bluuebunny/crossref_metadata_2025 huggingface dataset:
Point group symmetry and deformation-induced symmetry breaking of superlattice materials
Authors: Zhang Pu , To Albert C.
Published: September 2015

The point group symmetry of materials is closely related to their physical properties and quite important for material modelling. However, superlattice materials have more complex symmetry conditions than crystals due to their multi-level structural feature. Thus, a theoretical framework is proposed to characterize and determine the point group symmetry of non-magnetic superlattice materials systematically. A variety of examples are presented to show the symmetry features of superlattice materials in different dimensions and scales. In addition, the deformation-induced symmetry-breaking phenomenon is also studied for superlattice materials, which has potential application in tuning physical properties by imposing a strain field.
Analysis of crystallization data in the Protein Data Bank
Authors: Kirkwood Jobie , Hargreaves David , O'Keefe Simon , Wilson Julie
Published: September 2015

The Protein Data Bank (PDB) is the largest available repository of solved protein structures and contains a wealth of information on successful crystallization. Many centres have used their own experimental data to draw conclusions about proteins and the conditions in which they crystallize. Here, data from the PDB were used to reanalyse some of these results. The most successful crystallization reagents were identified, the link between solution pH and the isoelectric point of the protein was investigated and the possibility of predicting whether a protein will crystallize was explored.
Crystallization and X-ray analysis of the transcription-activator protein C1 of bacteriophage P22 in complex with the PREpromoter element
Authors: Mondal Avisek , Chattopadhyaya Rajagopal , Datta Ajit Bikram , Parrack Pradeep
Published: September 2015

The transcription-activator protein C1 of the temperate phage P22 ofSalmonella typhimuriumplays a key role in the lyticversuslysogenic switch of the phage. A homotetramer of 92-residue polypeptides, C1 binds to an approximate direct repeat similar to the transcription activator CII of coliphage λ. Despite this and several other similarities, including 57% sequence identity to coliphage CII, many biochemical observations on P22 C1 cannot be explained based on the structure of CII. To understand the molecular basis of these differences, C1 was overexpressed and purified and subjected to crystallization trials. Although no successful hits were obtained for the apoprotein, crystals could be obtained when the protein was subjected to crystallization trials in complex with a 23-mer promoter DNA fragment (PRE). These crystals diffracted very well at the home source, allowing the collection of a 2.2 Å resolution data set. The C1–DNA crystals belonged to space groupP21, with unit-cell parametersa= 87.27,b= 93.58,c= 111.16 Å, β = 94.51°. Solvent-content analysis suggests that the asymmetric unit contains three tetramer–DNA complexes. The three-dimensional structure is expected to shed light on the mechanism of activation by C1 and the molecular basis of its specificity.
Overexpression, purification and crystallization of the response regulator NsrR involved in nisin resistance
Authors: Khosa Sakshi , Hoeppner Astrid , Kleinschrodt Diana , Smits Sander H. J.
Published: September 2015

A number of Gram-positive bacteria produce a class of bacteriocins called `lantibiotics'. These lantibiotics are ribosomally synthesized peptides that possess high antimicrobial activity against Gram-positive bacteria, including clinically challenging pathogens, and are therefore potential alternatives to antibiotics. All lantibiotic producer strains and some Gram-positive nonproducer strains express protein systems to circumvent a suicidal effect or to become resistant, respectively. Two-component systems consisting of a response regulator and a histidine kinase upregulate the expression of these proteins. One of the best-characterized lantibiotics is nisin, which is produced by Lactococcus lactis and possesses bactericidal activity against various Gram-positive bacteria, including some human pathogenic strains. Within many human pathogenic bacterial strains inherently resistant to nisin, a response regulator, NsrR, has been identified which regulates the expression of proteins involved in nisin resistance. In the present study, an expression and purification protocol was established for the NsrR protein from Streptococcus agalactiae COH1. The protein was successfully crystallized using the vapour-diffusion method, resulting in crystals that diffracted X-rays to 1.4 Å resolution.
Structure of the complex of carboxypeptidase B and N-sulfamoyl-L-arginine
Authors: Akparov Valery , Sokolenko Nikolay , Timofeev Vladimir , Kuranova Inna
Published: September 2015

Porcine pancreatic carboxypeptidase B (EC 3.4.23.6) was complexed with a stable transition-state analogue, N-sulfamoyl-L-arginine, in which an S atom imitates the sp
3-hybridized carbon in the scissile-bond surrogate. Crystals were grown in a form belonging to the same space group, P41212, as the uncomplexed enzyme. X-ray data were collected to a resolution of 1.25 Å. The molecule was refined and the positions of non-H atoms of the inhibitor and water molecules were defined using difference Fourier maps. The enzyme–inhibitor complex and 329 water molecules were further refined to a crystallographic R factor of 0.159. The differences in conformation between the complexed and uncomplexed forms of carboxypeptidase B are shown. The inhibitor is bound in a curved conformation in the active-site cleft, and the sulfamide group is bound to the Zn ion in an asymmetric bidentate fashion. The complex is stabilized by hydrogen bonds between the N1/N2 guanidine group of the inhibitor and the Asp255 carboxyl of the enzyme. The side-chain CH2 groups of the inhibitor are in van der Waals contact with Leu203 and Ile247 in the enzyme. This study provides useful clues concerning how the transition state of arginine may bind to carboxypeptidase B and therefore provides an insight into the structural basis of carboxypeptidase B selectivity, which is useful for the rational design of a carboxypeptidase with improved selectivity for industrial recombinant pro-insulin processing.
Histochemical Study of Heparin‐positive Mast Cells in the Terminal Part of Porcine Ductus Choledochus and Papilla Duodeni Major
Authors: Stefanov I. S. , Vodenicharov A. P. , Tsandev N. S. , Sevrieva D.
Published: September 2015

