bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors Associated with Craniosynostosis: A Case Control Study
Authors: Ardalan Maryam , Rafati Ali , Nejat Farideh , Farazmand Behnood , Majed Masood , El Khashab Mostafa
Published: February 2013

Background: Craniosynostosis is a relatively common congenital abnormality. The underlying etiology and most probable risk factors of nonsyndromic craniosynostosis are unknown. We conducted a study to identify the risk factors for craniosynostosis. Materials and Methods: In this case-control project, 70 children with craniosynostosis (syndromic or nonsyndromic) hospitalized at the Children's Hospital Medical Center from September 2010 to 2011 were studied for the potential risk factors. At the same time, 70 age- and sex-matched children hospitalized with other congenital anomalies were reviewed. Information from case and control groups was obtained via personal interviews with parents of patients and a prepared checklist was filled out for each child. Results: The mean (±SE) age at admission time in the case-control group was 13 ± 1.95 (1.5-96) months, and almost half of them were boys (n = 37 or 53%). The most frequent sutures involved in craniosynostosis were coronal (n = 30 or 42.9%) and then metopic sutures (n = 16 or 22.9%), multiple (n = 12 or 17.1%), sagittal (n = 11 or 15.7%) and lambdoid (n = 1 or 1.4%). In the case group, maternal diabetes mellitus and thyroid disease were found in 8 (11.6%) and 6 (8.6%) patients, respectively. The most frequent medication used by mothers (n = 66 or 94%) in the case group during pregnancy were vitamins (including iron supplements, omega 3, folic acid and multivitamins). Conclusion: A positive family history of craniosynostosis [odds ratio (OR) 19.01 and 95% confidence interval (CI) 2.24-160.7] and using clomiphene citrate for infertility (OR 12.71 and 95% CI 1.42-113.6) were the strongest independent risk factors for craniosynostosis. More comprehensive studies with a larger sample size are required to confirm the role of environmental factors in order to decrease the occurrence of craniosynostosis.
Neuronal Migration Defect of the Developing Cerebellar Vermis in Substrains of C57BL/6 Mice: Cytoarchitecture and Prevalence of Molecular Layer Heterotopia
Authors: Mangaru Zareema , Salem Elsaid , Sherman Matthew , Van Dine Sarah E. , Bhambri Ankur , Brumberg Joshua C. , Richfield Eric K. , Gabel Lisa A. , Ramos Raddy L.
Published: February 2013

Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia, a malformation of neuronal migration, in the cerebellar vermis of C57BL/6 mice and closely-related strains. In particular, we found a diverse number of cell-types affected by these malformations including Purkinje cells, granule cells, inhibitory interneurons (GABAergic and glycinergic), and glia. Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.
Quality of Life of Children and Adolescents with Type 1 Diabetes in Kuwait
Authors: Abdul-Rasoul M. , AlOtaibi F. , Abdulla A. , Rahme Z. , AlShawaf F.
Published: February 2013

Objectives: To evaluate the health-related quality of life (HRQoL) of children and adolescents with type 1 diabetes (T1DM) in Kuwait using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scale and PedsQL 3.0 Diabetes Module, and to identify the risk factors associated with unsatisfactory QoL and their effects on metabolic control. Subjects and Methods: A total of 436 patients (2-18 years) with T1DM (>6 months) and 389 healthy controls, with the parents of both groups, completed the Arabic Generic Core Scale. Those with T1DM also completed the Arabic Diabetes Module. Results: The mean total score of the PedsQL Diabetes Module was 70.2 ± 9.8 reported by children and 59.9 ± 11.1 reported by parents (higher scores indicate better QoL). Young age and long duration of diabetes were associated with poor QoL (p < 0.001). Boys had better total scores than girls in most age groups (70.3 ± 9.3 vs. 52.3 ± 7.2, p < 0.001); however, girls did better than boys regarding treatment barriers and adherence (71.3 ± 7.8 vs. 68.1 ± 6.2, p < 0.005). Higher HbA1c values were associated with lower QoL scores (31.1 ± 5.1 at HbA1c of 15% vs. 82.5 ± 6.1 at HbA1c of 6%, p < 0.0001). Conclusion: HRQoL of children and adolescents with T1DM was consistently poorer than controls. Parents consistently reported poorer QoL scores than their children. We recommend that more support should be provided for the care of children with diabetes in Kuwait.
Genomic, Transcriptomic, and Lipidomic Profiling Highlights the Role of Inflammation in Individuals With Low High-density Lipoprotein Cholesterol
Authors: Laurila Pirkka-Pekka , Surakka Ida , Sarin Antti-Pekka , Yetukuri Laxman , Hyötyläinen Tuulia , Söderlund Sanni , Naukkarinen Jussi , Tang Jing , Kettunen Johannes , Mirel Daniel B. , Soronen Jarkko , Lehtimäki Terho , Ruokonen Aimo , Ehnholm Christian , Eriksson Johan G. , Salomaa Veikko , Jula Antti , Raitakari Olli T. , Järvelin Marjo-Riitta , Palotie Aarno , Peltonen Leena , Orešič Matej , Jauhiainen Matti , Taskinen Marja-Riitta , Ripatti Samuli
Published: February 2013

