bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Follow-up on Sagittal Fracture at the Temporal Root of the Zygomatic Arch: Does It Need Open Reduction?
Authors: Cheon Ji Seon , Seo Bin Na , Yang Jeong Yeol , Son Kyung Min
Published: September 2013

Background The zygoma is a major portion of the midfacial contour. When deformity occurs in this area, a reduction should be conducted to correct it. If a sagittal fracture at the temporal root of the zygomatic arch occurs, this also requires reduction, but it is difficult to approach due to its anatomical location, and the possibility of fixation is also limited. Thus, the authors attempted the reduction of sagittal fracture by two- or three-point fixation and the Gillies approach without direct manipulation. The preoperative and postoperative results of the patients were evaluated. Follow-up was performed to establish a treatment guideline.

Methods A retrospective study was done with 40 patients who had sagittal fractures at the temporal root of the zygomatic arch from March 2009 to June 2012. Only two- or three-point fixation was performed for the accompanying zygomatic-orbital-maxillary fracture. The Gillies approach was used for complex fractures of the zygomatic arch, while the temporal root of the zygomatic arch was only observed without reduction. Preoperative and postoperative computed tomography and X-ray scans were performed to examine the results.

Results The result of the paired t-test on preoperative and postoperative bone gap differences, the depression level, and the degree of temporal protrusion showed a marked decrease in the mean difference at a 95% confidence interval. The results were acceptable.

Conclusions In the treatment of sagittal fractures at the temporal root of the zygomatic arch, it is acceptable to use indirect reduction and non-fixation methods. This leads to a satisfactory aesthetic and functional outcome.
Direct Brow Lift Combined with Suspension of the Orbicularis Oculi Muscle
Authors: Lee Jeong Woo , Cho Byung Chae , Lee Kyung Young
Published: September 2013

Background Although the conventional direct brow lift operation provides a simple means of managing lateral brow ptosis, the scars produced have been unacceptable. However, using the modifications proposed here, scarring showed remarkable improvement. This article reviews our experiences with the presented technique, mainly with respect to postoperative scarring.

Methods Measured amounts of supra-eyebrow skin and subcutaneous fat were excised en bloc in the conventional manner under 'hyper-hydrated' local infiltration anesthesia. The lower flap and the edge of the upper flap were undermined above the muscular plane, and the orbicularis oculi muscle was directly suture-plicated and suspended upward to the distal frontalis muscle. Skin closure was performed in a basic plastic surgical manner.

Results From April 2007 to April 2012, a consecutive series of 60 patients underwent surgery using the above method. The average width of the excised skin was 8 mm (range, 5-15 mm) at the apex of the eyebrow. Preoperative complaints were resolved without occurrence of significant complications. The surgical scars showed remarkable improvement and were negligible in the majority of the cases.

Conclusions The direct brow lift operation combined with plication/suspension of the superior and lateral portion of the orbicularis oculi muscle provides a simple, safe, and predictable means of correcting lateral brow ptosis. The scars were acceptable to all of the patients. For proper management of the frontalis tone, upper blepharoplasty and/or repair of eyelid levator function must be considered in addition to brow lift procedures.
L-Shaped Columellar Strut in East Asian Nasal Tip Plasty
Authors: Dhong Eun-Sang , Kim Yeon-Jun , Suh Man Koon
Published: September 2013

Background Nasal tip support is an essential consideration for rhinoplasty in East Asians. There are many techniques to improve tip projection, and among them, the columellar strut is the most popular technique. However, the conventional design is less supportive for rotating the tip. The amount of harvestable septal cartilage is relatively small in East Asians. For an optimal outcome, we propose an L-shaped design for applying the columellar strut.

Methods To evaluate the anthropometric outcomes, the change in nasal tip projection and the columella-labial angle were analyzed by comparing preoperative and postoperative photographs. The anthropometric study group consisted of 25 patients who underwent the same operative technique of an L-shaped strut graft using septal cartilage and were followed up for more than 9 months.

Results There were statistically significant differences between the preoperative and postoperative values in the nasal tip projection ratio and columella-labial angle. We did not observe any complications directly related to the L-shaped columellar strut in the anthropometric study group.

Conclusions The L-shaped columellar strut has advantages not only in the controlling of tip projection and rotation, but in that it needs a smaller amount of cartilage compared to the conventional septal extension graft. It can therefore be an alternative technique for nasal tip plasty when there is an insufficient amount of harvestable septal cartilage.
Experience of ReCell in Skin Cancer Reconstruction
Authors: Gilleard Onur , Segaren Nicholas , Healy Ciaran
Published: September 2013

