bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility Study of Utilizing Ultraportable Projectors for Endoscopic Video Display (With Videos)
Authors: Tang Shou-jiang , Fehring Amanda , Mclemore Mac , Griswold Michael , Wang Wanmei , Paine Elizabeth R. , Wu Ruonan , To Filip
Published: October 2013

Background. Modern endoscopy requires video display. Recent miniaturized, ultraportable projectors are affordable, durable, and offer quality image display. Objective. Explore feasibility of using ultraportable projectors in endoscopy. Methods. Prospective bench-top comparison; clinical feasibility study. Masked comparison study of images displayed via 2 Samsung ultraportable light-emitting diode projectors (pocket-sized SP-HO3; pico projector SP-P410M) and 1 Microvision Showwx-II Laser pico projector. Bench-top feasibility study: Prerecorded endoscopic video was streamed via computer. Clinical comparison study: Live high-definition endoscopy video was simultaneously displayed through each processor onto a standard liquid crystal display monitor and projected onto a portable, pull-down projection screen. Endoscopists, endoscopy nurses, and technicians rated video images; ratings were analyzed by linear mixed-effects regression models with random intercepts. Results. All projectors were easy to set up, adjust, focus, and operate, with no real-time lapse for any. Bench-top study outcomes: Samsung pico preferred to Laser pico, overall rating 1.5 units higher (95% confidence interval [CI] = 0.7-2.4), P < .001; Samsung pocket preferred to Laser pico, 3.3 units higher (95% CI = 2.4-4.1), P < .001; Samsung pocket preferred to Samsung pico, 1.7 units higher (95% CI = 0.9-2.5), P < .001. The clinical comparison study confirmed the Samsung pocket projector as best, with a higher overall rating of 2.3 units (95% CI = 1.6-3.0), P < .001, than Samsung pico. Conclusions. Low brightness currently limits pico projector use in clinical endoscopy. The pocket projector, with higher brightness levels (170 lumens), is clinically useful. Continued improvements to ultraportable projectors will supply a needed niche in endoscopy through portability, reduced cost, and equal or better image quality.
Idiopathic granulomatous mastitis with erythema nodosum simulating breast abscess in pregnancy: A case report
Authors: Lucas Romeo , Gussman Debra , Polis Rachael L , Rattigan Meghan I , Matulewicz Theodore J
Published: October 2013

Granulomatous mastitis is a rare benign inflammatory condition of the breast and is known to be associated with pregnancy. A 25-year-old Hispanic G2P1 at 17 weeks gestation presented to the emergency department with findings consistent of a breast abscess. The abscess failed to resolve with incision and drainage followed by multiple courses of antibiotic therapy. A biopsy was then obtained and yielded a diagnosis of granulomatous lobulitis. The patient was treated with steroids and her symptoms resolved. Granulomatous lobulitis may present with characteristics of various clinical entities including neoplasm or, as in this case, abscess. Clinicians should consider a diagnosis of granulomatous mastitis in cases of recalcitrant breast abscess.
Influence of melt-draw ratio on the structure and properties of poly(vinylidiene fluoride) cast film
Authors: Hu Bing , Lei Caihong , Xu Ruijie , Shi Wenqiang , Cai Qi , Mo Haibin , Chen Changbin
Published: October 2013

The polyvinylidene fluoride cast film was prepared with different melt-draw ratios by a cast extrusion process. The structure and properties of the prepared films were characterized by differential scanning calorimetry, X-ray diffraction, Fourier transform infrared and scanning electrical microscopy. The results showed that with increasing melt-draw ratio, the crystalline orientation increased and the crystalline morphology transformed from spherulites to parallel lamellae perpendicular to the extrusion direction. At the same time, necking behavior in the stress–strain curves disappeared and strain-hardening behavior became apparent. The lamellae thickness distribution became uniform. The polarized Fourier transform infrared results also indicated the existence of some β-phase for the samples with different melt-draw ratios.
A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit
Authors: Wang Chengbao , Huang Baicheng , Kong Ning , Li Qiongyi , Ma Yuping , Li Zhijun , Gao Jiming , Zhang Chong , Wang Xiangpeng , Liang Chao , Dang Lu , Xiao Shuqi , Mu Yang , Zhao Qin , Sun Yani , Almazan Fernando , Enjuanes Luis , Zhou En-Min
Published: October 2013

Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3′-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.
Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor
Authors: Du Qian , Wu Jinling , Wang Hua , Wang Xin , Xu Lin , Zhang Zhiyong , Liu Jiamei , Zhang Juan , Chen Jin , Hakonarson Hakon , Hu Aihua , Zhang Lin
Published: October 2013

Background

Autoantibodies specific to the angiotensin II type I receptor (anti-AT1-AR) have been implicated in the pathology of congestive heart failure (CHF). Anti-AT1-AR may be associated with left ventricular function in CHF patients treated with perindopril.

