bluuebunny/crossref_metadata_2025 huggingface dataset:
Exome sequencing shows a novel de novo mutation in ATL1
Authors: Koh Kishin , Ishiura Hiroyuki , Miwa Michiaki , Doi Koichiro , Yoshimura Jun , Mitsui Jun , Goto Jun , Morishita Shinichi , Tsuji Shoji , Takiyama Yoshihisa
Published: January 2014

Background and Aim

We experienced treating a male patient born to healthy parents, who presented with spastic gait from childhood, and his son and daughter similarly presented with spastic gait, raising the possibility of a de novo mutation in the patient. With the hypothesis of a de novo mutation in the patient, we carried out exome sequencing of the patient and his parents to identify the gene with a disease‐causative mutation in the patient.

Methods

The genomic DNA obtained from the patient and his parents were subjected to exome sequencing. We applied various filters to identify candidate de novo mutations.

Results

We identified three de novo mutations, namely, PLB1 c.3601T>A p.C1201S, PHF2 c.2678C>T p.S893L and ATL1 c.1259A>C p.Q420P. Two of these mutations (ATL1 and PHF2) cosegregated with the disease phenotype in this family. Because the clinical presentations of the affected individuals in this family are typical for spastic paraplegia type 3A, the novel mutation (p.Q420P) in ATL1 is likely the cause of early‐onset spastic paraplegia in this family.

Conclusion

In the present, study we confirm the efficacy and usefulness of exome sequencing of parent–child trios for establishing the molecular diagnosis of patients with neurological diseases, in whom de novo mutations are suspected.
Case of familial amyotrophic lateral sclerosis showing gadolinium‐enhanced cranial nerves on magnetic resonance imaging associated with rapid progression of facial nerve palsy
Authors: Mizuno Masayuki , Ueki Yoshino , Sakurai Keita , Okita Kenji , Endo Fumito , Yamanaka Koji , Morita Mitsuya , Matsukawa Noriyuki
Published: January 2014

The evaluation of cranial nerves in magnetic resonance imaging (MRI) at early developmental stage has not been established in amyotrophic lateral sclerosis (ALS). A 23‐year‐old man with familial ALS developed peripheral facial nerve palsy, and showed the striking gadolinium enhancement on MRI in those nerves at an early stage. His symptoms progressed rapidly and he died approximately 3 months after onset. We identified a missense mutation in exon 1 of the Cu/Zn superoxide dismutase gene (SOD‐1), resulting in a Cys6Gly (C6G) amino acid substitution. Based on the rapid progression and neurotoxicity resulting from SOD‐1 protein aggregation, the gadolinium enhancement of facial nerves might be caused by the rapid Wallerian degeneration and blood–brain barrier disruption at the early phase of progression.
The future in the past: Hildegard Peplau and interpersonal relations in nursing
Authors: D'Antonio Patricia , Beeber Linda , Sills Grayce , Naegle Madeline
Published: January 2014

Researchers, educators and clinicians have long recognized the profound influence of the mid‐twentieth century focus on interpersonal relations and relationships on nursing. Today, in nursing, as well as in medicine and other social sciences, neuroanatomy, neurobiology and neurophysiology have replaced interpersonal dynamics as keys to understanding human behavior. Yet concerns are being raised that the teaching, research and practice of the critical importance of healing relationships have been overridden by a biological focus on the experiences of health and illness. As a way to move forward, we return to Hildegard Peplau's seminal ideas about the transformative power of relationships in nursing. We propose that Peplau's formulations and, in particular, her seminal Interpersonal Relations in Nursing can provide direction. We do not propose that her formulations or her book be simply transposed from the 1950s to today's classroom and clinic. But we do believe that her ideas and writings are dynamic documents containing concepts and derived operations that can be brought to life in clinical practice. Finally, we explore Peplau's transformative idea that nursing is, at its core, an interpersonal process both to acknowledge an idea that has shaped our past and can guide us into our future.
Nursing under the skin: a netnographic study of metaphors and meanings in nursing tattoos
Authors: Eriksson Henrik , Christiansen Mats , Holmgren Jessica , Engström Annica , Salzmann‐Erikson Martin
Published: January 2014

The aims of this study were to present themes in nursing motifs as depicted in tattoos and to describe how it reflects upon nursing in popular culture as well as within professional nursing culture. An archival and cross‐sectional observational study was conducted online to search for images of nursing tattoos that were freely available, by utilizing the netnographic methodology. The 400 images were analyzed in a process that consisted of four analytical steps focusing on metaphors and meanings in the tattoos. The findings present four themes: angels of mercy and domination; hegemonic nursing technology; embodying the corps; and nurses within the belly of the monster. The tattoos serve as a mirror of popular culture and the professional culture of nurses and nursing practice within the context of body art. Body art policy statements have been included in nursing personnel dress code policies. Usually these policies prohibit tattoos that are sexist, symbolize sex or could contribute and reproduce racial oppression. The results show that the tattoos can be interpreted according to several layers of meanings in relation to such policies. We therefore stress that this is an area highly relevant for further analyses in nursing research.
Bourdieu at the bedside: briefing parents in a pediatric hospital
Authors: LeGrow Karen , Hodnett Ellen , Stremler Robyn , McKeever Patricia , Cohen Eyal
Published: January 2014