The ReCell system (Avita Medical) is a cell culture product that allows the immediate processing of a small split-thickness skin biopsy to produce a complete population of cells including keratinocytes, melanocytes, Langerhans cells and fibroblasts. This series is the first to highlight the reconstructive applications of ReCell following ablative skin cancer surgery. The ReCell system was utilized for three patients following skin cancer excision. In two cases, the cells were applied to forehead flap donor sites following nasal reconstruction. In one case, the cells were applied to the calvarial periosteum following wide local excision of a melanoma scar. Assessment of the treated area was performed using the patient and observer scar assessment scale after 1 year. The Patient and Observer Scar Assessment Scale (POSAS) scores for the 2 patients treated with ReCell following forehead flap surgery were 22 and 32. The score for the patient that underwent wide local excision of a melanoma scar was 45. The absence of a donor site, accelerated healing and the satisfactory aesthetic appearance of the mature scars in this series suggest that ReCell may play a useful role in reconstruction following skin cancer excision.
Role of the Surgical Glove in Modified Vacuum-Assisted Wound Healing
Authors: Hemmanur Shankar Ram , Siddha Loka Vijayan
Published: September 2013

Vacuum-assisted wound healing has been proven to be more efficacious than conventional dressings. Vacuum dressing has been frequently modified given the restrictions in resources available. Here we present a modified method of vacuum dressing by using surgical or gynaecological gloves for lower and upper limb wounds. Vacuum dressing was applied with parts of a surgical or gynaecological glove and Opsite with T-tailing of the suction outlet. Vacuum-assisted wound healing using the surgical gloves showed relatively good wound healing in the amputation stump, finger, arm, and leg in the cases studied.
Osteoporoza prouzrokovana lekovima
Authors: Nestorović Vojkan , Rašić Јulijana , Janićijević Hudomal Snežana
Published: September 2013

Sve je veći broj istraživanja koja otkrivaju da mnogi lekovi ispoljavaju neželjene efekte na mineralnu gustinu i strukturu koštanog tkiva. Brojne studije su pokazale da neki lekovi mogu biti „štetni za kost” kao što su: glukokortikoidi, hormoni štitaste žlezde, antiepileptici, antidepresivi, aromatični inhibitori, gonadotropin oslobađajući agensi, kontraceptivi, antiretrovirusni lekovi, diuretici Henleove petlje, inhibitori protonske pumpe (IPP) i drugi. Uravnoteženi balans u primeni lekova za vreme dugotrajne terapije izazovan je i zahtevan posao lekara u primarnoj i sekundarnoj praksi i zavisi od njihove upućenosti o odnosu između koristi i štetnosti primenjenih medikamenata. Određivanje statusa skeleta pacijenta pre započinjanja terapije nekim od tzv. ”lekova štetnih za kost”, veoma je važno i omogućava individualan pristup u terapiji.
Anaemia and zidovudine‐containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS
Authors: Renner Lorna A , Dicko Fatoumata , Kouéta Fla , Malateste Karen , Gueye Ramatoulaye D , Aka Edmond , Eboua Tanoh K , Azondékon Alain , Okomo Uduok , Touré Pety , Ekouévi Didier , Leroy Valeriane ,   IeDEA West Africa Paediatric Collaboration
Published: September 2013

Introduction

There is a risk of anaemia among HIV‐infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first‐line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV‐containing regimen in HIV‐infected children included in the IeDEA West African database.

Methods

Standardized collection of data from HIV‐infected children (positive PCR<18 months or positive serology ≥18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child‐years of follow‐up over the duration of first‐line antiretroviral therapy.

Results

As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight‐for‐age z‐score was −2.7; and 1772 (60.4%) had a first‐line ZDV‐containing regimen. At baseline, 70% of the children with a first‐line ZDV‐containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first‐line follow‐up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child‐years of follow‐up in those on a ZDV‐containing regimen versus 4.25 in those not (p≤0.01). Adjusted for age at ART initiation and first‐line regimen, a weight‐for‐age z‐score ≤−3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01).

Conclusions

Severe anaemia is frequent at baseline and guides the first‐line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care.
The structure of the COPII transport-vesicle coat assembled on membranes
Authors: Zanetti Giulia , Prinz Simone , Daum Sebastian , Meister Annette , Schekman Randy , Bacia Kirsten , Briggs John AG
Published: September 2013

Coat protein complex II (COPII) mediates formation of the membrane vesicles that export newly synthesised proteins from the endoplasmic reticulum. The inner COPII proteins bind to cargo and membrane, linking them to the outer COPII components that form a cage around the vesicle. Regulated flexibility in coat architecture is essential for transport of a variety of differently sized cargoes, but structural data on the assembled coat has not been available. We have used cryo-electron tomography and subtomogram averaging to determine the structure of the complete, membrane-assembled COPII coat. We describe a novel arrangement of the outer coat and find that the inner coat can assemble into regular lattices. The data reveal how coat subunits interact with one another and with the membrane, suggesting how coordinated assembly of inner and outer coats can mediate and regulate packaging of vesicles ranging from small spheres to large tubular carriers.
MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons
Authors: Engelhard Caitlin , Sarsfield Sarah , Merte Janna , Wang Qiang , Li Peng , Beppu Hideyuki , Kolodkin Alex L , Sucov Henry M , Ginty David D
Published: September 2013