The study presented in detail the localization and density of mast cells (MCs) in the intramural part of the common bile duct (CBD) and in the major duodenal papilla (MDP) of domestic swine. MCs' density (number/mm2) in different layers of both of the duct and papilla was evaluated after toluidine blue staining. Their number was higher in the lamina propria mucosae than in the tunica muscularis of the studied structures. The localization of berberine‐positive, (heparin containing) MCs and the ratio between them and toluidine blue‐positive MCs with γ‐ma metachromasia was also established. Ratios of heparin‐containing MCs in comparison with all toluidine blue‐positive MCs were found as follows: ductus choledochus – 32% in the subglandular connective tissue of lamina propria mucosae in the intramural part of the duct; m. sphincter ductus choledochus – 31% in the circular and 0.06% in the longitudinal muscle layer; subserosa – 59%; papilla duodeni major – 0.03% in the subepithelial connective tissue and 34% in the subglandular connective tissue of lamina propria mucosae, respectively. The established large difference in heparin‐positive MCs in both the subepithelial and subglandular connective tissues of CBD and MDP, respectively, is an evidence for the existence of mucosal and connective tissue MCs.
A Significance Test for Graph-Constrained Estimation
Authors: Zhao Sen , Shojaie Ali
Published: September 2015

Graph-constrained estimation methods encourage similarities among neighboring covariates presented as nodes of a graph, and can result in more accurate estimates, especially in high-dimensional settings. Variable selection approaches can then be utilized to select a subset of variables that are associated with the response. However, existing procedures do not provide measures of uncertainty of estimates. Further, the vast majority of existing approaches assume that available graph accurately captures the association among covariates; violations to this assumption could severely hurt the reliability of the resulting estimates. In this article, we present a new inference framework, called the Grace test, which produces coefficient estimates and corresponding p-values by incorporating the external graph information. We show, both theoretically and via numerical studies, that the proposed method asymptotically controls the type-I error rate regardless of the choice of the graph. We also show that when the underlying graph is informative, the Grace test is asymptotically more powerful than similar tests that ignore the external information. We study the power properties of the proposed test when the graph is not fully informative and develop a more powerful Grace-ridge test for such settings. Our numerical studies show that as long as the graph is reasonably informative, the proposed inference procedures deliver improved statistical power over existing methods that ignore external information.
Using the Whole Cohort in the Analysis of Countermatched Samples
Authors: Rivera C. , Lumley T.
Published: September 2015

We present a technique for using calibrated weights to incorporate whole-cohort information in the analysis of a countermatched sample. Following Samuelsen's approach for matched case-control sampling, we derive expressions for the marginal sampling probabilities, so that the data can be treated as an unequally-sampled case-cohort design. Pseudolikelihood estimating equations are used to find the estimates. The sampling weights can be calibrated, allowing all whole-cohort variables to be used in estimation; in contrast, the partial likelihood analysis makes use only of a single discrete surrogate for exposure. Using a survey-sampling approach rather than a martingale approach simplifies the theory; in particular, the sampling weights need not be a predictable process. Our simulation results show that pseudolikelihood estimation gives lower efficiency than partial likelihood estimation, but that the gain from calibration of weights can more than compensate for this loss. If there is a good surrogate for exposure, countermatched sampling still outperforms case-cohort and two-phase case-control sampling even when calibrated weights are used. Findings are illustrated with data from the National Wilms’ Tumour Study and the Welsh nickel refinery workers study.
An orthogonal experimental study of phytolith size of Phragmites communis in northeast China
Authors: Liu Lidan , Jie Dongmei , Liu Hongyan , Gao Zhuo , Gao Guizai , Li Nannan , Guo Jixun , Qiao Zhihe
Published: September 2015

Based on the widespread distribution and abundant phytoliths produced by Phragmites communis, phytoliths of P. communis in northeast China were investigated to identify the primary influencing factors on phytolith size using an orthogonal experimental method. Temperature and precipitation were found to be the prominent factors influencing the sizes of short‐cell phytoliths including the saddle and the rondel morphotypes, whereas there were no obvious variations in the width‐to‐length ratios of short‐cell phytoliths in response to environmental factors. These results indicate that short‐cell phytoliths are genetically stable, confirming that they can be used for the classification of grasses. Moreover, precipitation was the main factor influencing the sizes of the lanceolate phytoliths and silicified stomata, and their width‐to‐length ratios changed significantly in response to precipitation and habitat differences. These findings reveal that lanceolate and silicified stomata phytoliths are sensitive to environmental changes, indicating their usefulness for palaeoenvironment reconstruction. Moreover, variations in their width‐to‐length ratios and their sizes may provide some information for plant classification, even at species level. Finally, the results of a principal component analysis of the sizes of P. communis phytoliths further verify the reliability of the orthogonal experiment results, in that temperature and precipitation were the prominent factors influencing the size of all P. communis phytoliths except for the length of saddle and width of the saddle morphotypes. This research into the primary environmental significance of the sizes of P. communis phytoliths may contribute to improving the precision of plant classification and the model for quantitative reconstruction of the palaeoenvironment to aid in reconstructions of palaeovegetation and palaeoclimate.
The chronostratigraphy of the latest Middle Pleistocene aeolian and alluvial activity on the Island of Hvar, eastern Adriatic, Croatia
Authors: Wacha Lara , Vlahović Igor , Tsukamoto Sumiko , Kovačić Marijan , Hasan Ozren , Pavelić Davor
Published: September 2015

