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Ribavirin is an inosine monophosphate dehydrogenase inhibitor with demonstrated activity against coronaviruses, including SARS-CoV-2. Five hospitalized patients with COVID-19 (confirmed by positive tests for SARS-CoV-2) received treatment with ribavirin for inhalation solution (ribavirin aerosol) as part of a compassionate use program. Patients included four men and one woman, with an age range of 29–72years. Patients were managed according to international and Italian treatment guidelines for COVID-19. In addition, therapy with ribavirin aerosol 100mg/mL was administered for 30min twice daily for 6days (i.e., 12 doses) in all patients. In order to address concerns about a possible increase in viral dispersal with the use of a nebulizer, healthcare providers remained outside the patient room during ribavirin aerosol administration. Pretreatment chest computed tomography (CT) scans showed pseudonodular areas of parenchymal thickening in the upper right lobe with associated ground glass opacities, multiple areas of parenchymal consolidation in both lower lobes with associated ground glass opacities, bilateral parenchymal thickening and multiple associated ground glass areas, or focal ground glass areas in the upper lobes bilaterally, which were almost completely resolved (three patients) or moderately cleared (one patient) on imaging at the end of ribavirin treatment. For a fifth patient, CT scans showed a stable pulmonary picture at the end of ribavirin treatment. No adverse reactions to ribavirin treatment were observed in any of the five patients. All patients recovered fully, and nasopharyngeal swabs obtained after hospital discharge tested negative for SARS-CoV-2. Ribavirin aerosol appears to be efficacious in the treatment of patients with COVID-19. A controlled trial of ribavirin aerosol is ongoing and will provide additional data across a broader patient population.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce conjunctivitis signs and symptoms. However, limited information is available on their impact on COVID-19 disease phenotype. Quantification of ocular signs/symptoms can provide a rapid, non-invasive proxy for predicting clinical phenotype. Moreover, the existence and entity of conjunctival viral shedding is still debated. This has relevant implications to manage disease spread. The purpose of this study was to investigate conjunctivitis signs and symptoms and their correlation with clinical parameters, conjunctival viral shedding in patients with COVID-19. Methods Fifty-three patients hospitalized between February 25th and September 16th, 2020 at the San Raffaele Hospital, in Milan, Lombardy, Italy with a confirmed diagnosis of SARS-CoV-2 were evaluated. Presence of interstitial pneumonia was confirmed with computed tomography scan imaging. Ocular signs and symptoms, anosmia/ageusia, clinical/laboratory parameters, and reverse transcriptase–polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for COVID-19 virus were analyzed. Results Forty-six out of 53 patients showed a positive nasopharyngeal swab for SARS-CoV-2 infection at the time of conjunctival evaluation. All the conjunctival swabs were negative. Conjunctivitis symptoms were present in 37% of patients. Physician-assessed ocular signs were detected in 28% of patients. Patients with ocular symptoms or signs tended to be older: 76.8 years (62.4–83.3) vs 57.2 years (48.1–74.0), p = 0.062 and had a longer hospitalization: 38 days (18–49) vs. 14 days (11–21), p = 0.005. Plasma levels of Interleukin-6 were higher in patients with signs or symptoms in comparison with those without them: 43.5 pg/ml (19.7–49.4) vs. 8 pg/ml (3.6–20.7), p = 0.02. Red cell distribution width was also significantly higher: 15 (14.3–16.7) vs 13.2 (12.4–14.4), p = 0.001. Conclusions We found that over a third of the patients had ocular signs or symptoms. These had higher prevalence in patients with a more severe infection. No viral shedding was detected in the conjunctiva. Our results suggest that prompt detection of conjunctivitis signs/symptoms can serve as a helpful proxy to predict COVID-19 clinical phenotype.