Bone morphogenetic protein (BMP) signaling has emerged as an important regulator of sensory neuron development. Using a three-generation forward genetic screen in mice we have identified Megf8 as a novel modifier of BMP4 signaling in trigeminal ganglion (TG) neurons. Loss of Megf8 disrupts axon guidance in the peripheral nervous system and leads to defects in development of the limb, heart, and left-right patterning, defects that resemble those observed in Bmp4 loss-of-function mice. Bmp4 is expressed in a pattern that defines the permissive field for the peripheral projections of TG axons and mice lacking BMP signaling in sensory neurons exhibit TG axon defects that resemble those observed in Megf8−/− embryos. Furthermore, TG axon growth is robustly inhibited by BMP4 and this inhibition is dependent on Megf8. Thus, our data suggest that Megf8 is involved in mediating BMP4 signaling and guidance of developing TG axons.
Document authentication at molecular levels using desorption atmospheric pressure chemical ionization mass spectrometry imaging
Authors: Li Ming , Jia Bin , Ding Liying , Hong Feng , Ouyang Yongzhong , Chen Rui , Zhou Shumin , Chen Huanwen , Fang Xiang
Published: September 2013

Molecular images of documents were obtained by sequentially scanning the surface of the document using desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI‐MS), which was operated in either a gasless, solvent‐free or methanol vapor‐assisted mode. The decay process of the ink used for handwriting was monitored by following the signal intensities recorded by DAPCI‐MS. Handwritings made using four types of inks on four kinds of paper surfaces were tested. By studying the dynamic decay of the inks, DAPCI‐MS imaging differentiated a 10‐min old from two 4 h old samples. Non‐destructive forensic analysis of forged signatures either handwritten or computer‐assisted was achieved according to the difference of the contour in DAPCI images, which was attributed to the strength personalized by different writers. Distinction of the order of writing/stamping on documents and detection of illegal printings were accomplished with a spatial resolution of about 140 µm. A Matlab® written program was developed to facilitate the visualization of the similarity between signature images obtained by DAPCI‐MS. The experimental results show that DAPCI‐MS imaging provides rich information at the molecular level and thus can be used for the reliable document analysis in forensic applications. © 2013 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.
Evaluating the Morbidity and Efficacy of Reoperative Surgery in the Central Compartment for Persistent/Recurrent Papillary Thyroid Carcinoma
Authors: Lang Brian Hung‐Hin , Lee George C. C. , Ng Cathy P. C. , Wong Kai Pun , Wan Koon Yat , Lo Chung‐Yau
Published: September 2013

Background

Although reoperative surgery in the central compartment (RCND) is indicated for bulky or progressive persistent/recurrent papillary thyroid carcinoma (PTC), its associated morbidity and disease outcomes remain unclear. We evaluated RCND outcomes by comparing them with those of patients who underwent primary central neck dissection (CND).

Methods

After matching for age, sex, tumor size, and initial tumor stage, the morbidity and outcomes of 50 consecutive patients who underwent RCND were compared with data from 75 patients who underwent primary therapeutic CND during the same period. Matching was performed blind to the morbidity and disease outcome of each patient. A stimulated thyroglobulin (sTg) <2 ng/ml was considered undetectable.

Results

Relative to primary CND, the incidence of extranodal extension (p = 0.010) and size of metastatic lymph nodes (p < 0.001) were significantly greater in the RCND group. Postoperative hypoparathyroidism and vocal cord palsy rates were comparable in the groups. There were two esophageal injuries in the RCND group and none in the primary CND group. The secondary CND group achieved a significantly lower undetectable postablation sTg rate (12.0 vs. 52.0 %, p = 0.001) and worse 10‐year disease‐free survival (35.6 vs. 91.8 %, p = 0.001) and cancer‐specific survival (82.0 vs. 98.5 %, p = 0.001) than the primary CND group.

Conclusions

Although RCND for persistent/recurrent PTC was performed with morbidity comparable to that seen with primary CND, it was associated with some serious complications. Short‐ and long‐term disease control appeared moderate with approximately one‐tenth of patients having an undetectable sTg level 6 months after ablation and one‐third remaining clinically disease‐free after 10 years.
Prognostic Significance of MicroRNA‐16 Expression in Human Colorectal Cancer
Authors: Qian Jun , Jiang Bin , Li Min , Chen Juan , Fang Mingzhi
Published: September 2013

Background

MicroRNAs (miRNAs), small noncoding RNAs, have been reported to be highly involved in the formation and progression of all types of human cancer including colorectal cancer (CRC). Therefore, miRNAs are also potential prognostic biomarkers in CRC patients. The aim of this study was to detect the expression of miR‐16 in human CRC tissues and investigate its clinicopathologic or prognostic significance.

Methods

TaqMan quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assay was performed to determine the expression of miR‐16 in 143 primary CRC tissues and 18 corresponding normal colonic mucosa from patients who had undergone surgery. The association of miR‐16 expression with clinicopathologic features of CRC patients was statistically analyzed. Kaplan–Meier analyses were used to assess patient survival. Univariate and multivariate Cox analyses were performed.

Results

The relative level of miR‐16 in 18 CRC tissues was significantly lower than that in corresponding normal colonic mucosa (p < 0.001). Statistical analyses revealed that the status of miR‐16 expression was closely associated with tumor differentiation, lymph node metastasis, L category, V category, TNM stage, and tumor recurrence of CRC (p = 0.001, 0.003, 0.001, 0.005, 0.003, and 0.017, respectively). Kaplan–Meier analyses indicated that patients with low‐miR‐16 had lower 5‐year overall survival than those with high‐miR‐16 (31.2 vs. 58.3 %; p = 0.0012). Multivariate Cox regression analyses indicated that the status of miR‐16 expression might be an independent prognostic factor for CRC patients (hazard ratio 1.67; 95 % confidence interval 1.22–2.54; p = 0.018).

Conclusions

Down‐regulation of miR‐16 plays critical roles in CRC progression. Low miR‐16 expression is an independent factor predicting a poor prognosis for CRC patients.
Defining Engagement in Adolescent Substance Abuse Treatment
Authors: Pullmann Michael D. , Ague Starcia , Johnson Tamara , Lane Stephanie , Beaver Kevon , Jetton Elizabeth , Rund Evangejalynn
Published: September 2013

Youth engagement in substance use treatment is an important construct for research and practice, but it has been thinly and inconsistently defined in the literature. Most research has measured engagement by initiation, attendance, and retention in treatment. Because youth generally enter substance use treatment as a result of compliance with external requirements, defining engagement in this way might be insufficient. This qualitative participatory research study describes five focus groups with 31 adults working with youth in substance use treatment. Focus groups were designed and conducted by youth researchers in collaboration with university‐based partners. We categorized participants’ descriptions of engagement into five domains, identified as “CARES”: Conduct, Attitudes, Relationships, Empowerment, and Social Context. These domains represent a comprehensive and ecologically‐based definition of engagement that situates engagement in the context and trajectory of youth development, has clear implications for assertive clinical practice, and provides a foundation for developing an operationalized measure.
Maleinization of Soybean Oil Glycerides Obtained from Biodiesel‐Derived Crude Glycerol
Authors: Echeverri David A. , Perez William A. , Rios Luis A.
Published: September 2013

Glycerides obtained from the glycerolysis of soybean oil with crude glycerol were acylated with maleic anhydride at 80–100 °C. Both uncatalyzed and catalyzed reactions with 2‐methylimidazole (2‐MI) were evaluated. Formation of maleated glycerides was confirmed by 1H‐NMR and FTIR analyses. Consumption of maleic anhydride as a function of time was followed by acid value titration. High conversion (ca. 95 %) of hydroxyl groups was obtained at 90 °C in 60 min without catalyst. Under these conditions, a product with 1.9 maleate moieties per glyceride molecule was obtained. Catalyzed reactions afforded lower conversions of hydroxyl groups and lower maleate yields compared to uncatalyzed reactions.
Internalizing symptoms and rumination: The prospective prediction of familial and peer emotional victimization experiences during adolescence
Authors: Shapero Benjamin G. , Hamilton Jessica L. , Liu Richard T. , Abramson Lyn Y. , Alloy Lauren B.
Published: September 2013

Adolescence is marked by increases in stressful life events. Although research has demonstrated that depressed individuals generate stress, few studies investigate the generation of emotional victimization. The current study examined the effects of rumination and internalizing symptoms on experiences of peer victimization and familial emotional abuse.

Participants were 216 adolescents (M = 14‐years‐old; 58% female; 47% African–American) who completed two assessments. Results showed that rumination predicted peer victimization and emotional abuse. The effect of rumination on emotional victimization is heightened for those who have higher levels of depression symptoms. That is, individuals who ruminate and who have depression symptoms experience increases in both peer emotional victimization and parental emotional abuse.

This study builds upon prior research and indicates that rumination may be a stronger predictor of emotional victimization than symptoms of depression or anxiety. Identifying underlying mechanisms may yield targets for interventions aimed at addressing the chronic nature of depression.
The Influence of Private Labels on Retailer Cooperation
Authors: Zippel Christian , Wilkinson John , Vogler Thomas
Published: September 2013

Retailers’ private labels are unlike normal competitors to manufacturers’ national brands. From a channel viewpoint, retailers’ private labels do not merely compete on a horizontal level with manufacturers’ national brands. Competition between national brands and private labels also influences the vertical channel relationships between manufacturers and retailers, potentially reducing the level of cooperation manufacturers can obtain from retailers with respect to their national brands.

In contrast to recent studies focusing on the influence of private labels on store image, success factors of private labels, and the marketing approaches by manufacturers in response to that success, this exploratory study examines the influence of retailers’ private labels on the level of cooperation between manufacturers and large retail chains. Surprisingly, preliminary results suggest that private labels can have a positive effect on cooperation in some situations and may offer manufacturers an opportunity to increase the level of cooperation obtained from retailers.
A comparative study of the neuropsychiatric and neurocognitive phenotype in two microdeletion syndromes: Velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes
Authors: Zarchi O. , Diamond A. , Weinberger R. , Abbott D. , Carmel M. , Frisch A. , Michaelovsky E. , Gruber R. , Green T. , Weizman A. , Gothelf D.
Published: September 2013

Purpose:

22q11.2 deletion syndrome (22q11.2DS) and Williams syndrome (WS) are common neurogenetic microdeletion syndromes. The aim of the present study was to compare the neuropsychiatric and neurocognitive phenotypes of 22q11.2DS and WS.

Methods:

Forty-five individuals with 22q11.2DS, 24 with WS, 22 with idiopathic developmental disability (DD) and 22 typically developing (TD) controls were compared for the rates of psychiatric disorders as well as cognitive executive and visuospatial functions.

Results:

We found that while anxiety, mood and disruptive disorders had an equally high prevalence among individuals with 22q11.2DS, WS and DDs, the 22q11.2DS group had the highest rates of psychotic disorders and the WS group had the highest rates of specific phobia. We also found that the WS group demonstrated more severe impairments in both executive and visuospatial functions than the other groups. WS and 22q11.2DS subjects had worse Performance-IQ than Verbal-IQ, a feature typical of non-verbal learning disorders.

Conclusion:

These findings offer a wide perspective on unique versus common phenotypes in 22q11.2DS and WS.
Improving global accountability: The ICC and nonviolent crimes against humanity
Authors: ALOYO EAMON
Published: September 2013

Scholars have proposed a number of different ways to improve global accountability, but none has adequately addressed how individuals who commit widespread or systematic nonviolent wrongs can be held to account. I argue that for moral reasons individuals should be held accountable for nonviolent crimes against humanity and that an existing legal institution, the International Criminal Court (ICC), has the authority to prosecute such crimes. The ICC’s prosecutor should start exercising this legal authority because widespread or systematic nonviolent harms can be just as morally wrong as violent ones. What matters on my account is the gravity of a wrong, not whether it was committed violently or nonviolently. I situate these arguments in contemporary discussions of accountability, and provide evidence that individuals can cause widespread or systematic nonviolent harms that meet the legal definition of a crime against humanity in the Rome Statute, the ICC’s foundational document.
Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering
Authors: Srinivas Girish , Möller Steffen , Wang Jun , Künzel Sven , Zillikens Detlef , Baines John F. , Ibrahim Saleh M.
Published: September 2013

Susceptibility to chronic inflammatory diseases is determined by immunogenetic and environmental risk factors. Resident microbial communities often differ between healthy and diseased states, but whether these differences are of primary aetiological importance or secondary to the altered inflammatory environment remains largely unknown. Here we provide evidence for host gene–microbiota interactions contributing to disease risk in a mouse model of epidermolysis bullosa acquisita, an autoantibody-induced inflammatory skin disease. Using an advanced intercross, we identify genetic loci contributing to skin microbiota variability, susceptibility to skin blistering and their overlap. Furthermore, by treating bacterial species abundances as covariates with disease we reveal a novel disease locus. The majority of the identified covariate taxa are characterized by reduced abundance being associated with increased disease risk, providing evidence of a primary role in protection from disease. Further characterization of these putative probiotic species or species assemblages offers promising potential for preventative and therapeutic treatment development.
Artificial Cilia
Authors:   Royal Society of Chemistry
Published: September 2013

Natural cilia are tiny hairs on cells which have generated and sensed fluid flow in biological systems for billions of years. Mimicking this action in artificial systems presents interesting opportunities for flow control in lab-on-a-chip devices. Research into this field began almost a decade ago, and this book presents the state-of-the-art in this rapidly developing field of research inspired by nature.

Establishing a link between nature and technology is a major attraction to those entering the field, which encompasses materials, processing, fluid mechanics, fluid-structure interaction, and biomedical applications. Artificial Cilia will appeal to anyone working in these areas and presents beautiful examples of how a biological system can form the successful basis for research and technical applications.

The editors have been pioneers in the field since establishing a major European project on artificial cilia in 2005, and they are joined by leading experts from across the globe in presenting a comprehensive digest of this exciting new technology.
Introduction
Authors: Jaap den Toonder  , Onck Patrick
Published: September 2013

This book is about artificial cilia. The use of artificial cilia to create pumping and/or mixing in micro‐fluidic devices is a recent development, inspired by nature. Cilia are small hairs that can be found in biology and are used for (fluid) actuation and sensing. Microscopic actuators resembling cilia, actuated to move under the influence of various stimuli such as electrostatic fields, magnetic fields and even light, have been developed by a number of groups and shown to be capable of generating flow and mixing in micro‐fluidic environments. The research on artificial cilia started about a decade ago, and is rapidly expanding. In addition to being relevant for potential application in lab‐on‐a‐chip devices, the work on artificial cilia forms a beautiful example of how a biological system can form the successful basis for both scientific research and technological applications. In this introductory chapter we discuss the structure and working principle of biological cilia, touch upon the potential micro‐fluidic applications of artificial cilia, give an overview of chapters included in this book, and we conclude with providing a perspective on future developments in artificial cilia.
Parkinson’s Disease: Symptoms, Unmet Needs and New Therapeutic Targets
Authors: Kurtis Mónica M. , Martinez‐Martín Pablo
Published: September 2013

Parkinson’s disease is classically defined by the presence of two or more of the following cardinal motor symptoms: bradykinesia, rigidity, tremor at rest, and gait disturbances. In the past two decades, the non‐motor symptom complex of the disease has gained increasing attention, warranted by the impact it has on patient quality of life. In this introductory chapter, the clinical characterization of the motor and non‐motor symptoms is extensively described and the possible pathophysiological mechanisms underlying each symptom are delineated. Furthermore, the subtypes of Parkinson’s disease, based on empirical and data‐driven systems, are discussed. An updated summary of the current state‐of‐the‐art in diagnosis and treatment is briefly covered. Finally, the currently unmet needs and direction of investigative efforts are analyzed, focusing on the non‐dopamine responsive symptoms and the search for biomarkers, cause‐directed effective treatments and neuroprotective therapies.
Molecular Pathogenesis and Pathophysiology of Parkinson’s Disease: New Targets for New Therapies
Authors: Castaño José G. , González Carmen , Obeso José A. , Rodriguez Manuel
Published: September 2013

Parkinson’s disease (PD) is a complex chronic neurodegenerative disease of unknown etiology. A conceptual framework for all chronic diseases involves a series of channels or pathways (aging, genetic, environment, oxidative stress, mitochondrial damage, protein aggregation, etc.) and their interactions. Those channels with specificities may explain the ‘developmental’ program that through transcriptional reprogramming results in stressed dopamine neurons that eventually become dysfunctional or die, giving rise to the clinical manifestations of PD. In Chapter 2 we review the molecular mechanisms of those channels that may be implicated in the pathogenesis of PD and the pathophysiology of the disease based on the anatomo‐physiological complexity of the basal ganglia. This illustrates that understanding the molecular mechanisms of a disease may not be enough, or we have to reach an adequate system level to understand the disease process. Finally, we suggest that common therapies used for the treatment of other chronic diseases may be useful for the treatment (or help to advance the understanding) of PD, as well as new targets for new therapies that may be useful in the prevention of, or to stop the progression of, PD and other synucleinopathies.
Protein Phosphatases in Parkinson’s Disease
Authors: Heneberg Petr
Published: September 2013

Phosphorylation and dephosphorylation are among the key mechanisms underlying the pathogenesis of Parkinson's disease (PD). Accumulating genetic evidence implicates the dysfunction of several kinases and phosphatases, as well as the upstream regulatory proteins and the downstream targets. So far, there is direct evidence for the involvement of at least six tyrosine phosphatases (RPTPβ/ζ, PTP-PEST, STEP, SHP-2, tyrosine and lipid phosphatase PTEN, and the dual-specificity phosphatase DUSP1), and for the involvement of at least four serine/threonine phosphatases (PP1, PP2A, PP3/calcineurin, and PHLPP1). The critical dephosphorylation mechanisms provide number of potential targets for drug discovery. Modulation of the activity of protein phosphatases or of other members of their signaling pathways has the potential to serve as the next generation of PD therapeutic targets.
New Approaches to Neuroprotection in Parkinson’s Disease
Authors: Mena María Angeles , Perucho Juan , López-Sendón José Luis , Yébenes Justo García de
Published: September 2013

Parkinson's disease (PD) is a neurodegenerative disorder characterized by akinesia, rigidity, tremor at rest and postural abnormalities, as well as other symptoms involving the central and the autonomic nervous system. PD affects up to 300 patients per 100 000 inhabitants with a higher prevalence in males. The neuropathological features of PD include a severe neuronal loss in the dopamine-rich substantia nigra and other monoamine rich brain stem nuclei, and a severe loss of striatal levels of dopamine and its metabolites. The vast majority of patients with PD show intraneuronal inclusion bodies immunoreactive to α-synuclein in their nigrostriatal dopamine cells, as well as in neurons of other nuclei from the central and autonomic nervous system.

The treatment of PD is one of the greatest successes in the history of medicine, since in the last half century a large number of pharmaceutical compounds, and surgical intervention, have completely changed the prognosis of this disease. These treatments have returned patients with PD to a normal life expectancy and allow for a good quality of life for many years after diagnosis. The treatments available, however, do not stop the progression of the disease and most patients surviving for long periods of time after the initiation of therapy develop complications such as fluctuations, dyskinesias, disturbances related to lack of control of impulses and several types of cognitive deterioration.