Pleistocene aeolian sands and alluvial deposits can frequently be traced along the Mediterranean coast. Such deposits also exist along the eastern Adriatic coast and the nearby islands. Four stratigraphical sections of these deposits were studied on the Island of Hvar with the purpose of establishing a chronological framework of the aeolian–alluvial depositional system, using luminescence dating and magnetic susceptibility stratigraphy. Luminescence dating was applied on coarse‐grained feldspar and quartz grains separated from the sands. Both quartz optically stimulated luminescence (OSL) and feldspar post‐IR infrared stimulated luminescence (pIRIR) age estimates are in good agreement, with values ranging between 167±24 to 120±12 ka (OSL) and 179±18 to 131±18 ka (pIRIR measured at 290 °C) after a fading correction for the pIRIR signal. The results can be clearly correlated to around the end of oxygen isotope stage (OIS) 6 and the beginning of OSI 5, indicating that the aeolian accumulation of sands was a result of the Penultimate Glacial and climate fluctuations at the beginning of the Last Interglacial. Variations in magnetic susceptibility (MS) data can be interpreted alongside these dating results; several stronger peaks detected at the very end of the Penultimate Glacial and the initial stage of the Last Interglacial cycle most probably indicates more intensive pedogenesis resulting from a more favourable climate, probably because of climate changes. Breccias related to major bounding surfaces in association with evidence of soil formation and bioturbation could be the result of more favourable climate conditions and changes during the transition from OIS 6 to OIS 5 (Penultimate Glacial–Last Interglacial). These results are in agreement with similar data from the wider Mediterranean area.
Loss of 5‐lipoxygenase activity protects mice against paracetamol‐induced liver toxicity
Authors: Pu Shiyun , Ren Lin , Liu Qinhui , Kuang Jiangying , Shen Jing , Cheng Shihai , Zhang Yuwei , Jiang Wei , Zhang Zhiyong , Jiang Changtao , He Jinhan
Published: September 2015

Background and Purpose

Paracetamol (acetaminophen) is the most widely used over‐the‐counter analgesic and overdosing with paracetamol is the leading cause of hospital admission for acute liver failure. 5‐Lipoxygenase (5‐LO) catalyses arachidonic acid to form LTs, which lead to inflammation and oxidative stress. In this study, we examined whether deletion or pharmacological inhibition of 5‐LO could protect mice against paracetamol‐induced hepatic toxicity.

Experimental Approach

Both genetic deletion and pharmacological inhibition of 5‐LO in C57BL/6J mice were used to study the role of this enzyme in paracetamol induced liver toxicity. Serum and tissue biochemistry, H&E staining, and real‐time PCR were used to assess liver toxicity.

Key Results

Deletion or pharmacological inhibition of 5‐LO in mice markedly ameliorated paracetamol‐induced hepatic injury, as shown by decreased serum alanine transaminase and aspartate aminotransferase levels and hepatic centrilobular necrosis. The hepatoprotective effect of 5‐LO inhibition was associated with induction of the antitoxic phase II conjugating enzyme, sulfotransferase2a1, suppression of the pro‐toxic phase I CYP3A11 and reduction of the hepatic transporter MRP3. In 5‐LO−/− mice, levels of GSH were increased, and oxidative stress decreased. In addition, PPAR α, a nuclear receptor that confers resistance to paracetamol toxicity, was activated in 5‐LO−/− mice.

Conclusions and Implications

The activity of 5‐LO may play a critical role in paracetamol‐induced hepatic toxicity by regulating paracetamol metabolism and oxidative stress.
The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI‐101 prevents cisplatin‐induced nephrotoxicity
Authors: Mukhopadhyay Partha , Baggelaar Marc , Erdelyi Katalin , Cao Zongxian , Cinar Resat , Fezza Filomena , Ignatowska‐Janlowska Bogna , Wilkerson Jenny , van Gils Noortje , Hansen Thomas , Ruben Marc , Soethoudt Marjolein , Heitman Laura , Kunos George , Maccarrone Mauro , Lichtman Aron , Pacher Pál , Van der Stelt Mario
Published: September 2015

Background and Purpose

Here, we have characterized 3‐cyclopropyl‐1‐(4‐(6‐((1,1‐dioxidothiomorpholino)methyl)‐5‐fluoropyridin‐2‐yl)benzyl)imidazolidine‐2,4‐dione hydrochloride (LEI‐101) as a novel, peripherally restricted cannabinoid CB2 receptor agonist, using both in vitro and in vivo models.

