bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated serum IgE in recurrent aphthous stomatitis and associations with disease characteristics
Authors: Almoznino G , Zini A , Mizrahi Y , Aframian DJ
Published: May 2013

Objectives

To characterize demographic, clinical and serological parameters in recurrent aphthous stomatitis (RAS) patients and analyse their association with serum immunoglobulin E (IgE) levels.

Subjects and Methods

Forty‐nine patients with RAS responded to a questionnaire that included demographic background, stress status, smoking habits, history and course of RAS episodes. They were also subjected to relevant laboratory tests, including determination of serum IgE levels.

Results

A familial history of RAS was reported by 47.9% of the patients, stress in the previous year by 51.1% and smoking by 18.4%. Non‐Caucasian origin, familial history of RAS, stress and smoking were associated with increased severity of RAS episodes. Haematological deficiencies were observed in 18.7% of RAS patients. Average IgE levels were increased and were significantly associated ‎with younger ‎age, ‎≤12 years of schooling, ‎female gender, ‎RAS ‎episode frequency of every ‎2 weeks‎,‎ early onset of RAS episodes and elevated C reactive protein levels.

Conclusion

Immunoglobulin E levels may be considered as part of the RAS patient's work‐up. Further research is needed to identify biological mechanisms that account for the observed associations.
MiR‐99a exerts anti‐metastasis through inhibiting myotubularin‐related protein 3 expression in oral cancer
Authors: Kuo Y‐Z , Tai Y‐H , Lo H‐I , Chen Y‐L , Cheng H‐C , Fang W‐Y , Lin S‐H , Yang C‐L , Tsai S‐T , Wu L‐W
Published: May 2013

Objective

We aimed at studying the role of the most deregulated miR‐99a, identifying its downstream targets, and exploring the clinical potential of miR‐99a and its target(s) in oral cancer.

Subjects and Methods

Following confirmation of miR‐99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR‐99a‐manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR‐99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR‐99a and its target(s) was examined in clinical specimens using real‐time PCR and Western blot analysis.

Results

MiR‐99a down‐regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR‐99a expression inhibited oral cancer cell migration and invasion. Anti‐miR‐99a, silencing miR‐99a functions, had the opposite effect. Myotubularin‐related protein 3 (MTMR3) with one evolutionarily conserved seed region in the 3′‐untranslated region was a novel miR‐99a target. Depleting MTMR3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR‐99a and MTMR3 protein in oral cancer lines and clinical specimens.

Conclusion

miR‐99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression. MTMR3 may serve as a therapeutic target for oral cancer treatment.
Cognitive‐behavioural therapy for schizophrenia: A critical commentary on the Newton‐Howes and Wood meta‐analysis
Authors: Hutton Paul
Published: May 2013

Newton‐Howes and Wood (published online, this journal, 8 Dec 2011) report the results of their systematic review and meta‐analysis of clinical trials of cognitive‐behavioural therapy (CBT) for schizophrenia. They ran a random effects analysis of endpoint data from trials where participants were randomly allocated to receive either CBT or a control therapy, which could be inactive (e.g., befriending) or active (e.g., analytic supportive psychotherapy), found no difference between the groups and concluded ‘it (CBT) does not outperform supportive therapy in effecting change in phenomenology.’ Such a conclusion is premature, if not unwarranted, for a number of reasons, including basic mistakes, lack of transparency, and failure to consider dose.
Carotenoid accumulations and carotenogenic gene expressions in the petals of Eustoma grandiflorum
Authors: Liu Hui , Kishimoto Sanae , Yamamizo Chihiro , Fukuta Naoko , Ohmiya Akemi
Published: May 2013

Eustoma grandiflorum is one of the leading cut‐flowers in Japan. There are market demands for cultivars with deep‐yellow flowers, but they have never been bred successfully. By investigating the carotenoid accumulation and carotenogenic gene expressions, this study attempted to explore the reasons that block the formation of deep‐yellow colour in Eustoma. High performance liquid chromatography analysis showed that the carotenoid compositions in petals were similar to those in leaves, accumulating mainly lutein, violaxanthin and β‐carotene. The total carotenoid contents decreased as the petals matured in all the cultivars tested. Quantitative real‐time PCR analysis showed that the expression levels of PSY, LCYB, ZDS and LCYE showed significant differences between white and pale‐yellow petals or between petals and leaves, indicating that these enzymes may play a key role in the carotenoid biosynthesis in E. grandiflorum. The expression levels of CCD4 were high in both pale‐yellow and white petals during development, suggesting that carotenoid degradation activity is high in the petals. We then conclude that the total carotenoid accumulation level could be determined by the balance between carotenoid biosynthesis and degradation activities.
The likelihood of sunburn in sunscreen users is disproportionate to the SPF
Authors: Pissavini Marc , Diffey Brian
Published: May 2013

Background/Objective

Sunburn is a common feature in sunscreen users. The purpose of this paper is to estimate the expected frequency and magnitude of sunburn resulting from typical use of sunscreens labelled SPF15 and SPF30 by people spending long periods outdoors in strong summer sunshine.

