bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis
Authors: Mendoza-Milla Criselda , Valero Jiménez Ana , Rangel Claudia , Lozano Alfredo , Morales Violeta , Becerril Carina , Chavira Roberto , Ruiz Víctor , Barrera Lourdes , Montaño Martha , Pardo Annie , Selman Moisés
Published: November 2012

Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic degenerative diseases.

We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts.

Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2–29.2)versus6.7 (2.1–15.2) ng·mL−1, p<0.01; DHEA-S: 47 (15.0–211)versus85.2 (37.6–247.0) μg·dL−1, p<0.001), while in females only DHEA-S was significantly decreased (32.6 (15.0–303.0)versus68.3 (16.4–171) μg·dL−1, p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-induced fibroblast migration.

These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.
Surgical treatment of chronic thromboembolic pulmonary hypertension
Authors: Jenkins David P. , Madani Michael , Mayer Eckhard , Kerr Kim , Kim Nic , Klepetko Walter , Morsolini Marco , Dartevelle Philippe
Published: November 2012

It is likely that chronic thromboembolic pulmonary hypertension (CTEPH) is more prevalent than currently recognised. Imaging studies are fundamental to decision making with respect to operability. All patients with suspected CTEPH should be referred to an experienced surgical centre. Currently, there is no risk scoring stratification system to guide operability assessment and it is predominantly based on surgical experience.

The aim of pulmonary endarterectomy (PEA) is the removal of obstructive material to immediately reduce pulmonary vascular resistance. PEA affords the best chance of cure, but is difficult to perfect. Recognition and clearance of distal segmental and subsegmental disease is the main problem. The basic surgical techniques include: median sternotomy incision, cardiopulmonary bypass, arteriotomy incisions within pericardium, and a true endarterectomy with meticulous full distal dissection. Deep hypothermic circulatory arrest is recommended as the best means of reducing blood flow in the pulmonary artery to allow a clear field for dissection. In the recent PEACOG (PEA and COGnition) trial there was no evidence of cognitive impairment post-PEA.

Reperfusion pulmonary oedema and residual pulmonary hypertension are unique post-operative complications post-PEA and are associated with increased mortality. However, in-hospital mortality is now <5% in experienced centres.
Barrier responses of human bronchial epithelial cells to grass pollen exposure
Authors: Blume Cornelia , Swindle Emily J. , Dennison Patrick , Jayasekera Nivenka P. , Dudley Sarah , Monk Phillip , Behrendt Heidrun , Schmidt-Weber Carsten B. , Holgate Stephen T. , Howarth Peter H. , Traidl-Hoffmann Claudia , Davies Donna E.
Published: November 2012

The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells.

Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 releaseviaa post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3α, CCL22/monocyte-derived chemokine and tumour necrosis factor-α was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-γ-induced protein-10 were reduced in nonasthmatic cultures.

The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
Outcomes of noncardiac, nonobstetric surgery in patients with PAH: an international prospective survey
Authors: Meyer Stephanie , McLaughlin Vallerie V. , Seyfarth Hans-Juergen , Bull Todd M. , Vizza Carmine D. , Gomberg-Maitland Mardi , Preston Ioana R. , Barberà Joan A. , Hassoun Paul M. , Halank Michael , Jaïs Xavier , Nickel Nils , Hoeper Marius M. , Humbert Marc
Published: November 2012

We conducted an international, prospective, 3-year questionnaire-based survey among 11 pulmonary hypertension centres to assemble data from patients with pulmonary arterial hypertension (PAH) undergoing noncardiac and nonobstetric surgery.

Data were collected between July 2007 and June 2010 from 114 patients with PAH (70% female, mean age 57 years) who underwent major surgery. At the time of surgery, 43% were in functional class III/IV. 82% of the interventions were performed under general anaesthesia and 18% under spinal anaesthesia. Major complications occurred in seven (6.1%) of the patients, of whom four died, resulting in an overall perioperative mortality rate of 3.5%. The mortality rate was 15% (two out of 13) in emergency procedures, compared with 2% (two out of 101) in nonemergency procedures (p=0.01). Risk factors for major complications were an elevated right atrial pressure (OR 1.1, 95% CI 1.0–1.3; p=0.01), a 6-min walking distance <399 m at the last preoperative assessment (OR 2.2, 95% CI 1.1–3.7; p=0.04), the perioperative use of vasopressors (OR 1.5, 95% CI 1.2–2.7; p=0.03) and the need for emergency surgery (OR 2.4, 95% CI 1.4–3.6; p=0.01).

