bluuebunny/crossref_metadata_2025 huggingface dataset:
Wealth Effects, Local Area Attributes, and Economic Prospects: On the Relationship between House Prices and Mental Wellbeing
Authors: Ratcliffe Anita
Published: November 2013

This research exploits large variations in local house prices to investigate whether house prices correlate with mental wellbeing, and uses contrasting implications for the effect of house prices on the mental wellbeing of homeowners and renters to shed light on why this correlation might arise. I document a positive correlation between house prices and the mental wellbeing of both homeowners and non‐homeowners, which is inconsistent with a pure wealth effect. Instead this finding suggests that local house prices provide a reflection of available amenities and economic opportunities in the area.
Who is Deprived? Who Feels Deprived? Labor Deprivation, Youth, and Gender in Morocco
Authors: Serajuddin Umar , Verme Paolo
Published: November 2013

The paper provides a method to better understand how objective conditions of deprivation are translated into subjective feelings of deprivation using a strand of the recent literature on relative deprivation, and applies this method to labor deprivation in Morocco. We postulate that gender norms are associated with identity and the reference group that people compare themselves with. We find that the reference group plays a pivotal role in understanding how feelings of labor deprivation are generated and this can explain the apparent mismatch between objective conditions of deprivation and subjective feelings of deprivation related to joblessness among young men and women. It can also potentially help governments design public policies that address objective conditions of deprivation, such as unemployment, with a better understanding of subjective implications.
A Proposal to Compare Consistently the Inequality Among the Poor
Authors: Aristondo Oihana , Goerlich Gisbert Francisco J. , Lasso De La Vega Casilda
Published: November 2013

A poverty index should be sensitive to the number of poor people, the extent of the shortfall of the poor, and the inequality among the poor. A difficulty arises when inequality among the poor needs to be assessed. The inequality may be analyzed in terms of either incomes or gaps. Depending on what side we focus on, the inequality level comparisons may be contradictory. This paper proposes a reinterpretation of the inequality component involved in the decompositions of well‐known poverty indices. The alternative indices we introduce measure equally the income and gap inequality among the poor. The comparisons in inequality as measured by these indices are then independent of the viewpoint. An empirical application illustrates the proposal.
Psychometric properties and validation of thePolishCP QOL‐Child questionnaire: a pilot study
Authors: Dmitruk Elżbieta , Mirska Anna , Kułak Wojciech , Kalinowska Anna K. , Okulczyk Kamila , Wojtkowski Janusz
Published: November 2013

Aim

Translate, determine the psychometric properties and validate thePolishCP QOL‐Child questionnaire.

Materials and methods

A double translation of the questionnaire fromEnglish intoPolish and back was executed. The questionnaire was distributed to 55 parents/legal guardians of children with cerebral palsy aged 4–12 years. The psychometric properties of the questionnaire were determined on the basis of its internal consistency and the internal consistency of each of the investigated aspects, as well as on the assessment of the relationship between quality of life and such data as child's age, parent's age, place of residence andGMFCSlevel.

Results

The results showed high levels of internal consistency of thePolish version of theCP QOL‐Child questionnaire –Cronbach's α was between 0.77 and 0.82, which is comparable to the original scale, where it was 0.74–0.92. In addition, we found no relationship between child's age and parent's age and the child's quality of life. Whereas we determined dependencies between the child'sGMFCSlevel and quality of life in areas such as emotional state (p = 0.025), pain and the effects of disability (p = 0.033), and to a lesser extent participation in social life (p = 0.045). However,Spearman test presented that only domain pain and impact of disability reported positive correlation r = 0.43.

Conclusion

Studies showed thatEnglish language theCP QOL‐Child questionnaire was successful translated intoPolish which is confirmed by the results of the assessment of the psychometric properties and validation of thePolish language questionnaire. The results of our study indicate that thePolish language version of theCP QOL‐Child questionnaire is an appropriate tool to assess the quality of life ofPolish‐speaking children with cerebral palsy aged 4–12 years.
Parental stress and dyadic consensus in early parenthood among mothers and fathers in Sweden
Authors: Widarsson Margareta , Engström Gabriella , Berglund Anders , Tydén Tanja , Lundberg Pranee
Published: November 2013

Background

Parental stress can negatively affect the parent–child relationship and reduce the well‐being of the whole family. Family disagreement is associated with parental divorce and with psychological problems in children.

Aims

The aim was to examine perceived parental stress and draw comparisons among mothers and among fathers, in relation to educational level, parental experience, existence of a parental role model and sense of coherence. The aim was also to examine perceived dyadic consensus and its association with perceived parental stress within couples.

Methods

Questionnaires were completed by 320 mothers and 315 fathers at 1 week and 18 months post‐partum. The Swedish Parenthood Stress Questionnaire, the Sense of Coherence Scale and the Dyadic Consensus Subscale were used.