Objective—

Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450).

Approach and Results—

In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the
HLA
region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the
HLA
region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies–identified HDL genes.

Conclusions—

Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel
cis
-expression quantitative trait loci (
cis
-eQTL) variants in
HLA
region to be associated with low HDL-C.
Mutation in Vascular Endothelial Growth Factor-C, a Ligand for Vascular Endothelial Growth Factor Receptor-3, Is Associated With Autosomal Dominant Milroy-Like Primary Lymphedema
Authors: Gordon Kristiana , Schulte Dörte , Brice Glen , Simpson Michael A. , Roukens M. Guy , van Impel Andreas , Connell Fiona , Kalidas Kamini , Jeffery Steve , Mortimer Peter S. , Mansour Sahar , Schulte-Merker Stefan , Ostergaard Pia
Published: February 2013

Rationale:

Mutations in vascular endothelial growth factor (VEGF) receptor-3 (
VEGFR3 or FLT4)
cause Milroy disease, an autosomal dominant condition that presents with congenital lymphedema. Mutations in
VEGFR3
are identified in only 70% of patients with classic Milroy disease, suggesting genetic heterogeneity.

Objective:

To investigate the underlying cause in patients with clinical signs resembling Milroy disease in whom sequencing of the coding region of
VEGFR3
did not reveal any pathogenic variation.

Methods and Results:

Exome sequencing of 5 such patients was performed, and a novel frameshift variant, c.571_572insTT in
VEGFC
, a ligand for VEGFR3, was identified in 1 proband. The variant cosegregated with the affected status in the family. An assay to assess the biological function of VEGFC activity in vivo, by expressing human VEGFC in the zebrafish floorplate was established. Forced expression of wild-type human VEGFC in the floorplate of zebrafish embryos leads to excessive sprouting in neighboring vessels. However, when overexpressing the human c.571_572insTT variant in the floorplate, no sprouting of vessels was observed, indicating that the base changes have a marked effect on the activity of VEGFC.

Conclusions:

We propose that the mutation in
VEGFC
is causative for the Milroy disease-like phenotype seen in this family. This is the first time a mutation in one of the ligands of VEGFR3 has been reported to cause primary lymphedema.
Clarifying Differences Among Thrombolysis in Cerebral Infarction Scale Variants
Authors: Suh Sang Hyun , Cloft Harry J. , Fugate Jennifer E. , Rabinstein Alejandro A. , Liebeskind David S. , Kallmes David F.
Published: February 2013

Background and Purpose—

Although thrombolysis in cerebral infarction (TICI) 2b/3 has been regarded as a successful angiographic outcome, the definition or subclassification of TICI 2 has differed between the original (o-TICI) and modified TICI (m-TICI). We sought to compare interobserver variability for both scores and analyze the subgroups of the TICI 2.

Methods—

Five readers interpreted angiographies independently using a 6-point scale as follows: grade 0, no antegrade flow; grade 1, flow past the initial occlusion without tissue reperfusion; grade 2, partial reperfusion in <50% of the affected territory; grade 3, partial reperfusion in 50% to 66%; grade 4, partial reperfusion in ≥67%; grade 5, complete perfusion. Readings using this scale were then converted into o-TICI and m-TICI score. Statistical analysis was performed according to TICI 2 subgroups.

