bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictability and Dynamics of a Nonintensifying Tropical Storm: Erika (2009)
Authors: Munsell Erin B. , Zhang Fuqing , Stern Daniel P.
Published: April 2013

In this study, the predictability of Tropical Storm Erika (2009) is evaluated by analyzing a 60-member convection-permitting ensemble initialized with perturbations from a real-time ensemble Kalman filter (EnKF) system. Erika was forecast to intensify into a hurricane by most operational numerical models, but in reality it never exceeded 50 kt (1 kt = 0.51 m s−1). There is a fairly large spread in the final intensities of the 60 ensemble members indicating large uncertainty in the deterministic prediction of Erika's intensity at 36–48-h lead times. An investigation into which factors prevented intensification of the weaker ensemble members provides insight that may aid in the forecasting of the intensity of future tropical cyclones under similar conditions.

A variety of environmental and storm-related factors are examined, and the parameters that have the greatest relation to future intensity are determined based on ensemble sensitivity and correlation analysis. It appears that midlevel relative humidity, absolute vorticity, and the distribution of convection relative to the storm center all play a role in determining whether a given ensemble member intensifies or not. In addition, although differences in deep-layer shear among ensemble members are difficult to discern, many of the ensemble members that do not intensify fail to do so because of apparent dry air intrusions that wrap around the centers of the storms, particularly in the 700–500-hPa layer. In the presence of moderate shear, this dry air is able to penetrate the cores of the cyclones, thereby preventing further development.
Response of the Midlatitude Jets, and of Their Variability, to Increased Greenhouse Gases in the CMIP5 Models
Authors: Barnes Elizabeth A. , Polvani Lorenzo
Published: April 2013

This work documents how the midlatitude, eddy-driven jets respond to climate change using model output from phase 5 of the Coupled Model Intercomparison Project (CMIP5). The authors consider separately the North Atlantic, the North Pacific, and the Southern Hemisphere jets. The analysis is not limited to annual-mean changes in the latitude and speed of the jets, but also explores how the variability of each jet changes with increased greenhouse gases.

All jets are found to migrate poleward with climate change: the Southern Hemisphere jet shifts poleward by 2° of latitude between the historical period and the end of the twenty-first century in the representative concentration pathway 8.5 (RCP8.5) scenario, whereas both Northern Hemisphere jets shift by only 1°. In addition, the speed of the Southern Hemisphere jet is found to increase markedly (by 1.2 m s−1 between 850 and 700 hPa), while the speed remains nearly constant for both jets in the Northern Hemisphere.

More importantly, it is found that the patterns of jet variability are a strong function of the jet position in all three sectors of the globe, and as the jets shift poleward the patterns of variability change. Specifically, for the Southern Hemisphere and the North Atlantic jets, the variability becomes less of a north–south wobbling and more of a pulsing (i.e., variation in jet speed). In contrast, for the North Pacific jet, the variability becomes less of a pulsing and more of a north–south wobbling. These different responses can be understood in terms of Rossby wave breaking, allowing the authors to explain most of the projected jet changes within a single dynamical framework.
A novel piezohydraulic aerospace servovalve. Part 1: design and modelling
Authors: Sangiah Dhinesh K , Plummer Andrew R , Bowen Christopher R , Guerrier Paul
Published: April 2013

Servovalves are compact, accurate and high-bandwidth modulating valves widely used in aerospace, defence, industrial and marine applications. However, manufacturing costs are high due to high part count and tight tolerances required, particularly in the first stage of the valve, and due to manual adjustments required as part of the set-up process. In this research, a novel servovalve concept is investigated that has the potential to be more cost-effective. In particular, for the first time, a piezoelectric first-stage actuator is developed to move a servovalve spool using the deflector jet principle; this is especially suited to aerospace actuation requirements. In the new valve, the conventional electromagnetic torque motor is replaced by a multilayer bimorph piezoelectric actuator. The bimorph deflects a jet of fluid to create a pressure differential across the valve spool; hence the spool moves. A feedback wire is used to facilitate proportional spool position control via mechanical feedback. The bimorph is directly coupled to the feedback wire and is immersed in hydraulic fluid. A high-order non-linear model of the valve has been developed and used to predict valve static and dynamic characteristics and is described in this article. This makes use of stiffness constants derived analytically for the bimorph-feedback wire assembly and cross-referenced to finite element analysis predictions. The model of the flow force acting on the deflector is an approximation of the force characteristic found from computation fluid dynamic analysis. The measured characteristics of the prototype valve are in good agreement with the simulation results and prove that the operational concept is viable.
Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia
Authors: Uckun Fatih M. , Qazi Sanjive , Cely Ingrid , Sahin Kazim , Shahidzadeh Anoush , Ozercan Ibrahim , Yin Qian , Gaynon Paul , Termuhlen Amanda , Cheng Jianjun , Yiv Seang
Published: April 2013

Key Points

SYK is a suitable molecular target for nanotechnology-enabled therapy against ALL. Nanoscale liposomal formulation of SYK inhibitor C61 displayed a promising preclinical profile as an antileukemic drug candidate.
Expression of SHH signaling molecules in the developing human primary dentition
Authors: Hu Xuefeng , Zhang Shuo , Chen Guimiao , Lin Chensheng , Huang Zhen , Chen YiPing , Zhang Yanding
Published: April 2013

Background

Our current knowledge on tooth development derives primarily from studies in mice. Very little is known about gene expression and function during human odontogenesis. Sonic Hedgehog (SHH) signaling has been demonstrated to play crucial roles in the development of multiple organs in mice, including the tooth. However, if SHH signaling molecules are expressed and function in the developing human embryonic tooth remain unknown.