Major surgery in patients with PAH continues to be a high-risk procedure, particularly when emergency interventions are needed.
Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia
Authors: Malardo Thiago , Batalhão Marcelo E , Panunto-Castelo Ademilson , Almeida Luciana P , Padilha Everton , Fontoura Isabela C , Silva Célio L , Carnio Evelin C , Coelho-Castelo Arlete AM
Published: November 2012

Background

Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert) as therapeutic agent requires further investigation.

Results

Here, we showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and TNF-α by lipopolysaccharide (LPS)-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 μg of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP) drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP), a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO) production.

Conclusion

Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases.
Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study
Authors: Nativ Ofer , Patel Bababhai , Shen Jessica , Batiller Jonathan , Horn Sara , Hart James C
Published: November 2012

Background

Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages.

Methods

We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level.

Results

Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled.

Conclusions

The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage.

Trial registration

Phase I/II trial, NCT00598130
Knowledge of patients’ visual experience during cataract surgery: a survey of eye doctors in Karachi, Pakistan
Authors: Tauqir Mohammad Zain , Chaudhry Tanveer Anjum , Mumtaz Sehreen , Ahmad Khabir
Published: November 2012

Background

Several recent studies have recommended that ophthalmologists must be aware of the visual sensations (and their associated anxiety/fear) experienced by patients undergoing cataract surgery. We assessed the knowledge of a group of eye doctors in Pakistan regarding these phenomena.

Methods

This was a cross-sectional survey. Eye doctors (ophthalmologists, residents and medical officers) attending the Ophthalmological Society of Pakistan Annual Conference 2011, in Karachi were invited to participate in the study. A self-administered structured questionnaire was used to examine their knowledge of visual sensations and their associated anxiety/fear experienced by patients during cataract surgery. Simple frequencies and proportions were calculated to describe the data.

Results

A total of 150 ophthalmologists, residents and medical officers were invited to participate in the study. Of these, 68 (45.3%) responded. The mean age (±SD) of the participants was 42.9 (13.2) years. The proportion of participants who thought that patients could experience visual sensations during cataract surgery under regional anaesthesia was 89.7% and that under topical anaesthesia was 73.5%. The most frequently cited sensations included: light perception, changes in light brightness, movements, instruments and surgeon’s hands or fingers.

The eye doctors estimated that 38.9% and 64.3% patients would see at least something during cataract surgery under regional anaesthesia and topical anaesthesia, respectively. They also believed that 24.2%-36.9% of patients may experience anxiety/fear as a result of visual sensations during such surgery. Approximately half of the eye doctors did not think that retained vision was a source of fear or anxiety for the patients. While most of them acknowledged the importance of preoperative counselling in helping to alleviate such fear/anxiety, the majority of them did not regularly counsel their patients on what to expect during the surgery.

Conclusion

Our study reveals that a significant proportion of eye doctors do not have adequate knowledge of the visual phenomenon and their associated anxiety or fear, that patients can experience during cataract surgery. Targeted educational interventions are needed to increase awareness of this phenomenon among eye care professionals.
Urethral obstruction from dislodged bladder Diverticulum stones: a case report
Authors: Okeke Linus I , Takure Augustine O , Adebayo Sikiru A , Oluyemi Olukayode Y , Oyelekan Abimbola AA
Published: November 2012

Background

Secondary urethral stone although rare, commonly arises from the kidneys, bladder or are seen in patients with urethral stricture. These stones are either found in the posterior or anterior urethra and do result in acute urinary retention. We report urethral obstruction from dislodged bladder diverticulum stones. This to our knowledge is the first report from Nigeria and in English literature.

Case presentation

A 69 year old, male, Nigerian with clinical and radiological features of acute urinary retention, benign prostate enlargement and bladder diverticulum. He had a transurethral resection of the prostate (TURP) and was lost to follow up. He re-presented with retained urethral catheter of 4months duration. The catheter was removed but attempt at re-passing the catheter failed and a suprapubic cystostomy was performed. Clinical examination and plain radiograph of the penis confirmed anterior and posterior urethral stones. He had meatotomy and antegrade manual stone extraction with no urethra injury.

Conclusions

Urethral obstruction can result from inadequate treatment of patient with benign prostate enlargement and bladder diverticulum stones. Surgeons in resource limited environment should be conversant with transurethral resection of the prostate and cystolithotripsy or open prostatectomy and diverticulectomy.
Dual fluorescent labelling of the human malaria parasite Plasmodium falciparum for the analysis of the ABC type transporter pfmdr2
Authors: Rosental Benyamin , Hadad Uzi , Sinay Rosa , Braiman Alex , Porgador Angel , Pollack Yaakov
Published: November 2012

Background

The study of thePlasmodium falciparumheavy metal transporter genepfmdr2employed radioactive labelled heavy metal. As the use of radioactive isotopes shrank considerably during the last few years, resulting in the cessation of the production of some isotopes, amongst them Cadmium109which was used for that purpose, a different approach had to be developed. Herein, a dual fluorescent labelling of heavy metals accumulation in theP. falciparumparasite is proposed as an alternative to the use of radioactive labelled heavy metals.