The philosophy of family‐centered care (FCC) promotes partnerships between families and staff to plan, deliver, and evaluate services for children and has been officially adopted by a majority of pediatric hospitals throughout North America. However, studies indicated that many parents have continued to be dissatisfied with their decision‐making roles in their child's care. This is particularly salient for parents of children with chronic ongoing complex health problems. These children are dependent upon medical technology and require frequent hospitalizations during which parents must contribute to difficult decisions regarding their child's care. Given this clinical issue, an alternative theoretical perspective was explored to redress this problem. Pierre Bourdieu's theoretical concepts of field, capital, and habitus were used to analyze the hierarchical relationships in pediatric acute care hospitals and to design a briefing intervention aimed at improving parents' satisfaction with decision making in that health care setting.
Seed dispersal in time can counteract the effect of gene flow between natural populations of Arabidopsis thaliana
Authors: Falahati‐Anbaran Mohsen , Lundemo Sverre , Stenøien Hans K.
Published: January 2014

Plants may escape unfavorable environments by dispersing to new sites, or by remaining in an ungerminated state at a given site until environmental conditions become favorable. There is limited evidence regarding the occurrence, interplay and relative importance of dispersal processes in time and space in plant populations.

Thirty‐six natural populations of the annual ruderal species Arabidopsis thaliana were monitored over five consecutive years, sampling both seed bank and above‐ground cohorts.

We show that immigration rates are considerably higher than previously inferred, averaging 1.7% per population yr–1. On the other hand, almost one‐third of the individuals in a given above‐ground cohort result from seeds shed 2 or 3 yr back in time in 10 of the studied populations. Populations that disappeared one year were recolonized by regeneration from the seed bank the subsequent year.

Thus, dispersal in both time and space is an important contributor to the structuring of genetic variability in natural populations of A. thaliana, where a high dispersal rate in time may partly counteract the homogenizing effects of spatial seed and pollen dispersal.
Advantages and challenges of integration: opportunities for integrating early childhood development and nutrition programming
Authors: DiGirolamo Ann M. , Stansbery Pablo , Lung'aho Mary
Published: January 2014

A growing body of evidence supports the notion that integrated programs addressing nutrition and stimulation provide stronger impacts on nutritional and developmental outcomes than either intervention alone. When translating evidence into practice, several advantages and challenges for integration can be noted. Combined interventions may be more efficient than separate interventions, because they are intended for the same population and make use of the same facilities, transportation, and client contacts. In addition, for families, particularly for those most at risk, combined interventions can also lead to increased access to services. However, in order for integrated nutrition and early childhood development interventions to be successful, a variety of challenges must be addressed. These include workload of staff and supervisors, communication and coordination among different ministries and among staff in different sectors, and common language and measurement. It must be acknowledged at both the national and community levels that comprehensive, integrated care addressing both the physical and developmental needs of the child is key to promoting optimal health, growth, and development for children.
A job analysis of community health workers in the context of integrated nutrition and early child development
Authors: Phuka John , Maleta Kenneth , Thomas Mavuto , Gladstone Melisa
Published: January 2014

Stunting and poor child development are major public health concerns in Malawi. Integrated nutrition and early child development (ECD) interventions have shown potential to reduce stunting, but it is not known how these integrated approaches can be implemented in Malawi. In this paper, we aimed to evaluate the current jobs status of community health workers and their potential to implement integrated approaches. This was accomplished by a desk review of nutrition and ECD policy documents, as well as interviews with key informants, community health workers, and community members. We found that Malawi has comprehensive policies and well‐outlined coordination structures for nutrition and ECD that advocate for integrated approaches. Strong multidisciplinary interaction exists at central levels but not at the community level. Integration of community health workers from different sectors is limited by workload, logistics, and a lack of synchronized work schedules. Favorable, sound policies and well‐outlined coordination structures alone are not enough for the establishment of integrated nutrition and ECD activities. Balanced bureaucratic structures, improved task allocation, and synchronization of work schedules across all relevant sectors are needed for integrated intervention in Malawi.
The association between brain injury, perioperative anesthetic exposure, and 12‐month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study
Authors: Andropoulos Dean B. , Ahmad Hasan B. , Haq Taha , Brady Ken , Stayer Stephen A. , Meador Marcie R. , Hunter Jill V. , Rivera Carlos , Voigt Robert G. , Turcich Marie , He Cathy Q. , Shekerdemian Lara S. , Dickerson Heather A. , Fraser Charles D. , Dean McKenzie E. , Heinle Jeffrey S. , Blaine Easley R.
Published: January 2014

Background

Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI).

Methods

Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7‐day postoperative brain MRI and 12‐month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley‐III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life.

Results

From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley‐III (P < 0.02).