Methods

Synthetic angiotensin II type 1 receptor (AT1-R) peptides served as the target antigen. ELISA was used to screen the sera of 156 CHF patients, which were divided into positive and negative groups based on their anti-AT1-AR reactivity. Echocardiography and a 6-minute walk test were performed at baseline and after one year of perindopril therapy. The end-point events were compared over a 5-year follow-up.

Results

Final analysis covered 138 patients, including 82 positive and 56 negative. The frequency and geometric mean titre of anti-AT1-AR were significantly lower in the positive group after one year of treatment (all P < 0.01, from 100% to 73.2% and from 1:125.3 ± 1.0 to 1:69.2 ± 1.1). Of these, 22 patients showed no antibodies. Both groups showed improvement in left ventricular end-diastole, end-systolic dimensions, ejection fraction, and a 6-minute walk test by perindopril in combination with standard treatment regime for one year (all P < 0.01). However, the 82 patients positive for anti-AT1-AR showed more pronounced improvement than the 56 negative patients (all P < 0.05). However, after 5 years of follow-up, the rate of all causes and cardiovascular mortality attributable to any cause and the re-hospitalisation rate showed no significant differences between the two groups (all P > 0.05).

Conclusions

Perindopril treatment significantly decreased the frequency and geometric mean titre in patients positive for anti-AT1-AR, even to complete ablation. These patients showed greater improvement in left ventricular remodeling and heart function than negative that in patients after one year of perindopril treatment in combination with standard treatment, but no significant differences in endpoint events were observed in the following 5 years. Anti-AT1-AR might be a useful biomarker of over-activation of the renin-angiotensin-aldosterone system for clinical medication.
How confidence intervals become confusion intervals
Authors: McCormack James , Vandermeer Ben , Allan G Michael
Published: October 2013

Background

Controversies are common in medicine. Some arise when the conclusions of research publications directly contradict each other, creating uncertainty for frontline clinicians.

Discussion

In this paper, we review how researchers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear understanding of confidence intervals. The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings. We describe three examples of controversy around the potential benefit of a medication, a comparison between new medications, and a medication with a potential harm. The examples include the highest levels of evidence, both meta-analyses and randomized controlled trials. We will show how in each case the confidence intervals and point estimates were very similar. The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance.

These opposing conclusions are false disagreements that create unnecessary clinical uncertainty. We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results.
High prevalence of type 2 diabetes among the urban middle class in Bangladesh
Authors: Saquib Nazmus , Khanam Masuma Akter , Saquib Juliann , Anand Shuchi , Chertow Glenn M , Barry Michele , Ahmed Tahmeed , Cullen Mark R
Published: October 2013

Background

The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.

Methods

In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).

Results

Mean age and Quételet’s (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m2; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.

Conclusions

The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.
Niños Sanos, Familia Sana: Mexican immigrant study protocol for a multifaceted CBPR intervention to combat childhood obesity in two rural California towns
Authors: de la Torre Adela , Sadeghi Banafsheh , Green Richard D , Kaiser Lucia L , Flores Yvette G , Jackson Carlos F , Shaikh Ulfat , Whent Linda , Schaefer Sara E
Published: October 2013

Background

Overweight and obese children are likely to develop serious health problems. Among children in the U.S., Latino children are affected disproportionally by the obesity epidemic. Niños Sanos, Familia Sana (Healthy Children, Healthy Family) is a five-year, multi-faceted intervention study to decrease the rate of BMI growth in Mexican origin children in California’s Central Valley. This paper describes the methodology applied to develop and launch the study.

Methods/Design

Investigators use a community-based participatory research approach to develop a quasi-experimental intervention consisting of four main components including nutrition, physical activity, economic and art-community engagement. Each component’s definition, method of delivery, data collection and evaluation are described. Strategies to maintain engagement of the comparison community are reported as well.

Discussion

We present a study methodology for an obesity prevention intervention in communities with unique environmental conditions due to rural and isolated location, limited infrastructure capacity and limited resources. This combined with numerous cultural considerations and an unstable population with limited exposure to researcher expectations necessitates reassessment and adaptation of recruitment strategies, intervention delivery and data collection methods. Trial registration # NCT01900613.

Trial registration

NCT01900613.
Evaluation of antihyperglycemic and antinociceptive activity of Xanthium indicum stem extract in Swiss albino mice
Authors: Haque Md Ezazul , Rahman Shahnaz , Rahmatullah Mohammed , Jahan Rownak
Published: October 2013

Background

Xanthium indicum stem is used in folk medicine of Bangladesh to control sugar in diabetic patients and to alleviate pain. The objective of the study was to evaluate antihyperglycemic and antinociceptive activity of methanolic extract of Xanthium indicum stems (XISE) in mice.