Methods

By combining the probability distribution of the measured sun protection factor (SPF) in vivo with those for the average application thickness and the uniformity of application over the skin surface, a simulation model was developed to estimate the variation in delivered protection over the exposed skin surface from consumer use of sunscreens.

Results

While either sunscreen, if delivering the nominal SPF over the entire exposed skin, would be sufficient to prevent any erythema, the simulation indicates that the combination of the average quantity applied with the variability in thickness over the skin surface will lead to erythema, especially in SPF15 sunscreen users.

Conclusion

People who intend spending long periods outside in strong sunshine would be better advised to use SPF30 labelled sunscreens than SPF15 sunscreens, and to apply the product carefully over exposed skin if they wish to minimize their risk of sunburn and, by implication, skin cancer.
Photopatch testing in Asians: a 5‐year experience in Singapore
Authors: Chuah Sai Yee , Leow Yung Hian , Goon Anthony Teik Jin , Theng Colin Thiam Seng , Chong Wei‐Sheng
Published: May 2013

Background

Photopatch testing is important for diagnosing photoallergic contact dermatitis. We aimed to evaluate the use of photopatch test at the National Skin Centre, Singapore.

Methods

All patients who had photopatch tests done between 2007 and 2011 at the National Skin Centre were included.

Results

Twenty‐two patients were included. The mean age was 40.2. Female : male ratio was 3.4. The ethnic groups were Chinese (68%), Malay (4%), Indian (14%) and others (14%). Ten out of 22 patients (45.5%) had a positive photopatch test. There were 20 positive photopatch test reactions found in these 10 patients, and all 20 positive reactions were of current relevance. The frequencies of the positive photopatch test reactions were 2‐hydroxy‐4‐methoxybenzophenone (oxybenzone) (n = 6), 2‐hydroxymethoxymethylbenzophenone (mexenone) (n = 3), 2‐ethylhexyl‐4‐dimethylaminobenzoate (n = 1), ketoprofen gel (n = 1) and the patient's own product (n = 9).

Conclusions

Our study suggests that sunscreen is the most common photoallergen to date as opposed to musk ambrette, which was the most common photoallergen in our earlier study in 1991–1993. This finding is similar to the recent European Multicentre Photopatch Test Study.
UV responses in Native Hawaiians and Pacific Islanders, and, Asians residing in Hawai'i and in Maryland
Authors: Colmenares Leticia U. , Coelho Sergio , Miller Sharon A. , Boomer K. B. , Beer Janusz Z.
Published: May 2013

Background

UV exposure causes a wide range of skin damage including cutaneous melanoma. The mechanisms of cellular and molecular damage, as well as those of erythemal and pigmentation responses to UV exposure, have largely been studied in the White population.

Methods

This study systematically investigates responses to UV exposure in the Native Hawaiian and Pacific Islander (NHPI) and Asian populations living in Hawai'i (A/HI) as well as in Asians living in Maryland (A/MD).

Results

Our analyses indicate that the NHPI population is less sensitive to UV exposure than the A/HI population. Comparisons between the two Asian groups suggest that, despite slightly but not statistically different baseline constitutive pigmentation (pre‐UV exposure), the A/HI and A/MD had similar UV sensitivity, measured as minimal erythemal dose (MED). However, the A/MD population had higher levels of oxyhemoglobin at doses of 2.0, 2.8 and 4.0 MED. Unexpectedly, the A/MD subjects retained higher levels of pigmentation 2 weeks post‐UV exposure.

Conclusion

This study provides insight into UV responses of the inhabitants of Hawai'i and shows that such responses are statistically significant for relatively small samples of NHPI and for A/HI and A/MD.
A case of cutaneous lichen sclerosus et atrophicus effectively treated by extracorporeal photochemotherapy
Authors: Brouillard Clotilde , Granel‐Brocard Florence , Cuny Jean‐François , Truchetet François , Schmutz Jean‐Luc
Published: May 2013

Lichen sclerosus et atrophicus (LSA) is an inflammatory disease that affects the genitals, which was first described by Hallopeau in 1887 and is of unknown etiology. Only 15% of patients have an associated extra‐genital form, and 2.5% have an isolated extra‐genital form. LSA treatment remains poorly codified and mostly empirical. Here, we report a case of LSA, of mainly cutaneous form, which was effectively treated using extracorporeal photochemotherapy (ECP). Remission was achieved quickly, after the fourth session, with excellent treatment tolerance. ECP is now recognized as an effective treatment for erosive lichen planus, graft‐versus‐host disease (GVHD), and scleroderma. Thus, we began ECP treatment for our cases of LSA based on clinical and/or anatomopathological similarities between LSA and these commonly ECP‐treated disorders. The fact that ECP is effective in LSA, GVHD, erosive lichen planus, and scleroderma strengthen the hypothesis that there is a common link between these four conditions.
Identification and characterisation of maize microRNAs involved in developing ears
Authors: Ding D. , Li W. , Han M. , Wang Y. , Fu Z. , Wang B. , Tang J.
Published: May 2013