Results

We conducted microarray assay to reveal the expression profile of SHH signaling pathway molecules. We then used in situ hybridization to validate and reveal spatial and temporal expression patterns of a number of selected molecules, including SHH, PTC1, SMO, GLI1, GLI2, and GLI3, in the developing human embryonic tooth germs, and compared them with that in mice. We found that all these genes exhibit similar but slightly distinct expression patterns in the human and mouse tooth germ at the cap and bell stages.

Conclusions

Our results demonstrate the operation of active SHH signaling in the developing human tooth and suggest a conserved function of SHH signaling pathway during human odontogenesis.
A carrier-assisted ChIP-seq method for estrogen receptor-chromatin interactions from breast cancer core needle biopsy samples
Authors: Zwart Wilbert , Koornstra Rutger , Wesseling Jelle , Rutgers Emiel , Linn Sabine , Carroll Jason S
Published: April 2013

Background

The Estrogen Receptor alpha (ERα) is the key transcriptional regulator in luminal breast cancer and is therefore the main target for adjuvant treatment of this subtype. Luminal gene signatures are dictated by the transcriptional capacities of ERα, which are a direct consequence of the receptors binding preference at specific sites on the chromatin. The identification of ERα binding signatures on a genome-wide level has greatly enhanced our understanding of Estrogen Receptor biology in cell lines and tumours, but the technique has its limitations with respect to its applicability in limited amounts of tumour tissue.

Results

Here, we present a refinement of the ChIP-seq procedures to enable transcription factor mapping on limited amounts of tissue culture cells as well as from a limited amount of tumor tissue derived from core needle biopsies. Our approach uses a carrier that can be removed prior to DNA amplification and sequencing.

Conclusion

We illustrate the applicability of this refined technology by mapping the ERα genome-wide chromatin binding landscape in core needle biopsy material from primary breast tumours. With this, our refined technology permits for a high-resolution transcription factor mapping even from clinical samples.
Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats
Authors: Zhang Liying , Hu Xiquan , Luo Jing , Li Lili , Chen Xingyong , Huang Ruxun , Pei Zhong
Published: April 2013

Background

Physical exercise improves functional recovery after stroke through a complex mechanism that is not fully understood. Transient focal cerebral ischemia induces autophagy, apoptosis and neurogenesis in the peri-infarct region. This study is aimed to examine the effects of physical exercise on autophagy, apoptosis and neurogenesis in the peri-infarct region in a rat model of transient middle cerebral artery occlusion (MCAO).

Results

We found that autophagosomes, as labeled by microtubule-associated protein 1A light chain 3-II (LC3-II), were evident in the peri-infarct region at 3 days after 90-minute MCAO. Moreover, 44.6% of LC3-positive cells were also stained with TUNEL. The number of LC3 positive cells was significantly lower in physical exercise group than in control group at 14 and 21 days after MCAO. Suppression of autophagosomes by physical exercise was positively associated with improvement of neurological function. In addition, physical exercise significantly decreased the number of TUNEL-positive cells and increased the numbers of Ki67-positive, a proliferative marker, and insulin-like growth factor-1 (IGF-1) positive cells at 7, 14, and 21 days after MCAO.

Conclusions

The present results demonstrate that physical exercise enhances neurological function possibly by reduction of autophagosome accumulation, attenuation of apoptosis and enhancement of neurogenesis in the peri-infarct region after transient MCAO in rats.
Genetic variations of the A13/A14 repeat located within the EGFR3′ untranslated region have no oncogenic effect in patients with colorectal cancer
Authors: Sarafan-Vasseur Nasrin , Sefrioui David , Tougeron David , Lamy Aude , Blanchard France , Le Pessot Florence , Di Fiore Frédéric , Michel Pierre , Bézieau Stéphane , Latouche Jean-Baptiste , Frebourg Thierry , Sesboüé Richard
Published: April 2013

Background

The EGFR 3′ untranslated region (UTR) harbors a polyadenine repeat which is polymorphic (A13/A14) and undergoes somatic deletions in microsatellite instability (MSI) colorectal cancer (CRC). These mutations could be oncogenic in colorectal tissue since they were shown to result into increased EGFR mRNA stability in CRC cell lines.

Methods

First, we determined in a case control study including 429 CRC patients corresponding to different groups selected or not on age of tumor onset and/or familial history and/or MSI, whether or not, the germline EGFR A13/A14 polymorphism constitutes a genetic risk factor for CRC; second, we investigated the frequency of somatic mutations of this repeat in 179 CRC and their impact on EGFR expression.