Methods

Antihyperglycemic activity was measured by oral glucose tolerance tests in glucose-loaded Swiss albino mice. Antinociceptive activity was determined by observed decreases in abdominal constrictions in acetic acid-induced gastric pain model in mice.

Results

The methanol extract of stems showed dose-dependent and statistically significant antihyperglycemic activity at doses of 50, 100, 200 and 400 mg per kg body weight (p values, respectively, < than 0.01, 0.01, 0.005, and 0.01). Highest reduction in blood glucose level (31.2%) was observed with the highest dose (400 mg) of the extract. A standard antihyperglycemic drug, glibenclamide, reduced blood glucose levels by 46.2%, when administered at a dose of 10 mg per kg body weight. In antinociceptive activity tests, the extract when administered at the afore-mentioned four doses, reduced the number of abdominal constrictions in mice, respectively, by 41.7, 50.0, 54.2, and 61.0%. In comparison, a standard antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight, reduced the number of abdominal constrictions by 37.5%.

Conclusion

The experimental results obtained in the present study validate the use of X. indicum stems in folk medicines of Bangladesh to lower blood sugar in diabetic patients and to alleviate pain.
Genomic testing to determine drug response: measuring preferences of the public and patients using Discrete Choice Experiment (DCE)
Authors: Najafzadeh Mehdi , Johnston Karissa M , Peacock Stuart J , Connors Joseph M , Marra Marco A , Lynd Larry D , Marra Carlo A
Published: October 2013

Background

The extent to which a genomic test will be used in practice is affected by factors such as ability of the test to correctly predict response to treatment (i.e. sensitivity and specificity of the test), invasiveness of the testing procedure, test cost, and the probability and severity of side effects associated with treatment.

Methods

Using discrete choice experimentation (DCE), we elicited preferences of the public (Sample 1, N = 533 and Sample 2, N = 525) and cancer patients (Sample 3, N = 38) for different attributes of a hypothetical genomic test for guiding cancer treatment. Samples 1 and 3 considered the test/treatment in the context of an aggressive curable cancer (scenario A) while the scenario for sample 2 was based on a non-aggressive incurable cancer (scenario B).

Results

In aggressive curable cancer (scenario A), everything else being equal, the odds ratio (OR) of choosing a test with 95% sensitivity was 1.41 (versus a test with 50% sensitivity) and willingness to pay (WTP) was $1331, on average, for this amount of improvement in test sensitivity. In this scenario, the OR of choosing a test with 95% specificity was 1.24 times that of a test with 50% specificity (WTP = $827). In non-aggressive incurable cancer (scenario B), the OR of choosing a test with 95% sensitivity was 1.65 (WTP = $1344), and the OR of choosing a test with 95% specificity was 1.50 (WTP = $1080). Reducing severity of treatment side effects from severe to mild was associated with large ORs in both scenarios (OR = 2.10 and 2.24 in scenario A and B, respectively). In contrast, patients had a very large preference for 95% sensitivity of the test (OR = 5.23).

Conclusion

The type and prognosis of cancer affected preferences for genomically-guided treatment. In aggressive curable cancer, individuals emphasized more on the sensitivity rather than the specificity of the test. In contrast, for a non-aggressive incurable cancer, individuals put similar emphasis on sensitivity and specificity of the test. While the public expressed strong preference toward lowering severity of side effects, improving sensitivity of the test had by far the largest influence on patients’ decision to use genomic testing.
The influence of a low glycemic index dietary intervention on maternal dietary intake, glycemic index and gestational weight gain during pregnancy: a randomized controlled trial
Authors: McGowan Ciara A , Walsh Jennifer M , Byrne Jacinta , Curran Sinead , McAuliffe Fionnuala M
Published: October 2013

Background

Maternal diet is known to impact pregnancy outcome. Following a low glycemic index (GI) diet during pregnancy has been shown to improve maternal glycemia and reduce infant birthweight and may be associated with a higher fibre intake. We assessed the impact of a low GI dietary intervention on maternal GI, nutritional intake and gestational weight gain (GWG) during pregnancy. Compliance and acceptability of the low GI diet was also examined.

Method

Eight hundred women were randomised in early pregnancy to receive low GI and healthy eating dietary advice or to receive standard maternity care. The intervention group received dietary advice at a group education session before 22 weeks gestation. All women completed a 3 day food diary during each trimester of pregnancy. Two hundred and thirty five women from the intervention arm and 285 women from the control arm returned complete 3x3d FDs and were included in the present analysis.

Results

Maternal GI was significantly reduced in the intervention group at trimester 2 and 3. The numbers of women within the lowest quartile of GI increased from 37% in trimester 1 to 52% in trimester 3 (P < 0.001) among the intervention group. The intervention group had significantly lower energy intake (P < 0.05), higher protein (% TE) (P < 0.01) and higher dietary fibre intake (P < 0.01) post intervention. Consumption of food groups with known high GI values were significantly reduced among the intervention group. Women in the intervention low GI group were less likely to exceed the Institute of Medicine’s GWG goals.