In maize, kernel row number trait is determined during the period when spikelet pair meristems (SPMs) give rise to spikelet meristems (SMs). Expression levels of many genes change during this period due to regulation at transcriptional and post‐transcriptional levels. MicroRNAs (miRNAs) act as key regulating factors of post‐transcriptional gene expression. To discover miRNAs involved in maize ear development, Solexa deep sequencing was performed on a maize inbred line, Zong3. Ears at the stage when SPMs produce SMs were harvested to extract RNA. Deep sequencing revealed 85 conserved miRNAs belonging to 17 miRNA families. miRNA families differed greatly in their abundance, from over 160,000 to only five reads. In addition, 31 novel maize miRNAs were identified using stringent criteria. The results show that miRNA‐mediated regulation of gene expression is present in developing maize ears at the stage when SPMs produce SMs; both conserved and novel miRNAs are involved.
Significance of microalgal–bacterial interactions for aquaculture
Authors: Natrah Fatin M. I. , Bossier Peter , Sorgeloos Patrick , Yusoff Fatimah Md. , Defoirdt Tom
Published: May 2013

Knowledge on the importance of associations between bacteria and microalgae in aquatic ecosystems is rather limited at the moment, mostly due to a lack of studies at the molecular and biochemical level of microorganisms. This paper discusses the current knowledge on microalgae–bacteria interactions and their potential impacts on the productivity, efficiency and sustainability of aquaculture. Current findings suggest that the interactions are complex and specific. The release of stimulatory products by bacteria that enhance the growth of microalgae, and vice versa, indicates the existence of mutualistic relations. Other factors, such as signalling between bacteria and microalgae, may also play an important role. Although these interactions may be of significant importance, to date, only a few findings have been reported on the use of consortia consisting of microalgae and bacteria for practical purposes. Interestingly, these results pointed out that a combination of microalgae and bacteria is often better than using either of them alone. Further research is needed to obtain a thorough understanding of the mechanisms behind the interactions between these microorganisms, including the identification of active compounds. This knowledge will enable the selection of appropriate consortia for different applications in aquaculture, including disease control and high and sustainable production of feed.
Virulence mechanisms of bacterial aquaculture pathogens and antivirulence therapy for aquaculture
Authors: Defoirdt Tom
Published: May 2013

Although aquaculture continues to be the fastest‐growing food‐producing industry worldwide, the sector faces important challenges with respect to controlling infectious diseases. Indeed, the frequent use of antibiotics, which are traditionally the most important line of defence against bacterial disease, has raised problems related to the development and spread of resistance. As a result, we currently are in a race to develop novel therapeutics that should allow us to continue controlling bacterial disease in the future. In this respect, scientific progress of the past years has allowed us to start understanding the mechanisms by which bacterial pathogens are causing disease. This knowledge in its turn opens up novel possibilities to combat infections by interfering with these mechanisms, a strategy that has been termed antivirulence therapy. In this review, the current knowledge with respect to pathogenicity mechanisms of bacterial aquaculture pathogens is discussed, including adhesion mechanisms, production of extracellular polysaccharides and biofilm formation, production of lytic enzymes (e.g. haemolysins and proteases), mechanisms of iron acquisition, secretion systems and regulatory mechanisms such as quorum sensing and host–pathogen signalling with catecholamine stress hormones. Furthermore, an overview is given of the first steps towards antivirulence therapy for aquaculture, with a focus on quorum sensing disruption as a proof of concept.
A rare presentation of multiple primary squamous cell carcinoma of the tongue in a patient with recurrent hepatitis C infection
Authors: Stoopler Eric T. , Sia Ying Wai , Chalian Ara A. , O'Malley Bert W. , Alawi Faizan
Published: May 2013

Hepatitis C virus (HCV) infection has been implicated as a risk factor for development of oral squamous cell carcinoma (SCC). Multiple primary sites of oral SCC associated with HCV infection occurs infrequently. This case report describes a rare presentation of multiple primary SCCs of the tongue in a patient with recurrent HCV cirrhosis status post liver transplant that required interdisciplinary medical and surgical management. It is important for oral health care providers to understand the local and systemic implications of HCV infection and perform routine clinical examinations to monitor for development of oral lesions and associated complications.
Food Allergen–Induced Mast Cell Degranulation is Dependent on PI3K‐Mediated Reactive Oxygen Species Production and Upregulation of Store‐Operated Calcium Channel Subunits
Authors: Yang B. , Yang C. , Wang P. , Li J. , Huang H. , Ji Q. , Liu J. , Liu Z.
Published: May 2013