Results—

Interobserver agreement was good for the o-TICI and m-TICI scores (intraclass correlation coefficient, 0.73 and 0.67, respectively). Our grade 3 (partial perfusion with 50% to 66%) occupied 19% of total readings, which would have been classified as grade 2a in o-TICI, but as 2b in m-TICI. The m-TICI was more likely to predict good clinical outcome than o-TICI (odds ratio, 2.01 versus 1.63, in reads with TICI 2b/3 versus 0/2a).

Conclusions—

Both TICI scales showed good agreement among readers. However, the variability in partial perfusion thresholds leads to different grading in ≈20% of cases and may result in significantly different rates of accurate outcome prediction.
A Risk Factor-based Predictive Model of Outcomes in Carotid Endarterectomy
Authors: Bekelis Kimon , Bakhoum Samuel F. , Desai Atman , Mackenzie Todd A. , Goodney Philip , Labropoulos Nicos
Published: February 2013

Background and Purpose—

Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA.

Methods—

We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database.

Results—

Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death.

Conclusions—

This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies
Comparison of Oral and Intravenous Glucose Tolerance Test Derived Sensitivity and Secretory Indices in Obese Adolescents
Authors: Brar Preneet C. , Koren Dorit , Gallagher Paul R. , Pendurthi Bhavana , Katz Lorraine E. Levitt
Published: February 2013

Background. Insulin resistance increases type 2 diabetes risk in obese adolescents. Thus, quantitative tools measuring insulin sensitivity and secretion are important for risk assessment. Methods. Forty-four obese pubertal adolescents underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). We correlated OGTT-derived whole body sensitivity index (WBISI) with FSIGT-derived insulin sensitivity index (Si). Insulinogenic index (IGI) from OGTT was compared with acute insulin response to glucose (AIRg) from FSIGT. Results. Fasting insulin ( r = −.64, P < .0005) and glucose ( r = −.39 P ≤ .0005) predicted Si. The OGTT-derived index WBISI correlated with the FSIGT-derived Si ( r = .608, P < .0005). IGI correlated with AIRg from FSIGT ( r = .704, P < .0005). Conclusions. OGTT-based measures correlated with FSIGT-derived measures of insulin sensitivity and secretion. In particular, we demonstrated that WBISI can be a reliable alternative to FSIGT-derived Si in clinical settings where OGTT is a more feasible option.
Pushes and Pulls
Authors: Godin Benoit , Lane Joseph P.
Published: February 2013

Much has been written about the linear model of innovation. While it may have been the dominant model used to explain technological innovation for decades, alternatives did exist. One such alternative—generally discussed as being the exact opposite of the linear model—is the demand-pull model. Beginning in the 1960s, people from different disciplines started looking at technological innovation from a demand rather than a supply perspective. The theory was that technological innovation is stimulated by market demand rather than by scientific discoveries. However, few traces of the demand-pull model remain in the literature today. This article looks at what happened to the demand-pull model from a historical perspective, at three points in time: birth, crystallization, and death. It suggests that the idea of demand as a factor explaining technological innovation emerged in the 1960s, was formalized into models in the 1970-1980s, then got integrated into “multidimensional” models. From then on, the demand-pull model disappeared from the literature, existing only as an object of the past, like the linear model of innovation.
Using Land-Use Planning Tools to Mitigate Hazards
Authors: Osland Anna C.
Published: February 2013

Critical infrastructure such as hazardous liquid and natural gas transmission pipelines has received little attention by planning scholars even though local development management decisions have far-reaching consequences for homeland security, environmental damage, and human exposure. Using a survey of planning directors in North Carolina, the article identifies frequently used tools for mitigating pipeline hazards and examines factors associated with tool adoption. Despite the risks associated with pipeline rupture, most localities use few mitigation tools, and adoption of regulatory and informational tools appear associated with divergent factors. Whereas stakeholder participation, commitment, capacity, and community context were associated with total tool and information tool use, only stakeholder participation and capacity factors were associated with regulatory tool use.
Critical Reading and Critical Thinking—Study Design and Methodology
Authors: Lipman Timothy O.
Published: February 2013