Results

No statistically significant difference in allelic frequencies of the EGFR polyA repeat polymorphism was observed between CRC patients and controls. Somatic mutations affecting the EGFR 3′UTR polyA tract were detected in 47/80 (58.8%) MSI CRC versus 0/99 microsatellite stable (MSS) tumors. Comparative analysis in 21 CRC samples of EGFR expression, between tumor and non malignant tissues, using two independent methods showed that somatic mutations of the EGFR polyA repeat did not result into an EGFR mRNA increase.

Conclusion

Germline and somatic genetic variations occurring within the EGFR 3′ UTR polyA tract have no impact on CRC genetic risk and EGFR expression, respectively. Genotyping of the EGFR polyA tract has no clinical utility to identify patients with a high risk for CRC or patients who could benefit from anti-EGFR antibodies.
Work ability assessment in a worker population: comparison and determinants of Work Ability Index and Work Ability score
Authors: El Fassi Mehdi , Bocquet Valery , Majery Nicole , Lair Marie Lise , Couffignal Sophie , Mairiaux Philippe
Published: April 2013

Background

Public authorities in European countries are paying increasing attention to the promotion of work ability throughout working life and the best method to monitor work ability in populations of workers is becoming a significant question. The present study aims to compare the assessment of work ability based on the use of the Work Ability Index (WAI), a 7-item questionnaire, with another one based on the use of WAI’s first item, which consists in the worker’s self-assessment of his/her current work ability level as opposed to his/her lifetime best, this single question being termed “Work Ability score” (WAS).

Methods

Using a database created by an occupational health service, the study intends to answer the following questions: could the assessment of work ability be based on a single-item measure and which are the variables significantly associated with self-reported work ability among those systematically recorded by the occupational physician during health examinations? A logistic regression model was used in order to estimate the probability of observing “poor” or “moderate” WAI levels depending on age, gender, body mass index, smoking status, position held, firm size and diseases reported by the worker in a population of workers aged 40 to 65 and examined between January 2006 and June 2010 (n=12389).

Results

The convergent validity between WAS and WAI was statistically significant (rs=0.63). In the multivariable model, age (p<0.001), reported diseases (OR=1.13, 95%CI [1.11-1.15]) and holding a position mostly characterized by physical activity (OR=1.67, 95%CI [1.49-1.87]) increased the probability of reporting moderate or poor work ability. A work position characterized by the predominance of mental activity (OR=0.71, 95%CI [0.61-0.84]) had a favourable impact on work ability. These relations were observed regardless of the work ability measurement tool used.

Conclusion

The convergent validity and the similarity in results between WAI and WAS observed in a large population of employed workers should thus foster the use of WAS for systematic screening of work ability. Ageing, overweight, decline in health status, holding a mostly physical job and working in a large-sized firm increase the risk of presenting moderate or poor work ability.
Community knowledge, attitude and practice about malaria in a low endemic setting of Shewa Robit Town, northeastern Ethiopia
Authors: Abate Andargie , Degarege Abraham , Erko Berhanu
Published: April 2013

Background

Since malaria is one of the foremost public health problems in Ethiopia, assessment of situation of the disease, and communities’ knowledge and perceptions about malaria is necesary to institute appropriate preventive and control measures. Thus, the aim of this study was to assess malaria prevalence and knowledge, attitude and practice (KAP) about the disease among ShewaRobit Town community, northeastern Ethiopia.

Methods

A community-based cross-sectional study was conducted in Shewa Robit Town from October to November 2011. A multi-stage random sampling technique was used to select the study participants. A total of 425 individuals were examined for malaria using thin and thick Giemsa stained blood film, and 284 of the participants were interviewed to assess their KAP about malaria. Logistic regression analysis was used to assess predictor factors for malaria prevalence.

Results

All respondents had ever heard of malaria. Most of the respondents (85.2%) attributed the cause of malaria to mosquito bite. However, some of the respondents (>20%) mentioned lack of personal hygiene, exposure to cold weather, hunger, chewing maize stalk, body contact with malaria patient and flies as the causes of malaria. Sleeping under mosquito nets, draining stagnant water and indoor residual spraying were the most frequently mentioned malaria preventive measures perceived and practiced by the respondents. Among 425 individuals examined for malaria, only 2.8% were positive for Plasmodium parasites. Living in houses made of wall without hole, sprayed with insecticide within the last 12 hours and located at a distance of greater than 500 meters from potential mosquito breeding sites as well as knowing and using of mosquito net were significant predictors of low malaria prevalence among the study participants.

Conclusions

A high level of knowledge about the cause, transmission and preventive methods of malaria was detected among the community in Shewa Robit Town. However, a considerable proportion had misconception about the cause and transmission of malaria suggesting the necessity of health education to raise the community’s awareness about the disease.
Fibroin and fibroin blended three-dimensional scaffolds for rat chondrocyte culture
Authors: Chomchalao Pratthana , Pongcharoen Sutatip , Sutheerawattananonda Manote , Tiyaboonchai Waree
Published: April 2013

Background

In our previous study, we successfully developed 3-D scaffolds prepared from silk fibroin (SF), silk fibroin/collagen (SF/C) and silk fibroin/gelatin (SF/G) using a freeze drying technique. The blended construct showed superior mechanical properties to silk fibroin construct. In addition, collagen and gelatin, contain RGD sequences that could facilitate cell attachment and proliferation. Therefore, in this study, the ability of silk fibroin and blended constructs to promote cell adhesion, proliferation and production of extracellular matrix (EMC) were compared.