The importance of Ca2+ influx via store‐operated calcium channels (SOCs) leading to mast cell degranulation is well known in allergic disease. However, the underlying mechanisms are not fully understood. With food‐allergic rat model, the morphology of degranulated mast cell was analysed by toluidine blue stain and electron microscope. Ca2+ influx via SOCs was checked by Ca2+ imaging confocal microscope. Furthermore, the mRNA and protein expression of SOCs subunits were investigated using qPCR and Western blot. We found that ovalbumin (OVA) challenge significantly increased the levels of Th2 cytokines and OVA‐specific IgE in allergic animals. Parallel to mast cell activation, the levels of histamine in serum and supernatant of rat peritoneal lavage solution were remarkably increased after OVA treatment. Moreover, the Ca2+ entry through SOCs evoked by thapsigargin was increased in OVA‐challenged group. The mRNA and protein expressions of SOC subunits, stromal interaction molecule 1 (STIM1) and Orail (calcium‐release‐activated calcium channel protein 1), were dramatically elevated under food‐allergic condition. Administration of Ebselen, a scavenger of reactive oxygen species (ROS), significantly attenuated OVA sensitization‐induced intracellular Ca2+ rise and upregulation of SOCs subunit expressions. Intriguingly, pretreatment with PI3K‐specific inhibitor (Wortmannin) partially abolished the production of ROS and subsequent elevation of SOCs activity and their subunit expressions. Taken together, these results imply that enhancement of SOC‐mediated Ca2+ influx induces mast cell activation, contributing to the pathogenesis of OVA‐stimulated food allergy. PI3K‐dependent ROS generation involves in modulating the activity of SOCs by increasing the expressions of their subunit.
Inhibitors of BTK and ITK: State of the New Drugs for Cancer, Autoimmunity and Inflammatory Diseases
Authors: Vargas L. , Hamasy A. , Nore B. F. , E. Smith C. I.
Published: May 2013

BTK and ITK are cytoplasmic tyrosine kinases of crucial importance for B and T cell development, with loss‐of‐function mutations causing X‐linked agammaglobulinemia and susceptibility to severe, frequently lethal, Epstein–Barr virus infection, respectively. Over the last few years, considerable efforts have been made in order to develop small‐molecule inhibitors for these kinases to treat lymphocyte malignancies, autoimmunity or allergy/hypersensitivity. The rationale is that even if complete lack of BTK or ITK during development causes severe immunodeficiency, inactivation after birth may result in a less severe phenotype. Moreover, therapy can be transient or only partially block the activity of BTK or ITK. Furthermore, a drug‐induced B cell deficiency is treatable by gamma globulin substitution therapy. The newly developed BTK inhibitor PCI‐32765, recently renamed Ibrutinib, has already entered several clinical trials for various forms of non‐Hodgkin lymphoma as well as for multiple myeloma. Experimental animal studies have demonstrated highly promising treatment effects also in autoimmunity. ITK inhibitors are still under the early developmental phase, but it can be expected that such drugs will also become very useful. In this study, we present BTK and ITK with their signalling pathways and review the development of the corresponding inhibitors.
Psychometric properties of the Norwegian version of the Childhood Trauma Questionnaire in high‐risk groups
Authors: Dovran Anders , Winje Dagfinn , Øverland Simon N. , Breivik Kyrre , Arefjord Kjersti , Dalsbø Anita S. , Jentoft Mette B. , Hansen Anita L. , Waage Leif
Published: May 2013

The Childhood Trauma Questionnaire ‐ Short Form (CTQ‐SF) is widely used to measure childhood abuse of all types. In the present study, we examined the psychometric properties of the Norwegian version of the instrument. The participants constituted four subsamples (n = 517): substance abusers (n = 126), psychiatric patients (n = 210), prisoners (n = 109) and adolescents in out‐of‐home placements (n = 72). Confirmatory factor analysis revealed a reasonable fit of the data to the original five‐factor structure of the CTQ‐SF. Measurement invariance was found across gender and the four subsamples. It was concluded that the Norwegian version of the CTQ‐SF has acceptable psychometric properties, with good reliability and satisfactory accuracy, to assess different dimensions of childhood trauma.
Influence of wastewater treatment on sludge production and processing
Authors: Barber William Pablo Freese
Published: May 2013

The challenge of stricter wastewater standards is resulting in configuration changes to wastewater treatment. As facilities upgrade, the type of sludge produced is changing, with growing quantities of secondary and chemical sludge at the expense of primary sludge. It is already understood that secondary sludge is harder to treat than its primary equivalent; therefore, increasing the quantity of this type of sludge will have detrimental impacts downstream. As legislation tightens further, extended aeration times may be required during processing to remove more nutrients. Work has shown that extended aeration further exacerbates the treatability of secondary sludge. This paper explains how tightening wastewater legislation fundamentally alters the nature of the sludge produced, and how these alterations impact further processing, especially with respect to sludge production and type; sludge energy content; performance of anaerobic digestion and dewatering, and potential for thermal energy recovery.
Voluntary locomotion linked with cerebral activation is mediated by vasopressin V1a receptors in free‐moving mice
Authors: Masuki Shizue , Sumiyoshi Eri , Koshimizu Taka‐aki , Qian Jinze , Higuchi Keiichi , Tsujimoto Gozoh , Nose Hiroshi
Published: May 2013

Key points

Arterial blood pressure rises at the onset of voluntary locomotion, which is probably advantageous for increasing blood flow to contracting muscles without delay.

We previously reported in free‐moving mice that the feedback control of arterial blood pressure through peripheral baroreceptors, which was dominant at rest, was suppressed during activation of the cerebral cortex; however, no neurotransmitter for the mechanisms has been identified.

Central suppression of the feedback control of arterial blood pressure at the onset of voluntary locomotion was abolished in vasopressin V1a receptor‐deficient mice and by local infusion of a V1a receptor antagonist into the brainstem area, termed the nucleus tractus solitarii, of control mice.

Thus, central vasopressin might play an important role as a neurotransmitter in the pressor response at the onset of voluntary locomotion.