The volume of medical literature grows exponentially. Yet we are faced with the necessity to make clinical decisions based on the availability and quality of scientific information. The general strength (reliability, robustness) of any interpretation that guides us in clinical decision making is dependent on how information was obtained. All information and medical studies and, consequently, all conclusions are not created equal. It is incumbent upon us to be able to assess the quality of the information that guides us in the care of our patients. Being able to assess medical literature critically requires use of critical reading and critical thinking skills. To achieve these skills, to be able to analyze medical literature critically, takes a combination of education and practice, practice, and more practice.
Size tolerancing revisited: A basic notion and its evolution in standards
Authors: Morse Edward P , Srinivasan Vijay
Published: February 2013

Size is a fundamental descriptor of objects—it allows us to quantify “how big” objects are and to compare and classify objects based on this notion. In the world of International Organization for Standardization Geometrical Product Specification and Verification, size is defined much more narrowly: it is restricted to features of size, and the methods of inducing size values from an actual workpiece are strictly controlled. The release of ISO 14405-1:2010 has introduced a rich new set of size specification modifiers, which includes two-point and spherical local sizes, least squares, maximum inscribed and minimum circumscribed associations, as well as calculated diameters (inferred from the circumference, area, or volume of the feature of interest). Further modifiers allow the specification of statistics of local size measurements, such as maximum, minimum, range, average, and others. This article will present “size” as a fundamental engineering notion from several viewpoints and trace its evolution in engineering drawings. It will then discuss the implications of the use of the recently standardized size modifiers in engineering design and investigate the issues that may arise in the application and interpretation of these extensions to size.
Opening “Openness to Change”
Authors: Dinas Elias
Published: February 2013

The impressionable years thesis asserts that early adulthood is accompanied by increased attitudinal vulnerability. Although there is tentative empirical evidence to support this idea, it remains unclear whether this sensitivity is due to exposure to change-inducing circumstances, typically encountered in early adulthood, or due to the weight attached by young people to new information. I address this question, focusing on a political event—the Watergate—that offers a test of youth’s heightened susceptibility, holding exposure constant. The results confirm the impressionable years thesis and shed light on how it is most likely to be manifested empirically.
Meteorological Variables and Behavior of Learners With Autism
Authors: VanBuskirk Sabrina E. , Simpson Richard L.
Published: February 2013

For this study, we collected classroom behavioral data for three children with autism relative to daily meteorological conditions. Meteorological data, including barometric pressure, humidity, outdoor temperature, and moon illumination, were obtained from the National Weather Service. Relationships between children’s individual target behaviors and meteorological conditions were evaluated via scatterplots. Results revealed independence between children’s behavior and meteorological conditions. Study results are discussed along with implications for professional practice.
Auditory Hypersensitivity in Children With Autism Spectrum Disorders
Authors: Lucker Jay R.
Published: February 2013

A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting that criteria were reviewed. All participants had normal hearing. Tolerance was measured up to 110 dBHL. Findings revealed a smaller-than-expected percentage of children were unable to tolerate loud sounds. The conclusion drawn is that auditory hypersensitivity is not based in the auditory system, but rather is a conditioned response to sounds perceived as aversive or annoying. Treatments for auditory hypersensitivity should not be auditory based but should include desensitization training. Implications for practice are provided.
Symptom overlap in anxiety and multiple sclerosis
Authors: Ó Donnchadha Seán , Burke Teresa , Bramham Jessica , O’Brien Marie Claire , Whelan Robert , Reilly Richard , Kiiski Hanni , Lonergan Róisín , Kinsella Katie , Kelly Siobhán , McGuigan Christopher , Hutchinson Michael , Tubridy Niall
Published: February 2013

Background:

The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales.

Objective:

This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI).

Methods:

Participants underwent a neurological examination and completed the BAI.

Results:

A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one (‘wobbliness’ and ‘unsteady’) grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered ‘anxious’ by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%.

