Sharp Border Research Articles

“A new approach for the Classification of Advanced Vehicles in Transportation Systems”

Automated vehicles represent one of the most active research topic in different engineering fields in the recent years; in particular, transportation systems theory, mathematical modeling, informatics and electronics are all involved in the development of more efficient, accurate and error resilient systems regarding this topic. For modeling purpose, it is useful to introduce a vehicle classification, but the current 6 SAE levels are too detailed, without sharp borders in some case, to be useful for practical applications; thus a 2-class meta-classification has been proposed but it seems too coarse. This paper starts from an analysis of the 6 SAE levels and of sensors developed and used in modern vehicles to establish a relationship between them; this study is useful to devise a new effective 3-class meta-classification useful to transport systems analysis involving automated vehicles.

Characterization of Choroidal Nevi with Dark-Field Infrared Scanning Laser Ophthalmoscopy

To compare dark-field (DF) scanning laser ophthalmoscopy (SLO) against en face OCT and color fundus photography (CFP) in imaging of choroidal nevi and determining lesion area and to describe the characteristics of choroidal nevi using DF SLO. Prospective cohort study. Multimodal imaging, including DF SLO, OCT, and CFP, was performed in 24 patients (24 eyes; 10 men and 14 women; mean age, 45.1±13.4 years) with choroidal nevi and 14 healthy age-matched volunteers (24 eyes). For each imaging method, the area under the receiver operating characteristic curve was constructed to evaluate the ability to identify choroidal nevi. Using DF SLO, each nevus was characterized according to the intensity of the shadow, clarity of the borders, and presence of additional pigmentation. The lesion area was measured by 2 graders for each imaging method. The intraclass correlation coefficient and intergrader correlation coefficient were calculated. Agreement of DF SLO with CFP and en face OCT in visualization of choroidal nevi. Dark-field SLO showed the highest area under the receiver operating characteristic curve, 1.0, compared with en face OCT and CFP, 0.9 (P= 0.04) and 0.88 (P= 0.025), respectively. Using DF SLO in 17 patients (70.8%) and 7 patients (29.2%), nevus demonstrated dense and partially transparent shadow, respectively. In 10 patients (41.7%) and 14 patients (58.3%), nevus demonstrated sharp and blurred borders, respectively. Additional pigmentation was found in 5 patients (20.8%). The agreement in the evaluation of the area of the nevus between DF SLO and en face OCT and between DF SLO and CFP for grader 1 was 0.89 and 0.95, respectively, and for grader 2 was 0.95 and 0.95, respectively. Weighted κ values in reproducibility analysis for DF SLO, en face OCT, and CFP were 0.8, 0.71, and 0.67, respectively. Dark-field SLO demonstrated excellent potential for identifying choroidal nevi and was in full agreement with conventional methods in the evaluation of the area of choroidal nevi.

Viruses and Evolution - Viruses First? A Personal Perspective.

The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution. Viruses are the most abundant biological entities on Earth. They are present everywhere, in our surrounding, the oceans, the soil and in every living being. Retroviruses contributed to about half of our genomic sequences and to the evolution of the mammalian placenta. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. How far back can we trace their contribution? Earliest replicating and evolving entities are the ribozymes or viroids fulfilling several criteria of life. RNA can perform many aspects of life and influences our gene expression until today. The simplest structures with non-protein-coding information may represent models of life built on structural, not genetic information. Viruses today are obligatory parasites depending on host cells. Examples of how an independent lifestyle might have been lost include mitochondria, chloroplasts, Rickettsia and others, which used to be autonomous bacteria and became intracellular parasites or endosymbionts, thereby losing most of their genes. Even in vitro the loss of genes can be recapitulated all the way from coding to non-coding RNA. Furthermore, the giant viruses may indicate that there is no sharp border between living and non-living entities but an evolutionary continuum. Here, it is discussed how viruses can lose and gain genes, and that they are essential drivers of evolution. This discussion may stimulate the thinking about viruses as early possible forms of life. Apart from our view “viruses first”, there are others such as “proteins first” and “metabolism first.”

Can digital breast tomosynthesis accurately predict whether circumscribed masses are benign or malignant in a screening population?

To evaluate whether digital breast tomosynthesis (DBT) can predict if circumscribed masses are benign or malignant by assessing margin sharpness. Circumscribed masses were evaluated on co-registered two-dimensional digital mammography (2DDM) and DBT. Lesions were categorised as follows: category 1=visible sharp border 0-25% of the total margin; category 2 = 26-50% category 3= 51-75%, and category 4=76-100%. Changes in category between 2DDM and DBT were analysed; if the category was lower on DBT the change was negative, if higher the change was positive. Of 759 lesions, 121 masses classified as circumscribed on DBT were included; 25 were malignant and 96 benign. Of the benign lesions, 8/96 were within category 3 or 4 on 2DDM compared with 48/96 benign lesions within category 3 or 4 on DBT (Fisher's exact test p<0.000527). Forty-eight of 51 (94.1%) lesions categorised as 3 or 4 on DBT were benign and 65/67 (97.01%) of the positive category change group were benign. Lesions in category 1 on DBT had 45.4% chance of being malignant (20/44) compared with 22.72% (20/88) on 2DDM (chi-squared test p<0.001). Sixty-five of 67 (97.01%) lesions in the positive category change group were benign and 23/54 (42.6%) lesions with either no or negative category change were malignant. The present study demonstrates 97% accuracy in predicting circumscribed lesions as benign when using positive category change and 94% accuracy when >50% of the margin is sharply defined on DBT.

Surface-Free Protocol for Computing PKA's (DelPhiPKa): Applications to Protein-Protein Interactions

DelPhiPKa is widely used for accurate prediction of pKa's of ionizable residues in proteins, DNAs and RNAs. DelPhiPKa approach is unique because it does not define the molecular surface, rather it uses a smooth Gaussian-based dielectric function throughout the space. The new development considers the presence of salt in the modeling protocol in a non-trivial manner via desolvation penalty term within the Boltzmann factor of Poisson-Boltzmann equation. This factor penalizes the salt ions to enter in the solute interior in a smooth manner without requiring sharp border between solute-solvent. Therefore, the presence of salt near macromolecule is determined by a combination of favorable electrostatic interactions and desolvation penalty. The DelPhiPKa-computed pKa's are in very good agreement with the experimentally determined pKa, having RMSD of 0.74. The unique approach of Gaussian-based smooth dielectric results in improved pKa's predictions compared to the standard method of two dielectric regions. DelPhiPKa also enables the calculations of pKa's of polar residues such as serine, cysteine, tyrosine and threonine. It has been demonstrated that DelPhiPKa outperforms all the other existing methods, even the explicit water models, while benchmarking the calculated pKa's against experimental pKa's of cysteine. Furthermore, we calculated the pKa's shifts due to the mutations in the protein-protein complexes taken from the SKEMPI database. We demonstrate that significant fraction of mutations listed in SKEMPI database results in unusual pKa's for introduced mutation or induce pKa's shifts of neighboring titratable groups. This is discussed in term of altering pH-dependence of the binding free energy.

The diagnostic significance of repeat ultrasound-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results

IntroductionTo determine the diagnostic yield of repeat ultrasound (US)-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results, and to explore predictive factors for success of repeat biopsy. Materials and methodsThis retrospective study included 42 patients who underwent a repeat (second) US-guided biopsy session to target a musculoskeletal soft-tissue lesion because an initial US-guided biopsy session provided inconclusive results. Both biopsy sessions were performed in a tertiary referral center for soft-tissue sarcomas. ResultsThe diagnostic yield of repeat US-guided biopsy was 47.6%. Malignant nature of the lesion (P = 0.031), sharp lesion borders on US (P = 0.011), and good to very good lesion visibility on US (P = 0.017) were significantly associated with a diagnostic repeat US-guided biopsy. There was also a trend towards significance (P = 0.073) for a higher number of biopsy passes through the lesion. Other patient characteristics (age and gender), magnetic resonance imaging features (lesion homogeneity on T1-weighted, T2-weighted, and gadolinium chelate enhanced sequences, borders, enhancement pattern, depth and size), US features (lesion appearance, vascular flow, and depth), biopsy-related factors (days between initial and repeat US-guided biopsy, needle diameter, maximum length of acquired samples), and operator-related factors (same or different radiologists/pathologists for initial and repeat biopsies), were not associated with the diagnostic success of the repeat US-guided biopsy. ConclusionsRepeat US-guided biopsy of a musculoskeletal soft-tissue lesion with initially inconclusive biopsy results can be useful to establish a final diagnosis. Lesion features on US (borders and visibility) may be used to prospectively determine the utility of a repeat US-guided biopsy.

Involvement of Colletotrichum coccodes causing atypical symptoms of potato tubers in Turkey

In 2015 and 2017, potato storages were surveyed for the prevalence of atypical potato tuber rots in Nevsehir and Isparta Provinces of Turkey. About 4–5 months after harvesting, 80% of the potatoes cv. Melody, that were stored at 4–5 °C and 65–75% relative humidity, were affected by the disease. The symptoms of the disease were similar to gangrene caused by Boeremia exigua var. foveata including superficial, dark lesions or dark brown, sunken lesions that have a sharp border with healthy tissue on tubers. A fungus was consistently isolated from necrotic tuber tissues. The pathogen was identified as Colletotrichum coccodes (Wallr.) Hughes based on morphological characteristics and the analysis of sequence of the internal transcribed spacer region of the rDNA. Pathogenicity was tested by tuber inoculation with mycelial agar discs. After 4–6 weeks, irregular and dark brown sunken lesions developed on potato tubers, while control tubers remained symptomless. This is the first report of C. coccodes that caused extraordinary symptoms on potato tubers in Turkey.

Development of Steps in an Automated Process Chain for Piezoceramic-Metal Compound Production

The potential of adaptronic applications has been proven in many conceptual studies. A broad use in high-efficiency branches is often hindered by the absence of an appropriate assembly method. Especially for piezoceramic foil transducers, the application on structural parts can be simplified using a semi-finished part that includes the transducer. The part is then shaped in a final forming operation. The purpose of the present study is the investigation of process limits in automated process chains for producing semi-finished parts. An adhesive is used in the process, which is only locally cured. This bi-conditioned state is achieved using cooling and heating elements. The process limits are mainly affected by the choice of temperature and curing time between adhesive application and forming operation. Several tests with a rotational rheometer were carried out to investigate the curing behavior. An appropriate process window was identified varying processing time and temperature. The results were then used to build a model of the curing behavior. A mathematical approach had to be used to find the best configuration because no sharp border exists between the two adhesive conditions of liquid and solid state. The process parameters were proven with runs inside and outside of the process limits.

Assessment of efficacy of ultrasonography in cervical lymphadenopathy in oral malignancies.

Aims and Objectives:To substantiate the use of ultrasonography in diagnosis of cervical lymphadenopathy in oral malignancies and to assess if ultrasonographic examination done prior to lymph node (LN) biopsy can yield important information regarding the diagnosis.Materials and Methods:Twenty subjects with histopathologically confirmed oral malignant lesions with clinically palpable and untreated cervical LNs included into study. These patients were subjected to clinical examination (number of LNs, shape, size, location, overlying temperature, overlying skin, tenderness, consistency, and fixity to the underlying structures), and ultrasonographic evaluation (number of LNs, shape, size (mm), location, borders, matting, peripheral halo, hilum, calcification, necrosis, reticulation, and echogenicity) of the LNs, and finally, histological assessment was done after surgical excision during the course of treatment.Results:Predominantly male (65%) patients were having with malignant LN involvement with age group of 60–69 years, i.e., 35%. Ultrasonogram is superior to clinical examination as it detected additional 49 nodes. Malignant nodes tend to have longest axial diameter (17 mm with standard deviation of 8.7 mm). Over all 52 malignant nodes were round, whereas 35 nodes were oval in shape. Most of the nodes were detected in submandibular region. Around 61 (70.9%) nodes had sharp borders and 26 (29.9%) had smooth borders. Loss of echogenic hilus is a common feature of malignancy showing 70% sensitivity and 67% specificity. Most of malignant nodes were hypoechoic. Around 51 (58.6%) of nodes showed intranodal necrosis, whereas it was absent in 36 (41.4%) nodes. Matting and edema were present 25 (28.7%) nodes. Intranodal calcification was present in 37 nodes. Sensitivity of USG was 90%, whereas specificity was 100%.Conclusion:Ultrasonographic examination of cervical LNs can yield important information regarding the diagnosis. Ultrasound examination should be done prior to FNAC and ideally an ultrasound-guided FNAC.

Cross-Sectional Study of Dermatoscopic Findings in Relation to Activity in Vitiligo: BPLeFoSK Criteria for Stability.

Background:Stability in vitiligo is an important concept in guiding patient management and a vital prerequisite before vitiligo surgery. Disease activity of vitiligo based on patient’s history is imprecise. It is practically impossible to perform biopsy from all lesions of vitiligo to ascertain stability. Dermatoscopy can be used to examine all clinical lesions in a patient of vitiligo. There is a need to validate many reported dermatoscopic findings for universal use.Aims:To analyze the significance of dermatoscopic findings in the activity of vitiligo and to devise a cutoff score for stable vitiligo.Materials and Methods:Dermatoscopic examination was performed in 85 patients clinically diagnosed with vitiligo. Six dermatoscopic parameters, namely, border, pigment network, perilesional hyperpigmentation, perifollicular pigmentation, satellite lesions, and micro-Koebner phenomenon (acronym: BPLeFoSK) were evaluated against Wood’s lamp findings as standard. Chi-square test was used to test association between categorical variables. Cutoff values for stability for these six parameters were plotted in receiver operating curve.Results:A total of 131 vitiligo lesions were analyzed with dermatoscopy. Absence of satellite lesions and absence of micro-Koebner phenomenon were the most sensitive parameters (96.7% and 100%, respectively). Sharp border and absent or reticulate pigment network within the vitiligo patch were the most specific findings (100% and 91.5%, respectively).Conclusion:A cutoff score of more than or equal to 1.5 using the “BPLeFoSK criteria” indicates stability in the vitiligo lesion.

Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape

The mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for how the 3D genome is organized. The Xi shows weakened topologically associated domains and is instead organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not precede Xist expression or Xi gene silencing. Deleting Dxz4 disrupts the sharp megadomain border, whereas deleting Firre weakens intra-megadomain interactions. However, deleting Dxz4 and/or Firre has no impact on Xi silencing and gene escape. Nor does it affect Xi nuclear localization, stability, or H3K27 methylation. Additionally, ectopic integration of Dxz4 and Xist is not sufficient to form megadomains on autosomes. We conclude that Dxz4 and megadomains are dispensable for Xi silencing and escape from X-inactivation.

Trastuzumab induced radiation recall dermatitis: an interesting case

Radiation recall dermatitis (RRD) is the appearance of skin reactions in previously irradiated skin which is triggered by the administration of certain drugs. Surgery, chemotherapy, and radiotherapy are the mainstay of treatment in breast cancer. RRD induced by trastuzumab has been rarely reported in India. This is a case report of a 56-year-old woman presented to the medical oncology outpatient department of our hospital with breast lump, and she was diagnosed to have human epidermal growth factor receptor 2 (HER-2/neu) positive invasive ductal carcinoma of left breast of stage T2N3cM0. She was treated with neoadjuvant chemotherapy, and she underwent modified radical mastectomy with axillary lymph node dissection. The treating oncologist was planned to start on adjuvant chemotherapy with injection trastuzumab for every four weeks, for 15 cycles. Patient received first dose of injection trastuzumab (450 mg) intravenously in the right (contralateral) arm and developed painful, swollen, erythematous blisters, and maculopapular rashes following the sharp linear borders of her previous radiation fields. She was reviewed by the medical oncologist and diagnosed as a rare case of RRD and treated with topical betamethasone cream. Causality assessment for RRD to trastuzumab was done using Naranjo and WHO-UMC scale and found to be in the category of probable and probable/ likely respectively.

Intraarterial indocyanine green (ICG) fluorescence augmentation by marking embryonal resection areas in colorectal surgery: a feasibility study in a porcine model

Aim: In this pilot animal study we examined whether it is possible to visualize the embryonal resection layers by using intraarterial indocyanine green (ICG) staining when performing total mesorectal excision (TME) for carcinoma of the rectum. Material and methods: We injected ICG into the inferior mesenteric artery (AMI) of four swines to see whether the watershed area of the arterial supply zone can be sufficiently visualized by fluorescence imaging in order to mark the right dissection area along the fascia parietalis before and during resection. Results: We observed a fluorescence signal in all the supplied areas of AMI but not in other parts of the abdominal cavity or other organs. Additionally, the mesorectum also showed a sharp border between colored and non-colored tissue. Conclusion: In this study we present that resection borders may be determined before resection based on ICG-perfusion and we showed that intraoperative exclusive coloring of the rectum including the mesorectum is possible. Visualizing resection borders based on ICG-perfusion before settling the first cut may be a new approach in oncological surgery.

Orientation-selective edge enhancement of phase objects

Abstract We present a method for the orientation-selective enhancement of the first derivatives − i.e. the edges − of a pure phase object. The proposed method is based on the transport-of-intensity equation (TIE). The TIE contains a term proportional to the scalar product of the phase gradient and an intensity gradient, which plays the role of amplifying factor of the first derivatives. We will show that if the intensity gradient is implemented in the optical setup as a moving amplitude mask with a relatively sharp border − or eventually, a digital shifting mask displayed in a liquid crystal display − it is possible to generate a synthetic image of the phase object with enhanced edges. The proposed technique is potentially useful in biological and biomedical research. Validation experiments and preliminary qualitative results illustrating the generation of synthetic images with enhanced edges are presented.

Netrin Signaling Defines the Regional Border in the Drosophila Visual Center

SummaryThe brain consists of distinct domains defined by sharp borders. So far, the mechanisms of compartmentalization of developing tissues include cell adhesion, cell repulsion, and cortical tension. These mechanisms are tightly related to molecular machineries at the cell membrane. However, we and others demonstrated that Slit, a chemorepellent, is required to establish the borders in the fly brain. Here, we demonstrate that Netrin, a classic guidance molecule, is also involved in the compartmental subdivision in the fly brain. In Netrin mutants, many cells are intermingled with cells from the adjacent ganglia penetrating the ganglion borders, resulting in disorganized compartmental subdivisions. How do these guidance molecules regulate the compartmentalization? Our mathematical model demonstrates that a simple combination of known guidance properties of Slit and Netrin is sufficient to explain their roles in boundary formation. Our results suggest that Netrin indeed regulates boundary formation in combination with Slit in vivo.

Alloy broadening of the transition to the nontrivial topological phase of Pb1−xSnxTe

Transition between the topologically trivial and non-trivial phase of Pb_{1-x}Sn_{x}Te alloy is driven by the increasing content $x$ of Sn, or by the hydrostatic pressure for $x<0.3$. We show that a sharp border between these two topologies exists in the Virtual Crystal Approximation only. In more realistic models, the Special Quasirandom Structure method and the supercell method (with averaging over various atomic configurations), the transitions are broadened. We find a surprisingly large interval of alloy composition, $0.3<x<0.6$, in which the energy gap is practically vanishing. A similar strong broadening is also obtained for transitions driven by hydrostatic pressure. Analysis of the band structure shows that the alloy broadening originates in splittings of the energy bands caused by the different chemical nature of Pb and Sn, and by the decreased crystal symmetry due to spatial disorder. Based on our results of ab initio and tight binding calculations for Pb_{1-x}Sn_{x}Te we discuss different criteria of discrimination between trivial and nontrivial topology of the band structure of alloys.

Clinical presentation of ductal carcinoma in situ of breast with intraluminal crystalloids: Radiologic-histologic correlation

Intraluminal crystalloids have rarely been described in the breast, particularly in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of DCIS of the breast associated with numerous intraluminal crystalloids. The patient presented with a mass in the right breast, and microcalcifications were detected on screening and diagnostic mammograms; the patient underwent needle biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic crystalloids, with variable morphologies including rectangular, triangular and needle-like with sharp borders, were observed within the lumina of DCIS, besides calcium phosphate microcalcifications. We report this case together with a literature review on crystalloid-containing lesions in breast and non-breast tissues. We also studied radiologic findings of these crystalloids using a specimen radiograph.

Ultra-wide field imaging of pigmented para-venous retino-choroidal atrophy.

To describe the ultra-wide field imaging features of pigmented para-venous retino-choroidal atrophy. Retrospective review at a tertiary care centre. Eight eyes of five patients with pigmented para-venous retino-choroidal atrophy who presented to our retina clinic over last 2 years. Retrospective review of ultra-wide field pseudo-colour and short wave autofluorescence imaging was performed. In vivo histology of the macula and areas of retino-choroidal atrophy was studied with swept source optical coherence tomography (SS-OCT). The median age was 40 years (range: 22-67 years). Best corrected visual acuity ranged from perception of light to 20/20. The para-venous retino-choroidal atrophy and pigment clumping not only involved the major arcade vessels but also extended into the peripapillary area and retinal periphery. The affected areas demonstrated hypoautofluorescence with sharp hyperautofluorescent borders. Macular atrophy, epiretinal membrane and optic disc pallor were noted in two eyes each. In all cases, the affected pigmentary area had disorganization of inner retinal layers, disruption of outer retinal layers and retinal pigment epithelium and markedly thinned out choroid on swept source optical coherence tomography. Concurrent involvement with retinitis pigmentosa in the fellow eye was noted in two patients. Ultra-wide field imaging of pigmented para-venous retino-choroidal atrophy sheds light onto the widespread retino-choroidal abnormalities. Concurrent disc and macular involvement may jeopardize the visual function. Pigmented para-venous retino-choroidal atrophy may be considered as a self-limited form of retinitis pigmentosa.

An unusual case report of primary vitreoretinal lymphoma

BackgroundPrimary vitreoretinal lymphoma (PVRL) is a rare ocular condition and its diagnosis remains a challenge. The clinical presentation is variable and it can masquerade as chronic intermediate or posterior uveitis. We report an unusual case of primary central nervous system lymphoma (PCNSL) presenting as migrating retinal lesions with unique shapes. The diagnostic challenges are described and the clinical features of intraocular lymphoma are reviewed.Case presentationA 53 year-old gentleman presented with unilateral visual disturbance and a wide area of retinal whitening with sharp borders temporal to the macula, corresponding to hyper-reflective subretinal changes on optical coherence tomography (OCT). The lesion resolved spontaneously after 6 weeks but was replaced by multiple punctate sub-retinal and sub-retinal pigment epithelial lesions. The second eye was involved 4 months later and there were new areas of hyper-reflective changes in both eyes, which migrated nasally within a week, with no evidence of scarring in the previous sites. The diagnosis of diffuse B-cell lymphoma was made on brain biopsy when the patient subsequently presented with acute confusion and magnetic resonance imaging brain scan showed a frontal lesion. Following systemic chemotherapy, the sub-retinal changes resolved with complete restoration of retinal architecture and improvement in visual acuity.ConclusionWe report an unusual case of PVRL presenting as migrating retinal lesions with unique shapes. PVRL is a great imitator and a high index of clinical suspicion is required in unexplained ocular lesions to prevent a delay in diagnosis.

Establishing sharp and homogeneous segments in the hindbrain.

Studies of the vertebrate hindbrain have revealed parallel mechanisms that establish sharp segments with a distinct and homogeneous regional identity. Recent work has revealed roles of cell identity regulation and its relationships with cell segregation. At early stages, there is overlapping expression at segment borders of the Egr2 and Hoxb1 transcription factors that specify distinct identities, which is resolved by reciprocal repression. Computer simulations show that this dynamic regulation of cell identity synergises with cell segregation to generate sharp borders. Some intermingling between segments occurs at early stages, and ectopic egr2-expressing cells switch identity to match their new neighbours. This switching is mediated by coupling between egr2 expression and the level of retinoic acid signalling, which acts in a community effect to maintain homogeneous segmental identity. These findings reveal an interplay between cell segregation and the dynamic regulation of cell identity in the formation of sharp patterns in the hindbrain and raise the question of whether similar mechanisms occur in other tissues.