Methods

Plasmodium falciparumCd resistant and sensitive strains at the trophozoite stage were used in this study. The cells were cultured at different CdCl2concentrations and for different time periods followed by staining of the infected red blood cells with Fluo-3/AM for Cd detection and Hoechst 33342 for parasite DNA labelling. The fluorescent analysis was done by flow cytometry and confocal microscopy.

Results

The results show that the sensitive strain has a higher Fluo-3/AM fluorescence in a Cd concentration and time dependent manner, whereas in the resistant strain Fluo-3/AM fluorescence levels were negligible and increased only at high concentrations of Cd and at long incubation periods, but to a much lesser extent than the sensitive strain.No Cd uptake is observed in uninfected red blood cells populations originating from cultures infected with either sensitive or resistant strain. In addition, confocal microscopy overlay of Fluo-3/AM and Hoechst staining shows that the Cd metal accumulates in the parasite itself.

Conclusions

The dual fluorescent labelling is a valid method for detecting heavy metal accumulation inP. falciparum. Furthermore, in contrast to the use of radioactive labelled heavy metal, the fluorescent labelling enables us to differentiate between the different populations existing in aP. falciparuminfected red blood cells cultures and thus actually study a phenomenon at the level of a single cell.
Curvature-driven diffusion-based mathematical image registration models
Authors: Akinlar Mehmet Ali , Kurulay Muhammet , Secer Aydin , Celenk Mehmet
Published: November 2012

This paper introduces several mathematical image registration models. Image registration, an ill-posed optimization problem, is formulated as the minimization of the sum of an image similarity metric and a regularization term. Curvature-driven diffusion-based techniques, in particular Perona-Malik, anisotropic diffusion, mean curvature motion (MCM), affine invariant MCM (AIMCM), are employed as a regularization term in this optimal control formulation. Adopting the steepest-descent marching with an artificial time t, Euler-Lagrange (EL) equations with homogeneous Neumann boundary conditions are obtained. These EL equations are approximately solved by the explicit Petrov-Galerkin scheme. The method is applied to the registration of brain MR images of size

257
×
257

. Computational results indicate that all these regularization terms produce similarly good registration quality but that the cost associated with the AIMCM approach is, on average, less than that for the others.

MSC:68U10, 65D18, 65J05, 97N40.
Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development
Authors: Goñi Natalia , Iriarte Andrés , Comas Victoria , Soñora Martín , Moreno Pilar , Moratorio Gonzalo , Musto Héctor , Cristina Juan
Published: November 2012

Background

Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed.

Results

We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process.

Conclusions

A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.
Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants
Authors: Zhu Yumin , Yu Xiaoming , Huang Fenfen , Yu Ruisong , Dong Shijuan , Si Fusheng , Zhang Yuanshu , Li Zhen
Published: November 2012

Background

Four major genotypes of hepatitis E virus (HEV), the causative agent of hepatitis E, have so far been recognized. While genotypes 3 and 4 are both zoonotic, the disease symptoms caused by the latter tend to be more severe. To examine if specific nucleotide/amino acid variations between genotypes 3 and 4 play a role in determining the severity of hepatitis E disease, the complete genome of one swine HEV genotype 4 isolate, SAAS-FX17, was determined and compared with other genotype 4 and genotype 3 genomes to identify putative HEV genotype 4 virulence determinants.

Results

A total of 42 conformable nt/aa variations between genotype 3 and 4 HEVs were detected, of which 19 were proposed to be potential disease severity determinants for genotype 4 strains.

Conclusions

One potential determinant was located in each of the 5'-UTR and 3'-UTR, 3 and 12 within ORF1 and ORF2 respectively, and 2 in the junction region.
Association of age at menarche with metabolic syndrome and its components in rural Bangladeshi women
Authors: Akter Shamima , Jesmin Subrina , Islam Mazedul , Sultana Sayeeda Nusrat , Okazaki Osamu , Hiroe Michiaki , Moroi Masao , Mizutani Taro
Published: November 2012

Background

Early age at menarche is associated with increased risk of metabolic syndrome in both China and the West. However, little is known about the impact of age at menarche and metabolic syndrome in South Asian women, including those from low-income country, where age at menarche is also falling. The aim of the present study was to investigate whether age at menarche is inversely associated with metabolic syndrome in Bangladeshi women, who are mostly poor and have limited access to and or poor health care facilities.