Methods

Articular chondrocytes were isolated from rat and cultured on the prepared constructs. Then, the cell viability in SF, SF/C and SF/G scaffolds was determined by MTT assay. Cell morphology and distribution were investigated by scanning electron microscopy (SEM) and histological analysis. Moreover, the secretion of extracellular matrix (ECM) by the chondrocytes in 3-D scaffolds was assessed by immunohistochemistry.

Results

Results from MTT assay indicated that the blended SF/C and SF/G scaffolds provided a more favorable environment for chondrocytes attachment and proliferation than that of SF scaffold. In addition, scanning electron micrographs and histological images illustrated higher cell density and distribution in the SF/C and SF/G scaffolds than that in the SF scaffold. Importantly, immunohistochemistry strongly confirmed a greater production of type II collagen and aggrecan, important markers of chondrocytic phenotype, in SF blended scaffolds than that in the SF scaffold.

Conclusion

Addition of collagen and gelatin to SF solution not only improved the mechanical properties of the scaffolds but also provided an effective biomaterial constructs for chondrocyte growth and chondrocytic phenotype maintenance. Therefore, SF/C and SF/G showed a great potential as a desirable biomaterial for cartilage tissue engineering.
Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer
Authors: Zhao Shu-Hua , Wang Yu , Wen Li , Zhai Zhen-Bo , Ai Zhen-Hua , Yao Nian-Ling , Wang Li , Liu Wen-Chao , Chen Bi-Liang , Li Yu , Yang Hong
Published: April 2013

Background

Basigin, which has four isoforms, has been demonstrated to be involved in progression of various human cancers. The aim of this study was to examine the prognostic value of basigin-2 protein expression in epithelial ovarian cancer. Furthermore, the function of basigin-2 in ovarian cancer was further investigated in cell culture models.

Methods

Immunohistochemistry staining was performed to investigate basigin-2 expression in a total of 146 ovarian tissue specimens. Kaplan Meier analysis and Cox proportional hazards model were applied to assess the relationship between basigin-2 and progression-free survival (PFS) and overall survival (OS). Real-time PCR, RT-PCR and western blot were used to explore basigin-2, basigin-3 and basigin-4 expression in ovarian cancer cell lines and tissues. To evaluate possible contributions of basigin-2 to MMP secretion and cell migration and invasion, the overexpression vectors pcDNA3.1-basigin-2 and basigin-2 siRNA were transfected into HO-8910 and HO-8910 PM cells respectively.

Results

High basigin-2 expression was associated with lymph-vascular space involvement, lymph node metastasis and poor prognosis of epithelial ovarian cancer. Multivariate analyses indicated that basigin-2 positivity was an independent prognostic factor for PFS (P = 0.006) and OS (P = 0.019), respectively. Overexpression of basigin-2 increased the secretion of MMP-2/9 and cancer cell migration and invasion of HO-8910 cells, whereas knockdown of basigin-2 reduced active MMP-2/9 production, migration and invasion of HO-8910 PM cells.

Conclusions

The expression of basigin-2 might be an independent prognostic marker and basigin-2 inhibition would be a potential strategy for epithelial ovarian cancer patients, especially in inhibiting and preventing cancer cell invasion and metastasis.
Phylogenetic analysis of the haemagglutinin gene of canine distemper virus strains detected from giant panda and raccoon dogs in China
Authors: Guo Ling , Yang Shao-lin , Wang Cheng-dong , Hou Rong , Chen Shi-jie , Yang Xiao-nong , Liu Jie , Pan Hai-bo , Hao Zhong-xiang , Zhang Man-li , Cao San-jie , Yan Qi-gui
Published: April 2013

Background

Canine distemper virus (CDV) infects a variety of carnivores, including wild and domestic Canidae. In this study, we sequenced and phylogenetic analyses of the hemagglutinin (H) genes from eight canine distemper virus (CDV) isolates obtained from seven raccoon dogs (Nyctereutes procyonoides) and a giant panda (Ailuropoda melanoleuca) in China.

Results

Phylogenetic analysis of the partial hemagglutinin gene sequences showed close clustering for geographic lineages, clearly distinct from vaccine strains and other wild-type foreign CDV strains, all the CDV strains were characterized as Asia-1 genotype and were highly similar to each other (91.5-99.8% nt and 94.4-99.8% aa). The giant panda and raccoon dogs all were 549Y on the HA protein in this study, irrespective of the host species.

