bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient particulate matter affects occludin distribution and increases alveolar transepithelial electrical conductance
Authors: CARABALLO Juan C. , YSHII Cecilia , WESTPHAL Whitney , MONINGER Thomas , COMELLAS Alejandro P.
Published: December 2010

Background and objective:  Inhaled particulate matter (PM) causes lung inflammation and epithelial dysfunction. However, the direct effect of PM on alveolar epithelial barrier integrity is not well understood. Our aim is to determine whether PM exposure affects the alveolar epithelial cells (AEC) transepithelial electrical conductance (Gt) and tight junction (TJ) proteins.

Methods:  Human AEC (A549) and primary rat AEC were exposed to PM of <10 µm in size (PM10) and diesel exhaust particles (DEP), using titanium dioxide (TiO2) as a control for particle size effects. Gt and permeability to fluorescein isothiocyanate‐dextran (FITC‐Dextran) were measured to assess barrier integrity. TJ integrity was evaluated by analysing penetration of Lanthanum nitrate (La3+) under transmission electron microscopy. Surface proteins were labelled with biotin and analysed by western blot. Immunofluorescence was performed to assess colocalization of TJ proteins including occludin and zonula occludens‐1 (ZO‐1). PM induced dissociation of occludin‐ZO‐1 was evaluated by co‐immunoprecipitation.

Results:  PM10 and DEP increased Gt and disrupted TJ after 3 h of treatment. PM10 and DEP induced occludin internalization from the plasma membrane into endosomal compartments and dissociation of occludin from ZO‐1. Overexpression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and catalase, prevented PM‐induced Gt increase, occludin reduction from the plasma membrane and its dissociation from ZO‐1.

Conclusions:  PM induces alveolar epithelial dysfunction in part via occludin reduction at the plasma membrane and ZO‐1 dissociation in AEC. Furthermore, these effects are prevented by overexpression of two different antioxidant enzymes.
Psychological stress‐induced changes in salivary alpha‐amylase and adrenergic activity
Authors: Kang Younhee
Published: December 2010

The aim of the study was to examine the relationships among salivary alpha‐amylase, plasma catecholamines, blood pressure, and heart rate during psychological stress. This study used a pretest–post‐test experimental design with a control group, using repeated measures. A total of 33 participants was divided into the experimental group (n = 16) that underwent a college academic final test as the psychological stress and the control group (n = 17) that did not undergo the test. The levels of salivary alpha‐amylase and plasma catecholamines, blood pressure, and heart rate were measured seven times and stress and anxiety were measured once and twice, respectively, as subjective stress markers. Significant changes in the level of salivary alpha‐amylase were found in response to psychological stress. However, the correlations of salivary alpha‐amylase with the plasma catecholamines, blood pressure, and heart rate were only partially found to be statistically significant. In conclusion, it was shown that salivary alpha‐amylase was sensitive to stress throughout this study. Thus, salivary alpha‐amylase may be used to measure stress uninvasively in both clinical settings and nursing research where the effects of stress might be scrutinized. Furthermore, the mechanisms of illnesses that are induced by stress could be explored.
Analgesia and sedation after pediatric cardiac surgery
Authors: Wolf Andrew R. , Jackman Lara
Published: December 2010

In recent years, the importance of appropriate intra‐operative anesthesia and analgesia during cardiac surgery has become recognized as a factor in postoperative recovery. This includes the early perioperative management of the neonate undergoing radical surgery and more recently the care surrounding fast‐track and ultra fast‐track surgery. However, outside these areas, relatively little attention has focused on postoperative sedation and analgesia within the pediatric intensive care unit (PICU). This reflects perceived priorities of the primary disease process over the supporting structure of PICU, with a generic approach to sedation and analgesia that can result in additional morbidities and delayed recovery. Management of the marginal patient requires optimisation of not only cardiac and other attendant pathophysiology, but also every aspect of supportive care. Individualized sedation and analgesia strategies, starting in the operating theater and continuing through to hospital discharge, need to be regarded as an important aspect of perioperative care, to speed the process of recovery.
Trends of e‐learning research from 2000 to 2008: Use of text mining and bibliometrics
Authors: Hung Jui‐long
Published: December 2010

This study investigated the longitudinal trends of e‐learning research using text mining techniques. Six hundred and eighty‐nine (689) refereed journal articles and proceedings were retrieved from the Science Citation Index/Social Science Citation Index database in the period from 2000 to 2008. All e‐learning publications were grouped into two domains with four groups/15 clusters based on abstract analysis. Three additional variables: subject areas, prolific countries and prolific journals were applied to data analysis and data interpretation. Conclusions include that e‐learning research is at the early majority stage and foci have shifted from issues of the effectiveness of e‐learning to teaching and learning practices. Educational studies and projects and e‐learning application in medical education and training are growing fields with the highest potential for future research. Approaches to e‐learning differ between leading countries and early adopter countries, and government policies play an important role in shaping the results.
Promoting positive parenting practices in primary pare: Outcomes and mechanisms of change in a randomized controlled risk reduction trial
Authors: REEDTZ CHARLOTTE , HANDEGÅRD BJØRN HELGE , MØRCH WILLY‐TORE
Published: December 2010

Reedtz, C., Handegård, B.H. & Mørch, W.‐T. (2011). Promoting positive parenting practices in primary pare: Outcomes and mechanisms of change in a randomized controlled risk reduction trial. Scandinavian Journal of Psychology 52, 131–137.