Abstract  We previously reported that cerebral activation suppressed baroreflex control of heart rate (HR) at the onset of voluntary locomotion. In the present study, we examined whether vasopressin V1a receptors in the brain were involved in these responses by using free‐moving V1a receptor knockout (KO, n= 8), wild‐type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n= 8) and control mice (CNT, n= 8). Baroreflex sensitivity (ΔHR/ΔMAP) was determined from HR response (ΔHR) to a spontaneous change in mean arterial pressure (ΔMAP) every 4 s during the total resting period, which was ∼8.7 h, of the 12 h measuring period in the three groups. ΔHR/ΔMAP was determined during the periods when the cross‐correlation function (R(t)) between ΔHR and ΔMAP was significant (P < 0.05). Cerebral activity was determined from the power density ratio of θ to δ wave band (θ/δ) on the electroencephalogram every 4 s. Spontaneous changes in θ/δ were significantly correlated with R(t) during 62 ± 3% of the total resting period in CNT (P < 0.05), but only 38 ± 4% in KO and 47 ± 2% in BLK (vs. CNT, both P < 0.001). When R(t) and ΔHR/ΔMAP were divided into six bins according to the level of θ/δ, both were positively correlated with θ/δ in CNT (both P < 0.001), while neither was correlated in KO or BLK (all P > 0.05). Moreover, the probability that mice started to move after an increase in θ/δ was 24 ± 4% in KO and 24 ± 6% in BLK, markedly lower than 61 ± 5% in CNT (both P < 0.001), with no suppression of the baroreflex control of HR. Thus, central V1a receptors might play an important role in suppressing baroreflex control of HR during cerebral activation at the onset of voluntary locomotion.
Paired‐pulse facilitation at recurrent Purkinje neuron synapses is independent of calbindin and parvalbumin during high‐frequency activation
Authors: Bornschein Grit , Arendt Oliver , Hallermann Stefan , Brachtendorf Simone , Eilers Jens , Schmidt Hartmut
Published: May 2013

Key points

Endogenous Ca2+ binding proteins such as calbinding‐D28k (CB) and parvalbumin (PV) are considered important regulators of short‐term synaptic plasticity.

Cerebellar Purkinje neurons express large amounts of CB and PV and are laterally connected by inhibitory synapses that show paired‐pulse facilitation (PPF) during high‐frequency activation.

We report quantal synaptic release parameters of these synapses in wild‐type and in CB and PV knock‐out mice; evidence is provided that these synapses operate at nanodomain influx‐release coupling.

We find that PPF is independent of CB and PV, using a combination of paired electrophysiological recordings, synaptic Ca2+ imaging and numerical computer simulations.

Our results suggest that PPF during high‐frequency activation results from slow Ca2+ unbinding from the sensor for transmitter release, which is reminiscent of the ‘active Ca2+’ mechanism of PPF suggested by Katz and Miledi in 1968.

Abstract  Paired‐pulse facilitation (PPF) is a dynamic enhancement of transmitter release considered crucial in CNS information processing. The mechanisms of PPF remain controversial and may differ between synapses. Endogenous Ca2+ buffers such as parvalbumin (PV) and calbindin‐D28k (CB) are regarded as important modulators of PPF, with PV acting as an anti‐facilitating buffer while saturation of CB can promote PPF. We analysed transmitter release and PPF at intracortical, recurrent Purkinje neuron (PN) to PN synapses, which show PPF during high‐frequency activation (200 Hz) and strongly express both PV and CB. We quantified presynaptic Ca2+ dynamics and quantal release parameters in wild‐type (WT), and CB and PV deficient mice. Lack of CB resulted in increased volume averaged presynaptic Ca2+ amplitudes and in increased release probability, while loss of PV had no significant effect on these parameters. Unexpectedly, none of the buffers significantly influenced PPF, indicating that neither CB saturation nor residual free Ca2+ ([Ca2+]res) was the main determinant of PPF. Experimentally constrained, numerical simulations of Ca2+‐dependent release were used to estimate the contributions of [Ca2+]res, CB, PV, calmodulin (CaM), immobile buffer fractions and Ca2+ remaining bound to the release sensor after the first of two action potentials (‘active Ca2+’) to PPF. This analysis indicates that PPF at PN–PN synapses does not result from either buffer saturation or [Ca2+]res but rather from slow Ca2+ unbinding from the release sensor.
Synchronization of Networked Mechanical Systems With Communication Delays and Human Input
Authors: Liu Yen-Chen , Chopra Nikhil
Published: May 2013

The problem of controlling a group of networked mechanical systems to synchronize and follow a common trajectory is studied in this paper. We first address the results for networked mechanical systems to achieve synchronization when the interagent communication graph is balanced and strongly connected with communication delays. Subsequently, a control law is developed to guarantee synchronization and trajectory tracking for networked mechanical systems communicating on regular graphs when there are constant time delays in communication and the interconnection topology is time-varying. The case when a human operator input is introduced in the closed-loop system is also considered. It is demonstrated that a bounded human operator input results in bounded tracking and synchronization errors, even when there are constant time delays in communication. The simulation and experimental results are presented by utilizing the kinematic and dynamic models of PHANToM Omni derived in this paper.
Increasing the Power Density for Axial-Piston Swash-Plate Type Hydrostatic Machines
Authors: Manring Noah D. , Mehta Viral S. , Nelson Bryan E. , Graf Kevin J. , Kuehn Jeff L.
Published: May 2013