Purpose:To test the safety and efficacy of high frequency electrotherapy (ET) on the clinical signs and symptoms of patients affected by dry eye and meibomian gland dysfunction (MGD).Methods:Twenty-five patients affected by MGD were enrolled. Quantum Molecular Resonance ET was administered by means of the Rexon-Eye device 4 times, once per week for 4 weeks. Patients were reexamined 1 month after the last treatment. The primary endpoint was reduction in corneal fluorescein staining. Additional endpoints were tear break-up time, Ocular Surface Disease Index score, meibomian gland secretion score, and the number of expressible meibomian glands. Safety endpoints were Logarithm of the Minimum Angle of Resolution (LogMar) best spectacle-corrected visual acuity and intraocular pressure.Results:Corneal fluorescein staining improved by 62.5% (P < 0.0001), tear breakup time increased by 30.9% (P < 0.0001), and the Ocular Surface Disease Index score improved by 37% (P < 0.001). The meibum quality and the number of expressible meibomian glands also increased (35.7% and 12%, P < 0.001 and P < 0.0001, respectively). Schirmer test scores increased after treatment by 16.5% (P = 0.01). No adverse events were observed.Conclusions:Quantum Molecular Resonance ET appears to be safe and significantly reduces symptoms and signs associated with MGD. It may have a relevant role in the treatment of evaporative dry eye disease.

PURPOSE. The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain. METHODS. Eight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye wiping test was used to quantify ocular surface pain. SP content was quantified in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the cornea. Corneas were immunostained for β3-tubulin and NK1R, or CD45, to quantify leukocyte infiltration. RESULTS. TAC1-KO mice displayed a significant reduction of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL fosaprepitant applied topically to WT mice reduced ocular pain as compared to vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or oxybuprocaine reduced corneal nociception when compared to vehicle or fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of NK1R and β3-tubulin was detected in mouse corneas. CONCLUSIONS. Topical administration of the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release in the tear fluid and TG, and corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.

Purpose: To quantify the severity and location of corneal neovascularization (cNV) and its impact on the visual acuity and corneal sensitivity in a cohort of the patients referred to a specialist cornea clinic and also to describe the etiology of cNV in the cohort.Methods: We retrospectively evaluated the charts of 13,493 subjects referred to the San Raffaele Cornea Unit between January 2004 and December 2018 to search for cNV diagnosis. The corneal neovascularization severity was measured in the quadrants (range: 1–4) and location was defined as superficial, deep, or both. Best spectacle corrected visual acuity (BSCVA) was measured in logMar. We used the multiple regression analysis to identify the independent predictors of logMAR, after adjusting for age, gender, keratoconus, herpes keratitis, penetrating keratoplasty, trauma, and cataract surgery.Results: Corneal neovascularization was diagnosed in 10.4% of the patients analyzed. The most prevalent etiology of cNV in our population was non-infectious corneal dystrophies/degenerations followed by herpes simplex virus infection. cNV affected OD, OS, or both eyes in 35.6, 40.2, and 24.2 of cases, respectively. Mean BSCVA (SD) was 0.59 (0.76), 0.74 (0.94), and 1.24 (1.08) in cNV one, two, and three or four of the quadrant groups. Superficial, deep, or mixed cNV occurred in 1,029, 348, and 205 eyes. Severe cNV (three or four of the quadrants) was a significant predictor of low visual acuity (p < 0.001) and reduced corneal sensitivity (p < 0.05). cNV location and its severity were associated (p < 0.05). In addition, corneal anesthesia was associated with lower BSCVA (p < 0.001).Conclusion: Severe and deep cNV are associated with the reduced visual acuity and corneal sensitivity. Our data strongly support the relevance of appropriate follow-up as cNV is a major risk factor for graft rejection.