Results

Low education, lack of a role model and poor sense of coherence promoted stress in mothers in the subareassocial isolationandspouse relationship problems, while lack of a role model and poor sense of coherence promoted stress in fathers in the subareasocial isolation. Furthermore, parental experiences promoted stress among mothers in the subareaincompetencewhile this was not seen among fathers. Mothers perceived a higher level of dyadic consensus than fathers in the itemsrecreational activities, friends, aims and life goals, time spent together,anddecisions regarding career and personal development.Household taskswas the only item where fathers perceived a higher level of dyadic consensus than mothers. Additionally, there were associations between perceived parental stress and dyadic consensus in several items and in the total score.

Conclusions

To promote parents' health and family stability, health professionals should consider factors affecting stress and stress reactions, and take gender roles into account.
Smoking association with influenza infection in renal transplant recipients
Authors: Sparks J.A. , Brennan D.C. , Lawrence S.J.
Published: November 2013

We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3–76; P = 0.004).
Image‐based assessment of microvascular function and structure in collagen XV‐ and XVIII‐deficient mice
Authors: Rygh C. B. , Løkka G. , Heljasvaara R. , Taxt T. , Pavlin T. , Sormunen R. , Pihlajaniemi T. , Curry F. R. , Tenstad O. , Reed R. K.
Published: November 2013

Key points

Collagen XV and XVIII occur in muscle and connective tissue capillaries and are needed for maintaining a normal circulatory phenotype.

Lack of collagen XV in mice leads to increased vascular permeability, increased extraction fraction, and increased extravascular extracellular space in striated muscle.

Lack of collagen XVIII in mice leads to increased blood flow, permeability, permeability–surface area product and blood–tissue transvascular transfer in striated muscle tissue.

Our results show that functional imaging with MRI and subsequent data analysis provide reliable and robust data and are valuable tools for assessing detailed physiological information non‐invasively.

Collagen XV and XVIII are ubiquitous constituents of basement membranes. We aimed to study the physiological roles of these two components of the permeability barrier non‐invasively in striated muscle in mice deficient in collagen XV or XVIII by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). Structural information was obtained with transmission electron microscopy (TEM). MR data were analysed by two different analysis methods to quantify tissue perfusion and microcirculatory exchange parameters to rule out data analysis method‐dependent results. Control mice (C57BL/6J Ola/Hsd strain) or mice lacking either collagen XV (Col15a1−/−) or XVIII (Col18a1−/−) were included in the study. MR images were acquired using a preclinical system using gadodiamide (Gd‐DTPA‐BMA, molecular weight 0.58 kDa) as a tracer. Exchange capacity (permeability (P)–surface area (S) product relative to blood flow (FB)) was increased in test mice compared to controls, but the contributions from P, S, and FB were different in these two phenotypes. FB was significantly increased in Col18a1−/−, but slightly decreased in Col15a1−/−. PS was significantly increased only in Col18a1−/− even though P was increased in both phenotypes suggesting S might also be reduced in Col15a1−/− mice. Immunohistochemistry and electron microscopy demonstrated alterations in capillary density and morphology in both knockout mouse strains in comparison to the control mice. Both collagen XV and XVIII are important for maintaining normal capillary permeability in the striated muscle. DCE‐MRI and the perfusion analyses successfully determined microvascular haemodynamic parameters of genetically modified mice and gave results consistent with more invasive methods.
Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells
Authors: Irie Tomohiko , Matsuzaki Yasunori , Sekino Yuko , Hirai Hirokazu
Published: November 2013

Key points

The cerebellum plays crucial roles in controlling sensorimotor functions, and patients with spinocerebellar ataxia type 13 exhibit cerebellar atrophy and cerebellar symptoms.

The disease is an autosomal dominant disorder caused by missense mutations in the voltage‐gated K+ channel Kv3.3, which is expressed intensely in the cerebellar Purkinje cells, the sole output neurons from the cerebellar cortex.

Here, we examined how these mutations cause the cerebellar disease by lentiviral expression of the mutant Kv3.3 in mouse cultured Purkinje cells.

Expression of the mutant Kv3.3 suppressed outward currents, broadened action potentials and elevated basal intracellular calcium concentration in Purkinje cells. Moreover, the mutant‐expressing Purkinje cells showed impaired dendrites and extensive cell death, both of which were significantly rescued by blockade of P/Q‐type Ca2+ channels.

These results suggest that Purkinje cells in the patients also exhibit similar abnormalities, which may account for the pathology of the disease.