Power density is an assumed attribute of an axial-piston swash-plate type hydrostatic machine. As such, very little research has been conducted to examine the nature and limit of this machine's power density and the literature is all but void of this important topic. This paper is being written to fill this void, and to provide a thorough analysis of the machine's power density. This paper is also aimed at identifying the most significant parameters that may be adjusted to increase the power density for a typical machine. As shown in this research, the power density of an axial-piston machine depends upon four dimensionless quantities that are characteristic of the machine's rotating group. As it turns out, the allowable stress for the cylinder block is the most sensitive parameter that may be adjusted for increasing the power density of this machine. It is further shown that increasing the machine's swash-plate angle, and reducing the minimum overhang length for the pistons, will have a significant impact on the power density as well. It is significant to note that altering the number of pistons in the design has essentially no impact on the power density of the machine and therefore the selection of this design parameter must be based upon other design objectives. In conclusion, it is shown in this paper that the power density of a typical machine may be increased by as much as 64% by altering a few of these parameters within a realistic realm of constraint.
A Sampling Approach to Extreme Value Distribution for Time-Dependent Reliability Analysis
Authors: Hu Zhen , Du Xiaoping
Published: May 2013

Maintaining high accuracy and efficiency is a challenging issue in time-dependent reliability analysis. In this work, an accurate and efficient method is proposed for limit-state functions with the following features: The limit-state function is implicit with respect to time. There is only one stochastic process in the input to the limit-sate function. The stochastic process could be either a general strength or a general stress variable so that the limit-state function is monotonic to the stochastic process. The new method employs a sampling approach to estimate the distributions of the extreme value of the stochastic process. The extreme value is then used to replace the corresponding stochastic process. Consequently the time-dependent reliability analysis is converted into its time-invariant counterpart. The commonly used time-invariant reliability method, the first order reliability method, is then applied to calculate the probability of failure over a given period of time. The results show that the proposed method significantly improves the accuracy and efficiency of time-dependent reliability analysis.
Calculating Individual and Total Muscular Translational Stiffness: A Knee Example
Authors: Cashaback Joshua G. A. , Pierrynowski Michael R. , Potvin Jim R.
Published: May 2013

Research suggests that the knee joint may be dependent on an individual muscle's translational stiffness (KT) of the surrounding musculature to prevent or compensate for ligament tearing. Our primary goal was to develop an equation that calculates KT. We successfully derived such an equation that requires as input: a muscle's coordinates, force, and stiffness acting along its line of action. This equation can also be used to estimate the total joint muscular KT, in three orthogonal axes (AP: anterior-posterior; SI: superior-inferior; ML: medial-lateral), by summating individual muscle KT contributions for each axis. We then compared the estimates of our equation, using a commonly used knee model as input, to experimental data. Our total muscular KT predictions (44.0 N/mm), along the anterior/posterior axis (AP), matched the experimental data (52.2 N/mm) and was well within the expected variability (22.6 N/mm). We then estimated the total and individual muscular KT in two postures (0 deg and 90 deg of knee flexion), with muscles mathematically set to full activation. For both postures, total muscular KT was greatest along the SI-axis. The extensors provided the greatest KT for each posture and axis. Finally, we performed a sensitivity analysis to explore the influence of each input on the equation. It was found that pennation angle had the largest effect on SI KT, while muscle line of action coordinates largely influenced AP and ML muscular KT. This equation can be easily embedded within biomechanical models to calculate the individual and total muscular KT for any joint.
Encouraging Resource-Conscious Behavior Through Product Design: The Principle of Discretization
Authors: Srivastava Jayesh , Shu L. H.
Published: May 2013

Lead-user methods were applied to develop product design principles that encourage resource-conscious behavior in individuals. Old Order Mennonites (OOMs) were chosen as lead users because of their low-resource consumption lifestyles. Ethnographic analysis revealed that discretizing resource consumption facilitates and encourages conservation behaviors in OOMs. An experimental study demonstrated the effectiveness of discretization in reducing water consumption by non-OOMs. We then generated concepts for products that applied discretization and tested them with users. Concepts were revised and a prototype for saving water was created.
Design, Analysis, and Control of a Novel Safe Cell Micromanipulation System With IPMC Actuators
Authors: McDaid A. J. , Haemmerle E. , Xie S. Q. , Aw K. C.
Published: May 2013

This paper presents the design, analysis, and control of a novel micromanipulation system to facilitate the safe handling/probing of biological cells. The robotic manipulator has a modular design, where each module provides two degrees-of-freedom (2DOF) and the overall system can be made up of a number of modules depending on the desired level of dexterity. The module design has been optimized in simulation using an integrated ionic polymer-metal composite (IPMC) model and mechanical mechanism model to ensure the best system performance from the available IPMC material. The optimal system consists of two modules with each DOF actuated by a 27.5 mm long by 10 mm wide actuator. A 1DOF control structure has been developed, which is adaptively tuned using a model-free iterative feedback tuning (IFT) algorithm to adjust the controller parameters to optimize the system tracking performance. Experimental results are presented which show the tuning of the system improves the performance by 24% and 64% for the horizontal and vertical motion, respectively. Experimental characterization has also been undertaken to show the system can accurately achieve outputs of up to 7 deg and results for position tracking in both axes are also presented.
A Comparative Study of Evidence Theories in the Modeling, Analysis, and Design of Engineering Systems
Authors: Rao S. S. , Annamdas K. K.
Published: May 2013