Purpose: to assess the effect of topical administration of the Neurokin-1 receptor (NK1R) antagonist Fosaprepitant in a pre-clinical model of ocular Graft-versus-Host disease (GVHD). Methods: BALB/c mice were pre-conditioned by myeloablative total body irradiation and subjected to allogeneic bone marrow transplantation and mature T cell infusion (BM + T). BM-transplanted mice (BM) were used as controls. Ocular GVHD was specifically assessed by quantifying corneal epithelial damage, tear secretion, blepharitis and phimosis, 3 times/week for 28 days post-transplantation. A group of BM + T mice received Fosaprepitant 10 mg/mL, 6 times/day, topically, from day 7–29 after transplantation. After sacrifice, the expression of NK1R, CD45, CD3, and CXCL10 was quantified in the cornea, conjunctiva, and lacrimal gland by immunohistochemistry. Results: BM + T mice developed corneal epithelial damage (day 0–29, p < 0.001), blepharitis (day 0–29, p < 0.001), and phimosis (day 0–29, p < 0.01), and experienced decreased tear secretion (day 21, p < 0.01) compared to controls. NK1R was found upregulated in corneal epithelium (p < 0.01) and lacrimal gland (p < 0.01) of BM + T mice. Fosaprepitant administration significantly reduced corneal epithelial damage (p < 0.05), CD45+ (p < 0.05) and CD3+ (p < 0.01) immune cell infiltration in the cornea and conjunctiva (p < 0.001 and p < 0.001, respectively). In addition, Fosaprepitant reduced the expression of CXCL10 in the cornea (p < 0.05) and in the lacrimal gland (p < 0.05). Conclusions: Our results suggest that NK1R represents a novel druggable pathway for the therapy of ocular GVHD.

Purpose: To present a series of two patients affected by Tourette syndrome (TS) and progressive keratoconus. Case series: Two young male patients with keratoconus and TS were referred to our center. In both patients eye rubbing was present and in one patient, an ocular tic was present determining blepharospasm. Progression of keratoconus occurred in both cases and corneal collagen cross-linking (CXL) was performed. All treated eyes showed topographic stability with stable refraction and conserved visual acuity, with a follow-up period ranging from 1.5 to 2.5 years. Conclusion: Patients with keratoconus and TS should be observed frequently to document topographical and refractive changes, and in case of progressing disease, CXL should be performed in order to prevent further progression.

Purpose To review the literature on the etiopathogenesis of keratoconus (KC). Methods A literature search was conducted using PUBMED and Google Scholar for keratoconus. The authors analyzed epidemiology studies, reviews, and case reports. Results Atopy and ocular surface inflammation are a common features of KC and should lead to a reconsideration of the traditional definition of KC as a “non inflammatory” condition. Co-morbidities suggest that KC may be the ocular manifestation of a systemic disease. Finally, KC shows higher prevalence in certain ethnicities, which calls into question the status of KC as a rare disease, at least in these communities. Conclusion We believe that future studies should test whether selected, high prevalence populations exhibit specific genetic background and/or ethno-specific environmental risk factors.

Background/aimsTo evaluate the effectiveness of corneal collagen cross-linking (CXL) in paediatric patients.MethodsFifty-two eyes of 43 paediatric patients with progressive keratoconus were enrolled in a prospective cohort study. Corneal CXL was performed using a conventional technique with instillation of 0.1% riboflavin solution containing dextran 20% for 30 min during the soaking phase and during the 30 min ultraviolet A irradiation (3 mW/cm2). Visual outcomes, topographic keratometry, maximum keratometry (K-max), refractive astigmatism, demarcation line and endothelial cell density were measured postoperatively.ResultsA significant decrease of K-max from 59.30±7.08 to 57.07±6.46 (p2 (p=0.90).ConclusionCXL is an effective treatment for avoiding keratoconus progression in paediatric patients. The procedure is safe and successful in stabilising keratoconus in eyes with more advanced forms of the disease, characterised by topographic K-max values greater than 60 D.