Methods

This community-based cross-sectional study was performed using 1423 women aged between 15–75 years from rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between age at menarche and metabolic syndrome, with adjustment of potential confounding variables, including age, education, marital status, tobacco users, use of contraceptives and number of pregnancies.

Results

Early onset of menarche (<12 years) as compared to late onset (>13 years) was found to be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95 % confidence interval =1.05-2.30). Age at onset of menarche was also inversely associated with prevalence of high triglycerides (P for trend <0.01) and low high-density lipoprotein cholesterol (P for trend = 0.01), but positively associated with prevalence of high fasting blood glucose (P for trend =0.02). However, no significant association was found between age at menarche, high blood pressure and elevated waist circumference.

Conclusion

Early onset of menarche might promote or trigger development of metabolic syndrome. Thus, knowledge of the history of age at onset of menarche may be critical in identifying women at risk of developing metabolic syndrome and those likely to benefit the most from early interventions.
An ovine in vitro model for chondrocyte-based scaffold-assisted cartilage grafts
Authors: Endres Michaela , Neumann Katja , Zhou Bei , Freymann Undine , Pretzel David , Stoffel Marcus , Kinne Raimund W , Kaps Christian
Published: November 2012

Background

Scaffold-assisted autologous chondrocyte implantation is an effective clinical procedure for cartilage repair. From the regulatory point of view, the ovine model is one of the suggested large animal models for pre-clinical studies. The aim of our study was to evaluate the in vitro re-differentiation capacity of expanded ovine chondrocytes in biomechanically characterized polyglycolic acid (PGA)/fibrin biomaterials for scaffold-assisted cartilage repair.

Methods

Ovine chondrocytes harvested from adult articular cartilage were expanded in monolayer and re-assembled three-dimensionally in PGA-fibrin scaffolds. De- and re-differentiation of ovine chondrocytes in PGA-fibrin scaffolds was assessed by histological and immuno-histochemical staining as well as by real-time gene expression analysis of typical cartilage marker molecules and the matrix-remodelling enzymes matrix metalloproteinases (MMP) -1, -2 and −13 as well as their inhibitors. PGA scaffolds characteristics including degradation and stiffness were analysed by electron microscopy and biomechanical testing.

Results

Histological, immuno-histochemical and gene expression analysis showed that dedifferentiated chondrocytes re-differentiate in PGA-fibrin scaffolds and form a cartilaginous matrix. Re-differentiation was accompanied by the induction of type II collagen and aggrecan, while MMP expression decreased in prolonged tissue culture. Electron microscopy and biomechanical tests revealed that the non-woven PGA scaffold shows a textile structure with high tensile strength of 3.6 N/mm2 and a stiffness of up to 0.44 N/mm2, when combined with gel-like fibrin.

Conclusion

These data suggest that PGA-fibrin is suited as a mechanically stable support structure for scaffold-assisted chondrocyte grafts, initiating chondrogenic re-differentiation of expanded chondrocytes.
Association of a missense mutation in the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) with superovulation traits in Chinese Holstein heifers
Authors: Yu Yong , Pang Yunwei , Zhao Haichao , Xu Xiaoling , Wu Zhonghong , An Lei , Tian Jianhui
Published: November 2012

Background

Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor (LHCGR) is necessary for follicular maturation and ovulation, as well as luteal function. We detected mutations in the LHCGR gene and evaluated their association with superovulation.

Methods

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, we examined polymorphisms in LHCGR and the genotypes associated with superovulation traits in 127 Chinese Holstein heifers.

Results

A G/T polymorphism (ss52050737) in exon 11 was significantly associated with the total number of ova and the number of transferable embryos.

Conclusions

LHCGR may be a new predictor for superovulation in Chinese Holstein heifers.
“It Is I Who Have the Power”: Settling Women in Haggard's South African Imaginary
Authors: Free Melissa
Published: November 2012

H. Rider Haggard has long been known as the premier writer of the imperial adventure novel, which is described by scholars as predominantly devoid of colonial settlers, particularly women. Yet his most innovative contribution to the genre of adventure fiction is actually his most overlooked: the colonial settler heroine. Reading beyond King Solomon's Mines (1885), She (1887), and Allan Quatermain (1887), male imperial romances that have almost exclusively been allowed to represent Haggard's vast body of work, we encounter female colonial leadership on the South African frontier. An effect of Haggard's anxiety over burgeoning metropolitan female agency and Afrikaner political strength, the heroines of Haggard's female colonial romances enabled the author imaginatively to redirect feminist energy — from metropole to colony, from self (as he saw it) to service, from suffragism to soil. Though they expand the British Empire's, rather than simply their own, sphere of influence, they belie Haggard's imaginative mastery, for in domesticating the empire these heroines transcend domestication, commanding authority far beyond the garden gate. Through an analysis of The Ghost Kings (1908), Haggard's final female colonial romance, this article compares the subgenre to the male imperial romance, demonstrates Haggard's capacity to imagine positive female leadership, and, finally, suggests the limits of that imagination.
“Now It Will Soon Be Over”: Apocalyptic Redemption inThe Sword Went Out to Sea
Authors: Dustin Lheisa
Published: November 2012

This article argues that the creative autobiography The Sword Went Out to Sea and other later work of the modernist American writer H.D. evidence foreclosure: a mode of psychic “denegation,” as Jacques Lacan describes it, in which words, thoughts, and people are not differentiated from one another and the symbolic function of language is not apprehended. Sword testifies to the foreclosure of difference and a wish to establish it by means of its formal characteristics, apocalypticism, and witness to the spectral return of what cannot be symbolized in the form of the living dead, divinities, and individuals who are also multiplicities. It thus calls for different interpretative strategies than those usual in literary criticism: to read it primarily as symbolic communication is to lose perspective on the structures of thought and language that it grapples with. The article describes a “language disorder” that psychoanalysis associates with psychosis and thus with interminable suffering and loss of reality without drawing conclusions about the range of experiences that might be concurrent with asymbolic thought and writing.
Frs2α enhances fibroblast growth factor-mediated survival and differentiation in lens development
Authors: Madakashira Bhavani P. , Kobrinski Daniel A. , Hancher Andrew D. , Arneman Elizabeth C. , Wagner Brad D. , Wang Fen , Shin Hailey , Lovicu Frank J. , Reneker Lixing W. , Robinson Michael L.
Published: November 2012

Most growth factor receptor tyrosine kinases (RTKs) signal through similar intracellular pathways, but they often have divergent biological effects. Therefore, elucidating the mechanism of channeling the intracellular effect of RTK stimulation to facilitate specific biological responses represents a fundamental biological challenge. Lens epithelial cells express numerous RTKs with the ability to initiate the phosphorylation (activation) of Erk1/2 and PI3-K/Akt signaling. However, only Fgfr stimulation leads to lens fiber cell differentiation in the developing mammalian embryo. Additionally, within the lens, only Fgfrs activate the signal transduction molecule Frs2α. Loss of Frs2α in the lens significantly increases apoptosis and decreases phosphorylation of both Erk1/2 and Akt. Also, Frs2α deficiency decreases the expression of several proteins characteristic of lens fiber cell differentiation, including Prox1, p57KIP2, aquaporin 0 and β-crystallins. Although not normally expressed in the lens, the RTK TrkC phosphorylates Frs2α in response to binding the ligand NT3. Transgenic lens epithelial cells expressing both TrkC and NT3 exhibit several features characteristic of lens fiber cells. These include elongation, increased Erk1/2 and Akt phosphorylation, and the expression of β-crystallins. All these characteristics of NT3-TrkC transgenic lens epithelial cells depend on Frs2α. Therefore, tyrosine phosphorylation of Frs2α mediates Fgfr-dependent lens cell survival and provides a mechanistic basis for the unique fiber-differentiating capacity of Fgfs on mammalian lens epithelial cells.
Effect of Partial Fluorination in the Myristoyl Groups on Thermal and Interfacial Properties of Dimyristoylphosphatidylcholine
Authors: Yoshino Masaru , Takahashi Hiroshi , Takagi Toshiyuki , Baba Teruhiko , Morita Kohei , Amii Hideki , Kanamori Toshiyuki , Sonoyama Masashi
Published: November 2012

A novel partially fluorinated analog of DMPC, diF4H10-PC, was synthesized, and its thermal and interfacial properties were compared with those of DMPC. By fluorine substitution in the terminal butyl segment in the myristoyl group of DMPC, the novel partially fluorinated diF4H10-PC membrane shows higher stability and larger occupied area, while remarkable decrease in the phase transition temperature and more hydrophilic properties in the hydrophilic/hydrophobic interface region were observed.
A Four-spin Cobalt-radical Complex: Structure and Magnetic Properties
Authors: Wang Chao , Wang Ya L , Ma Yue , Wang Qing L , Li Li C , Liao Dai Z
Published: November 2012

A new complex {[Co(hfac)2]2(4P3NIT)2}·CHCl3 (1) (hfac: hexafluoroacetylacetonate, 4P3NIT: 2-[3-(4-pyridyl)phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) has been synthesized and characterized structurally and magnetically. The single-crystal structure revealed that two 4P3NIT molecules and two [Co(hfac)2] units construct a four-spin rectangle-like molecule. Effective-spin approach was also employed to evaluate the magnetic coupling J1 and J2 within this four-spin unit. The best fitting result gives J1 = −23.41 cm−1, J2 = 3.18 cm−1, which indicate the antiferromagnetic interaction between the Co(II) ion and directly bonded radical, and weak ferromagnetic interaction between the central Co(II) ion and organic radical through the pathway of pyridyl and phenyl ring.
Structural Formation Ability of Peptide Secondary Structure on Silica Biomineralization
Authors: Kuno Tatsuya , Nonoyama Takayuki , Hirao Kiyoshi , Kato Katsuya
Published: November 2012

To investigate the influence of the secondary structure of peptide on silica biomineralization, α-helix and β-sheet conformational peptides were synthesized and applied as catalyst in silica biomineralization.
Whole spine CT for evaluation of scoliosis in children: Feasibility of sub-milliSievert scanning protocol
Authors: Kalra Mannudeep K , Quick Petter , Singh Sarabjeet , Sandborg Michael , Persson Anders
Published: November 2012

Background

Optimization of CT radiation dose is important for children due to their higher risk of radiationinduced adverse effects. Anatomical structures with high inherent contrast, such as bones can be imaged at very low radiation doses by optimizing scan parameters.

Purpose

To assess feasibility of sub-milliSievert whole spine CT scanning protocol for evaluation of scoliosis in children.

Material and Methods

With approval of the ethical board, we performed whole spine CT for evaluation of scoliosis in 22 children (age range, 3-18 years; mean age, 13 years; 13 girls, 9 boys) on a 128-slice dual source multidetector-row CT scanner. Lowest possible quality reference mAs value (image quality factor for xy-z automatic exposure control or xyz-AEC, CARE Dose 4D) was selected on a per patient basis. Remaining parameters were held constant at 3.0:1 pitch, 128 × 0.6 mm detector collimation, 115.2 mm table feed per gantry rotation, 100 kVp, and 1 and 3 mm reconstructed sections. Average mAs, projected estimated dose savings with AEC, computed tomography dose index volume (CTDI vol), and dose length product (DLP) were recorded. Artifacts were graded on a four-point scale (1, no artifacts; 4, severe artifacts). Ability to identify vertebral and pedicular contours, and measure pedicular width and degree of vertebral rotation was graded on a three-point scale (1, unacceptable; 3, excellent).

Results

All CT examinations were deemed as reliable for identifying vertebral and pedicular contours as well as for measuring pedicular width (5.9 ± 1.6 mm) and degree of vertebral rotation (28.7±23.4°). Mean objective image noise and signal to noise ratio (SNR) were 57.5±21.5 and 4.7±2.3, respectively. With a mean quality reference mAs of 13, the scanner employed an average actual effective mAs of 10±3.8 (range, 6–18 mAs) with an estimated radiation dose saving of 43.5±16.3% with xyz-AEC compared with fixed mAs. The mean CTDI, DLP, and estimated effective doses were 0.4±0.1 mGy (0.2–0.7 mGy), 21±10 mGy.cm (8–41 mGy.cm), and 0.3±0.1 mSv (0.12–0.64 mSv), respectively.

Conclusion

Radiation dose for whole spine CT for evaluation of scoliosis in children can be minimized to less than one-third of a milliSievert while maintaining diagnostic image quality.
Flexible PMP Approach for Large-Size Cell Formation
Authors: Goldengorin Boris , Krushinsky Dmitry , Slomp Jannes
Published: November 2012

Lately, the problem of cell formation (CF) has gained a lot of attention in the industrial engineering literature. Since it was formulated (more than 50 years ago), the problem has incorporated additional industrial factors and constraints while its solution methods have been constantly improving in terms of the solution quality and CPU times. However, despite all the efforts made, the available solution methods (including those for a popular model based on the p-median problem, PMP) are prone to two major types of errors. The first error (the modeling one) occurs when the intended objective function of the CF (as a rule, verbally formulated) is substituted by the objective function of the PMP. The second error (the algorithmic one) occurs as a direct result of applying a heuristic for solving the PMP. In this paper we show that for instances that make sense in practice, the modeling error induced by the PMP is negligible. We exclude the algorithmic error completely by solving the adjusted pseudo-Boolean formulation of the PMP exactly, which takes less than one second on a general-purpose PC and software. Our experimental study shows that the PMP-based model produces high-quality cells and in most cases outperforms several contemporary approaches.
Heterogeneity of Epidermal Growth Factor Receptor Status and Mutations of KRAS/PIK3CA in Circulating Tumor Cells of Patients with Colorectal Cancer
Authors: Gasch Christin , Bauernhofer Thomas , Pichler Martin , Langer-Freitag Sabine , Reeh Matthias , Seifert Adrian M , Mauermann Oliver , Izbicki Jakob R , Pantel Klaus , Riethdorf Sabine
Published: November 2012