The application of different types of evidence theories in the modeling, analysis and design of engineering systems is explored. In most studies dealing with evidence theory, the Dempster–Shafer theory (DST) has been used as the framework not only for the characterization and representation of uncertainty but also for combining evidence. The versatility of the theory is the motivation for selecting DST to represent and combine different types of evidence obtained from multiple sources. In this work, five evidence combination rules, namely, Dempster–Shafer, Yager, Inagaki, Zhang, and Murrphy combination rules, are considered. The limitations and sensitivity of the DST rule in the case of conflicting evidence are illustrated with examples. The application of all the five evidence combination rules for the modeling, analysis and design of engineering systems is illustrated using a power plant failure example and a welded beam problem. The aim is to understand the basic characteristics of each rule and develop preliminary guidelines or criteria for selecting an evidence combination rule that is most appropriate based on the nature and characteristics of the available evidence. Since this work is the first one aimed at developing the guidelines or criteria for selecting the most suitable evidence combination rule, further studies are required to refine the guidelines and criteria developed in this work.
Actuator Limitations in Spatial Temperature Control of SOFC
Authors: Fardadi Mahshid , McLarty Dustin F. , Jabbari Faryar
Published: May 2013

A high performance multi-input multi-output feedback controller has been developed to minimize solid oxide fuel cell (SOFC) spatial temperature variation during load following. Cathode flow rate and its inlet temperature are used to minimize spatial temperature variations in the SOFC electrode electrolyte assembly for significant load perturbations. We focus on control design in the presence of nonideal actuation. This includes the effects of fuel processing delays, cathode inlet thermal delays, and parasitic power associated with the blower supplying air to the cathode. The controller, based on energy-to-peak minimization synthesis, is applied to a dynamic model of an anode-supported coflow planar SOFC stack. The results indicate that many of the problems associated with realistic and imperfect actuation can be addressed with relatively standard control synthesis modifications, but fuel flow delays can compromise power following significantly. Finally, a strategy that relies primarily on partial internal reformation for power following addresses many of the difficulties associated with reformer delays.
A Role for Hipk in the Hippo Pathway
Authors: Heidary Arash Emad , Attisano Liliana
Published: May 2013

The kinase HIPK enhances growth by promoting the activity of the transcriptional regulators of the Hippo pathway.
Science Signaling
Podcast: 14 May 2013
Authors: Dong Chen , VanHook Annalisa M.
Published: May 2013

A deubiquitinase helps control the inflammatory response.
Keeping in Synch
Authors: Ray L. Bryan
Published: May 2013

The cyanobacterial clock uses one circuit for rhythms and a second circuit for intercellular synchronous oscillations.
A Damaging Survival Signal
Authors: Gough Nancy R.
Published: May 2013

By delaying neutrophil death, cigarette smoke promotes lung damage.
Primed to Die
Authors: Gough Nancy R.
Published: May 2013

By inducing a low-affinity adenosine receptor, p53 poises cells for death in response to stresses that increase extracellular adenosine.
Caspofungin MICs Correlate with Treatment Outcomes among Patients with Candida glabrata Invasive Candidiasis and Prior Echinocandin Exposure
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Updike Cassaundra L. , Clancy Cornelius J.
Published: May 2013

Mutations in
Candida glabrata FKS
genes, which encode the echinocandin target enzyme, are independent risk factors for treatment failures during invasive candidiasis. We retrospectively compared the ability of caspofungin susceptibility testing methods to identify
C. glabrata
FKS
mutant isolates and predict outcomes among patients at our center. Eight percent (10/120) of sterile-site
C. glabrata
isolates harbored
FKS1
(
n
= 3) or
FKS2
(
n
= 7) mutations, including 32% (10/32) recovered from patients with prior echinocandin exposure. Median echinocandin exposures for mutant and nonmutant isolates were 55 (range, 7 to 188) and 13 (3 to 84) days, respectively (
P
= 0.004). Sensitivity and specificity of the CLSI caspofungin resistance breakpoint MIC (>0.12 μg/ml by broth microdilution using RPMI medium [BMD-RPMI]) were 90% (9/10) and 3% (3/110), respectively, for identifying
FKS
mutants. Sensitivity and specificity of receiver-operator characteristic (ROC) curve-derived breakpoints by BMD-RPMI, BMD-antibiotic medium 3, Etest, and YeastOne ranged from 70 to 100% and 89 to 95%, respectively; susceptibility rates varied from 83 to 90%. The 14-day echinocandin treatment success rate was 67% (44/66); failure was more likely with prior echinocandin exposure (
P
= 0.002) or infection with an
FKS
mutant (
P
= 0.0001) or echinocandin-resistant isolates by BMD-AM3, Etest, and YeastOne (
P
≤ 0.03). The failure rate among patients with prior exposure and infection with a resistant isolate was 91% (10/11); it was 22% (12/55) among others (
P
< 0.0001). In conclusion, ROC-derived caspofungin MIC breakpoints by several methods were sensitive and specific for identifying
C. glabrata
FKS
mutant isolates. Mutations were seen exclusively among patients with prior echinocandin exposure. A paradigm that considers prior echinocandin exposure and caspofungin MICs accurately classified treatment outcomes for
C. glabrata
invasive candidiasis.
Antimicrobial Activity of Nanoemulsion in Combination with Cetylpyridinium Chloride in Multidrug-Resistant Acinetobacter baumannii
Authors: Hwang Yoon Y. , Ramalingam Karthikeyan , Bienek Diane R. , Lee Valerie , You Tao , Alvarez Rene
Published: May 2013