Conclusion

A dietary intervention in early pregnancy had a positive influence on maternal GI, food and nutrient intakes and GWG. Following a low GI diet may be particularly beneficial for women at risk of exceeding the GWG goals for pregnancy.

Trial registration

Current Controlled Trials Registration Number: ISRCTN54392969.
Digital breast tomosynthesis image reconstruction using 2D and 3D total variation minimization
Authors: Ertas Metin , Yildirim Isa , Kamasak Mustafa , Akan Aydin
Published: October 2013

Background

Digital breast tomosynthesis (DBT) is an emerging imaging modality which produces three-dimensional radiographic images of breast. DBT reconstructs tomographic images from a limited view angle, thus data acquired from DBT is not sufficient enough to reconstruct an exact image. It was proven that a sparse image from a highly undersampled data can be reconstructed via compressed sensing (CS) techniques. This can be done by minimizing the l1 norm of the gradient of the image which can also be defined as total variation (TV) minimization. In tomosynthesis imaging problem, this idea was utilized by minimizing total variation of image reconstructed by algebraic reconstruction technique (ART). Previous studies have largely addressed 2-dimensional (2D) TV minimization and only few of them have mentioned 3-dimensional (3D) TV minimization. However, quantitative analysis of 2D and 3D TV minimization with ART in DBT imaging has not been studied.

Methods

In this paper two different DBT image reconstruction algorithms with total variation minimization have been developed and a comprehensive quantitative analysis of these two methods and ART has been carried out: The first method is ART + TV2D where TV is applied to each slice independently. The other method is ART + TV3D in which TV is applied by formulating the minimization problem 3D considering all slices.

Results

A 3D phantom which roughly simulates a breast tomosynthesis image was designed to evaluate the performance of the methods both quantitatively and qualitatively in the sense of visual assessment, structural similarity (SSIM), root means square error (RMSE) of a specific layer of interest (LOI) and total error values. Both methods show superior results in reducing out-of-focus slice blur compared to ART.

Conclusions

Computer simulations show that ART + TV3D method substantially enhances the reconstructed image with fewer artifacts and smaller error rates than the other two algorithms under the same configuration and parameters and it provides faster convergence rate.
Automatic Cryptosporidium and Giardia viability detection in treated water
Authors: Badsha Shahriar , Mokhtar Norrima , Arof Hamzah , Lim Yvonne Ai Lian , Mubin Marizan , Ibrahim Zuwairie
Published: October 2013

In the automatic detection of Cryptosporidium and Giardia (oo)cysts in water samples, low contrast and noise in the microscopic images can adversely affect the accuracy of the segmentation results. An improved partial differential equation (PDE) filtering that achieves a better trade-off between noise removal and edge preservation is introduced where the compass operator is utilized to attenuate noise while retaining edge information at the cytoplasm wall and around the nuclei of the (oo)cysts. Then the anatomically important information is separated from the unwanted background noise using the Otsu method to improve the detection accuracy. Once the (oo)cysts are located, a simple technique to classify the two types of protozoans using area, roundness metric and eccentricity is implemented. Finally, the number of nuclei in the cytoplasm of each (oo)cyst is counted to check the viability of individual parasite. The proposed system is tested on 40 microscopic images obtained from treated water samples, and it gives excellent detection and viability rates of 97% and 98%, respectively.
A modified root reinforcement technique for acute aortic dissection with a weakened aortic root: a modified Florida sleeve technique and two cases report
Authors: Heo Woon , Min Ho-Ki , Kang Do Kyun , Jun Hee Jae , Hwang Youn-Ho , Choi Jin Ho , Wi Jin Hong
Published: October 2013

Despite marvelous advances in repair for acute type A aortic dissection over past decades, it remains challenging to repair the aortic root when aortic dissection extended to the sinuses causes the fragile root because of its thinner layers, which are susceptible to suture trauma. Here, we describe a modified Florida sleeve technique to strengthen the weakened aortic root. After mobilization of the aortic root and the coronary arteries, a designed Dacron tube graft was wrapped outside the sinuses as neo-adventitia to reinforce the dissected weakened wall. During surgery for aortic dissection, our technique is easy and effective to reinforce a weakened root and avoid bleeding. Furthermore, this might be an alternative technique to restore and maintain the geometry of the aortic root.
Solving gap metabolites and blocked reactions in genome-scale models: application to the metabolic network of Blattabacterium cuenoti
Authors: Ponce-de-León Miguel , Montero Francisco , Peretó Juli
Published: October 2013

Background

Metabolic reconstruction is the computational-based process that aims to elucidate the network of metabolites interconnected through reactions catalyzed by activities assigned to one or more genes. Reconstructed models may contain inconsistencies that appear as gap metabolites and blocked reactions. Although automatic methods for solving this problem have been previously developed, there are many situations where manual curation is still needed.