Cell therapy for treatment of corneal lesions, with associated corneal (limbal) stem cell deficiency due to ocular burns, has recently gained regulatory approval from the European Medicines Agency (EMA), and it is the first choice to restore corneal surface integrity when corneal epithelial stem cells have been lost. LSCD can be due to a number of genetic, inflammatory, or traumatic disorders and frequently results in mono- or binocular blindness. In this chapter, we will review different limbal stem cell therapies for LSCD. We will do so by considering the epidemiology of LSCD and different types of cultivated limbal stem cell treatments. Alternative treatments will also be briefly reviewed. Potential advantages, and pitfalls, of autologous versus allogenic limbal stem cell transplantation will be considered.

The cornea is normally devoid of blood and lymphatic vessels; however, a number of infectious/inflammatory diseases can induce corneal neovascularization (CNV). Tumor necrosis factor (TNF)-α, a well known pro-inflammatory cytokine, acts on the vascular endothelium by promoting vasodilatation, edema, and leukocyte recruitment, which are all commonly associated with the development of CNV. Corneal neovascularization is the second cause of blindness worldwide; hence, pharmacological TNF-α inhibition might represent an attractive therapeutic option. Although none of the existing TNF-α antagonists has been registered as a CNV inhibitor, three of them (etanercept, adalimumab, and infliximab) have been proposed to control ocular inflammation. More specifically, it has been demonstrated that infliximab is also effective in reducing hemangiogenesis and lymphangiogenesis in different animal models of CNV. In this article, we review the role of TNF-α on the ocular surface and, in particular, its specific role in the process of CNV. Moreover, we review existing literature and speculate on the potential role of TNF-α inhibitors in the treatment of CNV.

Purpose The aim of this study was to test the efficacy of Neurokinin-1 Receptor (NK-1R) antagonist −Fosaprepitant− in inducing regression of established corneal neovascularization (CNV). Methods Twenty C57BL/6 mice underwent alkali burn. Seven days later, when corneal neovessels had developed, they received Fosaprepitant 10 mg/ml, administered topically six times a day in the right eye for 10 days. In parallel, a group of 20 causticated mice was treated with normal saline, as control. A second independent experiment was also performed (n = 10/group). Finally, ten healthy mice received the same topical treatment for 10 days to evaluate Fosaprepitant safety. Haemangiogenesis and lymphangiogenesis were measured by means of vesselj plugin (imagej). Secondary endpoints, such as leucocyte infiltration, corneal opacity and corneal fluorescein staining were also evaluated. Inflammatory cell composition was assessed by flow cytometry. Differences between groups were assessed using unpaired t-test, Mann–Whitney U-test or two-way anova, as appropriate. Results Topical Fosaprepitant administration induced a significant reduction of (i) CD31+ blood corneal neovessels (−27%, p = 0.0132), (ii) LYVE1+ lymphatic corneal neovessels (−31%, p = 0.0118) and (iii) CD45+ leucocyte infiltration (−36%; p = 0.0237). The second independent experiment confirmed these data. Moreover, Fosaprepitant-treated corneas showed a reduction in opacity, no impairment in corneal fluorescein staining and decreased infiltration of neutrophils (−72%, p

To provide an updated literature review on the status of cultivated limbal (corneal) epithelial transplantation. Cultivated limbal stem-cell transplantation recently received regulatory approval. We provide a comprehensive overview of recent developments in the field.The current article reviews and highlights recent developments in the field of cultivated limbal stem-cell transplantation as retrieved from a literature search for the last year.The implications of clinical/research findings in terms of transplanted cell source and cultivation methods in limbal stem-cell transplantation are reviewed.