Abstract  The cerebellum plays crucial roles in controlling sensorimotor functions. The neural output from the cerebellar cortex is transmitted solely by Purkinje cells (PCs), whose impairment causes cerebellar ataxia. Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominant disease, and SCA13 patients exhibit cerebellar atrophy and cerebellar symptoms. Recent studies have shown that missense mutations in the voltage‐gated K+ channel Kv3.3 are responsible for SCA13. In the rodent brain, Kv3.3 mRNAs are expressed most strongly in PCs, suggesting that the mutations severely affect PCs in SCA13 patients. Nevertheless, how these mutations affect the function of Kv3.3 in PCs and, consequently, the morphology and neuronal excitability of PCs remains unclear. To address these questions, we used lentiviral vectors to express mutant mouse Kv3.3 (mKv3.3) channels harbouring an R424H missense mutation, which corresponds to the R423H mutation in the Kv3.3 channels of SCA13 patients, in mouse cerebellar cultures. The R424H mutant‐expressing PCs showed decreased outward current density, broadened action potentials and elevated basal [Ca2+]i compared with PCs expressing wild‐type mKv3.3 subunits or those expressing green fluorescent protein alone. Moreover, expression of R424H mutant subunits induced impaired dendrite development and cell death selectively in PCs, both of which were rescued by blocking P/Q‐type Ca2+ channels in the culture conditions. We therefore concluded that expression of R424H mutant subunits in PCs markedly affects the function of endogenous Kv3 channels, neuronal excitability and, eventually, basal [Ca2+]i, leading to cell death. These results suggest that PCs in SCA13 patients also exhibit similar defects in PC excitability and induced cell death, which may explain the pathology of SCA13.
Improving spot‐scanning proton therapy patient specific quality assurance with HPlusQA, a second‐check dose calculation engine
Authors: Mackin Dennis , Li Yupeng , Taylor Michael B. , Kerr Matthew , Holmes Charles , Sahoo Narayan , Poenisch Falk , Li Heng , Lii Jim , Amos Richard , Wu Richard , Suzuki Kazumichi , Gillin Michael T. , Zhu X. Ronald , Zhang Xiaodong
Published: November 2013

Purpose:

The purpose of this study was to validate the use of HPlusQA, spot‐scanning proton therapy (SSPT) dose calculation software developed at The University of Texas MD Anderson Cancer Center, as second‐check dose calculation software for patient‐specific quality assurance (PSQA). The authors also showed how HPlusQA can be used within the current PSQA framework.

Methods:

The authors compared the dose calculations of HPlusQA and the Eclipse treatment planning system with 106 planar dose measurements made as part of PSQA. To determine the relative performance and the degree of correlation between HPlusQA and Eclipse, the authors compared calculated with measured point doses. Then, to determine how well HPlusQA can predict when the comparisons between Eclipse calculations and the measured dose will exceed tolerance levels, the authors compared gamma index scores for HPlusQA versus Eclipse with those of measured doses versus Eclipse. The authors introduce theαβγ transformation as a way to more easily compare gamma scores.

Results:

The authors compared measured and calculated dose planes using the relative depth, z/R × 100%, where z is the depth of the measurement and R is the proton beam range. For relative depths than less than 80%, both Eclipse and HPlusQA calculations were within 2 cGy of dose measurements on average. When the relative depth was greater than 80%, the agreement between the calculations and measurements fell to 4 cGy. For relative depths less than 10%, the Eclipse and HPlusQA dose discrepancies showed a negative correlation, −0.21. Otherwise, the correlation between the dose discrepancies was positive and as large as 0.6. For the dose planes in this study, HPlusQA correctly predicted when Eclipse had and had not calculated the dose to within tolerance 92% and 79% of the time, respectively. In 4 of 106 cases, HPlusQA failed to predict when the comparison between measurement and Eclipseˈs calculation had exceeded the tolerance levels of 3% for dose and 3 mm for distance‐to‐agreement.

Conclusions:

The authors found HPlusQA to be reasonably effective (79% ± 10%) in determining when the comparison between measured dose planes and the dose planes calculated by the Eclipse treatment planning system had exceeded the acceptable tolerance levels. When used as described in this study, HPlusQA can reduce the need for patient specific quality assurance measurements by 64%. The authors believe that the use of HPlusQA as a dose calculation second check can increase the efficiency and effectiveness of the QA process.
An elastography method based on the scanning contact resonance of a piezoelectric cantilever
Authors: Fu Ji , Li Faxin
Published: November 2013

Purpose:

Most tissues may become significantly stiffer than their normal states when there are lesions inside. The tissueˈs modulus can then act as an identification parameter for clinic diagnosis of tumors or fibrosis, which leads to elastography. This study introduces a novel elastography method that can be used for modulus imaging of superficial organs.

Methods:

This method is based on the scanning contact‐resonance of a unimorph piezoelectric cantilever. The cantilever vibrates in its bending mode with the tip pressed tightly on the sample. The contact resonance frequency of the cantilever‐sample system is tracked at each scanning point, from which the sampleˈs modulus can be derived based on a beam dynamic model and a contact mechanics model. Scanning is performed by a three‐dimensional motorized stage and the whole system is controlled by a homemade software program based on LabVIEW.