The aim of the present study was to evaluate whether a short parent‐training program (PT) reduces risk factors related to development of childhood socio‐emotional and behavior problems in a non‐clinical community sample. Data were obtained from parents in a randomized controlled trial (RCT) on PT for children aged 2 to 8 years (N = 186) at pre‐intervention, post‐intervention and one‐year‐follow up. There were significant differences in the changes in the two groups, with reductions in harsh parenting and child behavior problems, an enhancement of positive parenting and of the parents’ sense of competence in the intervention group. The effects on parenting and parents’ satisfaction all lasted through one‐year follow up. Our findings suggests that a shortened version of a well‐structured parenting intervention, The Incredible Years program, implemented in primary care at community level, reduces harsh parenting and strengthens positive parenting and parents’ sense of competence, as reported by the parents. Issues related to a public health approach to promote positive parenting are discussed.
Approximate Bayesian Inference for Survival Models
Authors: MARTINO SARA , AKERKAR RUPALI , RUE HÅVARD
Published: December 2010

Abstract. Bayesian analysis of time‐to‐event data, usually called survival analysis, has received increasing attention in the last years. In Cox‐type models it allows to use information from the full likelihood instead of from a partial likelihood, so that the baseline hazard function and the model parameters can be jointly estimated. In general, Bayesian methods permit a full and exact posterior inference for any parameter or predictive quantity of interest. On the other side, Bayesian inference often relies on Markov chain Monte Carlo (MCMC) techniques which, from the user point of view, may appear slow at delivering answers. In this article, we show how a new inferential tool named integrated nested Laplace approximations can be adapted and applied to many survival models making Bayesian analysis both fast and accurate without having to rely on MCMC‐based inference.
Semi‐supervised classification of facial expression using a mixture of multivariatetdistributions
Authors: Wang Haixian
Published: December 2010

Abstract:This paper addresses the semi‐supervised classification of facial expression images using a mixture of multivariate t distributions. The facial expression features are first extracted into labelled graph vectors using the Gabor wavelet transformation. We then learn a mixture of multivariate t distributions by using the labelled graph vectors, and set correspondence between the component distributions and the basic facial emotions. According to this correspondence, the classification of a given testing image is implemented in a probabilistic way according to its fitted posterior probabilities of component memberships. Specifically, we perform hard classification of the testing image by assigning it into an emotional class that the corresponding mixture component has the highest posterior probability, or softly use the posterior probabilities as the estimates of the semantic ratings of expressions. The experimental results on the Japanese female facial expression database, Ekman's Pictures of Facial Affect database and the AR database demonstrate the effectiveness of the proposed method.
Multiple scale neural architecture for enhancing regions in the colour image segmentation process
Authors: Díaz‐Pernas Francisco J. , Antón‐Rodríguez Míriam , Martínez‐Zarzuela Mario , Díez‐Higuera J. Fernando , González‐Ortega David , Boto‐Giralda Daniel
Published: December 2010

Abstract:A dynamic multi‐scale neural model for enhancing regions and extracting contours in the colour image segmentation process is proposed. This model combines colour and textural information to coherently enhance images through the operation of two main components: the colour opponent system (COS) and the chromatic segmentation system (CSS). First, the COS module transforms the RGB chromatic input signals into long‐ (L), middle‐ (M) and short‐ (S) wavelength cone activations and luminance signals and then it generates the luminance (black–white), L–M and S–(L+M) opponent channels. The CSS module incorporates contour extraction, double opponency mechanisms and diffusion processes to yield coherent enhancing regions in colour image segmentation. This enhancement allows the region labelling to be more efficient due to a reduction in the uncertainty of the images' region allocation. The CSS module is based on the boundary contour system/feature contour system, extending it to allow colour stimuli processing to obtain general purpose architecture for image segmentation with later applications in computer vision and object recognition. Simulations show the good visual results obtained and the robustness of the architecture when processing images presenting different levels of noise. A benchmark using the Berkeley Segmentation Dataset is included in order to quantify and compare the results obtained.
Evaluation of apoptosis regulatory markers in androgenetic alopecia
Authors: El‐Domyati Moetaz , Attia Sameh , Saleh Fatma , Bassyouni Mohamed , Barakat Manal , Abdel‐Wahab Hossam
Published: December 2010

Background  Androgenetic alopecia (AGA) is a common androgen‐induced progressive disorder; the pathways of which are regulated by local genetic codes and hormonal control. Meanwhile, it is unclear whether an altered proliferation or increased apoptosis could contribute to its pathogenesis.

Aims  To evaluate the role of some apoptosis regulatory markers and follicular proliferation in the pathogenesis of AGA.

Patients/Methods  Thirty biopsies were taken from the frontal (bald) area and occipital (hair‐bearing) area of 15 male patients with AGA, as well as five specimens from the frontal area of five age‐matched controls. The biopsies were stained with apoptosis regulatory markers (Bcl‐2, p53, Bax & Fas) and PCNA (proliferating cell nuclear antigen), as well as TUNEL (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end‐labeling) staining for the detection of DNA fragmentation in apoptotic cells.