Acinetobacter baumannii
has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four
Acinetobacter baumannii
isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against
A. baumannii
in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of
A. baumannii
was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic
A. baumannii
. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of
A. baumannii
.
Enhancing the Protective Immune Response against Botulism
Authors: Przedpelski Amanda , Tepp William H. , Kroken Abby R. , Fu Zhuji , Kim Jung-Ja P. , Johnson Eric A. , Barbieri Joseph T.
Published: May 2013

The need for a vaccine against botulism has increased since the discontinuation of the pentavalent (ABCDE) botulinum toxoid vaccine by the Centers for Disease Control and Prevention. The botulinum toxins (BoNTs) are the primary virulence factors and vaccine components against botulism. BoNTs comprise three domains which are involved in catalysis (LC), translocation (HCT), and host receptor binding (HCR). Recombinant HCR subunits have been used to develop the next generation of BoNT vaccines. Using structural studies and the known entry properties of BoNT/A, an HCR subunit vaccine against BoNT/A that contained the point mutation W1266A within the ganglioside binding pocket was designed. HCR/A(W1266A) did not enter primary neurons, and the crystal structure of HCR/A(W1266A) was virtually identical to that of wild-type HCR/A. Using a mouse model, experiments were performed using a high-dose vaccine and a low-dose vaccine. At a high vaccine dose, HCR/A and HCR/A(W1266A) elicited a protective immune response to BoNT/A challenge. At the low-dose vaccination, HCR/A(W1266A) was a more protective vaccine than HCR/A. α-HCR IgG titers correlated with protection from BoNT challenge, although titers to block HCR/A entry were greater in serum in HCR/A-vaccinated mice than in HCR/A(W1266A)-vaccinated mice. This study shows that removal of receptor binding capacity enhances potency of the subunit HCR vaccine. Vaccines that lack receptor binding capacity have the added property of limited off-target toxicity.
Resistant starch intake at breakfast affects postprandial responses in type 2 diabetics and enhances the glucose-dependent insulinotropic polypeptide – insulin relationship following a second meal
Authors: MacNeil Stacey , Rebry Rachel M. , Tetlow Ian J. , Emes Michael J. , McKeown Bruce , Graham Terry E.
Published: May 2013

Resistant starch (RS) consumption can modulate postprandial metabolic responses, but its effects on carbohydrate (CHO) handling in type 2 diabetics (T2D) are unclear. It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal, regardless of the amount of available CHO, and that in association with incretins, the effects would carry over to a 2nd meal. Using a randomized crossover design, 12 T2D ingested four different bagel treatments (their 1st meal) determined by available CHO and the weight or amount of bagel consumed: treatment A, without RS (50 g of available CHO); treatment B, with RS (same total CHO as in A); treatment C, with RS (same available CHO as in A); and treatment D, with the same RS as in B and available CHO as in A and C. A standard 2nd meal was ingested 3 h later. Following the first meal, B elicited a lower glucose incremental area under the curve (iAUC) than C (P < 0.05), D (P < 0.05), and A (trend; P = 0.07), lower insulin iAUC than A (P < 0.05) and C (P < 0.05), and lower glucose-dependent insulinotropic polypeptide (GIP) iAUC than A (P < 0.05). There was a positive correlation (P < 0.05) between GIP and insulin iAUCs after the 2nd meal, and C had a 3 times greater slope than the other treatments (r = 0.91, P < 0.001), yet lacked a significant concomitant improvement in glucose disposal. These results show that for the 1st meal, RS was effective when it replaced a portion of the available CHO, while ingesting more RS influenced the GIP–insulin axis following the 2nd meal.
A note on the stringy embeddings of certain N=2 dualities
Authors: Dasgupta Keshav , Seo Jihye
Published: May 2013

Seiberg–Witten theory can be embedded in F-theory using D3 branes probing an orientifold geometry. The nonperturbative corrections in the orientifold picture map directly to the instanton corrections in the corresponding gauge theory that convert the classical moduli space to the quantum one. In this short review we argue that the recently proposed class of conformal Gaiotto models may also be embedded in F-theory. The F-theory constructions help us not only to understand the Gaiotto dualities but also to extend to the nonconformal cases with and without cascading behaviors. For the conformal cases, the near horizon geometries in F-theory capture both the UV and IR behaviors succinctly.