Experimental Approach

We investigated the effects of LEI‐101 on binding and functional activity. We assessed its in vitro and in vivo selectivity. Efficacy of LEI‐101 was determined in a mouse model of cisplatin‐induced nephrotoxicity.

Key Results

LEI‐101 behaved as a partial agonist at CB2 receptors using β‐arrestin and GTPγS assays and was ~100‐fold selective in CB2 /CB1 receptor‐binding assays. It did not display any activity on endocannabinoid hydrolases and nor did it react with serine hydrolases in an activity‐based protein profiling assay. In mice, LEI‐101 had excellent oral bioavailability reaching high concentrations in the kidney and liver with minimal penetration into the brain. LEI‐101 up to a dose of 60 mg·kg−1 (p.o.) did not exert any CNS‐mediated effects in the tetrad assay, in mice. LEI‐101 (p.o. or i.p.) at 3 or 10 mg·kg−1 dose‐dependently prevented kidney dysfunction and/or morphological damage induced by cisplatin in mice. These protective effects were associated with improved renal histopathology, attenuated oxidative stress and inflammation in the kidney. These effects were absent in CB2 receptor knockout mice.

Conclusion and Implications

These results indicate that LEI‐101 is a selective, largely peripherally restricted, orally available CB2 receptor agonist with therapeutic potential in diseases that are associated with inflammation and/or oxidative stress, including kidney disease.
High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin‐4 competing with the neuromyelitis optica autoantibody, NMO‐IgG
Authors: Miyazaki‐Komine Kaori , Takai Yoshiki , Huang Ping , Kusano‐Arai Osamu , Iwanari Hiroko , Misu Tatsuro , Koda Katsushi , Mitomo Katsuyuki , Sakihama Toshiko , Toyama Yoshiaki , Fujihara Kazuo , Hamakubo Takao , Yasui Masato , Abe Yoichiro
Published: September 2015

Background and Purpose

Most of the cases of neuromyelitis optica (NMO) are characterized by the presence of an autoantibody, NMO‐IgG, which recognizes the extracellular domains of the water channel, aquaporin‐4. Binding of NMO‐IgG to aquaporin‐4 expressed in end‐feet of astrocytes leads to complement‐dependent disruption of astrocytes followed by demyelination. One therapeutic option for NMO is to prevent the binding of NMO‐IgG to aquaporin‐4, using high‐avidity, non‐pathogenic–chimeric, monoclonal antibodies to this water channel. We describe here the development of such antibodies.

Experimental Approach

cDNAs encoding variable regions of heavy and light chains of monoclonal antibodies against the extracellular domains of human aquaporin‐4 were cloned from hybridoma total RNA and fused to those encoding constant regions of human IgG1 and Igκ respectively. Then mammalian expression vectors were constructed to establish stable cell lines secreting mature chimeric antibodies.

Key Results

Original monoclonal antibodies showed high avidity binding to human aquaporin‐4, as determined by ELISA. Live imaging using Alexa‐Fluor‐555‐labelled antibodies revealed that the antibody D15107 more rapidly bound to cells expressing human aquaporin‐4 than others and strongly enhanced endocytosis of this water channel, while D12092 also bound rapidly to human aquaporin‐4 but enhanced endocytosis to a lesser degree. Chimeric D15107 prevented complement‐dependent cytotoxicity induced by NMO‐IgG from patient sera in vitro.

Conclusions and Implications

We have established non‐pathogenic, high‐avidity, chimeric antibodies against the extracellular domains of human aquaporin‐4, which provide a novel therapeutic option for preventing the progress and recurrence of NMO/NMO spectrum disorders.
Diverse applications for near infra‐red intraoperative imaging
Authors: Gossedge G. , Vallance A. , Jayne D.
Published: September 2015

Background

Near infra‐red angiography using Indocyanine Green (ICG) has increasingly used as a tool for intraoperative diagnostics.

Aims

The aim of this review is to explore the applications of ICG fluorescence angiography with particular emphasis on general surgical applications.

Materials and Methods

A literature review was conducted to identify and summarise the diverse range of applications of ICG fluorescence.

Results

ICG fluorescence angiography is increasingly used in a number of general surgical applications, including identification of colorectal liver metastases, assessment of skin flap perfusion, diagnosis of peritoneal endometriosis, ureteric identification, and localisation of colonic pathology.

Discussion

ICG fluorescence angiography has clinical application in many areas as a tool for guiding surgical resection.

Conclusion

With the technological developments in near infra‐red imaging it is likely that ICG fluorescence will play an increasing role in many routine surgical procedures.
Discriminatory influence of Pinpoint perfusion imaging on diversion ileostomy after laparoscopic low anterior resection
Authors: Ris F. , Buchs N. C. , Morel P. , Mortensen N. J. , Hompes R.
Published: September 2015

While still debated, it was advised to perform a protective temporary ileostomy after a low anterior resection (LAR). This might help to decrease the leak rate and therefore offers the patient better outcomes. Anastomotic leak can occur in many situations after a LAR and the control of the risk factors helps to adapt the need of an ileostomy. Near infrared technology allows assessing the microvascularisation of the anastomosis at the time of surgery and therefore might be an important tool to avoid a stoma in given situation. This article reviews the evidences with the use of this technology.
Near‐infrared laparoscopic fluorescence for pelvic side wall delta mapping in patients with rectal cancer‐ ‘PINPOINT’ nodal assessment
Authors: Kazanowski M. , Al Furajii H. , Cahill R. A.
Published: September 2015