Purpose To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant. Methods We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured. Results Substance P increased after injury in the corneal epithelium of both CNV models, and later in the suture model. Topical Lanepitant was nontoxic to the ocular surface and effective in reducing hemangiogenesis and lymphangiogenesis, corneal SP levels, and leukocyte infiltration, as soon as 4 days later in the alkali burn model. Topical Lanepitant, up to 7 days, was ineffective in the suture model. However, subconjunctival Lanepitant was effective in reducing lymphatic CNV, leukocyte infiltration, and SP levels in the suture model, after 10 days. Additionally, in the alkali burn model, subconjunctival Lanepitant significantly reduced blood CNV, corneal perforation rate, opacity, and leukocyte infiltration, and improved tear secretion. Finally, topical application of Befetupitant reduced CNV in the alkali burn model but was toxic owing to the vehicle (dimethyl sulfoxide [DMSO]); hence, Befetupitant was not tested in the suture model. Conclusions The NK1R antagonist Lanepitant is safe for the ocular surface and effective in reducing both corneal hemangiogenesis and lymphangiogenesis, and leukocyte infiltration. We suggest that inhibition of NK1R may represent an adjunctive tool in the treatment of CNV.

PURPOSE To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). METHODS This was a prospective, open-label, monocentric, uncontrolled noncomparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up period of 16 weeks. The main corneal NV outcome measures were: neovascular area, the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA. RESULTS Statistically significant decreases in neovascular area (55.3%, P < 0.001), which lasted through 16 weeks, and VC (59%, P < 0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P = 0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. CONCLUSIONS Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA.

The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected noninvasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation.

PURPOSE To quantify blood and lymph angiogenesis in mouse corneal flat mounts by means of a novel plug-in for ImageJ, called VesselJ, based on a dynamic threshold algorithm. METHODS Corneal neovascularization (CNV) was induced in the right corneas of 20 C57BL6/N mice by means of alkali burn (n = 10) or intrastromal sutures (n = 10). All corneal flat mounts were stained for blood vessels with CD31 and for lymphatics with LYVE1. Three independent operators measured blood and lymphatic CNV with both a published manual method (mCNV) and VesselJ (automatic method; aCNV). RESULTS Both methods showed a strong reliability, defined as intraclass correlation coefficient (ICC) > 0.90, in quantifying hemangiogenesis for sutures and alkali burn. However, reliability of lymphatic mCNV varied from moderate in alkali burn (ICC: 0.700) to poor in sutures (ICC: 0.415), whereas it remained high in aCNV (alkali ICC: 0.996; sutures ICC: 0.959). Among sutures, a significant correlation between mCNV and aCNV was found among all the three operators for blood vessels and just for one operator for lymphatic vessels (P < 0.001). In the alkali burn model, correlation between blood mCNV and aCNV was significant for all operators after excluding three noisy flat mounts (P < 0.001), whereas no significant correlation was seen for lymphatic vessels. CONCLUSIONS VesselJ is a semiautomatic, reliable, and fast method to quantify corneal hem- and lymphangiogenesis in corneal flat mounts. VesselJ can be easily used in the sutures model; it should be applied to other models (e.g., alkali burn) only after checking for background hyperfluorescence. Italian Abstract.

Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions; however, corneal avascularity can be compromised by pathologic conditions that negate the cornea's "angiogenic privilege." The clinical relevance of corneal neovascularization has long been recognized, but management of this condition has been hindered by a lack of safe and effective therapeutic modalities. Herein, the etiology, epidemiology, pathogenesis, and treatment of corneal neovascularization are reviewed. Additionally, the authors' recent findings regarding the clinical utility of topical ranibizumab (Lucentis®) and bevacizumab (Avastin®) in the treatment of corneal neovascularization are summarized. These findings clearly indicate that ranibizumab and bevacizumab are safe and effective treatments for corneal neovascularization when appropriate precautions are observed. Although direct comparisons are not conclusive, the results suggest that ranibizumab may be modestly superior to bevacizumab in terms of both onset of action and degree of efficacy. In order to justify the increased cost of ranibizumab, it will be necessary to demonstrate meaningful treatment superiority in a prospective, randomized, head-to-head comparison study.

