need to be engaged in the political bargaining of the issue. This article addresses the importance of engaging civil society more deeply in this process. Only by empowering citizens through greater awareness and engaging civil society will the political elites from all sides of the conflict be forced to act more responsibly and participate in a more sincere and significant dialogue based on compromise rather than threats. To break the current deadlock, a new citizen-based initiative is needed based on a willingness to humanize the alleged enemy, consider options other than war, realize that the lives of immediate family members are at stake, learn about the benefits of compromise, and engage in reconciliation processes.
Childhood and its Regimes of Visibility in Brazil
Authors: de Castro Lucia Rabello , Kosminsky Ethel V.
Published: March 2010

This article analyses the contribution of the social sciences to the visibility of children’s issues in Brazilian society from the 1960s to the present day. The first regime of visibility considered childhood a relevant structural component of social inequalities, a ‘social problem’, stimulating social scientists to support social policies. Studies of children’s labour and, most importantly, of educational issues stimulated a variety of research directions. The second regime of visibility disclosed the actor behind the child, revealing the child as a social actor and a subject of rights. Childhood studies gained impetus on account of new legislation following the internationalization of children’s rights. Despite the broader scope of issues that social research on childhood has addressed, more sustained investment is needed so that childhood can attain a more equal position vis-a-vis other more salient research topics, and secure, de facto, the role of active participants in social life for children.
How passive ‘face time’ affects perceptions of employees: Evidence of spontaneous trait inference
Authors: Elsbach Kimberly D , Cable Dan M , Sherman Jeffrey W
Published: March 2010

We examine how passive ‘face time’ (i.e. the amount of time one is passively observed, without interaction) affects how one is perceived at work. Findings from a qualitative study of professional office workers suggest that passive face time exists in two forms: 1) being seen at work during normal business hours — or expected face time, and 2) being seen at work outside of normal business hours — or extracurricular face time. These two forms of passive face time appear to lead observers to make trait inferences (i.e. they lead observers to perceive employees as either ‘dependable’ or ‘committed’, depending on the form of passive face time). Findings from an experimental study confirm our qualitative findings and suggest that trait inferences are made spontaneously (i.e. without intent or knowledge of doing so).We discuss the implications of our findings for theories of person perception and the practice of performance appraisal.
‭שוב‬ in the Psalms— Shame or Disappointment?
Authors: Avrahami Yael
Published: March 2010

Honour and Shame in the Hebrew Bible are commonly discussed within the framework of a pan-Mediterranean social-scientific approach. In order to evaluate this model, this article seeks to understand the meaning of the verbal forms of ‭שוב‬, as found in Lament Psalms, where more than one third of its occurrences appear. The meaning of the root is determined on the basis of contextual analysis as well as the synonymous and antonymous roots. Such investigation demonstrates that the meaning of ‭שוב‬ is often ‘disappointment’ rather than ‘shame’. The application of the pan-Mediterranean model for passages that include the verbal forms of ‭שוב‬ would therefore need to be re-evaluated in future studies. Thus, this study demonstrates the importance of close investigation of any term in the native language before the employment of external models on the text.