Results

We introduce a general definition of gap metabolite that allows its detection in a straightforward manner. Moreover, a method for the detection of Unconnected Modules, defined as isolated sets of blocked reactions connected through gap metabolites, is proposed. The method has been successfully applied to the curation of iCG238, the genome-scale metabolic model for the bacterium Blattabacterium cuenoti, obligate endosymbiont of cockroaches.

Conclusion

We found the proposed approach to be a valuable tool for the curation of genome-scale metabolic models. The outcome of its application to the genome-scale model B. cuenoti iCG238 is a more accurate model version named as B. cuenoti iMP240.
Discrete control for ensuring consistency between multiple autonomic managers
Authors: karé Gueye Soguy Mak , Palma Noël De , Rutten Eric , Tchana Alain , Hagimont Daniel
Published: October 2013

The increasing complexity of computer systems has led to the automation of administration functions, in the form of autonomic managers. Today many autonomic managers are available but they mostly address a specific administration aspect which makes necessary their coexistence for a complete autonomic system management. However, coordinating them is necessary for proper and effective global administration. Such coordination can be considered as a problem of synchronization and logical control of managers actions. We therefore investigate the use of reactive models with events and states, and discrete control techniques to solve this problem. This paper presents an application of the latter approach for coordinating autonomic managers addressing resource optimization, in the perspective of green computing. The managers control server provisioning (self-sizing manager) and CPU frequency (Dvfs manager), and the coordination controller controls the managers actions so as to avoid incoherent management decisions. The coordination controller is designed using synchronous programming and Discrete controller synthesis (DCS) which are well-suited for the design of reactive systems. Experimental results are presented to evaluate the efficacy of the approach.
Magnetostatic surface waves propagation at dissipative ferrite-MTMs-metal structure
Authors: Al-Sahhar Zeyad I , Shabat Mohammed M , El-Khozondar Hala J
Published: October 2013

The magnetostatic surface waves (MSSW) propagation in a layered structure composed of ferrite film covered by air and on top of metamaterial (MTM) placed on metal is discussed. Dispersion equations which relate the parameters of different layers are derived and used to analyse propagation of MSSW. It is found that the MSSW excitation band depends on the thickness of the MTM layer and ferrite layer.
Molecular structure and modeling studies of azobenzene derivatives containing maleimide groups
Authors: Cojocaru Corneliu , Airinei Anton , Fifere Nicusor
Published: October 2013

The molecular orbital calculations have been carried out to investigate the structure and stability of (E) / (Z) isomers of some azobenzene derivatives containing maleimide groups. A special attention has been devoted to the compound (E)-1, (E)-1-(4-(phenyldiazenyl)phenyl)-1H-pyrrole-2,5-dione, for which the available crystallographic experimental data have been used to validate the modeling structures computed at the theoretical levels AM1, PM3, RHF/6-31+G(d,p) and B3LYP/6-31+G(d,p). To this end, the discrepancy between experimental and calculated structural parameters has been ascertained in terms of root-mean-square deviation (RMSD). The quantum calculations at the level RHF/6-31+G(d,p) yield the most accurate results on (E)-1 structure giving a deviation error from crystallographic data of about 5.00% for bond lengths and 0.97% for interatomic angles. The theoretical electronic absorption spectra of azobenzene derivatives of concern have been computed by means of configuration-interaction method (CI) at the level of semi-empirical Hamiltonians (AM1 and PM3). Likewise, the molecular energy spectra, electrostatic potential and some quantitative structure activity relationship (QSAR) properties of studied molecules have been computed and discussed in the paper.
Modeling precision treatment of breast cancer
Authors: Daemen Anneleen , Griffith Obi L , Heiser Laura M , Wang Nicholas J , Enache Oana M , Sanborn Zachary , Pepin Francois , Durinck Steffen , Korkola James E , Griffith Malachi , Hur Joe S , Huh Nam , Chung Jongsuk , Cope Leslie , Fackler Mary Jo , Umbricht Christopher , Sukumar Saraswati , Seth Pankaj , Sukhatme Vikas P , Jakkula Lakshmi R , Lu Yiling , Mills Gordon B , Cho Raymond J , Collisson Eric A , van’t Veer Laura J , Spellman Paul T , Gray Joe W
Published: October 2013

Background

First-generation molecular profiles for human breast cancers have enabled the identification of features that can predict therapeutic response; however, little is known about how the various data types can best be combined to yield optimal predictors. Collections of breast cancer cell lines mirror many aspects of breast cancer molecular pathobiology, and measurements of their omic and biological therapeutic responses are well-suited for development of strategies to identify the most predictive molecular feature sets.