Conclusions

After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.
Incidence of pain after craniotomy in children
Authors: Bronco Alfio , Pietrini Domenico , Lamperti Massimo , Somaini Marta , Tosi Federica , Minguell del Lungo Laura , Zeimantz Elena , Tumolo Miriam , Lampugnani Elisabetta , Astuto Marinella , Perna Francesco , Zadra Nicola , Meneghini Luisa , Benucci Valentina , Bussolin Leonardo , Scolari Anna , Savioli Alessandra , Locatelli Bruno G. , Prussiani Viviana , Cazzaniga Michela , Mazzoleni Fabio , Giussani Carlo , Rota Matteo , Ferland Catherine E. , Ingelmo Pablo M.
Published: January 2014

Background

There is very few information regarding pain after craniotomy in children.

Objectives

This multicentre observational study assessed the incidence of pain after major craniotomy in children.

Methods

After IRB approval, 213 infants and children who were <10 years old and undergoing major craniotomy were consecutively enrolled in nine Italian hospitals. Pain intensity, analgesic therapy, and adverse effects were evaluated on the first 2 days after surgery. Moderate to severe pain was defined as a median FLACC or NRS score ≥4 points. Severe pain was defined as a median FLACC or NRS score ≥7 points.

Results

Data of 206 children were included in the analysis. The overall postoperative median FLACC/NRS scores were 1 (IQR 0 to 2). Twenty‐one children (16%) presented moderate to severe pain in the recovery room and 14 (6%) during the first and second day after surgery. Twenty‐six children (19%) had severe pain in the recovery room and 4 (2%) during the first and second day after surgery. Rectal codeine was the most common weak opiod used. Remifentanil and morphine were the strong opioids widely used in PICU and in general wards, respectively. Longer procedures were associated with moderate to severe pain (OR 1.30; CI 1.07–1.57) or severe pain (OR 1.41; 1.09–1.84; P < 0.05). There were no significant associations between complications, pain intensity, and analgesic therapy.

Conclusion

Children receiving multimodal analgesia experience little or no pain after major craniotomy. Longer surgical procedures correlate with an increased risk of having postoperative pain.
Cold tolerance in flour beetle species differing in body size and selection temperature
Authors: SCHARF INON , SBILORDO SONJA H. , MARTIN OLIVER Y.
Published: January 2014

Cold tolerance is an important trait directly related to survival and hence fitness. In the present study, the link is addressed between cold tolerance and body size, which is associated with many key fitness traits, at both the intra‐ and interspecific levels. Specifically, chill coma recovery time, as a metric of cold tolerance, is examined in five related flour beetle species (four of them belonging to the genus Tribolium), two additional Tribolium castaneum Herbst populations selected for higher temperatures, and a mutant showing reduced body size. Recovery times are negatively correlated with the species average body size but not within each species. Females usually recover faster than males, although this difference is significant in only a single species, and is unrelated to body size. Repeating the experimental procedure with the same individuals, after 2 days in isolation with a limited amount of food, results in longer recovery times. Therefore, even if cold acclimation takes place, its influence appears to be diminished by the deleterious effects associated with the experimental procedure. Hence, the findings provide evidence for an association between body size and cold tolerance in the genus Tribolium, with larger species recovering faster from chill than smaller species. By contrast, the smalleyed flour beetle Palorus ratzeburgii Wissmann does not follow this pattern. Additionally, a population of T. castaneum selected for the highest temperature takes longer to recover from chill coma, indicating a trade‐off between cold and heat adaptations and not to a cross‐protection effect, as sometimes demonstrated.
Bistable Retinal Schiff Base Photodynamics of Histidine Kinase Rhodopsin HKR1 from Chlamydomonas reinhardtii
Authors: Penzkofer Alfons , Luck Meike , Mathes Tilo , Hegemann Peter
Published: January 2014

The photodynamics of the recombinant rhodopsin fragment of the histidine kinase rhodopsin HKR1 from Chlamydomonas reinhardtii was studied by absorption and fluorescence spectroscopy. The retinal cofactor of HKR1 exists in two Schiff base forms RetA and RetB. RetA is the deprotonated 13‐cis‐retinal Schiff base (RSB) absorbing in the UVA spectral region. RetB is the protonated all‐trans RSB absorbing in the blue spectral region. Blue light exposure converts RetB fully to RetA. UVA light exposure converts RetA to RetB and RetB to RetA giving a mixture determined by their absorption cross sections and their conversion efficiencies. The quantum efficiencies of conversion of RetA to RetB and RetB to RetA were determined to be 0.096 ± 0.005 and 0.405 ± 0.01 respectively. In the dark thermal equilibration between RetA and RetB with dominant RetA content occurred with a time constant of about 3 days at room temperature. The fluorescence emission behavior of RetA and RetB was studied, and fluorescence quantum yields of ϕF(RetA) = 0.00117 and ϕF(RetB) = 9.4 × 10−5 were determined. Reaction coordinate schemes of the photodynamics are developed.
Hypericin as a Marker for Determination of Myocardial Viability in a Rat Model of Myocardial Infarction
Authors: Jiang Cuihua , Li Yue , Jiang Xiao , Yao Nan , Gao Meng , Zhang Xueli , Wang Junying , Wang Xiaoning , Sun Ziping , Zhang Jian , Ni Yicheng
Published: January 2014