Conclusions

These findings enhance our knowledge of the genetic characteristics of Chinese CDV isolates, and may facilitate the development of effective strategies for monitoring and controlling CDV for wild canids and non-cainds in China.
Chronic Pain after Lower Abdominal Surgery: Do Catechol-O-Methyl Transferase/Opioid Receptor μ−1 Polymorphisms Contribute?
Authors: Kolesnikov Yuri , Gabovits Boris , Levin Ariel , Veske Andres , Qin Li , Dai Feng , Belfer Inna
Published: April 2013

Background

Preoperative pain, type of operation and anesthesia, severity of acute postoperative pain, and psychosocial factors have been identified as risk factors for chronic postsurgical pain (CPP). Recently, it has been suggested that genetic factors also contribute to CPP. In this study, we aimed to determine whether the catechol-O-methyl transferase ( COMT) and opioid receptor μ−1 ( OPRM1) common functional polymorphisms rs4680 and rs1799971 were associated with the incidence, intensity, or duration of CPP in patients after lower abdominal surgery.

Methods

One hundred and two patients with American Society of Anesthesiologists (ASA) physical status I/II underwent either abdominal radical prostatectomy (n=45) or hysterectomy (n = 57). The incidences of CPP in the pelvic and scar areas were evaluated in all patients three months after surgery.

Results

Thirty-five (34.3%) patients experienced CPP after lower abdominal surgery. Within this group, six (17.1%) patients demonstrated symptoms of neuropathic pain. For COMT rs4680, 22 (21.6%) patients had Met158Met, 55 (53.9%) patients had Val158Met, and 25 (24.5%) patients had Val158Val. No association was found between CPP phenotypes (incidence, intensity, and duration) and different rs4680 genotypes. For OPRM1 rs1799971, only CPP patients carrying at least one copy of the G allele had higher pain intensity than A118A carriers (p=0.02). No associations with other phenotypes were found. No combined effect of COMT/OPRM1 polymorphisms on CPP phenotypes was observed.

Conclusions

OPRM1 genotype influences CPP following lower abdominal surgery. COMT didn't affect CPP, suggesting its potential modality-specific effects on human pain.
c-Met inhibitors
Authors: Mughal Anum , Aslam Hafiz Muhammad , Sheikh Asfandyar , Khan Agha Muhammad Hammad , Saleem Shafaq
Published: April 2013

c-Met is a receptor tyrosine kinase that encodes protein such as hepatocyte growth factor receptor (HGFR). Inappropriate activity of c-Met can cause wide variety of carcinomas. c-Met inhibitor are relatively new class of small molecules that inhibit the enzymatic activity of c-Met tyrosine kinase. Met inhibitors divided into two main classes: class I (SU-11274-like) and class II (AM7-like). The use of c-Met inhibitors with other therapeutic agents could be crucial for overcoming potential resistance as well as for improving overall clinical benefit. Met pathway inhibitors might be used in combination with other treatments, including chemo-, radio- or immunotherapy
Plasma RANTES, IL-10, and IL-8 levels in non–small-cell lung cancer patients treated with EGFR-TKIs
Authors: Umekawa Kanako , Kimura Tatsuo , Kudoh Shinzoh , Suzumura Tomohiro , Oka Takako , Nagata Misato , Mitsuoka Shigeki , Matsuura Kuniomi , Nakai Toshiyuki , Yoshimura Naruo , Kira Yukimi , Hirata Kazuto
Published: April 2013

Background

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), routinely used to treat advanced non-small-cell lung cancer (NSCLC) patients with activated EGFR mutations, are associated with excellent response and improved performance status. Recently, pro-inflammatory cytokines, such as regulated upon activation normal T cell expressed and secreted (RANTES), interleukin (IL)-10 and IL-8 have been proposed as mediators of cancer development. EGFR-TKIs have been found to affect this network of pro-inflammatory cytokines.

Methods

EGFR-TKIs (erlotinib, 150 mg/day; and gefitinib, 250 mg/day) were administered once per day. Treatment was continued until disease progressed or the patient developed intolerable symptoms of toxicity, or withdrew his/her consent for study participation. The treatment was a part of standard care. We investigated the correlation between plasma pro-inflammatory cytokines (including plasma RANTES, IL-10, and IL-8) levels and clinical outcomes following EGFR-TKI treatment in lung cancer patients. Pro-inflammatory cytokine levels were evaluated at diagnosis and on treatment day 30 after the first administration of EGFR-TKIs.

Results

Overall, 33 patients were enrolled. Plasma pro-inflammatory cytokine levels were determined for all patients at diagnosis. Plasma samples from 26 patients were obtained on treatment day 30. High level of RANTES at diagnosis was associated with severe general fatigue (P = .026). Low level of RANTES at diagnosis was significantly associated with long-term survival (P = .0032). Percent decrease change of IL-10 was associated with severity of rash (P = .037). The plasma IL-8 level on treatment day 30 (median, 5.48 pg/mL; range, 0.49–26.13 pg/mL) was significantly lower than the level at diagnosis (median 10.45 pg/mL; 3.04–54.86 pg/mL; P = .021).

Conclusions

These results suggest that EGFR-TKIs may suppress systemic inflammation and promote tumor shrinkage. The network of pro-inflammatory cytokines was affected by EGFR-TKI treatment for NSCLC. In addition, the clinical outcomes of EGFR-TKI treatment were influenced by the status of the plasma pro-inflammatory cytokines at diagnosis.
Scanning electron microscopy observations of the hedgehog stomach worm, Physaloptera clausa (Spirurida: Physalopteridae)
Authors: Gorgani Tahmine , Naem Soraya , Farshid Amir Abbass , Otranto Domenico
Published: April 2013

Background

Physaloptera clausa (Spirurida: Physalopteridae) nematodes parasitize the stomach of the European hedgehog (Erinaceus europaeus) and cause weight loss, anorexia and gastric lesions. The present study provides the first morphological description of adult P. clausa from the stomachs of infected hedgehogs, using scanning electron microscopy (SEM).

Methods

From June to October 2011, 10 P. clausa from European hedgehogs were fixed, dried, coated and subjected to SEM examination.

Results

Males and females (22–30 mm and 28–47 mm, respectively) were stout, with the cuticle reflecting over the lips to form a large cephalic collarette and showing fine transverse striations in both sexes. The mouth was characterized by two large, simple triangular lateral pseudolabia, each armed with external and internal teeth. Inside the buccal cavity, a circle of internal small teeth can be observed. Around the mouth, four sub-median cephalic papillae and two large amphids were also observed. The anterior end of both male and female bore an excretory pore on the ventral side and a pair of lateral ciliated cervical papillae. In the female worm, the vulva was located in the middle and the eggs were characterized by smooth surfaces. The posterior end of the female worm was stumpy with two large phasmids in proximity to its extremity. The posterior end of the male had large lateral alae, joined together anteriorly across the ventral surface, with subequal and dissimilar spicules, as well as four pairs of stalked pre-cloacal papillae, three pairs of post-cloacal papillae, and two phasmids. Three sessile papillae occured anteriorly and four posteriorly to the cloaca.

Conclusions

The present SEM study provides the first in-depth morphological characterization of adult P. clausa, and highlights similarities and differences with P. bispiculata P. herthameyerae, Heliconema longissimum and Turgida turgida.
Reliability and validity of the Microsoft Kinect for evaluating static foot posture
Authors: Mentiplay Benjamin F , Clark Ross A , Mullins Alexandra , Bryant Adam L , Bartold Simon , Paterson Kade
Published: April 2013

Background

The evaluation of foot posture in a clinical setting is useful to screen for potential injury, however disagreement remains as to which method has the greatest clinical utility. An inexpensive and widely available imaging system, the Microsoft Kinect™, may possess the characteristics to objectively evaluate static foot posture in a clinical setting with high accuracy. The aim of this study was to assess the intra‐rater reliability and validity of this system for assessing static foot posture.

Methods

Three measures were used to assess static foot posture; traditional visual observation using the Foot Posture Index (FPI), a 3D motion analysis (3DMA) system and software designed to collect and analyse image and depth data from the Kinect. Spearman's rho was used to assess intra‐rater reliability and concurrent validity of the Kinect to evaluate foot posture, and a linear regression was used to examine the ability of the Kinect to predict total visual FPI score.

Results

The Kinect demonstrated moderate to good intra‐rater reliability for four FPI items of foot posture (ρ = 0.62 to 0.78) and moderate to good correlations with the 3DMA system for four items of foot posture (ρ = 0.51 to 0.85). In contrast, intra‐rater reliability of visual FPI items was poor to moderate (ρ = 0.17 to 0.63), and correlations with the Kinect and 3DMA systems were poor (absolute ρ = 0.01 to 0.44). Kinect FPI items with moderate to good reliability predicted 61% of the variance in total visual FPI score.

Conclusions

The majority of the foot posture items derived using the Kinect were more reliable than the traditional visual assessment of FPI, and were valid when compared to a 3DMA system. Individual foot posture items recorded using the Kinect were also shown to predict a moderate degree of variance in the total visual FPI score. Combined, these results support the future potential of the Kinect to accurately evaluate static foot posture in a clinical setting.
Follicular stage-dependent regulation of apoptosis and steroidogenesis by prohibitin in rat granulosa cells
Authors: Wang Qi , Leader Arthur , Tsang Benjamin K
Published: April 2013

Background

Follicular growth and atresia are tightly regulated processes, which involve the participation of endocrine, autocrine and paracrine factors at the cellular level. Prohibitin (PHB) is a multifunctional intracellular protein playing an important role in the regulation of proliferation, apoptosis and differentiation. Here we examined the expression of PHB and its regulation by FSH in vitro and studied the role of PHB in the regulation of apoptosis and steroidogenesis in response to the apoptosis inducer staurosporine (STS) and to FSH, respectively.

Methods

Undifferentiated and differentiated granulosa cells were collected from diethylstilbestrol (DES)- and equine chronic gonadotropin (eCG)-primed immature rats, respectively and then cultured with various treatments (FSH, adenovirus infection, STS) according to experimental design. The apoptosis rate, the production of estradiol and progesterone, and the expression of distinct proteins (PHB, caspase-3, phospho- and total Akt) were assessed.

Results

PHB is anti-apoptotic and its action is dependent on the differentiated state of the granulosa cells. Data from gain- and loss-of-function experiments demonstrate that PHB inhibited STS-induced caspase-3 cleavage and apoptosis in undifferentiated granulosa cells, but was ineffective in differentiated cells. In contrast, PHB suppresses FSH-induced steroidogenesis and this response is evident irrespective of the differentiated state of granulosa cells.

Conclusion

These findings suggest that PHB regulates granulosa cell apoptosis and steroidogenesis in a follicular stage-dependent manner and that the dysregulation of PHB expression and action may be relevant to ovarian dysfunction.
Transcranial ultrasound analysis of cerebral blood flow during induced hypertension in acute ischemic stroke - a case series
Authors: List Jonathan , Röhl Jens E , Doepp Florian , Valdueza José M , Schreiber Stephan J
Published: April 2013

Background

Current recommendations of stroke treatment favour a moderately elevated blood pressure in the acute phase, based on the concept of an improved cerebral perfusion. Here, cerebral blood flow was assessed in a case series of patients with acute hemodynamic stroke by means of transcranial colour-coded sonography (TCCS) to study the effects of pharmacologically induced hypertension.

Findings

We investigated six patients with acute hemodynamic stroke and blood pressure-dependent clinical fluctuation of neurological symptoms. TCCS was performed during the initiation phase of catecholamine-induced controlled hypertension. A blood pressure-dependent increase of flow velocity in the ipsilesional middle and the posterior cerebral artery was found in all patients (mean increase 0.80% and 0.65% per mmHg, respectively).

Conclusions

Catecholamine-induced hypertension in severe hemodynamic stroke leads to an ultrasound-detectable rise of cerebral blood flow. This finding gives ‘proof-of-principle’ evidence, supporting active blood pressure management in this selected group of stroke patients. Outcome-related questions of target blood pressure, treatment duration or applicability to other forms of stroke, however, remain to be studied. In this, transcranial ultrasound may be a valuable tool for patient selection and subsequent bedside monitoring.
Comparison of endogenous and overexpressed MyoD shows enhanced binding of physiologically bound sites
Authors: Yao Zizhen , Fong Abraham P , Cao Yi , Ruzzo Walter L , Gentleman Robert C , Tapscott Stephen J
Published: April 2013

Background

Transcription factor overexpression is common in biological experiments and transcription factor amplification is associated with many cancers, yet few studies have directly compared the DNA-binding profiles of endogenous versus overexpressed transcription factors.

Methods

We analyzed MyoD ChIP-seq data from C2C12 mouse myotubes, primary mouse myotubes, and mouse fibroblasts differentiated into muscle cells by overexpression of MyoD and compared the genome-wide binding profiles and binding site characteristics of endogenous and overexpressed MyoD.

Results

Overexpressed MyoD bound to the same sites occupied by endogenous MyoD and possessed the same E-box sequence preference and co-factor site enrichments, and did not bind to new sites with distinct characteristics.

Conclusions

Our data demonstrate a robust fidelity of transcription factor binding sites over a range of expression levels and that increased amounts of transcription factor increase the binding at physiologically bound sites.
Increased expression of miR-221 is associated with shorter overall survival in T-cell acute lymphoid leukemia
Authors: Gimenes-Teixeira Hamilton L , Lucena-Araujo Antonio R , dos Santos Guilherme A , Zanette Dalila L , Scheucher Priscila S , Oliveira Luciana C , Dalmazzo Leandro F , Silva-Júnior Wilson A , Falcão Roberto P , Rego Eduardo M
Published: April 2013

Background

CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome.

Methods

The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples.

Results

miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56-
vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate.

Conclusions

miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.
The granulocyte colony stimulating factor pathway regulates autoantibody production in a murine induced model of systemic lupus erythematosus
Authors: Lantow Margareta , Sivakumar Ramya , Zeumer Leilani , Wasserfall Clive , Zheng Ying-Yi , Atkinson Mark A , Morel Laurence
Published: April 2013

Introduction

An NZB-derived genetic locus (Sle2c2) that suppresses autoantibody production in a mouse model of induced systemic lupus erythematosus contains a polymorphism in the gene encoding the G-CSF receptor. This study was designed to test the hypothesis that the Sle2c2 suppression is associated with an impaired G-CSF receptor function that can be overcome by exogenous G-CSF.

Methods

Leukocytes from B6.Sle2c2 and B6 congenic mice, which carry a different allele of the G-CSF receptor, were compared for their responses to G-CSF. Autoantibody production was induced with the chronic graft-versus-host-disease (cGVHD) model by adoptive transfer of B6.bm12 splenocytes. Different treatment regimens varying the amount and frequency of G-CSF (Neulasta®) or carrier control were tested on cGVHD outcomes. Autoantibody production, immune cell activation, and reactive oxygen species (ROS) production were compared between the two strains with the various treatments. In addition, the effect of G-CSF treatment was examined on the production autoantibodies in the B6.Sle1.Sle2.Sle3 (B6.TC) spontaneous model of lupus.