Results

We used least squares-support vector machines and random forest algorithms to identify molecular features associated with responses of a collection of 70 breast cancer cell lines to 90 experimental or approved therapeutic agents. The datasets analyzed included measurements of copy number aberrations, mutations, gene and isoform expression, promoter methylation and protein expression. Transcriptional subtype contributed strongly to response predictors for 25% of compounds, and adding other molecular data types improved prediction for 65%. No single molecular dataset consistently out-performed the others, suggesting that therapeutic response is mediated at multiple levels in the genome. Response predictors were developed and applied to TCGA data, and were found to be present in subsets of those patient samples.

Conclusions

These results suggest that matching patients to treatments based on transcriptional subtype will improve response rates, and inclusion of additional features from other profiling data types may provide additional benefit. Further, we suggest a systems biology strategy for guiding clinical trials so that patient cohorts most likely to respond to new therapies may be more efficiently identified.
Editorial: Btk—friend or foe in autoimmune diseases?
Authors: Barral Patricia
Published: October 2013

Discussion on the role of Bruton's tyrosine kinase (Btk) signaling in auto-reactive B cell development and activation.
Elastic imaging with exact wavefield extrapolation for application to ocean-bottom 4C seismic data
Authors: Ravasi Matteo , Curtis Andrew
Published: October 2013

A central component of imaging methods is receiver-side wavefield backpropagation or extrapolation in which the wavefield from a physical source scattered at any point in the subsurface is estimated from data recorded by receivers located near or at the Earth’s surface. Elastic reverse-time migration usually accomplishes wavefield extrapolation by simultaneous reversed-time ‘injection’ of the particle displacements (or velocities) recorded at each receiver location into a wavefield modeling code. Here, we formulate an exact integral expression based on reciprocity theory that uses a combination of velocity-stress recordings and quadrupole-dipole backpropagating sources, rather than the commonly used approximate formula involving only particle velocity data and dipole backpropagating sources. The latter approximation results in two types of nonphysical waves in the scattered wavefield estimate: First, each arrival contained in the data is injected upward and downward rather than unidirectionally as in the true time-reversed experiment; second, all injected energy emits compressional and shear propagating modes in the model simulation (e.g., if a recorded P-wave is injected, both P and S propagating waves result). These artifacts vanish if the exact wavefield extrapolation integral is used. Finally, we show that such a formula is suitable for extrapolation of ocean-bottom 4C data: Due to the fluid-solid boundary conditions at the seabed, the data recorded in standard surveys are sufficient to perform backpropagation using the exact equations. Synthetic examples provide numerical evidence of the importance of correcting such errors.
Whole population cell analysis of a landmark-rich mammalian epithelium reveals multiple elongation mechanisms
Authors: Economou Andrew D. , Brock Lara J. , Cobourne Martyn T. , Green Jeremy B. A.
Published: October 2013

Tissue elongation is a fundamental component of developing and regenerating systems. Although localised proliferation is an important mechanism for tissue elongation, potentially important contributions of other elongation mechanisms, specifically cell shape change, orientated cell division and cell rearrangement, are rarely considered or quantified, particularly in mammalian systems. Their quantification, together with proliferation, provides a rigorous framework for the analysis of elongation. The mammalian palatal epithelium is a landmark-rich tissue, marked by regularly spaced ridges (rugae), making it an excellent model in which to analyse the contributions of cellular processes to directional tissue growth. We captured confocal stacks of entire fixed mouse palate epithelia throughout the mid-gestation growth period, labelled with membrane, nuclear and cell proliferation markers and segmented all cells (up to ∼20,000 per palate), allowing the quantification of cell shape and proliferation. Using the rugae as landmarks, these measures revealed that the so-called growth zone is a region of proliferation that is intermittently elevated at ruga initiation. The distribution of oriented cell division suggests that it is not a driver of tissue elongation, whereas cell shape analysis revealed that both elongation of cells leaving the growth zone and apico-basal cell rearrangements do contribute significantly to directional growth. Quantitative comparison of elongation processes indicated that proliferation contributes most to elongation at the growth zone, but cell shape change and rearrangement contribute as much as 40% of total elongation. We have demonstrated the utility of an approach to analysing the cellular mechanisms underlying tissue elongation in mammalian tissues. It should be broadly applied to higher-resolution analysis of links between genotypes and malformation phenotypes.
Bazooka inhibits aPKC to limit antagonism of actomyosin networks during amnioserosa apical constriction
Authors: David Daryl J. V. , Wang Qiming , Feng James J. , Harris Tony J. C.
Published: October 2013