Low rectal cancers metastase lymphatically to the pelvic side wall in addition to cephalad spread alongside the superior rectal/inferior mesenteric arterial axis. Radical surgery in the West has focused resectional intent and effort on the midline en bloc oncological package by Total Mesorectal Excision. While neoadjuvant chemo/radiotherapy (now often administered to patients with radiologically locally advanced cancer) may contribute significant therapeutic effect to the lateral pelvic side walls, many patients with earlier preoperative stage low rectal cancer are offered surgery first (and indeed solely). Furthermore, some of those pretreated may have residual in situ lateral nodal disease and so risk understaging and undertreatment. Routine extended lymphadenectomy is on the otherhand unproven with respect to survival benefit and has likely no added role in the absence of definite (rather than possible) side‐wall involvement. Near‐infrared fluorescence pelvic side‐wall delta mapping, as illustrated here in five patients undergoing abdominoperineal resection for rectal cancer after neoadjuvant therapy, may give the technological capacity to identify tumor site‐draining nodes on the pelvic side and the focus the operating surgeon on this potential target for surgical resection (whether by berry picking or nerve sparing clearance) and prompt individualized diagnostic and therapeutic selection.
Humanitarian aid in the archives: introduction
Authors: Davey Eleanor , Scriven Kim
Published: September 2015

How might historical perspectives assist the goal of improving humanitarian responses? This introduction to a special issue of Disasters on the history of humanitarian action explores this question and outlines how the other submissions to the edition, each with its own approach and focus area from the nineteenth‐century to the present today, make different contributions to understanding of humanitarian action. The paper argues that the value of history lies not so much in the information it might offer, but in the challenges it can pose to habitual ways of thinking and in the skills of investigation and interpretation it fosters. These attributes make historical perspectives a potentially valuable addition to the critical questioning of humanitarian practitioners and policymakers. The paper advocates integrating history into a more reflective attitude to change and a more adventurous and holistic approach to innovation, as opposed to simply using it to ‘learn lessons’.
Save the Children, the humanitarian project, and the politics of solidarity: reviving Dorothy Buxton's vision
Authors: Baughan Emily , Fiori Juliano
Published: September 2015

This paper reflects on the foundational years of Save the Children, one of the oldest and largest Western humanitarian agencies and a mainstay of the humanitarian project. In doing so, it considers how and why, at an early stage, the organisation depoliticised its activities, centring its narrative on the innocent, pre‐political child—the image of unsullied humanity. In addition, it seeks to recover the internationalist vision of Save the Children's ‘forgotten founder', Dorothy Buxton. Save the Children's turn to non‐politics is indicative of the broader depoliticisation of Western humanitarian action. Given the intensely contested spaces in which Western humanitarian non‐governmental organisations (NGOs) operate, these entities cannot escape politics. This paper argues that Buxton's efforts to build an international solidarity network through humanitarian action after the end of the First World War in 1918 provide an instructive basis on which these NGOs can pursue a politics of solidarity in the present day.
Provenance of global seafood
Authors: Watson Reg A , Green Bridget S , Tracey Sean R , Farmery Anna , Pitcher Tony J
Published: September 2015

Knowing where and how seafood is caught or farmed is central to empowering consumers, and the importers that supply them, with informed choices. Given the wide‐ranging, complex and at times commercially sensitive nature of global seafood trade, it can prove very challenging to link imported seafood with information about its provenance. The databases involved are incomplete, at times vague and not harmonized. Here, we present a first attempt to link all global seafood imports through a virtual marketplace to exports and map their origins. Considerable work remains to ground‐truth the specific origins of all seafood commodities. We illustrate the flow of seafood and its evolution since the 1970s when supporting records began. This work allows the impact of fishing or marine farming to be associated with seafood imports.
How to calculate toric intraocular lenses in clinical practice?
Authors: Langenbucher A. , Szentmáry N. , Seitz B. , Spira C. , Eppig T.
Published: September 2015

There are several options for calculation of toric intraocular lenses, some are based on the classical intraocular lens calculation formulas and others utilize paraxial or numerical ray tracing techniques. Most online calculators use a two‐step system based on precalculated data for the equivalent monofocal lens. Other methods calculate intraocular lens power separately for both cardinal meridians. Advanced methods directly calculate spherocylindrical power by matrix or ray tracing techniques. Especially when considering superposition of regular and irregular astigmatic components, postoperative implant rotation or anisometropia and aniseikonia, the classical formula approach might be inadequate for estimating toric intraocular lens power. Therefore surgeons dealing with toric intraocular lenses require deeper knowledge on advanced calculation techniques to improve patient satisfaction.
Limbal stem cells and their application in ocular surface reconstruction
Authors: Meller D.
Published: September 2015