Results

B6.Sle2c2 and B6 leukocytes responded differently to G-CSF. G-CSF binding by B6.Sle2c2 leukocytes was reduced as compared to B6, which was associated with a reduced expansion in response to in vivo G-CSF treatment. G-CSF in vivo treatment also failed to mobilize bone-marrow B6.Sle2c2 neutrophils as it did for B6 neutrophils. In contrast, the expression of G-CSF responsive genes indicated a higher G-CSF receptor signaling in B6.Sle2c2 cells. G-CSF treatment restored the ability of B6.Sle2c2 mice to produce autoantibodies in a dose-dependent manner upon cGVHD induction, which correlated with restored CD4+ T cells activation, as well as dendritic cell and granulocyte expansion. Steady-state ROS production was higher in B6.Sle2c2 than in B6 mice. cGVHD induction resulted in a larger increase in ROS production in B6 than in B6.Sle2c2 mice, and this difference was eliminated with G-CSF treatment. Finally, a low dose G-CSF treatment accelerated the production of anti-dsDNA IgG in young B6.TC mice.

Conclusion

The different in vivo and in vitro responses of B6.Sle2c2 leukocytes are consistent with the mutation in the G-CSFR having functional consequences. The elimination of Sle2c2 suppression of autoantibody production by exogenous G-CSF indicates that Sle2c2 corresponds to a loss of function of G-CSF receptor. This result was corroborated by the increased anti-dsDNA IgG production in G-CSF-treated B6.TC mice, which also carry the Sle2c2 locus. Overall, these results suggest that the G-CSF pathway regulates the production of autoantibodies in murine models of lupus.
The use of wavelet transforms for improved interpretation of airborne transient electromagnetic data
Authors: Nenna Vanessa , Pidlisecky Adam
Published: April 2013

The continuous wavelet transform (CWT) is used to create maps of dominant spatial scales in airborne transient electromagnetic (ATEM) data sets to identify cultural noise and topographic features. The introduced approach is applied directly to ATEM data, and does not require the measurements be inverted, though it can easily be applied to an inverted model. For this survey, we apply the CWT spatially to B-field and dB/dt ATEM data collected in the Edmonton-Calgary Corridor of southern Alberta. The average wavelet power is binned over four ranges of spatial scale and converted to 2D maps of normalized power within each bin. The analysis of approximately 2 million soundings that make up the survey can be run on the order of minutes on a 2.4 GHz Intel processor. We perform the same CWT analysis on maps of surface and bedrock topography and also compare ATEM results to maps of infrastructure in the region. We find that linear features identified on power maps that differ significantly between B-field and dB/dt data are well correlated with a high density of infrastructure. Features that are well correlated with topography tend to be consistent in power maps for both types of data. For this data set, use of the CWT reveals that topographic features and cultural noise from high-pressure oil and gas pipelines affect a significant portion of the survey region. The identification of cultural noise and surface features in the raw ATEM data through CWT analysis provides a means of focusing and speeding processing prior to inversion, though the magnitude of this affect on ATEM signals is not assessed.
Das gefühlte Faktum der Vernunft. Skizze einer Interpretation und Verteidigung
Authors: Schönecker Dieter
Published: April 2013

Kant is by no means the pure rationalist that Husserl and others represented him as being. To the contrary I claim that Kant is an ethical intuitionist when it comes to our recognition of the validity of the moral law. Interpreting Kant’s famous thesis about the “fact of reason”, I will first argue for three interpretative theses: 1. The factum theory explains our insight into the binding character of the moral law; it is a theory of justification. 2. In our consciousness of the categorical imperative, the moral law is immediately given in its unconditional and binding validity. 3. The unconditional validity of the CI is given in the feeling of respect. Drawing on basic thoughts of Reformed Epistemology, I will then sketch a way to defend Kant’s theory.
Philosophie aktuell – Organtransplantation II: Aufklärung und Vertrauen. Gibt es eine moralische Pflicht zur Organspende? – Organtransplantation und Aufklärung – Achtung der Autonomie gegenüber Organspendern? – Vertrauen ist gut? Mitnichten immer!
Authors: Esser Andrea , Kersting Daniel , Gutmann Thomas , Rehbock Theda , Dabrock Peter
Published: April 2013

Dealing with the reform of the Transplantation Law, the first issue of the new rubric “Philosophie aktuell” met with strong and lively interest from our readers. Subsequent to this discussion a growing number of reports were published dealing with violations of mandatory rules of conduct in transplantation medicine. Therefore the topic is revisited here from the slightly different vantage point “organ transplantation II: elucidation and confidence”.
The Perils of Certain English Prisoners: Charles Dickens, Wilkie Collins, and the Limits of Colonial Government
Authors: Tickell Alex
Published: April 2013

This essay considers the theme of the contract as a metonym for failed government in Charles Dickens’s and Wilkie Collins’s collaborative Christmas story The Perils of Certain English Prisoners (1857), written to commemorate the Indian “Mutiny.” Building on critical studies by Myron Magnet, Grace Moore, and Lillian Nayder, and reviewing relevant contract theories of government in political philosophy, my analysis traces the proliferating tropes of the contract in this unusual narrative and suggests that as well as presenting a topical satire on circumlocutory colonial bureaucracy, these figures also encode Dickens’s suspicions about the sustainability of liberal forms of colonial rule. While noting further contexts for the contract-theme in The Perils of Certain English Prisoners, my paper goes on to suggest that, in replacing social-contractual and “constitutional” identities with bonds of chivalric loyalty, the text inadvertently anticipates important changes in the idiom of colonial rule in India in the post-“Mutiny” period.