Results:

Testing onin vitro beef tissues indicates that the fat and the muscle can be easily distinguished using this system, and the accuracy of the modulus measurement can be comparable with that of nanoindentation. Imaging on homemade gelatin phantoms shows that the depth information of the abnormalities can be qualitatively obtained by varying the pressing force. The detection limit of this elastography method is specially examined both experimentally and numerically. Results show that it can detect the typical lesions in superficial organs with the depth of several centimeters. The lateral resolution of this elastography method/system is better than 0.5 mm, and could be further enhanced by using more scanning points.

Conclusions:

The proposed elastography system can be regarded as a sensitive palpation robot, which may be very promising in early diagnosis of tumors in superficial organs such as breast and thyroid.
The Leaf Electroscope: A Take-Home Project of Unexpected Depth
Authors: Stewart John , Skinner Stephen , Stewart Gay
Published: November 2013

The leaf electroscope is a common piece of demonstration equipment found in many high school and introductory college physics laboratories. Its simplicity allows a compelling demonstration of electrostatic forces, and its versatility makes it useful in the demonstration of a number of physical phenomena. The electroscope has a long history; a device for detecting net static charge using a rotating needle, the versorium, was described by Gilbert in De Magnete in 1600.1 The leaf electroscope was invented by Bennet and described in a letter published by the Royal Society in 1787.2 This paper will describe the use of the leaf electroscope as a build-at-home project in the second-semester introductory calculus-based physics class at the University of Arkansas.
Service Learning in Introductory Astronomy
Authors: Orleski Michael
Published: November 2013

Service learning1 is a method of instruction where the students in a course use the course's content in a service project. The service is included as a portion of the students' course grades. During the fall semester 2010, service learning was incorporated into the Introduction to Astronomy course at Misericordia University. The class had eight students and the service project centered on hosting astronomy observations for fifth- and sixth-grade students from two nearby elementary schools. The astronomy students operated telescopes, pointed out constellations, and spoke to the audience members about the objects they were observing. Since service learning requires a minimum number of hours the students must log over the course of fulfilling the service project, the students planned alternative activities in case the weather did not allow the observations to be held. A key part of service learning is for the students to reflect on the service experience and how it influenced their learning of the course material.
Teaching Geophysics with a Vertical-Component Seismometer
Authors: van Wijk Kasper , Channel Ted , Viskupic Karen , Smith Martin L.
Published: November 2013

Earthquakes are some of the more dramatic expressions of the dynamics of our planet. The sudden release of stress built up slowly by tectonic or volcanic processes often has far-reaching consequences, and can be measured (in classrooms) around the world. This is one reason why designing and building seismometers has been a popular activity,1, 2 and why different versions of “Seismometer in Schools” projects thrive in the United States, Australia, and Europe. We present a cheap, robust, and easy-to-build seismometer—called the TC1 —to measure seismic displacements in the vertical direction. Its components are easy to obtain and assemble, yet the resulting instrument is accurate enough to record earthquakes from around the globe. The parts list and building instructions of the TC1 seismometer are freely available online. Alternatively, a complete kit can be purchased for around US$300. Assembling the system naturally introduces students to a number of concepts in physics and engineering, while upon completion seismic recordings trigger discussions about the dynamics and internal structure of the Earth. The discussions are fostered by service learning and shared in the network of TC1s called the Z-NET.
The Size of Earth from Seven Miles Up
Authors: Mottmann J.
Published: November 2013

While on a vacation flight from Hawaii to California, I observed sunset occurring on clouds far below. The view triggered a vague memory about a fun article1 published more than three decades earlier on the topic of “Doubling Your Sunsets.” Simple observations from my flight made it possible to compute the Earth's radius.
Thrombosis Prevention Without Bleeding Extension
Authors: Gough Nancy R.
Published: November 2013

Selectively inhibiting outside-in signaling prevents platelet spreading and prevents thrombosis without increasing bleeding time.
Making More Inhibitory Connections
Authors: Berndt Jason D.
Published: November 2013

NPAS4, an activity-dependent transcription factor, increases the number of inhibitory synapses to contribute to neuronal synaptic plasticity.
O
2
-Dependent Efficacy of Novel Piperidine- and Piperazine-Based Chalcones against the Human Parasite Giardia intestinalis
Authors: Bahadur Vijay , Mastronicola Daniela , Tiwari Hemandra Kumar , Kumar Yogesh , Falabella Micol , Pucillo Leopoldo Paolo , Sarti Paolo , Giuffrè Alessandro , Singh Brajendra Kumar
Published: November 2013

Giardia intestinalis
is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O
2
should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry,
1
H and
13
C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against
G. intestinalis
under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O
2
than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O
2
concentrations.
In Vitro
Study of Sequential Fluconazole and Caspofungin Treatment against Candida albicans Biofilms
Authors: Sarkar Semanti , Uppuluri Priya , Pierce Christopher G. , Lopez-Ribot Jose L.
Published: November 2013