The aim of this study was to investigate the necrosis‐avid agent hypericin as a potential indicator for determination of myocardial infarction (MI). Male Sprague‐Dawley rats (n = 30) weighing 350 ± 20 g were subjected to acute reperfused MI. Animals were divided into four groups (n = 6), in which hypericin was intravenously injected at 0, 1, 2 and 5 mg kg−1 respectively. One day after injection, rats were euthanized with their hearts excised for qualitative and quantitative studies by means of microscopic fluorescence examination to decide the dosage of hypericin. Another group was injected with hypericin at the decided dose and evaluated by fluorescence macroscopy in colocalization with triphenyltetrazoliumchloride (TTC) and histomorphology. Infarct‐to‐normal contrast ratio and relative infarct size were quantified. Hypericin‐induced red fluorescence was significantly brighter in necrotic than in viable myocardium as proven by a six times higher mean fluorescence density. Mean MI area was 35.66 ± 22.88% by hypericin fluorescence and 32.73 ± 21.98% by TTC staining (R2 = 0.9803). Global MI‐volume was 34.56 ± 21.07% by hypericin and 35.11 ± 20.47% by TTC staining (R2 = 0.9933). The results confirm that hypericin specifically labeled necrosis, and enhanced the imaging contrast between the infarcted and normal myocardium, suggesting its potential applications for the assessment of myocardial viability.
Effects of the Histone Methyltransferase Inhibitor UNC0638 on Histone H3K9 Dimethylation of Cultured Ovine Somatic Cells and Development of Resulting Early Cloned Embryos
Authors: Fu L , Yan F‐X , An X‐R , Hou J
Published: January 2014

Contents

Aberrant hypermethylation of histone H3 lysine 9 (H3K9) may be involved in the developmental failure of cloned embryos. UNC0638 is a type of small molecule that can specifically inhibit the enzyme activity of histone methyltransferase EHMT2 and reduce the H3K9 dimethylation (H3K9me2) levels in cells. The objective of this study was to investigate the effect of UNC0638 in regulating H3K9me2 and development of cloned embryos. Results showed that UNC0638 could efficiently reduce H3K9me2 levels of cultured sheep foetal fibroblast cells in a concentration‐dependent manner. Cloned embryos were subsequently produced from UNC0638‐treated donor cells with down‐regulated H3K9me2, but their in vitro development was not improved when compared with the control. Our study suggested that revision of the single histone H3K9me2 modification may be not sufficient for rescuing the development of cloned embryos. However, because of its low cellular toxicity, UNC0638 may still be a potential chemical that could be used in regulating epigenetic modification of cloned embryos.
Fertility in Dairy Cows After Artificial Insemination Using Sex‐Sorted Sperm or Conventional Semen
Authors: Karakaya E , Yilmazbas‐Mecitoglu G , Keskin A , Alkan A , Tasdemir U , Santos JEP , Gumen A
Published: January 2014

Contents

The aim of this study was to compare pregnancy per artificial insemination (P/AI) after timed AI with sex‐sorted sperm (SS) or conventional semen (CS) in lactating dairy cows. Cyclic cows (n = 302) were synchronized by Ovsynch and randomly assigned into two groups at the time of AI. Cows with a follicle size between 12 and 18 mm and clear vaginal discharge at the time of AI were inseminated with either frozen‐thawed SS (n = 148) or CS (n = 154) of the same bull. A shallow uterine insemination was performed into the uterine horn ipsilateral to the side of probable impending ovulation. Pregnancy per AI on Day 31 tended (p = 0.09) to be less for SS (31.8%) than CS (40.9%). Similarly, P/AI on Day 62 was less (p = 0.01) for cows inseminated with SS (25.7%) compared with CS (39.0%). The increased difference in fertility between treatments from Days 31 to 62 was caused by the greater (p = 0.02) pregnancy loss for cows receiving SS (19.2%) than CS (4.8%). Cow parity (p = 0.02) and season (p < 0.01) when AI was performed were additional factors affecting fertility. Primiparous cows had greater P/AI than multiparous cows both on Day 31 (41.7% vs 25.0% in SS and 53.0% vs 31.8% in CS groups) and on Day 62 (33.3% vs 20.5% in SS and 48.5% vs 31.8% in CS groups). During the hot season of the year, P/AI on Day 31 was reduced (p = 0.01) in the SS group (19.6%) when compared with the rates during the cool season (38.1%). In conclusion, sex‐sorted sperm produced lower fertility results compared to conventional semen even after using some selection criteria to select most fertile cows.
Complement Profile in Neonates of Different Gestational Ages
Authors: Grumach A. S. , Ceccon M. E. , Rutz R. , Fertig A. , Kirschfink M.
Published: January 2014