Results  Bcl‐2 expression was localized to epidermal basal layer and follicular dermal papilla with highly significant correlation with PCNA expression (P < 0.001). Perifollicular lymphocytic infiltrate of the bald area showed significant expression of Bcl‐2. However, pro‐apoptotic Bax and Fas were expressed in the epidermis and not in the hair follicles which does not show any apoptotic keratinocytes by TUNEL staining.

Conclusion  The low proliferation rate in the bald area of patients, together with persistent perifollicular inflammatory infiltrate as evidenced by the anti‐apoptotic Bcl‐2 expression in dermal lymphocytes, would result in follicular miniaturization and fibrosis.
A European evaluation of cosmetic treatment of facial volume loss with Juvéderm™ Voluma™ in patients previously treated with Restylane Sub‐Q™
Authors: Fischer Tanja C
Published: December 2010

Background  Juvéderm™ VOLUMA™ (Voluma) is a new injectable, long‐lasting, resorbable hyaluronic acid filler. It restores facial volume, resulting in a more youthful appearance.

Aims  To evaluate current in‐market perceptions of the aesthetic result and use of Voluma.

Patients/methods  Men and women >30 years who had received Restylane SubQ™ (Restylane) <2 years previously, now requiring re‐treatment and who consented to Voluma treatment were included.

Results  Eighty‐four patients (mean age 51 years, 88% women) were recruited. The mean total volume of Voluma injected was 2.73 mL/patient. This included treatment to both sides of the face, specifically in the malar and chin areas or both (mean 1.36 mL each to the right and left sides of the face). Seventy‐five percent of injectors found Voluma fairly/very easy to inject and 84.5% found it easy to sculpt/massage. Most patients (98%) and physicians (98%) rated the aesthetic effect of Voluma as improved. Injectors rated Voluma as better than previous Restylane use in 69.1% of patients (P < 0.001), and preference for Voluma was expressed in 61% of patients (P < 0.001). Ninety‐nine percent of injectors would recommend Voluma to colleagues and patients (100%); 96.4% of patients would recommend it to friends. Treatment was well tolerated.

Conclusions  Voluma is easy to use, sculpt, and massage. Physicians and patients rated the cosmetic effects highly, and both groups reported a preference for Voluma in those patients previously treated with Restylane.
Nonablative fractional laser resurfacing in Asian skin – a review
Authors: Sachdeva Silonie
Published: December 2010

Skin resurfacing has been a part of cosmetic dermatology for more than two decades now, and most of it has been ablative with traditional aggressive lasers including the CO2 and erbium. The last few years have seen a revolutionary change with the invention of nonablative lasers for skin tightening. Fractional resurfacing is a new concept of cutaneous remodeling whereby laser‐induced zones of microthermal injury are surrounded by normal untreated tissue that helps in quicker healing. The various wavelengths used are 1320, 1440, and 2940 nm with depth of penetration ranging from 25 μ to 1.2 mm. This article reviews the history of nonablative fractional laser resurfacing, its indications, contraindications, and a review of use in Asian skin with Fitzpatrick type III–VI.
Exogenous ochronosis – a diagnostic challenge
Authors: Tan Siak‐Khim (SK)
Published: December 2010

Exogenous ochronosis has been reported worldwide following long‐term application of skin‐lightening creams that contain hydroquinone, phenol or resorcinol. This report documents six patients presenting in Singapore with greatly differing facial dyschromias and discusses the diagnostic difficulties.
High‐power diode laser use on Fordyce granule excision: a case report
Authors: Baeder Fernando M , Pelino Jose E P , De Almeida Eliete R , Duarte Danilo A , Santos Maria T B R
Published: December 2010

Background  Fordyce granules are conventionally considered to be a developmental oral lesion with a higher incidence in men.

Objective  To report a clinical case of surgical lip Fordyce granule excision in a 19‐year‐old male.

Methods  Fordyce granules were excised using a high‐power diode laser (gallium arsenide [GaAs], Diode Vision®, MDL, 10 Dental Laser Unit, GmbH, Lower Saxony, Germany) with wavelength emission at 980 ± 10 nm, in a continuous wave mode, pulse width of 0.5 μs, fiber optic delivery system of 400 μm in diameter, at 2.5 W. Subsequently, low‐intensity laser therapy was applied (gallium‐aluminum‐arsenide [GaAlAs], at 670 nm, 50 mW, at 4 J/cm2; Dentoflex®, São Paulo, Brazil] in order to stimulate a faster wound tissue–healing process and less postoperative pain and inflammation.