Conclusion:

Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.
Technique for optimal placement of transducers for fault detection in rotating machines
Authors: Fatima Shahab , Dastidar Sabyasachi G , Mohanty Amiya Ranjan , Naikan Vallayil Narayana Achutha
Published: February 2013

Online fault detection and diagnosis of rotating machinery requires a number of transducers that can be significantly expensive for industrial processes. The sensitivity of various transducers and their appropriate positioning are dependent on different types of fault conditions. It is critical to formulate a method to systematically determine the effectiveness of transducer locations for monitoring the condition of a machine. In this article, number of independent sources analysis is used as an effective tool for reducing the number of vibration sources within the system, which is then followed by principal component analysis to identify the incoherent transducers to be employed for fault detection. This experiment is conducted on a machine fault simulator for unbalanced rotor, misaligned shaft, and cracked shaft. The validation of the proposed selection process is illustrated using spectral analysis for each defect.
Indoleamine 2,3-dioxygenase activity as a potential biomarker of immune suppression during visceral leishmaniasis
Authors: Gangneux Jean-Pierre , Poinsignon Yves , Donaghy Ludovic , Amiot Laurence , Tarte Karin , Mary Charles , Robert-Gangneux Florence
Published: February 2013

Leishmania parasites induce an immunomodulation by subverting the host immune response towards a CD4+ Th2 lymphocytic cell response that favors parasite persistence. Here, we report that after successful treatment of visceral leishmaniasis due to Leishmania infantum, an immune reconstitution syndrome revealing hip septic arthritis was associated with a switch from Th2 towards a Th1 cytokine profile, and a decrease in the level of immunomodulating factors, such as soluble HLA-G and indoleamine 2,3-dioxygenase (IDO) activity. We then measured IDO activity in a cohort of 39 patients and uninfected control subjects. Results showed significantly enhanced IDO activity in patients with visceral Leishmania infection, compared with uninfected control subjects ( P < 0.001), but also compared with treated patients ( P < 0.05). A decrease in IDO activity could constitute a relevant biomarker for the restoration of the immune response during visceral leishmaniasis.
Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo
Authors: McGoldrick Suzanne M. , Bleakley Marie E. , Guerrero Abraham , Turtle Cameron J. , Yamamoto Tori N. , Pereira Shalini E. , Delaney Colleen S. , Riddell Stanley R.
Published: February 2013

Key Points

Priming of CMV-specific CD4+ and CD8+ T cells occurs as early as day 42 in patients undergoing UCBT. Lack of CMV control in UCBT patients could be related to low absolute frequency of T cells and lack of in vivo expansion of T cells.
A highly expressed miR-101 isomiR is a functional silencing small RNA
Authors: Llorens Franc , Bañez-Coronel Mónica , Pantano Lorena , del Río Jose Antonio , Ferrer Isidre , Estivill Xavier , Martí Eulàlia
Published: February 2013

Background

MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression usually producing translational repression and gene silencing. High-throughput sequencing technologies have revealed heterogeneity at length and sequence level for the majority of mature miRNAs (IsomiRs). Most isomiRs can be explained by variability in either Dicer1 or Drosha cleavage during miRNA biogenesis at 5’ or 3’ of the miRNA (trimming variants). Although isomiRs have been described in different tissues and organisms, their functional validation as modulators of gene expression remains elusive. Here we have characterized the expression and function of a highly abundant miR-101 5’-trimming variant (5’-isomiR-101).

Results

The analysis of small RNA sequencing data in several human tissues and cell lines indicates that 5’-isomiR-101 is ubiquitously detected and a highly abundant, especially in the brain. 5’-isomiR-101 was found in Ago-2 immunocomplexes and complementary approaches showed that 5’-isomiR-101 interacted with different members of the silencing (RISC) complex. In addition, 5’-isomiR-101 decreased the expression of five validated miR-101 targets, suggesting that it is a functional variant. Both the binding to RISC members and the degree of silencing were less efficient for 5’-isomiR-101 compared with miR-101. For some targets, both miR-101 and 5’-isomiR-101 significantly decreased protein expression with no changes in the respective mRNA levels. Although a high number of overlapping predicted targets suggest similar targeted biological pathways, a correlation analysis of the expression profiles of miR-101 variants and predicted mRNA targets in human brains at different ages, suggest specific functions for miR-101- and 5’-isomiR-101.