Blood levels of regulators of the complement system in preterm babies were reported in few studies only. The aim of this study was to set up a complement profile in premature and term babies focusing on the development of blood levels of MBL, key regulatory proteins and on classical pathway activity, which may allow an estimation of potential susceptibility to infection. Complement activity (CH50), levels of mannan‐binding lectin (MBL), complement regulators (factors H and I, C1 inhibitor, properdin) and C3a as marker of complement activation were assessed in three groups of healthy newborns: (1) prematures (≤34 weeks); (2) late prematures (>34–<37 weeks) and (3) term neonates (≥37 weeks). CH50 increased with gestational age with lower titres in cord blood than in day 5 post‐delivery venous blood. MBL concentrations were not significantly different among groups. Quantitative and functional C1 inhibitor were below adult normal range in prematures <34 weeks and lower in cord blood as compared to day 5. Factor I, factor H and properdin remained below adult values in all groups. Low C3a levels excluded that low complement titres were due to activation‐induced consumption. These results demonstrate the relative immaturity of the complement system and its regulation, especially in premature infants.
Asymptotic Behavior of Conditional Least Squares Estimators for Unstable Integer‐valued Autoregressive Models of Order 2
Authors: Barczy Mátyás , Ispány Márton , Pap Gyula
Published: January 2014

In this paper, the asymptotic behavior of the conditional least squares estimators of the autoregressive parameters, of the mean of the innovations, and of the stability parameter for unstable integer‐valued autoregressive processes of order 2 is described. The limit distributions and the scaling factors are different according to the following three cases: (i) decomposable, (ii) indecomposable but not positively regular, and (iii) positively regular models.
From Affirmative Action to Diversity: Critical Reflections on Graduate Education in Sociology
Authors: Schneider Beth E. , Segura Denise A.
Published: January 2014

This article explores the contradictory results of the shift from a race‐conscious affirmative action discourse to a broader “diversity embrace” that advocates tolerance, equality, and respect for cultural differences on university campuses. Drawing on critical race theory and research on the practice of affirmative action in organizations, we argue that the diversity embrace subsumes recognition of racialized histories, social relations, and practices in favor of a “color‐blind” rhetoric that reinforces negative assumptions about the academic merit and worthiness of underrepresented minority students (URM). Our review of the status and condition of URM graduate students in sociology departments reveals that minority inclusion is part of a larger strategy that emphasizes individual and group differences rather than corrective action for past discrimination. We find that access and inclusion in graduate programs in sociology have been uneven with relatively few departments producing a majority of URM sociology doctorates. The diversity embrace obscures their continual low representation in graduate programs, fosters professionalization practices detrimental to these students, and undermines efforts to create a “critical mass” of faculty of color. Such practices constitute a racial project that preserves White privilege at the individual and institutional levels.
Urbanization and Carbon Emissions: A Nationwide Study of Local Countervailing Effects in the United States
Authors: Elliott James R. , Clement Matthew Thomas
Published: January 2014

Objective

This study advances a theoretical framework for examining the impact of urbanization on local carbon emissions over space and time. It conceptualizes urbanization at the local level as a set of three distinct but related subprocesses of population concentration, land‐use intensification, and systemic interaction, which join together to exert countervailing effects on local carbon emissions.

Methods

To test this framework we conduct cross‐sectional and panel regression analyses of carbon emissions at the county level across the continental United States, controlling for spatial autocorrelation.

Results

Findings strongly support our framework and show how different dimensions of urbanization push against one another at the local level to influence carbon emissions in ways that exert far more consistent effects than household density and alternative transit use.

Conclusion

These findings illuminate the complexities of urbanization as a local force of environmental transformation with increasingly global consequences.
Crystal structures of the phosphorylated BRI1 kinase domain and implications for brassinosteroid signal initiation
Authors: Bojar Daniel , Martinez Jacobo , Santiago Julia , Rybin Vladimir , Bayliss Richard , Hothorn Michael
Published: January 2014

Brassinosteroids, which control plant growth and development, are sensed by the membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Brassinosteroid binding to the BRI1 leucine‐rich repeat (LRR) domain induces heteromerisation with a SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK)‐family co‐receptor. This process allows the cytoplasmic kinase domains of BRI1 and SERK to interact, trans‐phosphorylate and activate each other. Here we report crystal structures of the BRI1 kinase domain in its activated form and in complex with nucleotides. BRI1 has structural features reminiscent of both serine/threonine and tyrosine kinases, providing insight into the evolution of dual‐specificity kinases in plants. Phosphorylation of Thr1039, Ser1042 and Ser1044 causes formation of a catalytically competent activation loop. Mapping previously identified serine/threonine and tyrosine phosphorylation sites onto the structure, we analyse their contribution to brassinosteroid signaling. The location of known genetic missense alleles provide detailed insight into the BRI1 kinase mechanism, while our analyses are inconsistent with a previously reported guanylate cyclase activity. We identify a protein interaction surface on the C‐terminal lobe of the kinase and demonstrate that the isolated BRI1, SERK2 and SERK3 cytoplasmic segments form homodimers in solution and have a weak tendency to heteromerise. We propose a model in which heterodimerisation of the BRI1 and SERK ectodomains brings their cytoplasmic kinase domains in a catalytically competent arrangement, an interaction that can be modulated by the BRI1 inhibitor protein BKI1.
In Vitro Mechanical Evaluation of Mandibular Bone Transport Devices
Authors: Zapata Uriel , Watanabe Ikuya , Opperman Lynne A. , Dechow Paul C. , Mulone Timothy , Elsalanty Mohammed E.
Published: January 2014