Various ocular surface diseases are caused by loss of corneal epithelial stem cells or dysfunction of limbal niche. Besides conventional transplantation of autologous or allogeneic limbal tissue recent advances in tissue‐engineering have led to the development of new culture and expansion techniques of human limbal stem and progenitor cells as a new strategy to treat successfully limbal stem cell deficiency (LSCD). From a small limbal biopsy with a limited amount of LSPC an epithelium ready for transplantation is achieved. Autologous grafting of cultured limbal epithelium led in most of the treated cases to a successful reconstruction of the corneal surface. However, allogeneic grafts of cultivated limbal epithelium show a higher graft failure. The etiology of the disease causing LSCD seems to influence the outcome of the procedure. In this presentation challenges and limitations associated with stem cell culture techniques for ocular surface reconstruction are reviewed.
Which margins for which tumors?
Authors: Mouriaux F.
Published: September 2015

Traditional surgical treatment of non‐melanoma skin cancer includes excision with subsequent surgical margins, the “security” margins leading to determine the theoretical level of recurrences. Thus, some authors favor a clinical excision margin of 4 mm for basal cell carcinoma and 6 mm for squamous cell carcinoma. However, such “security” margins could not be applied in all cases of eyelids tumors for anatomic and functional considerations because such recommendations may lead to severe ocular complications. Thus the best assurance of minimal excision with complete excision is obtained by extemporaneous examination of the resection margins by frozen section or by surgery in two times. The aim of this paper is to review these two techniques for eyelids (lid margins) and medial canthus. This article will discuss the concept of surgical margins in excisions of non‐melanoma skin cancer and the role of frozen section of the margins for minimizing the amount of tissue that must be excised.
Monogenic corneal disorders in children
Authors: Khan A.
Published: September 2015

Pediatric monogenic corneal disorders tend to be under‐recognized or misdiagnosed. However, careful phenotyping distinguishes several such conditions and can sometimes predict the underlying gene mutations. After this presentation, the attendee will be familiar with phenotype‐genotype correlations for selected monogenic corneal disorders in children.
Pluripotent stem cells, cornea fate and physiopathology
Authors: Aberdam D.
Published: September 2015

The human corneal surface epithelium is continuously repopulated by limbal stem cells (LSCs). Limbal Stem Cell Deficiency (LSCD) can lead to corneal opacity and vascularization, with consequent visual impairment or blindness. Chemical or thermal trauma and congenital diseases, such as congenital aniridia, can lead to LCSD by destruction of the LSC niche. Grafted autologous limbus or cultivated LCS can restore the vision, unless the two eyes are affected. We have recently developed novel culture systems to reprogram hair follicles into induced pluripotent stem cells (iPSCs) and differentiate them into LSC that could become an alternative to animal models for drug cytotoxicity and an alternative autologous source to the shortage of post‐mortem cornea transplantation.

Moreover, we identified miR‐450 as specific repressor of PAX‐6, the eye master gene responsible for proper embryonic eye formation and LSC pool maintenance. As most of the aniridia patients carry mutations on PAX‐6 that lead to haploinsufficiency, we are testing if manipulating the level or activity of miR‐450 could be used as a therapeutic strategy in aniridia.Thus, iPSCs are valuable for modeling corneal pathologies, and pave the way for future therapy.
Role of High‐mobility group box‐1 in diabetic retinal vasculopathy and neuropathy
Authors: Abu El Asrar A.
Published: September 2015

High‐mobility mobility group box‐1 (HMGB1) is a non‐histone DNA‐binding protein that plays an important role in chromatin organization and transcriptional regulation. Extracellular HMGB1 functions as a proinflammatory cytokine and triggers the inflammatory response through the activation of multiple receptors such as the receptor for advanced glycation end products (RAGE), toll‐like receptor‐2 (TLR2), TLR4 and TLR9. We demonstrated that HMGB1 and RAGE were expressed in fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR). In addition, we demonstrated increased levels of HMGB1 in the vitreous samples from patients with PDR and that there were significant positive correlations between the vitreous levels and HMGB1 and the levels of the biomarkers of inflammation and oxidative injury. Furthermore, we demonstrated that diabetes induced significant upregulation of the expression of HMGB1 and RAGE in the retinas of rats and mice and that HMGB1 mediates diabetes‐induced oxidative stress, activation of inflammatory signaling pathways, breakdown of the blood‐retinal barrier and neuropathy in the retina. Therefore, compounds inhibiting HMGB1 may be novel therapeutic agents for diabetic retinopathy.
Neuro‐vascular coupling – molecular mechansims and potential clinical applications
Authors: Garhofer G.
Published: September 2015

The coupling between neural activity, metabolism and blood flow is an essential physiological mechanism to assure constant supply of the tissue with oxygen and nutrients. Further, it has been shown that several ocular diseases, such as glaucoma or diabetic retinopathy are accompanied by a breakdown of this physiological mechanism. Despite many efforts, the signaling pathways that trigger the hyperemic response of the vasculature are still incompletely understood, which makes the significance of changes in the response during disease difficult to interpret. Recent experimental data from animal studies challenges the current view that NO is the key mediator of flicker induced vasodilatation and indicates a more complex interaction between neurons, blood vessels, vasodilating and vasoconstricting factors at the level of the retina.

This talk aims to summarize our current understanding of the mechanisms underlying neuro‐vascular coupling in the human retina. Further, the role of neuro‐vascular coupling and its potential application in the diagnosis and follow up in neuro‐degenerative diseases such as glaucoma will be discussed.
Caffeine, an in vivo oxidation protectant in the lens
Authors: Kronschläger M. , Yu Z. , Talebizadeh N. , Söderberg P.
Published: September 2015

The major avoidable cause of cataract is ultraviolet radiation (UVR). We aimed at investigating topical caffeine in UVR‐induced cataract.