Conclusion  The excellent esthetic result demonstrated the effectiveness of both high‐ and low‐intensity laser therapy on the excision of Fordyce granules.
Finasteride‐induced depression: new insights into possible pathomechanisms
Authors: Römer Benedikt , Gass Peter
Published: December 2010

5‐alpha‐reductase is involved as a rate‐imitating enzyme in the metabolism of steroids. Several 5‐alpha‐reduced steroids such as dihydrotestosterone, allopregnanolone or tetrahydrocorticosterone have neurotrophic, neuroprotective, and anxiolytic properties. Reduced 5‐alpha‐reductase activity has been observed during depressive illness in humans. Finasteride inhibits 5‐alpha‐reductase and can robustly induce anxious and depressive behaviors in rodents. In humans finasteride treatment has been linked to an increase of depressive symptoms. A recent study reported that finasteride treatment inhibits hippocampal neurogenesis in mice. As hippocampal neurogenesis has been linked to emotional behavior, this could be of possible relevance for the pathophysiology of affective disorders. Further studies are needed to evaluate potential neuropsychiatric side effects of finasteride treatment in humans.
Gender and History of the Postbellum U.S. South
Authors: Oglesby Catherine
Published: December 2010

Although gender as a category of analysis has been largely accepted in the discipline of history for its valuable insights, such acceptance was not without resistance. The difficulty of understanding how gender applies in all historical situations impeded early endorsement. In this article, I examine works of historians writing on the postbellum U.S. South, a time and place when all social and political relations were especially volatile and in flux. The chosen works reveal the ways gender has collapsed the divide between public and private, between social and political history, divisions that have defied resolution. They also provided a foundation for studies on the Civil War, Reconstruction, and Jim Crow, which followed.
Hyponatremia and Hypokalemia in Patients on Peritoneal Dialysis
Authors: Zanger Ron
Published: December 2010

Hypokalemia occurs in up to 60% of patients on peritoneal dialysis (PD) for end‐stage renal disease. It can be associated with poor clinical outcomes, including malnutrition and death. New evidence points to a link between hypokalemia and the risk of peritonitis. The serum Na+ concentration is determined by the ratio of exchangeable Na+ and K+ to total body water. Hyponatremia may be caused by excessive thirst, a particular problem in patients on PD. Consistent with the relationship among the serum sodium concentration, total body cation content, and total body water, hyponatremia may also be caused by total body potassium depletion. Ultra‐low sodium dialysis fluid may prove to have an important role in management of fluid overload and hypertension in patients on PD. Surprisingly, it is not associated with significant hyponatremia, for reasons that remain to be elucidated.
Multiple, Recurrent, Refractory Vascular Malformations as the Primary Presenting Feature of a PTEN Mutation
Authors: SHARABI SAFA E. , KOSHY JOHN C. , HOLLIER JR. LARRY H.
Published: December 2010

Abstract:  Complete history and physical examinations are very important in patients with a vascular anomaly. This brief report highlights the case of a five‐year‐old male who presented with recurrent arteriovenous malformations of the hand and forearm. The patient also demonstrated additional clinical and diagnostic imaging features consistent with a PTEN Hamartoma‐Tumor syndrome. The prompt identification of individuals with this condition is important, given the more locally aggressive nature to the malformations and the increased potential for future malignant disease. The etiology and clinical features associated with PTEN Hamartoma‐Tumor syndromes are reviewed in this case.
Acral persistent papular mucinosis: a case report and literature review
Authors: Luo Di‐Qing , Wu Liang‐Cai , Liu Jun‐Hua , Zhang Hai‐Yan
Published: December 2010

Acral persistent papular mucinosis is a rare subtype of localized lichen myxedematosus. It shows symmetric, asymptomatic, chronic, ivory to flesh‐colored, 2–5 mm sized papules arranged on the dorsa of the hands and extensor aspects of the distal forearms. Thirty‐two cases including two from China, appear to fit the proposed diagnostic criteria. We report a 31‐year‐old Chinese woman who presented with papules on the extensor aspects of her hands and distal forearms. Histopathology revealed a circumscribed area in the upper and mid reticular dermis with splaying of collagen fibers caused by amorphous deposits. The material was mucin, as it stained positively with alcian blue at pH 2.5. The thyroid profile was normal, and there was no evidence for lupus erythematous. The lesions were treated with electrofulguration and resolved leaving mild scars; there has been no recurrence at follow‐up after one year. We also review the literature on this rare form of mucinosis.
Issues in the Analysis of Chinese Tone
Authors: Zhang Jie
Published: December 2010

Chinese tone has played an important role in the development of phonological theory from distinctive features and autosegmental phonology to Optimality Theory and its various adaptations. This article reviews some past and current issues in the analysis of Chinese tone and points out how the development of theoretical phonology has shaped the highs and lows of this research enterprise. To fruitfully proceed into the future, I plead to phonologists working in this area to cultivate a new respect for empirical data based on well‐designed phonetic and psycholinguistic studies. This is necessitated by the observations that speakers’ knowledge of tone and tone sandhi may not be identical to their patterns in the lexicon, and impressionistic transcriptions, no matter how careful, can be inaccurate. Moreover, patterns of tone in Chinese are rich in variation, gradience, and exceptions due to dialectal contact and the influence from the dominant Standard Chinese, and existing research has shown that the productivity of Chinese tone sandhi patterns is influenced by both categorical factors such as phonological opacity and gradient factors such as the phonetic nature and the frequency of usage of the sandhi. An empirical basis built around these issues will allow the study of Chinese tone to make continued contributions to the development of phonological theory and our understanding of speakers’ phonological knowledge.
The Built Environment of Higher Education and Research: Architecture and the Expectation of Innovation
Authors: Van Heur Bas
Published: December 2010