Bone transport distraction osteogenesis (BTDO) is a surgical procedure that has been used over the last 30 years for the correction of segmental defects produced mainly by trauma and oncological resections. Application of BTDO has several clinical advantages over traditional surgical techniques. Over the past few years, several BTDO devices have been introduced to reconstruct mandibular bone defects. Based on the location and outline of the defect, each device requires a uniquely shaped reconstruction plate. To date, no biomechanical evaluations of mandibular BTDO devices have been reported in the literature. The present study evaluated the mechanical behavior of three different shaped prototypes of a novel mandibular bone transport reconstruction plate and its transport unit for the reconstruction of segmental bone defects of the mandible by using numerical models complemented with mechanical laboratory tests to characterize strength, fatigue, and stability. The strength test evaluated device failures under extreme loads and was complemented with optimization procedures to improve the biomechanical behavior of the devices. The responses of the prototypes were characterized to improve their design and identify weak and strong regions in order to avoid posterior device failure in clinical applications. Combinations of the numerical and mechanical laboratory results were used to compare and validate the models. In addition, the results remark the importance of reducing the number of animals used in experimental tests by increasing computational and in vitro trials.
Integrated Device for in Vivo Fine Needle Aspiration Biopsy and Elastic Scattering Spectroscopy in Preoperative Thyroid Nodules
Authors: Briggs John C. , A’amar Ousama , Bigio Irving , Rosen Jennifer E. , Lee Stephanie L. , Sharon Andre , Sauer-Budge Alexis F.
Published: January 2014

Thyroid nodules are a frequent clinical finding and the most common endocrine malignancy is thyroid cancer. The standard of care in the management of a patient with a thyroid nodule is to perform a preoperative fine needle aspiration (FNA) biopsy of the suspect nodule under ultrasound imaging guidance. In a significant percentage of the cases, cytological assessment of the biopsy material yields indeterminate results, the consequence of which is diagnostic thyroidectomy. Unfortunately, 75–80% of diagnostic thyroidectomies following indeterminate cytology result in benign designation by post-surgery histopathology, indicating potentially unnecessary surgeries. Clearly, the potential exists for the improvement in patient care and the reduction of overall procedure costs if an improved preoperative diagnostic technique was developed. Elastic scattering spectroscopy (ESS) is an optical biopsy technique that is mediated by optical fiber probes and has been shown to be effective in differentiating benign from malignant thyroid tissue in ex vivo surgical tissue samples. The goal of the current research was to integrate the ESS fiber optic probes into a device that can also collect cells for cytological assessment and, thus, enable concurrent spectroscopic interrogation and biopsy of a suspect nodule with a single needle penetration. The primary challenges to designing the device included miniaturizing the standard ESS fiber optic probe to fit within an FNA needle and maintaining the needle’s aspiration functionality. We demonstrate the value of the fabricated prototype devices by assessing their preliminary performance in an on-going clinical study with >120 patients. The devices have proven to be clinically friendly, collecting both aspirated cells and optical data from the same location in thyroid nodules and with minimal disruption of clinical procedure. In the future, such integrated devices could be used to complement FNA-based cytological results and have the potential to both reduce the number of diagnostic thyroidectomies on benign nodules and improve the surgical approach for patients with thyroid malignancies, thereby, decreasing healthcare costs and improving patient outcomes.
Correlations for Prediction of Pressure Gradient of Liquid-Liquid Flow Through a Circular Horizontal Pipe
Authors: Dasari Anjali , Desamala Anand B. , Ghosh Ujjal K. , Dasmahapatra Ashok K. , Mandal Tapas K.
Published: January 2014

We report a detailed investigation on the measurement and prediction of pressure gradient characteristics of moderately viscous lubricating oil-water flow through a horizontal pipe of 0.025 m internal diameter. Experiments are carried out over a wide range of phase velocities of both oil (USO = 0.015–1.25 m/s) and water (USW  =  0.1–1.1 m/s). Experimental pressure gradients yield significant errors when fitted to the existing correlations, which are largely used for gas-liquid flow. To predict pressure gradient characteristics for liquid-liquid flow, the existing correlations need to be modified. We propose two correlations, based on the Lockhart–Martinelli's approach (by modifying the correlation between the Lockhart–Martinelli parameter and a two-phase multiplier suitable for the present system) and dimensionless analysis, following the Buckingham's Pi-theorem. We observe significant improvement in the prediction of pressure gradient. The correlation based on the dimensionless analysis predicts better with an average absolute error of 17.9%, in comparison with the modified Lockhart–Martinelli correlation, which yields an average error of 22%, covering all the flow patterns. The present analysis shows better prediction as compared to two-fluid model Zhang et al. (2012, “Modeling High-Viscosity Oil/Water Concurrent Flow in Horizontal and Vertical Pipes,” SPE J., 17(1), pp. 243–250) and Al-Wahaibi (2012, “Pressure Gradient Correlation for Oil-Water Separated Flow in Horizontal Pipes,” Exp. Therm. Fluid Sci., 42, pp. 196–203) work.
Loss Mechanisms in Shear-Force Pump With Multiple Corotating Disks
Authors: Wang Baotong , Okamoto Koji , Yamaguchi Kazuo , Teramoto Susumu
Published: January 2014