Topical caffeine and a placebo were applied to the eyes of separate groups of Sprague Dawley rats that were exposed to sub‐doses of UVR and protective effect was evaluated. Penetration of topical caffeine in the rats to lens and blood was analysed by HPLC. Influence of topical caffeine on pupil diameter was measured in ketamine/xylazine anesthetized rats.

Topically administered caffeine protected against UVR‐induced cataract development with a Protection Factor, an objective relative measure of protective properties, of 1.23 and inhibited UVR‐induced apoptosis. Topical caffeine peaked at 30 min in the lens, increased up to 120 min in the blood and antagonized ketamine/xylazine‐induced mydriasis. Eyes treated with caffeine reacted with quick dilatation after tropicamide application.

In conclusion, topically applied caffeine protects against ultraviolet radiation cataract, reducing lens sensitivity 1.23 times. Considering that caffeine is a powerful antioxidant that is easily available and well tolerated our finding implicates that caffeine may be a clinically useful anticataract agent.
Migration of lens epithelial cells and IOL drug soaking
Authors: Wertheimer C. , Kueres A. , Mayer W. , Liegl R. , Eibl‐Lindner K.
Published: September 2015

Purpose

To assess the effect of EGFR Inhibitor Erlotinib and the downstream Inhibitor Erufosin (PI3K) soaked into intraocular lenses (IOLs) on human lensepithelialcell (LEC) proliferation in vitro.

Methods

Foldable IOLs were incubated with Erufosin or Erlotinib. Intraocular lenses of the same lot served as uncoated controls. Each IOL was placed into cell cultre containing proliferating human LECs. Cell survival was tested by the XTT‐dye reduction assay 5 days later. Furthermore IOLs were put into the Gotoh anterior chamber model. In addition, soaked IOLs were implanted into the human capsular bags and braught to cell‐culture. The time until full cell‐coverage of the capsular bag was measured.

Results

Erufosin (P<0.05) and Erlotinib (P<0.05) coated IOLs attenuated human LEC proliferation in all above described models. For both substances soaked hydrophilic acrylic IOLs were more effective inhibitors of human LEC proliferation than coated hydrophobic acrylic.

Conclusions

Results show that both substances are suitable agents for IOL‐soaking without linker molecules. Soaked IOLs can inhibit human LEC proliferation in our models and might become of clinical relevance in future.
TGF beta and fibrosis‐ironing out the wrinkles
Authors: Eldred J. , Wormstone M.
Published: September 2015

The fibrotic disorder Posterior Capsule Opacification (PCO) is the leading secondary ocular complication following cataract surgery. PCO causes a significant loss of vision for approximately 10–30% of patients, 2–5 years post cataract removal. The formation of PCO requires additional surgical treatment, presenting an additional and substantial burden on health care providers and affects the overall well‐being of cataract patients. Fibrotic disorders affect many organs of the body and are associated with hyperproliferation, cell transdifferentiation, matrix modification and contraction. Identifying the major control of these features is essential to our understanding of PCO development. Transforming growth factor beta (TGFβ) has long been implicated in fibrotic disorders and is commonly defined as the “master switch” of fibrosis. However the actions governed by TGFβ can be complex and diverse involving multiple signalling pathways and cross‐talk between many signalling cascades. Significant understanding of the key pathways regulating TGFβ induced modifications in PCO has been identified using human cell and tissue culture models. These important findings and how they may be used as therapeutic targets will be presented.
Therapeutic management of uveitis
Authors: Dick A.
Published: September 2015

This talk will overview the contemporary therapeutic approaches to treatment of noninfectious non‐infective ocular inflammatory disease. Treatment of non‐infectious uveitis has over past 15 years expanded from the use of traditional therapies including corticosteroids and immunosuppressants to the deployment of targetting the immune response with biologic therapies with monoclonal antibodies and immunoadhesins. Such use will be exemplified with case reports during the talk. Evidence of efficacy of immunosuppressants in the treatment of uveitis, the role of predicting steroid responsiveness, the use of monotherapy with immunosuppression and finally the pathways and evidence of success of biologic therapy will be provided.
Behçet's uveitis in Japan: evaluation of the long‐term efficacy and safety of infliximab treatment
Authors: Takeuchi M.
Published: September 2015

Retrospective 13 multicenter observational study were performed using a questionnaire of 164 Behçet's patients treated with infliximab for more than 1 year were studied in Japan. The mean age at initiation of infliximab treatment was 42 years, and the mean treatment duration was 33 months. The frequency of ocular attacks significantly decreased significantly after infliximab treatment, and best collected visual acuityand was improved in approximately 55% of the eyes after treatment in all groups. However, the mean uveitis relapsed in 59% of all patients after infliximab treatment, and approximately 80% of relapses occurred within a year after the initiation of infliximab treatment. Ninety percent of them were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 35%. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy. Infliximab was effective and safereduced the frequency of ocular attacks and improved visual acuity in patients with Behçet‐related uveitis, and was generally well tolerated with few serious adverse events.
Difficulties in the diagnosis of achromic and hemorragic lesions
Authors: Desjardins L.
Published: September 2015

Achromic choroidal lesions can be an achromic melanoma, a choroidal hemangioma or a metastasis.It is rarer to have scleritis ar the origin of an achromic chorodal mass but this can be seen in sarcoidosis rarely.

Achromic choroidal melanomas are not rare. They are often mushroom shape and have a typical ultrasonographic aspect.In the presence of an achromic melanoma, it is always important to rule out the possibility of a metastasis by doing a chest and abdominal CT.

Metastasis are easy to diagnose when they occur in a patient with known metastatic disease, when they are multiple or bilateral. They are trickier when they are unique with no known previous cancer. This is quite frequent in lung cancer where the choroidal mass is often the first manifestation Choroidal hemangioma have a typical orange color and can be easily diagnosed by indocyanin green angiography (early hyper and wash out on the late phase).

Hemorragic mass are frequent in older patient, especially in case of diabetes and high blood pressure. If there is a doubt MRI with gadolinium injections or dopler ultrasonography can easily differentiate a hematoma from, a choroidal tumor.
Classification of uveitis
Authors: Androudi S.
Published: September 2015

The uveitis is a condition that involves inflammation of the uveal tract (i.e. iris, ciliary body, choroid) or adjacent ocular structures (e.g. retina, optic nerve, vitreous, sclera). In most cases, the etiology remains elusive and is often of an autoimmune nature. Classification and standardization of uveitis is important, as it enhances the precision and comparability of clinical research from different centers and assists in the development of a complete picture of the course of the disorders and their response to treatment. Uveitis may be classified in a number of ways, according to several systems and multiple descriptors. The most widely used classification of uveitis is the one devised by the International Uveitis Study Group (IUSG) in 1987, based on the anatomical location of the inflammation. This classification includes anterior uveitis (iritis, iridocyclitis, and anterior cyclitis), intermediate uveitis (pars planitis, posterior cyclitis, and hyalitis), posterior uveitis (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis) or panuveitis (anterior chamber, vitreous, retina, and choroid).
The Initial Consultation – when and how to suspect non‐organic visual loss
Authors: Spileers W.
Published: September 2015

Purpose

When a patient reports visual loss and the doctor can not immediately find the etiology, a non‐organic visual loss has to be excluded.

Methods

Different testing methods can be of value in deciding on organic versus non‐organic visual loss: visual acuity and visual field measurements, pupillary reflexes, electrophysiologic testing, imaging techniques.

Results

The value of these different methods will be discussed and illustrated.

Conclusion

The investigation of possible non‐organic visual loss is a complex task.
Active caspase‐3 in the lens and its response to oxidative stress induced by in vivo exposure to UVR
Authors: Talebizadeh N.
Published: September 2015

Purpose

To determine the time evolution of active caspase‐3 protein expression after exposure to low dose UVR‐300 nm.

Methods

Forty rats were unilaterally exposed in vivo to 1 kJ/m2 UVR‐300 nm for 15 min. All lenses were processed for immunohistochemistry. Time evolution of active caspase‐3 expression was determined based on the differences in the probability of active caspase‐3 expression at 0.5, 8, 16, and 24 hrs after the UVR exposure. A logistic model was introduced for the expression of active caspase‐3.

Results

Active caspase‐3 expression was higher in the exposed lenses. The mean differences between the exposed and non‐exposed lenses were 0.17 ± 0.02, 0.20 ± 0.03, 0.21 ± 0.03, and 0.11 ± 0.04 (95% CI) for the 0.5, 8, 16, and 24 hr time groups, respectively. There was a difference when comparing the 0.5 and 24 hrs groups to the 8 and 16 hrs groups (95% CI = 0.06 ± 0.03). Exposure to UVR‐300 nm impacted on the parameters of the logistic model by time.

Conclusions

Expression of active caspase‐3 in the lens epithelium increased after UVR exposure. The peak of expression was around 16 hrs after the exposure. The logistic model predicts the impact of exposure to UVR on the spatial distribution of active caspase‐3 expression, depending on time.
The origins of strabismus and loss of binocular vision. Implication of the corpus callosum
Authors: Bui Quoc E.
Published: September 2015

Strabismus and loss of binocular vision (BV) are often linked disorders because the parallelism of the eyes is necessary for a proper BV. But no BV may exist in the absence of strabismus. If the question of the consequences of strabismus and loss of BV on the brain has been explored for decades, the core question of their origins is less understood. Strabismus is a developmental disorder which causes are numerous as assessed by the various forms of strabismus. Peripheral causes are sometimes responsible. But central causes are mostly the primum movens of strabismus and loss of BV. Normal interhemispheric callosal connections (CC) being necessary for a proper unification of both visual hemifields and for normal BV along the vertical meridian, we propose here that an abnormal development of the CC might be responsible for strabismus and loss of BV. A misrouting of ganglion cell axons or abnormal development of neuronal activity in the visual system or abnormal development of neuronal activity in the oculomotor system are also proposed to be implicated.

Reference

Bui Quoc E, Milleret C. Origins of strabismus and loss of binocular vision. Front Integr Neurosci. 2014 Sep 25;8:71. doi: 10.3389/fnint.2014.00071. eCollection 2014.