Informed by the belief that higher education and research (HER) plays an important role in knowledge‐based innovation, the last decade in particular has seen a flurry of building activity in cities around the world. This has led to many new or restructured urban campuses and buildings dedicated in particular to supporting interactions between researchers, firm members and/or citizens which, in turn, are seen to contribute to urban and regional innovation. This article, first of all, briefly describes a few concrete examples of HER buildings to illustrate the expectations surrounding these built environments. This is followed by a more extensive analysis of three bodies of literature that study the production and use of HER buildings: (i) research on universities and real estate development, (ii) urban and regional studies on the role of HER institutes in generating human and social capital and (iii) science and technology studies on architecture and spaces of science. A concluding section points to some of the limitations of and possible productive interactions between these three strands. It argues that there is a major need for comparative synthetic research that can: evaluate finished and ongoing building projects; analyse the actual interactions between researchers, firm members and/or citizens in and as a result of these buildings; and provide concrete suggestions for the improvement of future HER buildings.
SpedeSTEM: a rapid and accurate method for species delimitation
Authors: ENCE DANIEL D. , CARSTENS BRYAN C.
Published: December 2010

We describe a software package (SpedeSTEM) that allows researchers to conduct a species delimitation analysis using intraspecific genetic data. Our method operates under the assumption that a priori information regarding group membership is available, for example that samples are drawn from some number of described subspecies, races or distinct morphotypes. SpedeSTEM proceeds by calculating the maximum likelihood species tree from all hierarchical arrangements of the sampled alleles and uses information theory to quantify the model probability of each permutation. SpedeSTEM is tested here against empirical and simulated data; results indicate that evolutionary lineages that diverged as few as 0.5N generations in the past can be validated as distinct using sequence data from little as five loci. This work enables speciation investigations to identify lineages that are evolutionarily distinct and thus have the potential to form new species before these lineages acquire secondary characteristics such as reproductive isolation or morphological differentiation that are commonly used to define species.
Functional interactions between OCA2 and the protein complexes BLOC‐1, BLOC‐2, and AP‐3 inferred from epistatic analyses of mouse coat pigmentation
Authors: Hoyle Diego J. , Rodriguez‐Fernandez Imilce A. , Dell’Angelica Esteban C.
Published: December 2010

The biogenesis of melanosomes is a multistage process that requires the function of cell‐type‐specific and ubiquitously expressed proteins. OCA2, the product of the gene defective in oculocutaneous albinism type 2, is a melanosomal membrane protein with restricted expression pattern and a potential role in the trafficking of other proteins to melanosomes. The ubiquitous protein complexes AP‐3, BLOC‐1, and BLOC‐2, which contain as subunits the products of genes defective in various types of Hermansky–Pudlak syndrome, have been likewise implicated in trafficking to melanosomes. We have tested for genetic interactions between mutant alleles causing deficiency in OCA2 (pink‐eyed dilution unstable), AP‐3 (pearl), BLOC‐1 (pallid), and BLOC‐2 (cocoa) in C57BL/6J mice. The pallid allele was epistatic to pink‐eyed dilution, and the latter behaved as a semi‐dominant phenotypic enhancer of cocoa and, to a lesser extent, of pearl. These observations suggest functional links between OCA2 and these three protein complexes involved in melanosome biogenesis.
Disturbance-Observer-Based Force Estimation for Haptic Feedback
Authors: Gupta Abhishek , O’Malley Marcia K.
Published: December 2010

In this paper, we propose the use of a nonlinear disturbance-observer for estimation of contact forces during haptic interactions. Most commonly used impedance-type haptic interfaces employ open-loop force control under the assumption of pseudostatic interactions. Advanced force control in such interfaces can increase simulation fidelity through improvement of the transparency of the device. However, closed-loop force feedback is limited both due to the bandwidth limitations of force sensing and the associated cost of force sensors required for its implementation. Using a disturbance-observer, we estimate contact forces at the tool tip, then use these estimates for closed-loop control of the haptic interface. Simulation and experimental results, utilizing a custom single degree-of-freedom haptic interface, are presented to demonstrate the efficacy of the proposed disturbance-observer (DO)-based control approach. This approach circumvents the traditional drawbacks of force sensing while exhibiting the advantages of closed-loop force control in haptic devices. Results show that the proposed disturbance-observer can reliably estimate contact forces at the human-robot interface. The DO-based control approach is experimentally shown to improve haptic interface fidelity over a purely open-loop display while maintaining stable and vibration-free interactions between the human user and virtual environment.
Correlation of Thermal Conduction Properties With Mechanical Deformation Characteristics of a Set of SiC–Si3N4 Nanocomposites
Authors: Tomar Vikas , Samvedi Vikas
Published: December 2010