Cell shape changes drive tissue morphogenesis during animal development. An important example is the apical cell constriction that initiates tissue internalisation. Apical constriction can occur through a phase of cyclic assembly and disassembly of apicomedial actomyosin networks, followed by stabilisation of these networks. Delayed negative-feedback mechanisms typically underlie cyclic behaviour, but the mechanisms regulating cyclic actomyosin networks remain obscure, as do mechanisms that transform overall network behaviour. Here, we show that a known inhibitor of apicomedial actomyosin networks in Drosophila amnioserosa cells, the Par-6-aPKC complex, is recruited to the apicomedial domain by actomyosin networks during dorsal closure of the embryo. This finding establishes an actomyosin-aPKC negative-feedback loop in the system. Additionally, we find that aPKC recruits Bazooka to the apicomedial domain, and phosphorylates Bazooka for a dynamic interaction. Remarkably, stabilising aPKC-Bazooka interactions can inhibit the antagonism of actomyosin by aPKC, suggesting that Bazooka acts as an aPKC inhibitor, and providing a possible mechanism for delaying the actomyosin-aPKC negative-feedback loop. Our data also implicate an increasing degree of Par-6-aPKC-Bazooka interactions as dorsal closure progresses, potentially explaining a developmental transition in actomyosin behaviour from cyclic to persistent networks. This later impact of aPKC inhibition is supported by mathematical modelling of the system. Overall, this work illustrates how shifting chemical signals can tune actomyosin network behaviour during development.
Blood flow dynamics in the snake spectacle
Authors: van Doorn Kevin , Sivak Jacob G.
Published: October 2013

The eyes of snakes are shielded beneath a layer of transparent integument referred to as the ‘reptilian spectacle’. Well adapted to vision by virtue of its optical transparency, it nevertheless retains one characteristic of the integument that would otherwise prove detrimental to vision: its vascularity. Given the potential consequence of spectacle blood vessels on visual clarity, one might expect adaptations to have evolved that mitigate their negative impact. Earlier research demonstrated an adaptation to their spatial layout in only one species to reduce the vessels' density in the region serving the foveal and binocular visual fields. Here, we present a study of spectacle blood flow dynamics and provide evidence of a mechanism to mitigate the spectacle blood vessels' deleterious effect on vision by regulation of blood flow through them. It was found that when snakes are at rest and undisturbed, spectacle vessels undergo cycles of dilation and constriction, such that the majority of the time the vessels are fully constricted, effectively removing them from the visual field. When snakes are presented with a visual threat, spectacle vessels constrict and remain constricted for longer periods than occur during the resting cycles, thus guaranteeing the best possible visual capabilities in times of need. Finally, during the snakes' renewal phase when they are generating a new stratum corneum, the resting cycle is abolished, spectacle vessels remain dilated and blood flow remains strong and continuous. The significance of these findings in terms of the visual capabilities and physiology of snakes is discussed.
Synthesis of Optically Active Thromboxane A2 and Leukotriene D4 Receptor Antagonists
Authors: Kawazoe Souichirou , Okamoto Yoshinori , Yokota Masaki , Kubota Hirokazu , Naito Ryo , Takeuchi Makoto , Ieda Shigeru , Okada Minoru , Oriyama Takeshi
Published: October 2013

Both (+)- and (−)-4-{[(2-{4-chlorophenylsulfonylamino}-1-{3-[(E)-2-(7-chloro-2-quinolyl)-vinyl]phenyl}ethyl)thio]methyl}benzoic acid (1), Thromboxane A2 and Leukotriene D4 receptor dual antagonist were synthesized. Racemic methyl 4-({[2-amino-1-(3-hydroxymethylphenyl)ethyl]thio}methyl)benzoate (2), and methyl 4-[({2-amino-1-[3-(1,3-dioxolan-2-yl)phenyl]ethyl}thio)methyl]benzoate (3) were derived from 2-(3-bromophenyl)-1,3-dioxolane (4). Compound 2 was resolved via di-p-toluoyl-d/l-tartaric acid salts to transform to (+)- and (−)-1, respectively. We also demonstrated that one optically active salt of compound 2 was converted to optically active (+)-1 without chromatography purification.
Design and Evaluation of Selective Recognition on Supramolecular Gel Using Soft Molecular Template Effect
Authors: Hashimoto Takeshi , Yamazaki Masafumi , Ishii Hiroyuki , Yamada Taiji , Hayashita Takashi
Published: October 2013

A supramolecular cyclodextrin (CyD) gel having selective monosaccharide recognition function was prepared by polymerization of γ-CyD containing a lipophilic phenylboronic acid azoprobe. The non-template gel exhibited galactose selectivity in adsorption, whereas the glucose-template gel exhibited glucose selectivity.
Tuning of Sol–Gel Transition Temperatures for Thermoreversible Ion Gels
Authors: Kitazawa Yuzo , Ueki Takeshi , Imaizumi Satoru , Lodge Timothy P , Watanabe Masayoshi
Published: October 2013