In a shear-force pump with multiple corotating disks, the pressure gain is obtained by utilizing the shear force produced on the surfaces of the rotating disks. Thus, it is expected to have advantages as a microfluid device compared to a conventional bladed compressor or pump, which suffers greatly from viscous loss. However, in previous studies, a shear-force pump could not achieve high efficiency in experiments, even though very good efficiencies were predicted in numerical and analytical studies on the flow field between corotating disks. Therefore, the objective of the present work was to investigate the internal flow dynamics and clarify the loss mechanisms in a complete shear-force pump device consisting of both rotor and stationary components. In order to achieve this goal, a numerical simulation using an independent rotor analysis was first performed on the internal flow field between two corotating disks to evaluate the isentropic efficiency and pressure coefficient that could be achieved. Then, an experimental test rig for a shear-force pump was designed and built, and an experiment was carried out to determine the performance of a complete pump device with the same corotating disk design as the independent rotor analysis. In addition, a numerical simulation was executed for the flow field of a pump system consisting of both rotor and stationary components based on the present test rig to investigate the flow field and loss factors of this device. The results of this independent rotor analysis showed that the corotating disks can achieve a fairly high efficiency at a low flow coefficient with a high dynamic pressure, and the flow direction is extremely close to the tangential direction at the disk outlet, which caused difficulties in the design of the diffuser and scroll. In the experimental test, the high total pressure loss in the parallel diffuser and scroll parts was observed. This was found to be the result of the significant friction loss caused by the long flow path due to strong recirculation in the diffuser and scroll volute, which was found in the simulation results for the internal flow in the whole pump system. In addition, a reverse flow appeared in the rotor part at a low flow coefficient, which significantly deteriorated the rotor performance. These conclusions provided some clues for improving the performance of a shear-force pump device in future work.
Hybrid Analysis of Gas Annular Seals With Energy Equation
Authors: Migliorini Patrick J. , Untaroiu Alexandrina , Witt William C. , Morgan Neal R. , Wood Houston G.
Published: January 2014

Annular seals are used in turbomachinery to reduce secondary flow between regions of high and low pressure. In a vibrating rotor system, the nonaxisymmetric pressure field developed in the small clearance between the rotor and the seal generate reactionary forces that can affect the stability of the entire rotor system. Traditionally, two analyses have been used to study the fluid flow in seals, bulk-flow analysis and computational fluid dynamics (CFD). Bulk-flow methods are computational inexpensive, but solve simplified equations that rely on empirically derived friction factor coefficients and are moderately accurate. CFD analyses generally provide more accurate results than bulk-flow codes, but solution time can vary between days and weeks. For gas damper seals, these analyses have been developed with the assumption that the flow can be treated as isothermal. However, some experimental studies have shown that the temperature change across the seal can be as much as 37%. Thus, a comprehensive analysis requires the solution of an energy equation. Recently, a new hybrid method that employs a CFD analysis for the zeroth-order flow and a bulk-flow analysis for the first-order, perturbed flow has been developed. This method has shown to compare well with full CFD analysis and experimental data while being computationally efficient. In this study, the previously developed hybrid method is extended to include the effects of nonisothermal flow. The hybrid method with energy equation is then compared with the isothermal hybrid method and experimental data for several test cases of hole-pattern seals and the importance of the use of energy equation is studied.
Small field in‐air output factors: The role of miniphantom design and dosimeter type
Authors: Warrener Kirbie , Hug Benjamin , Liu Paul , Ralston Anna , Ebert Martin A. , McKenzie David R. , Suchowerska Natalka
Published: January 2014

Purpose:

The commissioning of treatment planning systems and beam modeling requires measured input parameters. The measurement of relative output in‐air, Sc is particularly difficult for small fields. The purpose of this study was to investigate the influence of miniphantom design and detector selection on measured Sc values for small fields and to validate the measurements against Monte Carlo simulations.

Methods:

Measurements were performed using brass caps (with sidewalls) or tops (no sidewalls) of varying heights and widths. The performance of two unshielded diodes (60012 and SFD), EBT2 radiochromic film, and a fiber optic dosimeter (FOD) were compared for fields defined by MLCs (5–100 mm) and SRS cones (4–30 mm) on a Varian Novalis linear accelerator. Monte Carlo simulations were performed to theoretically predict Sc as measured by the FOD.

Results:

For all detectors, Sc agreed to within 1% for fields larger than 10 mm and to within 2.3% for smaller fields. Monte Carlo simulation matched the FOD measurements for all size of cone defined fields to within 0.5%.