New developments in high temperature ceramic materials technology have focused on obtaining nanocomposite materials with nanoscale features for an optimal control of thermal and mechanical properties. One example is the silicon carbide (SiC)–silicon nitride (Si3N4) nanocomposites with nanosized SiC particles placed either in microsized Si3N4 grains or along Si3N4 grain boundaries (GBs). This work focuses on analyzing the influence of GBs, interfaces, and impurities on thermal and mechanical properties of a set of SiC–Si3N4 nanocomposites at three different temperatures (300 K, 900 K, and 1500 K). Nanocomposite thermal conductivity values predicted in this study are smaller in comparison to the bulk Si3N4 values (∼30 W/m K). Even with the volume fraction of SiC phase being limited to maximum 40%, it is shown that the thermal conductivity values could be reduced to less than those of the bulk SiC phase (∼3 W/m K) by microstructural feature arrangement. Nanocomposite phonon spectral density values show a short rage structural order indicating a high degree of diffused phonon reflection. Visual analyses of the atomistic arrangements did not reveal any loss of crystallinity in the nanocomposites at high temperatures. This indicates that structural arrangement, not the phase change, is a factor controlling thermal conduction as a function of temperature. The nanocomposite deformation mechanism is a trade-off between the stress concentration caused by SiC particles and Si3N4–Si3N4 GB sliding. The temperature increase tends to work in favor of GB sliding leading to softening of structures. However, microstructural strength increases with increase in temperature when GBs are absent. GBs also contribute to reduction in thermal conductivity as well as increase in fracture strength. Replacement of sharp GBs by diffused GBs having C/N impurities, lowered thermal conductivity, and increased fracture strength. Decrease in SiC–Si3N4 interfaces by removal of SiC particles tends to favor an increase in thermal conductivity as well as fracture resistance. Overall, it is shown that for high temperature mechanical strength improvement, judicious placement of SiC particles and optimal control of GB atomic volume fraction are the main controlling factors.
Customized illumination for process window optimization and yield improvement in mask aligner lithography systems
Authors: Hornung Michael , Vogler Uwe , Voelkel Reinhard
Published: December 2010

A novel illumination system for mask aligners will be described. The illumination system provides improved exposure light uniformity and customized illumination. It is based on two consecutive Köhler integrators and an exchangeable illumination filter plate. It allows a free choice of illumination settings, e.g., ring-illumination, quadrupole, multipole, Maltese cross, and free-forms in a standard mask aligner. The so-called micro optical exposure optics significantly increases the field of applications for mask aligners. The well defined illumination allows optical proximity correction (OPC) of the mask pattern to compensate for the remaining image errors due to diffraction or process effects. Customized illumination and OPC-like structures introduce well-known tools of projection lithography for mask aligners for the first time. Lithography process simulations as well as experimental results will be shown.
Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex
Authors: Li Xiang-Yao , Ko Hyoung-Gon , Chen Tao , Descalzi Giannina , Koga Kohei , Wang Hansen , Kim Susan S. , Shang Yuze , Kwak Chuljung , Park Soo-Won , Shim Jaehoon , Lee Kyungmin , Collingridge Graham L. , Kaang Bong-Kiun , Zhuo Min
Published: December 2010

Pain in the Brain

One of the major challenges in pain research is finding ways to reverse chronic pain. Synaptic long-term potentiation (LTP) at spinal or cortical levels is a cellular model of chronic pain.

X.-Y. Li.
et al.

(p.
1400
) studied the role of the enzyme protein kinase M zeta (PKMζ) in neurons of the anterior cingulate cortex (ACC) in the maintenance of LTP and for enhanced pain sensitivity after peripheral nerve injury in mice. Nerve injury appeared to lead to the up-regulation and phosphorylation of PKMζ. This triggered LTP at some synapses in the ACC by increasing the number of AMPA receptors. LTP was restricted to ACC neurons that were activated by nerve injury. Blocking PKMζ in the ACC days after nerve injury normalized pain behavior. Thus, PKMζ may represent a promising target for the treatment of chronic pain.
The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
Authors: Levine Arnold J. , Puzio-Kuter Anna M.
Published: December 2010

Cells from some tumors use an altered metabolic pattern compared with that of normal differentiated adult cells in the body. Tumor cells take up much more glucose and mainly process it through aerobic glycolysis, producing large quantities of secreted lactate with a lower use of oxidative phosphorylation that would generate more adenosine triphosphate (ATP), water, and carbon dioxide. This is the Warburg effect, which provides substrates for cell growth and division and free energy (ATP) from enhanced glucose use. This metabolic switch places the emphasis on producing intermediates for cell growth and division, and it is regulated by both oncogenes and tumor suppressor genes in a number of key cancer-producing pathways. Blocking these metabolic pathways or restoring these altered pathways could lead to a new approach in cancer treatments.
Direct Exchange of Electrons Within Aggregates of an Evolved Syntrophic Coculture of Anaerobic Bacteria
Authors: Summers Zarath M. , Fogarty Heather E. , Leang Ching , Franks Ashley E. , Malvankar Nikhil S. , Lovley Derek R.
Published: December 2010

Wired for Life

Syntrophic bacteria live on the metabolic by-products of a partner species. The exchange of the by-products accompanies a flow of electrons in the opposite direction that helps some species grow in conditions that would otherwise be unfavorable. In mixed anaerobic cultures of two related
Geobacter
species,

Summers
et al.