Conclusions

These results suggest that isomiRs are functional variants and further indicate that for a given miRNA, the different isomiRs may contribute to the overall effect as quantitative and qualitative fine-tuners of gene expression.
A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways
Authors: Jia Luoqi , Jin Hongyan , Zhou Jiayi , Chen Lianghua , Lu Yiling , Ming Yanlin , Yu Yinhua
Published: February 2013

Background

Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells.

Methods

The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts.

Results

Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 μM, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 μM. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-β secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-β-induced stabilization of Snail. In contrast, a reduction of TGF-β secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-β secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways.

Conclusions

Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-β/AKT/ERK/Smad signaling pathways.
On the formation of blisters in annealed hydrogenated a-Si layers
Authors: Serényi Miklós , Frigeri Cesare , Szekrényes Zsolt , Kamarás Katalin , Nasi Lucia , Csik Attila , Khánh Nguyen Quoc
Published: February 2013

Differently hydrogenated radio frequency-sputtered a-Si layers have been studied by infrared (IR) spectroscopy as a function of the annealing time at 350°C with the aim to get a deeper understanding of the origin of blisters previously observed by us in a-Si/a-Ge multilayers prepared under the same conditions as the ones applied to the present a-Si layers. The H content varied between 10.8 and 17.6 at.% as measured by elastic recoil detection analysis. IR spectroscopy showed that the concentration of the clustered (Si-H)
n
groups and of the (Si-H2)
n
(n ≥ 1) polymers increased at the expense of the Si-H mono-hydrides with increasing annealing time, suggesting that there is a corresponding increase of the volume of micro-voids whose walls are assumed from literature to be decorated by the clustered mono-hydride groups and polymers. At the same time, an increase in the size of surface blisters was observed. Also, with increasing annealing time, the total concentration of bonded H of any type decreases, indicating that H is partially released from its bonds to Si. It is argued that the H released from the (Si-H)
n
complexes and polymers at the microvoid surfaces form molecular H2 inside the voids, whose size increases upon annealing because of the thermal expansion of the H2 gas, eventually producing plastic surface deformation in the shape of blisters.
Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion
Authors: Shultz Sandy R , Bao Feng , Weaver Lynne C , Cain Donald P , Brown Arthur
Published: February 2013

Background

Concussions account for the majority of traumatic brain injuries (TBI) and can result in cumulative damage, neurodegeneration, and chronic neurological abnormalities. The underlying mechanisms of these detrimental effects remain poorly understood and there are presently no specific treatments for concussions. Neuroinflammation is a major contributor to secondary damage following more severe TBI, and recent findings from our laboratory suggest it may be involved in the cumulative properties of repeated concussion. We previously found that an anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and adhesion molecule interaction following severe experimental TBI reduces neuroinflammation, oxidative activity, and tissue damage, and improves functional recovery. As similar processes may be involved in repeated concussion, here we studied the effects of the anti-CD11d treatment in a rat model of repeated concussion.

Methods

Rats were treated 2 h and 24 h after each of three repeated mild lateral fluid percussion injuries with either the CD11d antibody or an isotype-matched control antibody, 1B7. Injuries were separated by a five-day inter-injury interval. After the final treatment and either an acute (24 to 72 h post-injury) or chronic (8 weeks post-injury) recovery period had elapsed, behavioral and pathological outcomes were examined.

Results

The anti-CD11d treatment reduced neutrophil and macrophage levels in the injured brain with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The anti-CD11d treatment also improved outcome on tasks of cognition, sensorimotor ability, and anxiety.

Conclusions

These findings demonstrate that reducing inflammation after repeated mild brain injury in rats leads to improved behavioral outcomes and that the anti-CD11d treatment may be a viable therapy to improve post-concussion outcomes.
Congenital nasal pyriform aperture stenosis: diagnosis and management
Authors: Sesenna Enrico , Leporati Massimiliano , Brevi Bruno , Oretti Gabriele , Ferri Andrea
Published: February 2013

Background

Congenital nasal pyriform aperture stenosis is a rare and potentially lethal form of airway obstruction in newborns. Immediate recognition and appropriate therapy are mandatory for this potentially life-threating condition. This anomaly may present as an isolated malformation or may be associated with other cranial-facial anomalies. Clinically, CNPS shows unspecific symptoms of nasal airway obstruction such as apnoic crisis, episodic cyanosis and inability to nurse. The purpose of this report is to present author's experience in the surgical management of this rare pathology in 3 patients.