Neuroprotection in PD is difficult since this disease involves multiple different pathogenic mechanisms interacting with the patient's own process of aging. Mendelian genetic mechanisms causing PD include more than 16 canonical gene defects plus an increasing number of genetic risk factors. These molecular abnormalities responsible for PD include abnormalities of neurotransmitter metabolism, excessive free radicals, abnormal mitochondrial function, excessive accumulation of denatured proteins, abnormalities of kinases and others. Strategies for neuroprotection need to take into consideration the enormous variety of pathogenic mechanisms, and the need to design specific therapies for the specific molecular defects present in each case.
Dynamic conformational switching in the chemokine ligand is essential for G-protein-coupled receptor activation
Authors: Joseph Prem Raj B. , Sawant Kirti V. , Isley Angela , Pedroza Mesias , Garofalo Roberto P. , Richardson Ricardo M. , Rajarathnam Krishna
Published: September 2013

Chemokines mediate diverse functions from organogenesis to mobilizing leucocytes, and are unusual agonists for class-A GPCRs (G-protein-coupled receptors) because of their large size and multi-domain structure. The current model for receptor activation, which involves interactions between chemokine N-loop and receptor N-terminal residues (Site-I) and between chemokine N-terminal and receptor extracellular loop/transmembrane residues (Site-II), fails to describe differences in ligand/receptor selectivity and the activation of multiple signalling pathways. In the present study, we show in neutrophil-activating chemokine CXCL8 that the highly conserved GP (glycine-proline) motif located distal to both N-terminal and N-loop residues couples Site-I and Site-II interactions. GP mutants showed large differences from native-like to complete loss of function that could not be correlated with the specific mutation, receptor affinity or subtype, or a specific signalling pathway. NMR studies indicated that the GP motif does not influence Site-I interactions, but molecular dynamics simulations suggested that this motif dictates substates of the CXCL8 conformational ensemble. We conclude that the GP motif enables diverse receptor functions by controlling cross-talk between Site-I and Site-II, and further propose that the repertoire of chemokine functions is best described by a conformational ensemble model in which a network of long-range coupled indirect interactions mediate receptor activity.
A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model
Authors: Wiegman Coen H. , Li Feng , Clarke Colin J. , Jazrawi Elen , Kirkham Paul , Barnes Peter J. , Adcock Ian M. , Chung Kian F.
Published: September 2013

Ozone is an oxidizing environmental pollutant that contributes significantly to respiratory health. Exposure to increased levels of ozone has been associated with worsening of symptoms of patients with asthma and COPD (chronic obstructive pulmonary disease). In the present study, we investigated the acute and chronic effects of ozone exposure-induced oxidative stress-related inflammation mechanics in mouse lung. In particular, we investigated the oxidative stress-induced effects on HDAC2 (histone deacetylase 2) modification and activation of the Nrf2 (nuclear factor erythroid-related factor 2) and HIF-1α (hypoxia-inducible factor-1α) signalling pathways. Male C57BL/6 mice were exposed to ozone (3 p.p.m.) for 3 h a day, twice a week for a period of 1, 3 or 6 weeks. Control mice were exposed to normal air. After the last exposure, mice were killed for BAL (bronchoalveolar lavage) fluid and lung tissue collection. BAL total cell counts were elevated at all of the time points studied. This was associated with increased levels of chemokines and cytokines in all ozone-exposed groups, indicating the presence of a persistent inflammatory environment in the lung. Increased inflammation and Lm (mean linear intercept) scores were observed in chronic exposed mice, indicating emphysematous changes were present in lungs of chronic exposed mice. The antioxidative stress response was active (indicated by increased Nrf2 activity and protein) after 1 week of ozone exposure, but this ability was lost after 3 and 6 weeks of ozone exposure. The transcription factor HIF-1α was elevated in 3- and 6-week ozone-exposed mice and this was associated with increased gene expression levels of several HIF-1α target genes including Hdac2 (histone deacetylase 2), Vegf (vascular endothelial growth factor), Keap1 (kelch-like ECH-associated protein 1) and Mif (macrophage migration inhibitory factor). HDAC2 protein was found to be phosphorylated and carbonylated in nuclear and cytoplasm fractions, respectively, and was associated with a decrease in DNA-binding activity and protein expression of HDAC2. Decreased HDAC2 activity, most likely a direct result of protein modification, in combination with the loss of the antioxidative stress response and activation of the HIF-1α pathway, contribute to the inflammatory response and emphysema observed in ozone-exposed mice.
Flow focusing with viscoelastic liquids
Authors: Derzsi Ladislav , Kasprzyk Marta , Plog Jan Philip , Garstecki Piotr
Published: September 2013

We present an experimental comparative study of the effect of elasticity of the continuous liquid in generation of droplets in microfluidic flow focusing devices. For a wide range of values of dynamic viscosity of the Newtonian droplet phase we compare the dynamics of the formation of droplets in three different Newtonian and non-Newtonian, viscoelastic (Boger) fluid pairs of the same (and nearly constant) shear viscosities. In both Newtonian and viscoelastic systems we find similar regimes of operation of the system: (i) dripping without satellites, (ii) dripping with single satellites, (iii) formation of multiple satellites, and (iv) jetting. We find that the elasticity of the focusing liquid stabilizes the jets facilitating formation of smaller droplets, and leads to transitions between various regimes at lower ratios of flow and at lower values of the capillary numbers in comparison to the Newtonian focusing liquids. We also show that the polydispersity of Newtonian droplets produced in non-Newtonian continuous phases depend significantly on the viscosity of the droplet phase while this dependence is minor when the continuous liquid is Newtonian.
Vortex dynamics in 3D shock-bubble interaction
Authors: Hejazialhosseini Babak , Rossinelli Diego , Koumoutsakos Petros
Published: September 2013