BACKGROUND

Molecular characterization of circulating tumor cells (CTCs) is pivotal to increasing the diagnostic specificity of CTC assays and investigating therapeutic targets and their downstream pathways on CTCs. We focused on epidermal growth factor receptor (EGFR) and genes relevant for its inhibition in patients with colorectal cancer (CRC).

METHODS

We used the CellSearch® system for CTC detection in peripheral blood samples from 49 patients with metastatic CRC (mCRC) and 32 patients with nonmetastatic CRC (nmCRC). We assessed EGFR expression in 741 CTCs from 27 patients with mCRC and 6 patients with nmCRC using a fluorescein-conjugated antibody with the CellSearch Epithelial Cell Kit. DNA of a single CTC isolated by micromanipulation was propagated by whole-genome amplification and analyzed by quantitative PCR for EGFR gene amplification and sequencing for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma viral oncogene homolog B1), and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α) mutations.

RESULTS

At least 2 CTCs were detected in 24 of 49 patients with mCRC and 7 of 32 patients with nmCRC. In 7 of 33 patients, CTCs with increased EGFR expression were identified. Heterogeneity in EGFR expression was observed between CTCs from the same patient. EGFR gene amplification was found in 7 of 26 CTCs from 3 patients. The investigated BRAF gene locus was not mutated in 44 analyzed CTCs, whereas KRAS mutations were detected in 5 of 15 CTCs from 1 patient and PIK3CA mutations in 14 of 36 CTCs from 4 patients.

CONCLUSIONS

Molecular characterization of single CTCs demonstrated considerable intra- and interpatient heterogeneity of EGFR expression and genetic alterations in EGFR, KRAS, and PIK3CA, possibly explaining the variable response rates to EGFR inhibition in patients with CRC.
Oral Cancer Diagnosis via a Ferrocenylnaphthalene Diimide–Based Electrochemical Telomerase Assay
Authors: Mori Kumiko , Sato Shinobu , Kodama Masaaki , Habu Manabu , Takahashi Osamu , Nishihara Tatsuji , Tominaga Kazuhiro , Takenaka Shigeori
Published: November 2012

BACKGROUND

Telomerase is regarded as a good marker for cancer because it is unregulated in most tumor cells compared with normal cells. We evaluated telomerase activity in the lysate of tumor tissue and surrounding cells of oral cancer patients by an electrochemical technique, dubbed the electrochemical telomerase assay (ECTA).

METHODS

The assay used ferrocenylnaphthalene diimide (FND) as the probe. Electrochemical telomerase substrate (ETS) primer immobilized on the electrode was elongated by telomerase and FND bound to the product to give rise to a current. The data were standardized with the change in current before and after the elongation, respectively.

RESULTS

The change in current increased more than 30% in biopsy samples from most cancer patients, whereas the increase was 20% or lower in most healthy individuals. On the basis of this difference individual clinical samples were judged telomerase positive, ambiguous, or negative. The positive rates in the cancerous tissues and exfoliated cells (EOCs) of the patients were 85% and 90%, respectively, whereas the corresponding values were 50% and 10% by the telomerase repeat amplification protocol. Furthermore, the positive rate for the ECTA was 100% in early tumors smaller than 2 cm, and 95% and 82% of biopsy and exfoliated cells of healthy individuals were correctly judged as negative. Fifty-six unknown samples with EOCs tested were correctly judged to be cancerous or normal in 84% of cases.