Patients and Methods

Three cases of congenital nasal pyriform aperture stenosis were reviewed for presentation of the disorder, management and effectiveness of the surgical treatment.

Results

All the patients underwent a surgical correction of the pyriform aperture stenosis using a sublabial approach followed by nasal stenting. During the follow-up no cases of restenosis, respiratory failure or cyanosis were detected.

Conclusions

Congenital pyriform aperture stenosis should be suspected in newborns with clinical signs of severe nasal obstruction associated with a difficulty to pass a small catheter though the anterior nasal valve. Timely recognition is mandatory to prevent a potential deadly outcome. Surgical correction of the stenosis though a sublabial approach followed by a nasal stenting revealed to be most effective treatment for these patients.
Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery
Authors: Zuleger Nikolaj , Boyle Shelagh , Kelly David A , de las Heras Jose I , Lazou Vassiliki , Korfali Nadia , Batrakou Dzmitry G , Randles K Natalie , Morris Glenn E , Harrison David J , Bickmore Wendy A , Schirmer Eric C
Published: February 2013

Background

Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified.

Results

To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells.

Conclusions

The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.
Sepsis otopathy: experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea
Authors: Schmutzhard Joachim , Glueckert Rudolf , Pritz Christian , Blumer Michael J. F. , Bitsche Mario , Lackner Peter , Fille Manfred , Riechelmann Herbert , Harkamp Matthias , Sitthisak Thongrong , Schrott-Fischer Annelies
Published: February 2013

Hearing loss is frequent in intensive care patients and can be due to several causes. However, sepsis has not been examined as a possible cause. The aim of this study is to assess the influence of experimental sepsis on hearing thresholds and to evaluate pathological changes in the cochlea. The cecal ligation puncture technique was used to induce sepsis in 18 mice. Results were compared with those from 13 sham-operated and 13 untreated control mice. The hearing thresholds of the animals were evaluated with auditory evoked brainstem responses prior to the induction of sepsis and again at the peak of the disease. Immediately after the second measurement, the mice were sacrificed and the inner ears harvested and prepared for further evaluation. The cochleae were examined with light microscopy, electron microscopy and immunohistochemistry for Bax, cleaved caspase-3 and Bcl-2. The mice with sepsis showed a significant hearing loss but not the control groups. Induction of apoptosis could be shown in the supporting cells of the organ of Corti. Furthermore, excitotoxicity could be shown at the basal pole of the inner hair cells. In this murine model, sepsis leads to significant hearing impairment. The physiological alteration could be linked to apoptosis in the supporting cells of the organ of Corti and to a disturbance of the synapses of the inner hair cells.
The fracture behavior of birch and spruce in the radial-tangential crack propagation direction at the scale of the growth ring
Authors: Tukiainen Pekka , Hughes Mark
Published: February 2013

Crack-tip displacement fields have been computed based on digital image correlation for spruce (Picea abies [L.] Karst.) and birch (Betula pendula Roth.) wood, which were submitted to pure mode I loading in the RT-direction under both green and air-dried conditions. Moreover, crack propagation was modeled based on both linear elastic fracture mechanics (LEFM) and nonlinear fracture mechanics, relying on the fictitious crack model (FCM). The measured and modeled load versus the crack-mouth opening displacement (CMOD) curves and displacement fields were compared. In the case of spruce, the load-CMOD curves simulated by the FCM coincide well with the measured ones. On the contrary, measured near crack-tip displacement fields in both green and air-dried spruce are better comparable with the LEFM predictions than with the FCM predictions. In the case of green birch, the simulated FCM curve follows the measured curve quite well, but in air-dried birch the simulated FCM curve has a better fit than the LEFM-curve only before maximum load. In birch, the FCM predicts the displacement fields better than the LEFM. In both species, moisture content has a big effect on the softening behavior. In both spruce and birch, the FCM overestimates the displacements ahead of crack tip, whereas the LEFM model underestimates the displacements.
Inverse boundary value problem for the heat equation with
discontinuous coefficients
Authors: Nakamura Gen , Sasayama Satoshi
Published: February 2013