The dynamics of shock-bubble interaction involve an interplay of vortex stretching, dilation, and baroclinic vorticity generation. Here, we quantify the interplay of these contributions through high resolution 3D simulations for several Mach and Atwood numbers. We present a volume rendering of density and vorticity magnitude fields of shock-bubble interaction at M = 3 and air/helium density ratio η = 7.25 to elucidate the evolution of the flow structures. We distinguish the vorticity growth rates due to baroclinicity, stretching, and dilatation at low and high Mach numbers as well as the late time evolution of the circulation. The results demonstrate that a number of analytical models need to be revised in order to predict the late time circulation of shock-bubble interactions at high Mach numbers. To this effect, we propose a simple model for the dependence of the circulation to Mach number and ambient to bubble density ratio for air/helium shock-bubble interactions.
Monte Carlo simulation of flexible trimers: From square well chains to amphiphilic primitive models
Authors: Jiménez-Serratos Guadalupe , Gil-Villegas Alejandro , Vega Carlos , Blas Felipe J.
Published: September 2013

In this work, we present Monte Carlo computer simulation results of a primitive model of self-assembling system based on a flexible 3-mer chain interacting via square-well interactions. The effect of switching off the attractive interaction in an extreme sphere is analyzed, since the anisotropy in the molecular potential promotes self-organization. Before addressing studies on self-organization it is necessary to know the vapor liquid equilibrium of the system to avoid to confuse self-organization with phase separation. The range of the attractive potential of the model, λ, is kept constant and equal to 1.5σ, where σ is the diameter of a monomer sphere, while the attractive interaction in one of the monomers was gradually turned off until a pure hard body interaction was obtained. We present the vapor-liquid coexistence curves for the different models studied, their critical properties, and the comparison with the SAFT-VR theory prediction [A. Gil-Villegas, A. Galindo, P. J. Whitehead, S. J. Mills, G. Jackson, and A. N. Burgess, J. Chem. Phys. 106, 4168 (1997)]. Evidence of self-assembly for this system is discussed.
Impact of a vortex dipole with a semi-infinite rigid plate
Authors: Peterson Sean D. , Porfiri Maurizio
Published: September 2013

The physics of a two-dimensional vortex dipole impinging on the tip of a semi-infinite rigid plate is numerically examined. The dipole trajectory is initially orthogonal to the plate and aligned with its tip. The impact behavior is examined for three dipole Reynolds numbers. As the dipole approaches, vorticity is induced along the plate, as in the case of a dipole approaching a full wall, and is additionally shed from the tip. Upon impact, the dipole effectively splits, with half of it interacting with the vorticity induced on the plate and the other half with the vorticity shed from the tip. Each half of the original dipole forms a new secondary vortex pair whose behavior depends upon the Reynolds number of the original dipole. Contingent upon the rate of momentum diffusion, these secondary (and tertiary) vortex pairs may return and impact the plate again. Herein, we detail the interaction of the dipole impact at various Reynolds numbers, with a focus on the vortex dynamics and the distributed load imposed on the rigid plate by the fluid.
Dynamic of negative ions in potassium-D-ribose collisions
Authors: Almeida D. , Ferreira da Silva F. , García G. , Limão-Vieira P.
Published: September 2013

We present negative ion formation from collisions of neutral potassium atoms with D-ribose (C5H10O5), the sugar unit in the DNA/RNA molecule. From the negative ion time-of-flight (TOF) mass spectra, OH− is the main fragment detected in the collision range 50–100 eV accounting on average for 50% of the total anion yield. Prominence is also given to the rich fragmentation pattern observed with special attention to O− (16 m/z) formation. These results are in sharp contrast to dissociative electron attachment experiments. The TOF mass spectra assignments show that these channels are also observed, albeit with a much lower relative intensity. Branching ratios of the most abundant fragment anions as a function of the collision energy are obtained, allowing to establish a rationale on the collision dynamics.
Nonaxisymmetric droplet unpinning in vapor-liquid-solid-grown nanowires
Authors: Muralidharan Srevatsan , Voorhees Peter W. , Davis Stephen H.
Published: September 2013

It is well known that the morphology of nanowire grown using the Vapor-Liquid-Solid mechanism depends substantially on the stability and configuration of the catalyst droplet. Whereas many of the earlier studies have focused on the conditions under which the liquid droplet remains stable, in the present article, we enquire as to what happens if and when the liquid droplet unpins from the corner. We employ a perturbation approach and arrive at the fact that there is a much larger tendency for the liquid droplet to unpin in an asymmetric manner than in a symmetric manner even in the absence of any underlying geometric asymmetry or anisotropy. The implications of this to a number of experimental observations are discussed.