CONCLUSIONS

The ECTA yielded high hit rates for cancerous and normal cells, especially in EOCs, results indicating that this minimally invasive test is suitable for oral cancer diagnosis.
Copy Number and Expression Alterations of miRNAs in the Ovarian Cancer Cell Line OVCAR-3: Impact on Kallikrein 6 Protein Expression
Authors: Bayani Jane , Kuzmanov Uros , Saraon Punit , Fung William A , Soosaipillai Antoninus , Squire Jeremy A , Diamandis Eleftherios P
Published: November 2012

BACKGROUND

Kallikrein-related peptidase 6 (KLK6), a member of the serine protease family of kallikrein (KLK) genes, is dysregulated in ovarian carcinomas (OCa) and its overexpression is associated with poor prognosis. Regulation of its expression is poorly understood and is likely to be influenced by multiple mechanisms. The KLK locus is subject to copy number changes and heterogeneity in serous OCas. These copy number imbalances generally correlate with KLK6 protein expression; however, this is not always the case. In this study we explored the role of miRNAs in the posttranscriptional control of KLK6 expression and the contributions of copy numbers, not only of the KLK locus, but also of the miRNAs predicted to regulate it.

METHODS AND RESULTS

By miRNA profiling of the KLK6-overexpressing OCa cell line, OVCAR-3, we identified overexpressed and underexpressed miRNAs. Publically available miRNA databases identified the human miRNA lethal 7 (hsa-let-7) family members as putative regulating miRNAs, from which hsa-let-7a was chosen for functional analysis. The transient transfection of hsa-let-7a to OVCAR-3 resulted in a decrease of KLK6 secreted protein. Moreover, such transfection was also able to weakly affect the expression of another member of the KLK gene family, KLK10 (kallikrein-related peptidase 10). Cytogenomic analysis, including array comparative genomic hybridization, fluorescence in situ hybridization, and spectral karyotyping revealed the overall net copy number losses of hsa-let-7a and other miRNAs predicted to target KLK6.

CONCLUSIONS

The hsa-let-7 family member hsa-let-7a is a modulator of KLK6 protein expression that is independent of the KLK6 copy number status.
ExactDAS: An Exact Test Procedure for the Detection of Differential Alternative Splicing in Microarray Experiments
Authors: Mary-Huard Tristan , Jaffrezic Florence , Robin Stéphane
Published: November 2012

The aim of this paper is to propose a test procedure for the detection of differential alternative splicing across conditions for tiling array or exon chip data. While developed in a mixed model framework, the test procedure is exact (avoiding computational burden) and applicable to a large variety of contrasts, including several previously published ones. A simulation study is presented to evaluate the robustness and performance of the method. It is found to have a good detection power of genes under differential alternative splicing, even for five biological replicates and four probes per exon. The methodology also enables the comparison of various experimental designs through exact power curves. This is illustrated with the comparison of paired and unpaired experiments. The test procedure was applied to two publicly available cancer data sets based on exon arrays, and showed promising results.
Large-scale Parentage Inference with SNPs: an Efficient Algorithm for Statistical Confidence of Parent Pair Allocations
Authors: Anderson Eric C.
Published: November 2012

Advances in genotyping that allow tens of thousands of individuals to be genotyped at a moderate number of single nucleotide polymorphisms (SNPs) permit parentage inference to be pursued on a very large scale. The intergenerational tagging this capacity allows is revolutionizing the management of cultured organisms (cows, salmon, etc.) and is poised to do the same for scientific studies of natural populations. Currently, however, there are no likelihood-based methods of parentage inference which are implemented in a manner that allows them to quickly handle a very large number of potential parents or parent pairs. Here we introduce an efficient likelihood-based method applicable to the specialized case of cultured organisms in which both parents can be reliably sampled. We develop a Markov chain representation for the cumulative number of Mendelian incompatibilities between an offspring and its putative parents and we exploit it to develop a fast algorithm for simulation-based estimates of statistical confidence in SNP-based assignments of offspring to pairs of parents. The method is implemented in the freely available software SNPPIT. We describe the method in detail, then assess its performance in a large simulation study using known allele frequencies at 96 SNPs from ten hatchery salmon populations. The simulations verify that the method is fast and accurate and that 96 well-chosen SNPs can provide sufficient power to identify the correct pair of parents from amongst millions of candidate pairs.
Phototactic responses of Elachista antarctica (Phaeophyceae) spores of different ages across a broad irradiance range using new motion analysis software
Authors: Bucolo Philip , Amsler Charles D. , McClintock James B. , Baker Bill J.
Published: November 2012

Phototactic movements of Elachista antarctica spores were quantified across a wide range of irradiances from 10 to 800 μmol photons m-2 s-1 using the recently updated version of CellTrak 1.5 motion analysis software. Spores 0–12 h old exhibited phototactic attraction at 80 and 200 μmol photons m-2 s-1, which contributed to vertical movements up out of the boundary layer to be further dispersed hydrodynamically, but were repelled at 800 μmol photons m-2 s-1, causing spores to retreat from detrimental irradiances. No significant effects were observed among spores released 24–36 h before measuring phototaxis at 200 and 800 μmol photons m-2 s-1.