Conclusions:

Miniphantom design is the most important variable for reproducible and accurate measurements of the in‐air output ratio, Sc, in small photon fields (less than 30 mm). Sidewalls are not required for fields ≤ 30 mm and tops are therefore preferred over the larger caps. Unlike output measurements in water, Scp, the selection of detector type for Sc is not critical, provided the active dosimeter volume is small relative to the field size.
Dependency of EBT2 film calibration curve on postirradiation time
Authors: Chang Liyun , Ho Sheng‐Yow , Ding Hueisch‐Jy , Lee Tsair‐Fwu , Chen Pang‐Yu
Published: January 2014

Purpose:

The Ashland Inc. product EBT2 film model is a widely used quality assurance tool, especially for verification of 2‐dimensional dose distributions. In general, the calibration film and the dose measurement film are irradiated, scanned, and calibrated at the same postirradiation time (PIT), 1‐2 days after the films are irradiated. However, for a busy clinic or in some special situations, the PIT for the dose measurement film may be different from that of the calibration film. In this case, the measured dose will be incorrect. This paper proposed a film calibration method that includes the effect of PIT.

Methods:

The dose versus film optical density was fitted to a power function with three parameters. One of these parameters was PIT dependent, while the other two were found to be almost constant with a standard deviation of the mean less than 4%. The PIT‐dependent parameter was fitted to another power function of PIT. The EBT2 film model was calibrated using the PDD method with 14 different PITs ranging from 1 h to 2 months. Ten of the fourteen PITs were used for finding the fitting parameters, and the other four were used for testing the model.

Results:

The verification test shows that the differences between the delivered doses and the film doses calculated with this modeling were mainly within 2% for delivered doses above 60 cGy, and the total uncertainties were generally under 5%. The errors and total uncertainties of film dose calculation were independent of the PIT using the proposed calibration procedure. However, the fitting uncertainty increased with decreasing dose or PIT, but stayed below 1.3% for this study.

Conclusions:

The EBT2 film dose can be modeled as a function of PIT. For the ease of routine calibration, five PITs were suggested to be used. It is recommended that two PITs be located in the fast developing period (1∼6 h), one in 1 ∼ 2 days, one around a week, and one around a month.
Portal dosimetry for VMAT using integrated images obtained during treatment
Authors: Bedford James L. , Hanson Ian M. , Hansen Vibeke Nordmark
Published: January 2014

Purpose:

Portal dosimetry provides an accurate and convenient means of verifying dose delivered to the patient. A simple method for carrying out portal dosimetry for volumetric modulated arc therapy (VMAT) is described, together with phantom measurements demonstrating the validity of the approach.

Methods:

Portal images were predicted by projecting dose in the isocentric plane through to the portal image plane, with exponential attenuation and convolution with a double‐Gaussian scatter function. Appropriate parameters for the projection were selected by fitting the calculation model to portal images measured on an iViewGT portal imager (Elekta AB, Stockholm, Sweden) for a variety of phantom thicknesses and field sizes. This model was then used to predict the portal image resulting from each control point of a VMAT arc. Finally, all these control point images were summed to predict the overall integrated portal image for the whole arc. The calculated and measured integrated portal images were compared for three lung and three esophagus plans delivered to a thorax phantom, and three prostate plans delivered to a homogeneous phantom, using a gamma index for 3% and 3 mm. A 0.6 cm3 ionization chamber was used to verify the planned isocentric dose. The sensitivity of this method to errors in monitor units, field shaping, gantry angle, and phantom position was also evaluated by means of computer simulations.

Results:

The calculation model for portal dose prediction was able to accurately compute the portal images due to simple square fields delivered to solid water phantoms. The integrated images of VMAT treatments delivered to phantoms were also correctly predicted by the method. The proportion of the images with a gamma index of less than unity was 93.7% ± 3.0% (1SD) and the difference between isocenter dose calculated by the planning system and measured by the ionization chamber was 0.8% ± 1.0%. The method was highly sensitive to errors in monitor units and field shape, but less sensitive to errors in gantry angle or phantom position.

Conclusions:

This method of predicting integrated portal images provides a convenient means of verifying dose delivered using VMAT, with minimal image acquisition and data processing requirements.
Perceptual changes in place of stimulation with long cochlear implant electrode arrays
Authors: Landsberger David M. , Mertens Griet , Punte Andrea Kleine , Van De Heyning Paul
Published: January 2014

Long (31.5 mm) electrode arrays are inserted deeper into the cochlea than the typical 1.25 turn insertion. With these electrode arrays, the apical electrodes are closer to (and possibly extend past) the end of the spiral ganglion. Using multi-dimensional scaling with patients implanted with a 31.5 mm electrode array, the perceptual space between electrodes was measured. The results suggest that deeper insertion increases the range of place pitches, but the perceptual differences between adjacent electrodes become smaller in the apex.
Dependences of quantitative ultrasound parameters on frequency and porosity in water-saturated nickel foams
Authors: Il Lee Kang
Published: January 2014

The frequency-dependent phase velocity, attenuation coefficient, and backscatter coefficient were measured from 0.8 to 1.2 MHz in 24 water-saturated nickel foams as trabecular-bone-mimicking phantoms. The power law fits to the measurements showed that the phase velocity, the attenuation coefficient, and the backscatter coefficient were proportional to the frequency with exponents n of 0.95, 1.29, and 3.18, respectively. A significant linear correlation was found between the phase velocity at 1.0 MHz and the porosity. In contrast, the best regressions for the normalized broadband ultrasound attenuation and the backscatter coefficient at 1.0 MHz were obtained with the polynomial fits of second order.