The inversion (= reconstruction) scheme, called the dynamical probe method,
is applied to active thermography to identify unknown inclusions in an
heat conductor and their physical properties. We assume the physical
properties of the inclusions and heat conductor are isotropic and
homogeneous. The measured data for the active thermography are the so-called Neumann
to Dirichlet map. By defining some indicator function via the measured
data, the identification is done by looking at the behavior of the indicator
function. The underlying analysis is the short time asymptotic of
fundamental solution of the heat equation with discontinuous coefficients.
Frequency Domain Based Approach for Denoising of Underwater Acoustic Signal Using EMD
Authors: Veeraiyan Vijayabaskar , Velayutham Rajendran , Philip Mathews M.
Published: February 2013

Underwater communication is usually affected by ambient noise, which may be
generated by different sources, such as the wind origin sea-surface sources,
ships and under water life. The properties of background noise, which are
non-stationary in nature, depend on location, sea depth, wind speed and
sound propagation conditions in the area. Overall performance of underwater
acoustic instruments can be improved by denoising the underwater signals.
This paper proposes a novel denoising method using empirical mode
decomposition (EMD) technique. Frequency domain based thresholding has been
used to denoise the signal, which involves three steps: (i) EMD is
applied to the noisy signal to decompose the signal into intrinsic mode
functions (IMFs). (ii) Thresholding is applied to each IMF in the frequency
domain to remove the noise. (iii) Thresholded IMFs are added to obtain the
denoised signal. Real-time experiments were performed to validate the proposed
technique on the basis of the records of the ambient noise data recorded at
sea for various wind speed. It was observed that the experimental results
are in good agreement with the proposed algorithm under different wind-noise
levels.
Fine-Scale Heterogeneity in Crossover Rate in thegarnet-scallopedRegion of theDrosophila melanogasterX Chromosome
Authors: Singh Nadia D , Stone Eric A , Aquadro Charles F , Clark Andrew G
Published: February 2013

Homologous recombination affects myriad aspects of genome evolution, from standing levels of nucleotide diversity to the efficacy of natural selection. Rates of crossing over show marked variability at all scales surveyed, including species-, population-, and individual-level differences. Even within genomes, crossovers are nonrandomly distributed in a wide diversity of taxa. Although intra- and intergenomic heterogeneities in crossover distribution have been documented in Drosophila, the scale and degree of crossover rate heterogeneity remain unclear. In addition, the genetic features mediating this heterogeneity are unknown. Here we quantify fine-scale heterogeneity in crossover distribution in a 2.1-Mb region of the Drosophila melanogaster X chromosome by localizing crossover breakpoints in 2500 individuals, each containing a single crossover in this specific X chromosome region. We show 90-fold variation in rates of crossing over at a 5-kb scale, place this variation in the context of several aspects of genome evolution, and identify several genetic features associated with crossover rates. Our results shed new light on the scale and magnitude of crossover rate heterogeneity in D. melanogaster and highlight potential features mediating this heterogeneity.
Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium
Authors: Loh Po-Ru , Lipson Mark , Patterson Nick , Moorjani Priya , Pickrell Joseph K , Reich David , Berger Bonnie
Published: February 2013

Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.
Effect of the Load Resistance in the Linearity and Sensitivity of MIS Position Sensitive Detectors
Authors: Águas H. , Pereira L. , Fortunato L. Raniero E. , Martins R.
Published: February 2013

It is experimentally known that the linearity and sensitivity of the position sensitive detectors (PSD) are dependent on the resistance of the collecting layer and of the load resistance, mainly if the detection is based on the measurement of the photo-lateral voltage. To determine the value of the load resistance to be used in metal - insulator - semiconductor (MIS) PSDs structures that lead to the maximum value of sensitivity and linearity, we propose an electrical model through which it is able to simulate the proper sensor response and how the load resistance influence the results obtained. This model is valid for PSDs where the resistance of the collecting resistive layer is quite low (≤ 500 Ω), leading to a low output impedance. Under these conditions we conclude that the value of the load resistance should be of about 1 kΩ in order to achieve a good compromise between the linearity and the sensitivity of the PSD. This result is in agreement with the set of experiments performed.