Candida albicans
biofilms are generally considered to be resistant to azole antifungal agents but susceptible to echinocandins. We demonstrate that in a sequential therapy regimen, treatment with fluconazole first followed by caspofungin leads to a significant decrease of the efficacy of this echinocandin. Cellular stress responses induced by high fluconazole concentrations and mediated by Hsp90 and calcineurin play an important role in this phenomenon.
Baseline Hepatitis C Virus (HCV) NS3 Polymorphisms and Their Impact on Treatment Response in Clinical Studies of the HCV NS3 Protease Inhibitor Faldaprevir
Authors: Berger Kristi L. , Triki Ibtissem , Cartier Mireille , Marquis Martin , Massariol Marie-Josée , Böcher Wulf O. , Datsenko Yakov , Steinmann Gerhard , Scherer Joseph , Stern Jerry O. , Kukolj George
Published: November 2013

A challenge to the treatment of chronic hepatitis C with direct-acting antivirals is the emergence of drug-resistant hepatitis C virus (HCV) variants. HCV with preexisting polymorphisms that are associated with resistance to NS3/4A protease inhibitors have been detected in patients with chronic hepatitis C. We performed a comprehensive pooled analysis from phase 1b and phase 2 clinical studies of the HCV protease inhibitor faldaprevir to assess the population frequency of baseline protease inhibitor resistance-associated NS3 polymorphisms and their impact on response to faldaprevir treatment. A total of 980 baseline NS3 sequences were obtained (543 genotype 1b and 437 genotype 1a sequences). Substitutions associated with faldaprevir resistance (at amino acid positions 155 and 168) were rare (<1% of sequences) and did not compromise treatment response: in a phase 2 study in treatment-naive patients, six patients had faldaprevir resistance-associated polymorphisms at baseline, of whom five completed faldaprevir-based treatment and all five achieved a sustained virologic response 24 weeks after the end of treatment (SVR24). Among 13 clinically relevant amino acid positions associated with HCV protease resistance, the greatest heterogeneity was seen at NS3 codons 132 and 170 in genotype 1b, and the most common baseline substitution in genotype 1a was Q80K (99/437 [23%]). The presence of the Q80K variant did not reduce response rates to faldaprevir-based treatment. Across the three phase 2 studies, there was no significant difference in SVR24 rates between patients with genotype 1a Q80K HCV and those without Q80K HCV, whether treatment experienced (17% compared to 26%;P= 0.47) or treatment naive (62% compared to 66%;P= 0.72).
Evaluation of PD 404,182 as an Anti-HIV and Anti-Herpes Simplex Virus Microbicide
Authors: Chamoun-Emanuelli Ana M. , Bobardt Michael , Moncla Bernard , Mankowski Marie K. , Ptak Roger G. , Gallay Philippe , Chen Zhilei
Published: November 2013

PD 404,182 (PD) is a synthetic compound that was found to compromise HIV integrity via interaction with a nonenvelope protein viral structural component (A. M. Chamoun et al., Antimicrob. Agents Chemother. 56:672–681, 2012). The present study evaluates the potential of PD as an anti-HIV microbicide and establishes PD's virucidal activity toward another pathogen, herpes simplex virus (HSV). We show that the anti-HIV-1 50% inhibitory concentration (IC
50
) of PD, when diluted in seminal plasma, is ∼1 μM, similar to the IC
50
determined in cell culture growth medium, and that PD retains full anti-HIV-1 activity after incubation in cervical fluid at 37°C for at least 24 h. In addition, PD is nontoxic toward vaginal commensal
Lactobacillus
species (50% cytotoxic concentration [CC
50
], >300 μM), freshly activated human peripheral blood mononuclear cells (CC
50
, ∼200 μM), and primary CD4
+
T cells, macrophages, and dendritic cells (CC
50
, >300 μM). PD also exhibited high stability in pH-adjusted Dulbecco's phosphate-buffered saline with little to no activity loss after 8 weeks at pH 4 and 42°C, indicating suitability for formulation for transportation and storage in developing countries. Finally, for the first time, we show that PD inactivates herpes simplex virus 1 (HSV-1) and HSV-2 at submicromolar concentrations. Due to the prevalence of HSV infection, the ability of PD to inactivate HSV may provide an additional incentive for use as a microbicide. The ability of PD to inactivate both HIV-1 and HSV, combined with its low toxicity and high stability, warrants additional studies for the evaluation of PD's microbicidal candidacy in animals and humans.
Internalization and Trafficking of Nontypeable Haemophilus influenzae in Human Respiratory Epithelial Cells and Roles of IgA1 Proteases for Optimal Invasion and Persistence
Authors: Clementi Cara F. , Håkansson Anders P. , Murphy Timothy F.
Published: November 2013

Nontypeable
Haemophilus influenzae
(NTHI) is a leading cause of opportunistic infections of the respiratory tract in children and adults. Although considered an extracellular pathogen, NTHI has been observed repeatedly within and between cells of the human respiratory tract, and these observations have been correlated to symptomatic infection. These findings are intriguing in light of the knowledge that NTHI persists in the respiratory tract despite antibiotic therapy and the development of bactericidal antibodies. We hypothesized that intracellular NTHI avoids, escapes, or neutralizes the endolysosomal pathway and persists within human respiratory epithelial cells and that human IgA1 proteases are required for optimal internalization and persistence of NTHI. Virtually all strains encode a human IgA1 protease gene,
igaA
, and we previously characterized a novel human IgA1 protease gene,
igaB
, that is associated with disease-causing strains and is homologous to the IgA1 protease that is unique to pathogenic
Neisseria
spp. Here, we show that NTHI invades human bronchial epithelial cells
in vitro
in a lipid raft-independent manner, is subsequently trafficked via the endolysosomal pathway, and is killed in lysosomes after variable durations of persistence. IgaA is required for optimal invasion. IgaB appears to play little or no role in adherence or invasion but is required for optimal intracellular persistence of NTHI. IgaB cleaves lysosome-associated membrane protein 1 (LAMP1) at pHs characteristic of the plasma membrane, early endosome, late endosome, and lysosome. However, neither IgA1 protease inhibits acidification of intracellular vesicles containing NTHI. NTHI IgA1 proteases play important but different roles in NTHI invasion and trafficking in respiratory epithelial cells.
EatA, an Immunogenic Protective Antigen of Enterotoxigenic Escherichia coli, Degrades Intestinal Mucin
Authors: Kumar Pardeep , Luo Qingwei , Vickers Tim J. , Sheikh Alaullah , Lewis Warren G. , Fleckenstein James M.
Published: November 2013

Enterotoxigenic
Escherichia coli
(ETEC) is a major cause of morbidity and mortality due to infectious diarrhea in developing countries for which there is presently no effective vaccine. A central challenge in ETEC vaccinology has been the identification of conserved surface antigens to formulate a broadly protective vaccine. Here, we demonstrate that EatA, an immunogenic secreted serine protease of ETEC, contributes to virulence by degrading MUC2, the major protein present in the small intestinal mucous layer, and that removal of this barrier
in vitro
accelerates toxin access to the enterocyte surface. In addition, we demonstrate that vaccination with the recombinant secreted passenger domain of EatA (rEatA
p
) elicits high titers of antibody and is protective against intestinal infection with ETEC. These findings may have significant implications for development of both subunit and live-attenuated vaccines against ETEC and other enteric pathogens, including
Shigella flexneri
, that express similar proteins.
Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi
Authors: He Ming , Zhang Jun-Jie , Ye Meiping , Lou Yongliang , Yang X. Frank
Published: November 2013

As an obligate pathogen, the Lyme disease spirochete
Borrelia burgdorferi
has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for
B. burgdorferi
to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates
rpoS
expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating
rpoS
expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that
B. burgdorferi
utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.
Fungal Morphogenetic Pathways Are Required for the Hallmark Inflammatory Response during Candida albicans Vaginitis
Authors: Peters Brian M. , Palmer Glen E. , Nash Andrea K. , Lilly Elizabeth A. , Fidel Paul L. , Noverr Mairi C.
Published: November 2013

Vulvovaginal candidiasis, caused primarily by
Candida albicans
, presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability of
C. albicans
to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria for defining vaginitis immunopathology, the purpose of this study was to determine whether the yeast-to-hypha transition is required for the hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses of vaginal infection with
C. albicans
in C57BL/6 mice demonstrated that fungal burdens remained constant throughout the observation period, while polymorphonuclear leukocyte (PMN), S100A8, and interleukin-1β levels obtained from vaginal lavage fluid increased by day 3 onward. Lactate dehydrogenase activity was also positively correlated with increased effectors of innate immunity. Additionally, immunodepletion of neutrophils in infected mice confirmed a nonprotective role for PMNs during vaginitis. Determination of the importance of fungal morphogenesis during vaginitis was addressed with a two-pronged approach. Intravaginal inoculation of mice with
C. albicans
strains deleted for key transcriptional regulators (
bcr1
Δ/Δ,
efg1
Δ/Δ,
cph1
Δ/Δ, and
efg1
Δ/Δ
cph1
Δ/Δ) controlling the yeast-to-hypha switch revealed a crucial role for morphogenetic signaling through the Efg1 and, to a lesser extent, the Bcr1 pathways in contributing to vaginitis immunopathology. Furthermore, overexpression of transcription factors
NRG1
and
UME6
, to maintain yeast and hyphal morphologies, respectively, confirmed the importance of morphogenesis in generating innate immune responses
in vivo
. These results highlight the yeast-to-hypha switch and the associated morphogenetic response as important virulence components for the immunopathogenesis of
Candida
vaginitis, with implications for transition from benign colonization to symptomatic infection.
Sentinel lymph nodes with isolated tumour cells and micrometastases in breast cancer: clinical relevance and prognostic significance
Authors: Ahmed Syed Salahuddin , Thike Aye Aye , Iqbal Jabed , Yong Wei Sean , Tan Benita , Madhukumar Preetha , Ong Kong Wee , Ho Gay Hui , Wong Chow Yin , Tan Puay Hoon
Published: November 2013

Aim

We performed a retrospective review to determine the prognostic significance of isolated tumour cells (ITCs) and micrometastases to the sentinel lymph nodes of patients with breast cancer.

Methods

A total of 1044 patients with a diagnosis of invasive carcinoma of the breast who underwent surgical treatment including the sentinel lymph node biopsy procedure from July 2004 to October 2009 were included in the study.

Results

In 710 (68%) patients, no metastasis was seen to the sentinel lymph nodes. ITCs were detected in 22 (2.1%) patients, micrometastasis in 52 (5.0%) and macrometastases in 260 (24.9%). With a median follow-up of 28.8 months, disease recurrence was seen in 38 (3.6%) patients and 15 (1.5%) patients died of disease. No disease recurrence or deaths were recorded in women with ITCs in sentinel lymph nodes. In the micrometastasis group, 2 patients suffered disease recurrence and both died of disease.

Conclusions

We conclude that ITCs in the sentinel lymph nodes did not adversely impact disease free and overall survivals. Although only 2 recurrences with subsequent death occurred in the micrometastasis group, it may suggest a propensity for presence of micrometastases to augur a worse outcome, and justifies continued segregation of ITCs from micrometastasis.
Male hypercalciuric stone formers with low renal calcium reabsorption
Authors: Walker Valerie , Cook Paul , Griffin Damian G
Published: November 2013

Aims

Hypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors.

Methods

A retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium.

Results

276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175–371 and 153–316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative.

Conclusions

Hypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier.
ALL ORDER COVARIANT TUBULAR EXPANSION
Authors: MUKHOPADHYAY PARTHA
Published: November 2013

We consider tubular neighborhood of an arbitrary submanifold embedded in a (pseudo-) Riemannian manifold. This can be described by Fermi normal coordinates (FNC) satisfying certain conditions as described by Florides and Synge in [15]. By generalizing the work of Muller et al. in [54] on Riemann normal coordinate expansion, we derive all order FNC expansion of vielbein in this neighborhood with closed form expressions for the curvature expansion coefficients. Our result is shown to be consistent with certain integral theorem for the metric proved in [15].
SELF-SUPERVISED MRI TISSUE SEGMENTATION BY DISCRIMINATIVE CLUSTERING
Authors: GONÇALVES NICOLAU , NIKKILÄ JANNE , VIGÁRIO RICARDO
Published: November 2013

The study of brain lesions can benefit from a clear identification of transitions between healthy and pathological tissues, through the analysis of brain imaging data. Current signal processing methods, able to address these issues, often rely on strong prior information. In this article, a new method for tissue segmentation is proposed. It is based on a discriminative strategy, in a self-supervised machine learning approach. This method avoids the use of prior information, which makes it very versatile, and able to cope with different tissue types. It also returns tissue probabilities for each voxel, crucial for a good characterization of the evolution of brain lesions. Simulated as well as real benchmark data were used to validate the accuracy of the method and compare it against other segmentation algorithms.
GRASSMANNIAN-FRAMED BUNDLES AND GENERALIZED PARABOLIC STRUCTURES
Authors: BHOSLE USHA , BISWAS INDRANIL , HURTUBISE JACQUES
Published: November 2013

We build compact moduli spaces of Grassmannian-framed bundles over a Riemann surface, essentially replacing a group by a bi-equivariant compactification. We do this both in the algebraic and symplectic settings, and prove a Hitchin–Kobayashi correspondence between the two. The spaces are universal spaces for parabolic bundles (in the sense that all of the moduli can be obtained as quotients), and the reduction to parabolic bundles commutes with the correspondence. An analogous correspondence is outlined for the generalized parabolic bundles of Bhosle.
ASYMPTOTIC APPROXIMATIONS AND A BOREL-TYPE RESULT FOR CR FUNCTIONS
Authors: DELLA SALA GIUSEPPE , LAMEL BERNHARD
Published: November 2013

We show that for any smooth CR manifold which has a peak function (in a weak sense) at some point p, formal power series at p can be approximated asymptotically by continuous CR functions. Furthermore, if the peak function satisfies a certain growth property, the asymptotic approximation is actually smooth. This in fact allows to invert, in a Borel-type theorem, the natural map taking a smooth CR function to its formal Taylor series.
ON A MATHEMATICAL THEORY OF COMPLEX SYSTEMS ON NETWORKS WITH APPLICATION TO OPINION FORMATION
Authors: KNOPOFF D.
Published: November 2013

This paper presents a development of the so-called kinetic theory for active particles to the modeling of living, hence complex, systems localized in networks. The overall system is viewed as a network of interacting nodes, mathematical equations are required to describe the dynamics in each node and in the whole network. These interactions, which are nonlinearly additive, are modeled by evolutive stochastic games. The first conceptual part derives a general mathematical structure, to be regarded as a candidate towards the derivation of models, suitable to capture the main features of the said systems. An application on opinion formation follows to show how the theory can generate specific models.
FROM BRICKS TO QUASINORMAL MODES: A NEW PERSPECTIVE ON BLACK HOLE ENTROPY
Authors: ARZANO MICHELE , BIANCO STEFANO , DREYER OLAF
Published: November 2013

Calculations of black hole entropy based on the counting of modes of a quantum field propagating in a Schwarzschild background need to be regularized in the vicinity of the horizon. To obtain the Bekenstein–Hawking result, the short distance cut-off needs to be fixed by hand. In this note, we give an argument for obtaining this cut-off in a natural fashion. We do this by modeling the black hole by its set of quasinormal modes (QNMs). The horizon then becomes a extended region: the quantum ergosphere. The interaction of the quantum ergosphere and the quantum field provides a natural regularization mechanism. The width of the quantum ergosphere provides the right cut-off for the entropy calculation. We arrive at a dual picture of black hole entropy. The entropy of the black hole is given both by the entropy of the quantum field in the bulk and the dynamical degrees of freedom on the horizon.
A SIMPLIFIED TWO-BODY PROBLEM IN GENERAL RELATIVITY
Authors: HOD SHAHAR
Published: November 2013

General relativity, Einstein's theory of gravity, predicts a universe full of black holes and gravitational waves. The prospects of detecting gravitational waves from inspirals of compact astrophysical objects into supermassive black holes have made it highly important to analyze in detail the gravitational two-body problem. While the two-body problem in Newtonian gravity (the weak-field limit) has a well-defined compact analytic solution, the corresponding problem in general relativity (the strong-field regime) is very complex and cannot be solved analytically. In this paper, we propose to model the two-body problem in general relativity using the analytically solvable model of a ring of particles in orbit around a central black hole. We use our model to calculate the innermost stable circular orbit (ISCO) frequency which characterizes the two-body dynamics. Remarkably, our expression for the characteristic ISCO frequency through linear order in the ring's mass predicts with astonishing accuracy the actual value of this fundamental parameter.
MUONIC HYDROGEN AS A QUANTUM GRAVIMETER
Authors: ONOFRIO ROBERTO
Published: November 2013

High precision spectroscopy of muonic hydrogen has recently led to an anomaly in the Lamb shift, which has been parametrized in terms of a proton charge radius differing by seven standard deviations from the CODATA value. We show how this anomaly may be explained, within about a factor of three, in the framework of an effective Yukawian gravitational potential related to charged weak interactions, without additional free parameters with respect to the ones of the standard model. The residual discrepancy from the experimental result in this model should be attributable to the approximations introduced in the calculation, the uncertainty in the exact value of the Fermi scale relevant to the model and the lack of detailed knowledge on the gravitational radius of the proton. The latter cannot be inferred with electromagnetic probes due to the unknown gluonic contribution to the proton mass distribution. In this context, we argue that muonic hydrogen acts like a microscopic gravimeter suitable for testing a possible scenario for the reciprocal morphing between macroscopic gravitation and weak interactions, with the latter seen as the quantum, microscopic counterpart of the former.
NEUTRON–PROTON PAIRS IN NUCLEI
Authors: VAN ISACKER P.
Published: November 2013

A review is given of attempts to describe nuclear properties in terms of neutron–proton pairs that are subsequently replaced by bosons. Some of the standard approaches with low-spin pairs are recalled but the emphasis is on a recently proposed framework with pairs of neutrons and protons with aligned angular momentum. The analysis is carried out for general j and applied to N=Z nuclei in the 1f7/2 and 1g9/2 shells.
CHAOS, STRATEGY, AND ACTION: HOW NOT TO FIDDLE WHILE ROME BURNS
Authors: PHILLIPS FRED , SU YU-SHAN
Published: November 2013

The US financial meltdown has changed companies' situations not just fundamentally but pervasively. Institutions and channels of supply and communication have disappeared or become unreliable; we are literally managing in chaos, and traditional notions of strategy, planning, and implementation must be (temporarily, it is to be hoped) discarded. This presentation draws on classic management theory, newer ideas, and experiences from technology companies to outline principles for managing for survival in times of chaos. It introduces new management cycles as alternatives to Fayol's classic management cycle, and a corresponding taxonomy of organizational situations, including stable, chaos, edge of chaos, and disaster. It aims for a clear synthesis suitable for management education and training.