Thermoreversible gelation of ionic liquids (ILs) was demonstrated using a well-defined ABA triblock copolymer. The ABA triblock copolymer consisted of poly(phenylethyl methacrylate) terminal A blocks and a poly(methyl methacrylate) middle B block. Temperature-tunable thermosensitive sol–gel transition, i.e., low-temperature-sol–high-temperature-gel, can be realized because of the lower critical solution temperature aggregation behavior of the A blocks. The sol–gel transition behavior of polymer–IL composites can be precisely controlled not only by changing the chemical structure of the A blocks but also by changing that of the ILs.
Progress and challenges in the computational prediction of gene function using networks: 2012-2013 update
Authors: Pavlidis Paul , Gillis Jesse
Published: October 2013

In an opinion published in 2012, we reviewed and discussed our studies of how gene network-based guilt-by-association (GBA) is impacted by confounds related to gene multifunctionality. We found such confounds account for a significant part of the GBA signal, and as a result meaningfully evaluating and applying computationally-guided GBA is more challenging than generally appreciated. We proposed that effort currently spent on incrementally improving algorithms would be better spent in identifying the features of data that do yield novel functional insights. We also suggested that part of the problem is the reliance by computational biologists on gold standard annotations such as the Gene Ontology. In the year since, there has been continued heavy activity in GBA-based research, including work that contributes to our understanding of the issues we raised. Here we provide a review of some of the most relevant recent work, or which point to new areas of progress and challenges.
State-Society Conflicts under Hong Kong's Hybrid Regime
Authors: Fong Brian C. H.
Published: October 2013

Similar to its colonial predecessor, the post-colonial Hong Kong state relies on its business allies to mediate state-society relations. Nevertheless, because of the erosion of the intermediary role of business elites, the state-business alliance now struggles to accommodate the rising challenges of civil society. The case of Hong Kong offers an interesting case study to the literature on hybrid regimes.
Perioperative changes in cortical excitability, mood, and quality of life in patients with primary hyperparathyroidism: a pilot study using transcranial magnetic stimulation
Authors: Hermsen A , Eienbröker A , Haag A , Mylius V , Hamer H M , Menzler K , Karakas E , Rosenow F
Published: October 2013

Objective

Serum calcium (Ca2+) and parathyroid hormone (PTH), amongst others, modify cortical excitability. Alterations in cortical excitability were shown in patients with epilepsy as well as hyper- or hypoparathyroidism. In patients with primary hyperparathyroidism (pHPT), preoperative elevated serum calcium and parathyroidectomy (PTx) may affect mood and quality of life. We hypothesized that perioperative changes in Ca2+ and PTH in pHPT will affect cortical excitability and improve subjective health.

Design and methods

Transcranial magnetic stimulation (TMS) was performed before and after surgery in 15 pHPT patients. We measured resting motor threshold, cortical silent period (CSP), short intracortical inhibition, and intracortical facilitation. Health questionnaires were administered before, 1 day and 6 months after PTx, along with the disease-specific Pasieka's parathyroid assessment of symptoms (PAS), which was, to our knowledge, its first use in German.

Results

Surgery was successful in all patients. TMS-measurements remained unchanged when analyzing all patients in this pilot study. Postoperatively, depression declined (P=0.05) and quality of life improved significantly (P=0.001) in the SF-36-subscales: vitality, social functioning, mental health and subjective health transition (post-hoc analysis). The PAS proved early relief of disease-specific symptoms (P<0.001).

Conclusions

We found unchanged cortical excitability comparing pre- and post-PTx in this pilot study. Mood and quality of life improved postoperatively. The German PAS is valuable in detecting disease-specific changes early after PTx.
Carcinoid syndrome caused by a serotonin-secreting pituitary tumour
Authors: Lynggård Louise A , Nielsen Eigil Husted , Laurberg Peter
Published: October 2013

Background

Neuroendocrine tumours are most frequently located in the gastrointestinal organ system or in the lungs, but they may occasionally be found in other organs.

Case

We describe a 56-year-old woman suffering from a carcinoid syndrome caused by a large serotonin-secreting pituitary tumour. She had suffered for years from episodes of palpitations, dyspnoea and flushing. Cardiac disease had been suspected, which delayed the diagnosis, until blood tests revealed elevated serotonin and chromogranin A in plasma. The somatostatin receptor (SSR) scintigraphy showed a single-positive focus in the region of the pituitary gland and MRI showed a corresponding intra- and suprasellar heterogeneous mass. After pre-treatment with octreotide leading to symptomatic improvement, the patient underwent trans-cranial surgery with removal of the tumour. This led to a clinical improvement and to a normalisation of SSR scintigraphy, as well as serotonin and chromogranin A levels.

Conclusion

To our knowledge, this is the first reported case of a serotonin-secreting tumour with a primary location in the pituitary.
Differential sensitivities to lactate transport inhibitors of breast cancer cell lines
Authors: Morais-Santos Filipa , Miranda-Gonçalves Vera , Pinheiro Sílvia , Vieira André F , Paredes Joana , Schmitt Fernando C , Baltazar Fátima , Pinheiro Céline
Published: October 2013

The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of α-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy.