Deep Folds Research Articles

PEDOT:PSS/Grafted-PDMS Electrodes for Fully Organic and Intrinsically Stretchable Skin-like Electronics.

Skin-like electronics require materials that are conducting, soft, intrinsically stretchable, and highly robust. However, electronic devices often consist of multilayers, and the failure of the electronic devices mostly starts from the debonding of the layers because of poor interfacial adhesion and large mechanical mismatch. Herein, we introduce a fully organic and intrinsically stretchable electrode that achieves high robustness by grafting the substrate to improve the interfacial adhesion and by introducing deep folds and wrinkles to improve the stretchability. The electrode exhibits a sheet resistance of 90 Ω/□ and negligible change in resistance at strains of up to 100% and shows no fatigue over 10 000 cyclic stretches to 100% strain. An iontronic skin with the electrodes is capable of detecting tiny objects exemplified by walking ants or fruit flies weighing less than 1 mg, and the device can be cyclically stretched to 30% for 1000 times without fatigue. The high robustness and stretchability of the fully organic iontronic skin lie in the wrinkle structures, small mechanical mismatch, and high interfacial strength among different layers. This work offers a general way to fabricate highly stretchable and robust devices.

Cutis Verticis Gyrata Improved with Injected Hyaluronidase Treatments

Cutis verticis gyrata (CVG) is a condition of excessive skin growth on the scalp leading to deep furrows and folds that resemble the gyri of the brain. There are three main categories of CVG: primary essential, primary nonessential and secondary. Primary essential is idiopathic and presents only with cutaneous alterations. Primary nonessential has cutaneous findings that can be associated with neurological or opthalmoglical pathology.

Giant deer (Megaloceros giganteus) diet from Mid‐Weichselian deposits under the present North Sea inferred from molar‐embedded botanical remains

ABSTRACTThe molar of a giant deer, Megaloceros giganteus (Blumenbach, 1799), was discovered in sandy deposits of the North Sea, about 10 km west of the present shoreline of the Netherlands. Compacted masticated plant remains were preserved in the molar's deep folds. A palaeoecological analysis of these plant remains shows the complete dominance of pollen from Artemisia (sage) and other Asteraceae Tubuliflorae (Compositae), indicating that the animal foraged in a steppe environment, and may have preferred to eat Artemisia, which contain a high level of nutrients such as calcium and phosphorous components, which are important for antler building. Radiocarbon dating indicates that the plant remains are of mid‐Weichselian age [38 570 (+300, −290) 14C a BP, Greenland Interstadial‐11]. This is the first study of the food choice of M. giganteus based on palaeoecological evidence. We hypothesize about links between the extirpation of M. giganteus at the onset of the Holocene in North‐West Europe and the transition from a landscape with highly dynamic geomorphological processes and consequently prevalence of immature and nutrient‐rich soils, to a less dynamic landscape with stable, leached and acidifying soils, and the decline of Artemisia and other calciphilous plants.

Endothelial quality of eye bank-prestripped DMEK prepared form organ-cultured corneas with the Muraine technique.

Our aim was to measure the endothelial quality of prestripped Descemet membrane endothelial keratoplasty (DMEK) 48h after preparation in an eye bank with the Muraine technique and shipping in a distant center. Ten pairs of human corneas with similar eye bank endothelial cell density (ebECD) were stored in organ-culture (OC) for 25days (20, 28) [median (10-90 percentiles)]. One cornea was then randomized to DMEK preparation using the Moria Muraine trephine, the other served as control. The grafts were left attached to the center of the cornea, immersed in the OC medium (without Dextran) and shipped to a distant center. After 48h, the viable ECD (vECD) was assessed by image analysis after staining with Hoechst/Ethidium/Calcein-AM. In addition, immunostaining was performed on flat mounted tissues for structural (ZO-1, NCAM, CD166) and functional (Na+/K+ ATPase) proteins of ECs, and for collagen I. Just before stripping, ebECD was 2428 (2268-2669) cells/mm2 for DMEK and 2471 (2135-2714) for controls (P = 1). Forty-eight hours after stripping, vECD was 2057 (1829-2463) cells/mm2 for DMEK and 2119 (1496-2525) for controls (P = 0.508). The expression patterns of the 5 proteins were similar in ECs of both groups. Notably, the deep posterior folds observed in OC controls almost disappeared in prestripped DMEK due to the lack of a link between Descemet membrane and stroma. As a consequence of the elimination of mechanical stress in these zones, EC evenly covered the whole graft. In conclusion, DMEK prestripping with the Muraine technique and shipping away can be used safely by eye banks.

FIIND: Ferret Interactive Integrated Neurodevelopment Atlas

The first days after birth in ferrets provide a privileged view of the development of a complex mammalian brain. Unlike mice, ferrets develop a rich pattern of deep neocortical folds and cortico- cortical connections. Unlike humans and other primates, whose brains are well differentiated and folded at birth, ferrets are born with a very immature and completely smooth neocortex: folds, neocortical regionalisation and cortico-cortical connectivity develop in ferrets during the first postnatal days. After a period of fast neocortical expansion, during which brain volume increases by up to a factor of 4 in 2 weeks, the ferret brain reaches its adult volume at about 6 weeks of age. Ferrets could thus become a major animal model to investigate the neurobiological correlates of the phenomena observed in human neuroimaging. Many of these phenomena, such as the relationship between brain folding, cortico-cortical connectivity and neocortical regionalisation cannot be investigated in mice, but could be investigated in ferrets. Our aim is to provide the research community with a detailed description of the development of a complex brain, necessary to better understand the nature of human neuroimaging data, create models of brain development, or analyse the relationship between multiple spatial scales. We have already started a project to constitute an open, collaborative atlas of ferret brain development, integrating multi-modal and multi-scale data. We have acquired data for 28 ferrets (4 animals per time point from P0 to adults), using high-resolution MRI and diffusion tensor imaging (DTI). We have developed an open-source pipeline to segment and produce – online – 3D reconstructions of brain MRI data. We propose to process the brains of 16 of our specimens (from P0 to P16) using high-throughput 3D histology, staining for cytoarchitectonic landmarks, neuronal progenitors and neurogenesis. This would allow us to relate the MRI data that we have already acquired with multi-dimensional cell-scale information. Brains will be sectioned at 25 μm, stained, scanned at 0.25 μm of resolution, and processed for real-time multi-scale visualisation. We will extend our current web-platform to integrate an interactive multi-scale visualisation of the data. Using our combined expertise in computational neuroanatomy, multi-modal neuroimaging, neuroinformatics, and the development of inter-species atlases, we propose to build an open-source web platform to allow the collaborative, online, creation of atlases of the development of the ferret brain. The web platform will allow researchers to access and visualise interactively the MRI and histology data. It will also allow researchers to create collaborative, human curated, 3D segmentations of brain structures, as well as vectorial atlases. Our work will provide a first integrated atlas of ferret brain development, and the basis for an open platform for the creation of collaborative multi-modal, multi-scale, multi-species atlases.

Injections d’acides hyaluroniques au niveau de visages atteints de malformations faciales. Étude préliminaire de l’assouplissement des zones cicatricielles et de l’amélioration esthétique

Cross-linked hyaluronic acid-based fillers have gained rapid acceptance for treating facial wrinkles, deep tissue folds and sunken areas due to aging. This study evaluates, in addition to space-filling properties, their effects on softness and elasticity as a secondary effect, following injection of 3 commercially available cross-linked hyaluronic acid-based fillers (15mg/mL, 17,5mg/mL and 20mg/mL) in patients presenting with congenital or acquired facial malformations. We started injecting gels of cross-linked hyaluronic acid-based fillers in those cases in 2013; we performed 46 sessions of injections in 32 patients, aged from 13-32. Clinical assessment was performed by the patient himself and by a plastic surgeon, 15 days after injections and 6-18 months later. Cross-linked hyaluronic acid-based fillers offered very subtle cosmetic results and supplemented surgery with a very high level of satisfaction of the patients. When injected in fibrosis, the first session enhanced softness and elasticity; the second session enhanced the volume. Cross-linked hyaluronic acid-based fillers fill sunken areas and better softness and elasticity of scar tissues. In addition to their well-understood space-filling function, as a secondary effect, the authors demonstrate that cross-linked hyaluronic acid-based fillers improve softness and elasticity of scarring tissues. Many experimental studies support our observations, showing that cross-linked hyaluronic acid stimulates the production of several extra-cellular matrix components, including dermal collagen and elastin.

The Influence of Paranasal Augmentation on the Measurement of the Nose for the Treatment of Midfacial Concavity

A concave midface with its associated deep nasolabial folds is more aesthetically displeasing than a convex midface. Midfacial concavity may be addressed with autologous tissue and implants. The aim of this study was to determine the effect of paranasal augmentation on photogrammetric parameters. Between July 2013 and August 2016, 12 patients underwent paranasal augmentation to address midface concavity. Augmentation was performed with autologous rib cartilage, autologous mandibular bone, or preshaped porous polyethylene (PPE). All operations were performed through the upper gingivobuccal approach. Twelve patients who underwent malar reduction using the same approach acted as a control group to account for the influence of the approach on soft tissue change. Preoperative and postoperative measurements were made photogrammetrically. The average follow-up period was 12.8 months (range, 5-30 months) for both groups. The mean thickness of augmentation grafts was 5.18 mm (range, 3-7 mm). Alar width and alar base width increased 4.84% (P = 0.01) and 7.66% (P = 0.01), respectively. The nasolabial angle increased from 97.2°to 103.6° and the columellar inclination increased from 116.0° to 119.1° but neither were statistically significant. Photogrammetric parameters did not change significantly in the control group. Partial wound dehiscence occurred in one case. There was greater postoperative increase in alar width (P = 0.020), alar base width (P = 0.024), and nasolabial angle (P = 0.033) in the experimental group compared to the control group. Paranasal augmentation using PPE or autologous material generates measurable soft tissue changes designed to enhance paranasal aesthetics.

54. Primary cutis verticis gyrata associated to chronic migraine treated with ultrasound guided onabotulinum injections. A case report

Cutis verticis gyrata (CVG), also known as “bulldog” scalp syndrome was originally described in 1837 by Jean-Louis-Marc Alibert. CVG is a descriptive term for a condition of the scalp manifesting as convoluted folds and furrows formed from thickened skin of the scalp resembling cerebriform pattern. In 1953 Polan and Butterworth classified CVG into two forms: primary and secondary. The primary form can be divided in essential and non-essential, where the essential form do not present other abnormality (while primary nonessential can be associated with other pathologies or a combination of this. In the primary essential form, the etiology is not known, and, though most of the cases seem sporadic, autosomal recessive and autosomal dominant inheritance with variable expression have been described. In the primary nonessential form, the pathogenesis (beside the genetic determination) may have an endocrinologic basis. In the secondary form, the etiology depends on the underlying process (eg,inflammatory, neoplastic). Our patient was a 25 year old caucasian male who presented for three years scalp skin redundancy, with deep cerebriform folds and wrinkles, located in frontoparietal regions He denied comorbidities. He referred fronto temporal headache often unilateral with casual trigeminal diffusion, described as chronic and burning pain with allodinia. For those he performed a 3T MRI of head with a 3D reconstraction of scalp that excluded abnormality of the brain lobes and essentially revealed thickened dermis and a slight increase in the volume of subcutaneous fat and irregularly distributed cutaneous folds characteristic of CVG. Because neurologist considered patient with CM and inadequate response or intolerance to previous two prophylactic treatments he was treated with pericranial injections of about 150 UI of BoNT-A with the proposal to repeat treatment every 3–4 months and the purpose to increase dose up to 200 U in case of no response. After 3 months unfortunately patient achieved minimal reduction of pain of about 20–30% in headache frequency and intensity and during the 3 months follow-up period. The first weeks after BonT-A treatment he reduced NSAIDs and analgesics consumption but unfortunately after first stage he preferred to avoid further botulinum injections due to mini invasive procedure on scalp. Primary essential cutis verticis gyrata firstly because is a cosmetic problem, but also because eventual pain symptoms and psychological repercussions are very important issues. In this case both pain relief and reduction of folds width could be beneficials and therefore we encouraged the patient to treat both CM and CVG with BonT-A Injections.

Spatially Configuring Wrinkle Pattern and Multiscale Surface Evolution with Structural Confinement

AbstractSurface elastic instabilities, such as wrinkling and creasing, can enable a convenient strategy to impart reversible patterned topography to a surface. Here the classic system of a stiff layer on a soft substrate is focused, which famously produces parallel harmonic wrinkles at modest uniaxial compression that period‐double repeatedly at higher compressions and ultimately evolve into deep folds and creases. By introducing micrometer‐scale planar Bravais lattice holes to spatially pattern the substrate, these instabilities are guided into a wide variety of different patterns, including wrinkling in parallel bands and star shape bands, and radically reduce the threshold compression. The experimental patterns and thresholds are enabled to understand by considering a simple plane‐strain model for the patterned substrate‐deformation, decorated by wrinkling on the stiff surface layer. The experiments also show localized wrinkle‐crease transitions at modest compression, yielding a hierarchical surface with different generations of instability mixed together. By varying the geometrical inputs, control over the stepwise evolution of surface morphologies is demonstrated. These results demonstrate considerable control over both the patterns and threshold of the surface elastic instabilities, and have relevance to many emerging applications of morphing surfaces, including in wearable/flexible electronics, biomedical systems, and optical devices.

Complete form pachydermoperiostosis in Tunisia – A case series and literature review

IntroductionPachydermoperiostosis (PDP) or hypertrophic osteoarthropathy (HOA) is a rare disease that has genetic predisposition and defined clinical features. Aim of the workTo study and analyse the clinical features of Tunisian PDP patients and review the literature. Patients and methodsThe PDP cases attending the Rheumatology Department of the University Hospital Farhat Hached of Sousse in Tunisia were retrospectively studied over a period of 17years (2000–2017). Secondary causes were excluded. ResultsThe PDP cases had a primary and complete form of the disease and included 6 men at a frequency of 0.03% (6/20,000) of the total number of rheumatic diseases cases attending the rheumatology clinic. The mean age was 27±12.3years [18–46years]. Five patients had arthralgia and one polyarthritis. Thickening of the skin of the head and distal extremities (pachyderma) and deep folds and furrows of the skin of the forehead was observed in all cases. Digital clubbing of the fingers and toes and spade-like enlargement of the hands and feet was noted in 5 cases. Hyperhidrosis of the hands and feet was observed in 4 cases and seborrhea in 2. Elevated acute phase reactants were found in 4 cases. Hypergammaglobulinemia was present in one case. Periostosis of the long bones was observed in all cases. Treatment consisted of analgesics in all cases, non-steroidal anti-inflammatory drugs in 2 cases and tamoxifen in 2 cases. ConclusionsComplete form of primary PDP is rarely present among rheumatic diseases patients in Tunisia. A multicenter larger number longitudinal study is recommended.

Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects

During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems.

Effects of Objective 3-Dimensional Measures of Facial Shape and Symmetry on Perceptions of Facial Attractiveness

Meeting patient desires for enhanced facial esthetics requires that providers have standardized and objective methods to measure esthetics. The authors evaluated the effects of objective 3-dimensional (3D) facial shape and asymmetry measurements derived from 3D facial images on perceptions of facial attractiveness. The 3D facial images of 313 adults in Iowa were digitized with 32 landmarks, and objective 3D facial measurements capturing symmetric and asymmetric components of shape variation, centroid size, and fluctuating asymmetry were obtained from the 3D coordinate data using geo-morphometric analyses. Frontal and profile images of study participants were rated for facial attractiveness by 10 volunteers (5 women and 5 men) on a 5-point Likert scale and a visual analog scale. Multivariate regression was used to identify the effects of the objective 3D facial measurements on attractiveness ratings. Several objective 3D facial measurements had marked effects on attractiveness ratings. Shorter facial heights with protrusive chins, midface retrusion, faces with protrusive noses and thin lips, flat mandibular planes with deep labiomental folds, any cants of the lip commissures and floor of the nose, larger faces overall, and increased fluctuating asymmetry were rated as significantly (P<.001) less attractive. Perceptions of facial attractiveness can be explained by specific 3D measurements of facial shapes and fluctuating asymmetry, which have important implications for clinical practice and research.

Considering 3D topography of endothelial folds to improve cell count of organ cultured corneas.

The posterior side of the cornea is covered by the endothelial monolayer, which governs corneal transparency but cannot proliferate. Determination of endothelial cell density (ECD) is therefore the minimal and mandatory quality control in all eye banks. It avoids primary graft failures caused by endothelial insufficiency, and allows allocation of corneas to surgical techniques requiring different numbers of endothelial cells (ECs). Corneas stored in organ culture (17% of grafts worldwide), are characterized by heavy stromal swelling and numerous deep endothelial folds, up to 200µm high. During microscopic en face observation, flat surfaces are thus exceptional and EC counting is biased by parallax errors, resulting in overestimated eye bank ECD (ebECD). We used a motorized transmitted light microscope to acquire Z-stacks of images every 10µm, and processed them to reconstruct the 3D surface of the folded endothelium. This method (3D-ECD) takes into account the local point-by-point slope in order to correct ECD. On a set of 30 corneas, we compared 3D-ECD and ebECD determined on five identical zones at the center of the cornea. 3D reconstruction allowed us to visualize twice as many cells, and ebECD was 8.1±4.5% (95%CI 6.4-9.7) higher than 3D-ECD, with 1744±488 versus 1606±473 cells/mm2. 3D counting makes it possible to increase cell sampling and to correct overestimation by the conventional en face counting still routinely performed in eye banks.

Histological and histochemical characterization of the digestive tract of European catfish (Silurus glanis Linnaeus, 1758).

In this study was to examined the morphology, histology and histochemically the digestive tract of European catfish, Silurus glanis. Two-four age S. glanis obtained from Çelik Lake (Gölbaşı-Adıyaman, Turkey). Six S. glanis, 59-71 cm length, 1.5-3.2 kg weight used for in the investigation. The body cavity was opened and samples of digestive tract (esophagus, stomach and intestine) were fixed in neutral buffered 10% formalin and embedded in paraffin. Dewaxed section (5-6 µm) were deparaffinized and stained with haematoxylin and eosin (H&amp;E), Crossman triple, periodic acid-shiff (PAS), alcian blue (AB, pH 1.0 and 2.5) and PAS+AB pH 2.5 tecnique for different structures. The histological and histochemical structures of all specimens were viewed under a light microscope and microphotograph. The histological structure consists of four layer: tunica mucosa, submucosa, tunica muscularis and tunica serosa. The short esophagus of S. glanis have numerous deep longitudinal folds, squamous epithelium with numerous mucous cells which react positively to PAS and AB stains. The muscularis mucosa was organized in longitudinal and circular layers of striated muscular fibers. The stomach is sac-like shaped and its mucosa was formed by simple columnar epithelium with folds. Histologically, the stomach shows three different region: cardia, fundus and pylorus region. The surface epithelium of stomach reacted positively to PAS and AB (pH 1.0 and 2.5). The mucosal surface of intestine of S. glanis has numerous folds lined by simple tall columnar cells. There were large number goblet cells in the intestine. The goblet cells reacted to PAS and AB (pH 1.0 and 2.5).

Local Spectral Analysis of the Cerebral Cortex: New Gyrification Indices.

Gyrification index (GI) is an appropriate measure to quantify the complexity of the cerebral cortex. There is, however, no universal agreement on the notion of surface complexity and there are various methods in literature that evaluate different aspects of cortical folding. In this paper, we give two intuitive interpretations on folding quantification based on the magnitude and variation of the mean curvature of the cortical surface. We then present a local spectral analysis of the mean curvature to introduce two local gyrification indices that satisfy our interpretations. For this purpose, the graph windowed Fourier transform is extended to the framework of surfaces discretized with triangular meshes. An adaptive window function is also proposed to deal with the intersubject cortical size variability. The intrinsic nature of the method allows us to compute the degree of folding at different spatial scales. Our experiments show that while more classical surface area-based GIs may fail at differentiating deep folds from very convoluted ones, our spectral GIs overcome this issue. The method is applied to the cortical surfaces of 124 healthy adult subjects of OASIS database and average gyrification maps are computed and compared with other GI definitions. In order to illustrate the capacity of our method to capture and quantify important aspects of gyrification, we study the relationship between brain volume and cortical complexity, and design a scaling analysis with a power law model. Results indicate an allometric relation and confirm the well-known observations that larger brains are more folded. We also perform the scaling analysis at the vertex level to investigate how the degree of folding varies locally with the brain volume. Results reveal that in our healthy adult brain database, cortical regions which are the least folded on average show an increased folding complexity when brain size increases.

High Double Eyelid Fold Correction Using Wide Dual-Plane Dissection.

BackgroundThe ability to correct unnatural-appearing, high, and deep double eyelid folds has been limited by the lack of redundant upper eyelid skin and the presence of prior incision line scars in patients.MethodsFrom January 2000 to September 2011, 256 patients with high and deep double eyelid folds underwent our fold-lowering procedure. The first dissection was made at the superficial layer between the orbicularis oculi muscle and orbital septum/retroorbicularis oculi fat. The second dissection was at a deeper layer between the preaponeurotic fat and levator aponeurosis. The dissection proceeded 7 to 8 mm farther cephalad to the prior fold line to separate the upper flap and the floor from the prior fold line. The lower flap was undermined caudally to obtain normal skin tension, and the lower flap was secured to the septoaponeurosis junctional thickening or pretarsal tissue. Six months after surgery, the correction of the high fold scar and change in fold height (with eyes closed) was documented.ResultsUsing the authors' technique, unnatural-appearing, high, and deep double eyelid folds were converted to lower nondepressed folds. Although prior high fold incision scars could be seen postoperatively on close examination, they were not easily visible. Complications included fold height asymmetry in 10 cases, persistence of the prior fold in 5 cases, and redundant upper flap skin that needed further excision in 25 cases.ConclusionsUsing a wide double-layer dissection, high folds were lowered successfully even in situations where there was no redundant upper eyelid skin for excision.

How to make better, safer and easier endothelial controls of long‐term stored corneas with Specular Microscopy?

PurposeUnlike short term cold storage in which corneas remain clear and thin, long‐term organ cultured corneas cannot be rated by specular microscopy (SM) because of the storage‐induced stromal edema and deep endothelial folds. Aim: To present SM of corneas stored in our patented bioreactor (BR).MethodsHuman corneas were stored in our BR, with a commercial medium containing 2% foetal calf serum at 31°C. The BR restored the intraocular pressure while renewing the medium. By preventing from edema and folding, it improved endothelial cell (EC) viability in the long‐term. Two windows allowed easy multimodal corneal imaging. A new type of SM was developed (CMOS camera, ×10 objective, collimated LED, micrometric stage). For each cornea, 5 images (centre + 4 quadrants) were acquired at day 2 and 28 exactly in the same area, and treated with a custom‐made software and ImageJ to determine the EC density (ECD).ResultsAll corneas remained thin and clear, allowing SM without deconditioning nor deswelling in specific media. The field of view of 935 × 748 μm was 3 times greater than those of both commercial eyebank SM. At D2 and 28, despite shallow residual endothelial folds, large areas of ECs were clearly visualized. ECD could be determined on most images easily. Epithelial cells could also be observed.ConclusionsThe BR combines the advantages of cold storage (closed system) and organ culture (long‐term). SM allowed endothelial assessment of long term‐stored corneas in our closed BR: it could make endothelial controls safer, easier and increase the cell count reliability especially thanks to a wider field of view.

Structural geometrical analysis and simulation of decollement growth folds in piedmont Fauqi Anticline of Zagros Mountains, Iraq

Abstract This study carried out detailed structural analyses of the plane structural deformation pattern and sectional structural deformation styles of the Fauqi Anticline by the 3D seismic section with full cover collection, and carried out the kinematical simulation of the Fauqi anticlinal deep decollement coupling shallow growth folds and faults based on the fault decollement fold model and the forward balanced geological section technique. The study subsequently evaluated the differentiated petroleum enrichment mechanism of the Fauqi Anticline by utilizing the results of the structural analysis and combining the spatial-temporal relationship analysis of the source, the reservoir, and the caprock. The results showed that the differentiated plane structural deformation pattern and hierarchical sectional structural deformation style were developed by the superposed coupling of deep decollement, syntectonic sedimentation of shallow growth strata, and the compression of the south-west horizontal tectonic stress from the Zagros Mountains. It was found that the differentiated structural deformation caused the differentiated enrichment of petroleum in the Fauqi Anticline. It was also found that the horizontal slip distance of the Fauqi Anticlinal Folds reached around 3.5 km by the simulation of deep decollement coupling the movement of the shallow growth folds and the faults.

3D Images of the Endothelial Surface to Increase Accuracy of Cell Count in Eye Banks

Objectives: In eye banks, endothelial cell density (number of endothelial cells per surface unit, ECD) is the main criterion to validate the quality of corneal grafts. Stored corneas present numerous deep endothelial folds. Consequently only few endothelial areas are parallel to the microscope and parallax errors inevitably lead to overestimating ECD.Aim: to present an innovative method of ECs count on the reconstructed 3D topography of the endothelium.Materials and methods: Stacks of endothelial images were acquired using a Z motorized conventional transmitted light microscope. A depth map was obtained by researching maximized measurements of the focus in images (shape-from-focus method). Texture of the surface was built by summing image parts presenting the right focus leading to an all-in-focus image. By calculating first derivative in all directions of depth map, precise estimation of cells in folds surfaces could be found. Accuracy of slope detection was verified using artificial endothelial mosaics micro printed on a glass slide with known ECD. Slides were tilted with an angle of 20° and 45°. Gain in accuracy was calculated using human organ cultured donor corneas. For each cornea, the new 3D count was compared with the conventional 2D count of the same area as usually performed in eye banks. The mean difference between both counts and its 95% confidence interval was calculated.Results: The 3D reconstruction eliminated the areas that were usually blurred and therefore increased the number of visible cells that could be counted in each field. The 3D reconstruction algorithms precisely detected the local slopes. The conventional 2D counts overestimated the ECD by a mean 8.5% 95%CI(5.5–11.5), because of parallax error.Conclusion: The 3D endothelial cell counting is ready to be integrated in eye-banks in order to improve the accuracy of endothelial quality controls.

The Combination of the Novel Syk Inhibitor TAK659 with Decitabine Exerts Synergistic Cytotoxic Effects Against FLT3/ITD Mutated Acute Myeloid Leukemia Cells

Background: Effective treatment regimens for FLT3/ITD+ AML patients are lacking. Recent data on the effects of FLT3 tyrosine kinase inhibition showed promising clinical activity, but outcomes have been stunted by drug resistance. Targeting additional signaling pathways besides FLT3 might therefore offer therapeutic benefit. Spleen tyrosine kinase (syk) is frequently overexpressed and constitutively activated in primary AML FLT3/ITD+ blasts. Pharmacologic inhibition of syk has been associated with antileukemic potential, consisting of inhibition of cell growth and induction of differentiation in AML cells. Hypomethylating agents (DNMTis) such as Decitabine (DEC) have emerged as attractive agents in the treatment of AML, partially due to their proapoptotic and differentiation inducing effects. There is a strong rationale for combining FLT3- and syk- inhibitors with DNMTis for FLT3/ITD+ AML. Here, we investigated whether the antileukemic effects of the novel, dual FLT3/syk inhibitor TAK659 (TAK) can be enhanced by the co-administration of DEC.Methods: Molm14 (M14) cells were incubated in culture medium in the presence and absence of stromal cells (MS5) for 72 hours. TAK or DEC was added in single agent or combined mode at the indicated concentrations. After the incubation period, cell growth was determined by MTT assays. Apoptosis, autophagy and cell cycle status were assessed by FACS analysis. FLT3- and syk- phosphorylation levels were detected by western blotting. Differentiation was assessed by morphology. A combination index (CI) was calculated using Calcusyn Software.Results: TAK exerted dose dependent effects against M14 cells. However, the presence of stromal cells significantly blunted TAK mediated cytotoxicity (50nM: 61.9±1.3% [off stroma] vs. 10.9±3.1% [on stroma], p<.001; 500nM: 91.2±0.5% [off stroma] vs. 17.4±2.5% [on stroma], p<.001, n=3-9; IC50: 40.6nM [off stroma] vs. 3.9µM [on stroma]). Although less marked when stroma was present, TAK combined with DEC yielded synergistically enhanced growth inhibition (off stroma: 50.2±3.9% [TAK659 50nM], 58.1±3.0% [DEC 1µM], 76.7±3.1% [TAK659 50nM+DEC 1µM; CI=0.77]; on stroma: 9.5±3.0%[TAK659 50nM], 42.9±3.1% [DEC1µM], 57.0±5.2%[TAK659 50nM+DEC 1µM; CI=0.62]) compared to single agent treatment (off stroma: p<.001 vs. TAK, p< .001 vs. DEC, on stroma: p<.001 vs.TAK, p=.03 vs. DEC, n=3). In line with these findings, combined treatment yielded greater levels of FLT3- and syk- dephosphorylation compared to single agent treatment both when stroma was present and absent. When compared to untreated controls (11.6±0.7%), Annexin V/PI staining (n=3) showed that induction of apoptosis was increased with TAK (18.9±3.9%; p=NS), DEC (39.2±4.8%; p<.01), and greatest when the two drugs were combined (44.2±6.7%; p<.01) in the absence stoma. In the presence of stroma, single agent DEC, and when combined with TAK, increased the fraction of apoptotic cells by up to two fold whereas TAK did not induce any meaningful apoptosis. Consistent with the induction of cell death, cell cycle analysis demonstrated the greatest increase in subG0 phase when TAK and DEC were combined. Both in the presence and absence of stroma, autophagic flux was increased when M14 cells were treated with DEC, and when DEC was combined with TAK whereas no difference was observed with TAK alone. The combination of TAK and DEC led to changes consistent with differentiation, as shown by more abundant cytoplasm and nuclei with deep indentations, folds and lobulation compared to untreated cells. DEC treated cells also showed signs of differentiation although these changes were less marked. No evidence of differentiation was observed in M14 cells when treated with TAK alone.Conclusions: 1. Stroma conferred protective effects against all treatments. 2. TAK exerted dose dependent cytotoxicity against M14 cells in the nanomolar to low micromolar range in the absence and presence of stroma, respectively. 3. The cytotoxic effects of TAK were enhanced when TAK was combined with DEC. 4. The antileukemic effects of TAK combined with DEC are multifaceted and include inhibition of cell growth, induction of apoptosis, autophagy and differentiation. 5. The combination of TAK and DEC represents a potentially important novel approach for FLT3/ITD+ AML patients. 6. Clinical trials incorporating syk-inhibitors into standard AML treatment protocols are currently under way. DisclosuresDos Santos:Amgen: Employment.