(p.
1413
) observed that one species evolved to promote the transfer of electrons directly to the other, in large aggregated cell clusters, without coupling to common anaerobic by-products such as hydrogen or formate. Selection pressures in nine parallel populations all resulted in a point mutation that truncated a protein involved in the production of small hairlike projections involved in intercellular communication—pili—and indirectly increased the expression of a
c
-type multiheme cytochrome responsible for extracellular electron transfer. The evolved aggregates were conductive, suggesting that the direct exchange of electrons between partner species is a possible alternative route to anaerobic syntrophy rather than interspecies hydrogen transfer; indeed, deleting a gene that encodes a hydrogenase involved in hydrogen transfer conferred a growth advantage in the cocultures.
Opening the Cellular Poison Cabinet
Authors: Martin Seamus J.
Published: December 2010

The assembly and activation of a mitochondrial channel is triggered by direct interaction with signaling molecules that promote cell death.
Dedicated to Memory?
Authors: Eichenbaum Howard
Published: December 2010

Rats with a damaged perirhinal cortex exhibit false memory, raising questions about brain organization.
Shades of Gray in DNA Drama

Photograph 51
by Anna Ziegler; directed by Linsay Firman

Ensemble Studio Theatre, New York. 22 October–21 November 2010. A production of the EST/Alfred P. Sloan Foundation Science and Technology Project. www.ensemblestudiotheatre.org/photograph-51
Authors: Juncosa Barbara
Published: December 2010

Despite its harsh portrait of Rosalind Franklin, Ziegler's play offers an engaging perspective on her role in the discovery of the structure of DNA.
New HIV Infections Drop, But Treatment Demands Rise
Authors: Cohen Jon
Published: December 2010

Michel Sidibé, executive director of the Joint United Nations Programme on HIV/AIDS, is wrestling to renew the momentum in the battle against HIV/AIDS and turn the funding situation around in the aftermath of the global economic crisis 2 years ago. Sidibé spoke with
Science
from New York City, where he was visiting the U.N. headquarters.
Molecular Targets in Meningococci: Efficient Routine Characterization and Optimal Outbreak Investigation in Conjunction with Routine Surveillance of the Meningococcal Group B Vaccine Candidate, fHBP
Authors: Lucidarme Jay , Newbold Lynne S. , Findlow Jamie , Gilchrist Stefanie , Gray Stephen J. , Carr Anthony D. , Hewitt James , Kaczmarski Edward B. , Borrow Ray
Published: December 2010

In 2007, recommendations were proposed for the molecular typing of meningococci. Multilocus sequence typing (MLST) was recommended to guide national and international disease management and facilitate studies of population biology and evolution. Sequencing of
porA
variable regions (VRs) 1 and 2 and the
fetA
VR was recommended for monitoring antigenic distribution and investigating potential outbreaks.
porB
characterization was recommended if further resolution was required. Several investigational “group B” meningococcal vaccines, including two in the advanced stages of development, incorporate factor H-binding protein (fHBP). The requirement for routine surveillance of
fhbp
places additional pressure on reference laboratories, both financially and in terms of labor. This study investigated the optimal and most efficient molecular typing schemes for (i) routine meningococcal characterization and (ii) the investigation of potential outbreaks, in conjunction with routine surveillance of
fhbp.
All invasive disease isolates received by the Health Protection Agency Meningococcal Reference Unit between July 2007 and June 2008 (
n
= 613) were characterized in terms of capsular group,
porA
,
fetA
VR,
fhbp
, and sequence type (ST). Following capsular grouping and
porA
genosubtyping, several predominant capsular group-
porA
combinations were identified. The levels of additional resolution afforded by
fetA
and
fhbp
were comparable and partially complementary.
fhbp
constitutes an effective substitute for
fetA
as a routine marker of antigenic distribution, thereby reducing costs in conjunction with
fhbp
surveillance. MLST afforded markedly superior resolution overall and is the optimal scheme for investigating outbreaks in which (i) typing data are unavailable for the index case or (ii) the index case possesses a known, predominant capsular group-
porA
repertoire.
Comparison of Two Commercial Molecular Assays to a Laboratory-Developed Molecular Assay for Diagnosis of Clostridium difficile Infection
Authors: Karre Tess , Sloan Lynne , Patel Robin , Mandrekar Jayawant , Rosenblatt Jon
Published: December 2010

We compared two commercial PCR assays, the Prodesse ProGastro CD assay and the BD GeneOhm Cdiff assay, with a laboratory-developed
Clostridium difficile
toxin PCR assay with previously established performance characteristics. Results of all methods were in agreement for 333 (96%) of 346 stool specimens. No significant difference in performance among the assays was found (
P
values, >0.05).
Rickettsia typhi Infection with Interstitial Pneumonia in a Traveler Treated with Moxifloxacin
Authors: Schulze Marco H. , Keller Christian , Müller Andreas , Ziegler Uwe , Langen Heinz-Jakob , Hegasy Guido , Stich August
Published: December 2010

Rickettsial diseases may play an important part in the differential diagnosis of fever in returned travelers. The initial empirical treatment needs to take
Rickettsia
species into consideration to avoid the development of life-threatening courses. Here, we present a case of interstitial pneumonia associated with
Rickettsia typhi
infection treated with moxifloxacin.
Circulation of a Novel Pattern of Infections by Enteric Adenovirus Serotype 41 among Children below 5 Years of Age in Kolkata, India
Authors: Dey Rakhi Sharma , Ghosh Santanu , Chawla-Sarkar Mamta , Panchalingam Sandra , Nataro James P. , Sur Dipika , Manna Byomkesh , Ramamurthy Thandavarayan
Published: December 2010

Human adenovirus of strains subgenus F (AdV F) are the most common strains detected in acute gastroenteritis cases in developing countries. Subgenus F is represented by AdV serotype 40 (AdV-40) and AdV-41. Most of the reports have described the predominance of AdV-41 in acute gastroenteritis cases. To gain insight into the epidemiology and genetic variation of AdV-41 strains, we analyzed 1,053 stool specimens from children with diarrhea. Among them, 42 (4.0%) and 56 (5.3%) were positive for enteric adenovirus 40/41 by enzyme-linked immunosorbent assay (ELISA) and PCR, respectively. For 1,305 asymptomatic children, 9 (0.7%) and 22 (1.7%) samples were positive for enteric adenovirus 40/40 by ELISA and PCR, respectively. The age distribution revealed a higher frequency (90%) in children <24 months of age. AdV F infection was observed at a low frequency throughout the year, with an increased incidence occurring during February and March. Sequence analysis of one to three hypervariable regions (HVRs) of the hexon genes of 16 representative AdV-41 strains in this study confirmed circulation of a unique strain with genomic type cluster 1 (GTC1)/GTC2. However, sequence analysis of the fiber genes of these strains confirmed 15 amino acid deletions from the 15th repeat motif of the shaft region. The existence of two GTCs reflects the accumulation of amino acid mutations in the HVR of the hexon gene. The novel AdV-41 strain might follow the same infection pattern as AdV-40. There is no significant variation in the sequences of hexon and fiber genes among strains from symptomatic and asymptomatic children. Our data confirm the circulation of an AdV-41 strain with a novel pattern in Kolkata, India, among children below 5 years of age.
Inhibition of Influenza Virus Infection in Human Airway Cell Cultures by an Antisense Peptide-Conjugated Morpholino Oligomer Targeting the Hemagglutinin-Activating Protease TMPRSS2
Authors: Böttcher-Friebertshäuser Eva , Stein David A. , Klenk Hans-Dieter , Garten Wolfgang
Published: December 2010

Influenza A viruses constitute a major and ongoing global public health concern. Current antiviral strategies target viral gene products; however, the emergence of drug-resistant viruses highlights the need for novel antiviral approaches. Cleavage of the influenza virus hemagglutinin (HA) by host cell proteases is crucial for viral infectivity and therefore presents a potential drug target. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded-DNA-like antisense agents that readily enter cells and can act as antisense agents by sterically blocking cRNA. Here, we evaluated the effect of PPMO targeted to regions of the pre-mRNA or mRNA of the HA-cleaving protease TMPRSS2 on proteolytic activation and spread of influenza viruses in human Calu-3 airway epithelial cells. We found that treatment of cells with a PPMO (T-ex5) designed to interfere with TMPRSS2 pre-mRNA splicing resulted in TMPRSS2 mRNA lacking exon 5 and consequently the expression of a truncated and enzymatically inactive form of TMPRSS2. Altered splicing of TMPRSS2 mRNA by the T-ex5 PPMO prevented HA cleavage in different human seasonal and pandemic influenza A viruses and suppressed viral titers by 2 to 3 log
10
units, strongly suggesting that TMPRSS2 is responsible for HA cleavage in Calu-3 airway cells. The data indicate that PPMO provide a useful reagent for investigating HA-activating proteases and may represent a promising strategy for the development of novel therapeutics to address influenza infections.
Hypervariable Region 1 Differentially Impacts Viability of Hepatitis C Virus Strains of Genotypes 1 to 6 and Impairs Virus Neutralization
Authors: Prentoe Jannick , Jensen Tanja B. , Meuleman Philip , Serre Stéphanie B. N. , Scheel Troels K. H. , Leroux-Roels Geert , Gottwein Judith M. , Bukh Jens
Published: December 2010

Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma Huh7.5 cells. The 2a
ΔHVR1
, 5a
ΔHVR1
, and 6a
ΔHVR1
Core-NS2 recombinants retained viability in Huh7.5 cells, whereas 1a
ΔHVR1
, 1b
ΔHVR1
, 2b
ΔHVR1
, 3a
ΔHVR1
, and 4a
ΔHVR1
recombinants were severely attenuated. However, except for recombinant 4a
ΔHVR1
, viruses eventually spread, and reverse genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a
ΔHVR1
, 1b
ΔHVR1
, 2b
ΔHVR1
, and 3a
ΔHVR1
recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ∼1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles for the original viruses with these genotypes. In contrast, all HVR1-deleted viruses were highly sensitive with similar neutralization profiles.
In vivo
relevance for the role of HVR1 in protecting HCV from neutralization was demonstrated by
ex
vivo
neutralization of 2a and 2a
ΔHVR1
produced in human liver chimeric mice. Due to the high density and neutralization susceptibility of HVR1-deleted viruses, we investigated whether a correlation existed between density and neutralization susceptibility for the original viruses with genotypes 1 to 6. Only the 2a virus displayed such a correlation. Our findings indicate that HVR1 of HCV shields important conserved neutralization epitopes with implications for viral persistence, immunotherapy, and vaccine development.