Aims: To report the clinical and diagnostic findings of a patient with Acanthamoeba keratitis resistant to both polyhexamethylene biguanide (PHMB)-hexamidine and chlorhexidine-hexamidine treatment. Methods: Slit-lamp biomicroscopy, corneal cell scraping and histopathology were performed on a 39-year-old woman presenting with corneal ulcer in her left eye. Results: The patient was successfully treated with PHMB-chlorhexidine association therapy. Subsequent perforating keratoplasty remained clear at the last follow-up visit after 7 months and increased visual acuity to 20/20 with correction. Conclusions: This case emphasizes the proteiform aspects of Acanthamoeba drug resistance, and suggests that PHMB-chlorhexidine association might represent an additional option for cases resistant to standard therapy.

Purpose The purpose of this study was to investigate the role of substance P (SP) in patients affected with corneal neovascularization (CNV) and in three different Tac1-knockout (KO) murine models of CNV. Methods SP levels in tears were measured with a multiplex bead assay. The extent of human CNV was quantified as number of affected corneal quadrants. Murine CNV was induced in both strains by means of total disepithelization, alkali burn, and intrastromal sutures. After death, CNV (blood and lymphatic) and leukocyte infiltration were quantified by CD31, LYVE1, and CD45 immunofluorescence, respectively. Trigeminal ganglions were collected for quantitatitive PCR IL1β quantification. Hematoxylin-eosin corneal cross sections and whole-mounted β-3-tubulin nerve staining were used to compare anatomy and nerve density of wild-type (WT) versus Tac1-KO normal mice. Results SP tear levels correlate positively with CNV extension in patients (r = 0.49, P = 0.03). After disepithelization, Tac1-KO corneas showed reduced blood and lymphatic vascularization (-34% and -51% respectively) compared with the WT counterpart. CD45+ leukocytes infiltrating the cornea were reduced in Tac1-KO mice as opposed to WT in the disepithelization (P = 0.0001), alkali burn (P = 0.0258), and suture (P = 0.0149) models. Tac1-KO mice showed reduced IL1β expression in the trigeminal ganglion. Normal WT and Tac1-KO corneas did not show significant differences in transparency, thickness, and nerve density. Conclusions Our results suggest (1) the involvement of SP in human CNV; (2) the key role of SP in promoting inflammatory CNV in three different mouse models; and (3) that absence of SP is not associated with obvious ocular surface pathology in a KO model.

Scaling of Si MOSFETs beyond the 90 nm technology node requires performance boosters in order to satisfy the International Technology Roadmap for Semiconductors (ITRS) requirements for drive current in high-performance transistors. Amongst the preferred near term solutions are transport enhanced FETs utilising strained Si (SSi) channels. Additionally, high-kappa dielectrics are expected to replace SiO2 around or after the 45 nm node to reduce the associated gate leakage current problem, facilitating further scaling. However, in spite of significant recent technological achievements, in particular, in reducing charge trapping and crystallization of the dielectric, mobility degradation in the devices with the high-kappa gate stacks caused, in part, by the strong soft optical phonon scattering leaves room for further performance improvement. In this work we study the impact of soft optical phonon scattering on the mobility and device performance for conventional and strained Si n-MOSFETs with high-kappa dielectrics using a self-consistent Poisson Ensemble Monte Carlo device simulator, with effective gate lengths of 67 and 35 nm

A critical challenge for the microelectronics industry is the need for higher permittivity dielectrics to replace silicon dioxide. A number of different high-κ materials have been proposed and analyzed as SiO2 replacements in the next generation of MOSFETs. High-κ materials allow the use of a thicker gate dielectric, maintaining the gate capacitance with reduced gate leakage. However they all lead to mobility degradation due to, among other factors, the coupling of carriers to surface soft-optical (SO) phonons. A severe mobility degradation in the presence of high-κ becomes evident when comparing the vertical field dependence of mobility for a wide range of high-κ materials against SiO2. As oxides containing Hf presently appears to be the leading high-κ contenders, we have performed a detailed analysis of Hf-based gate stacks, exploiting alternative structures and compositions. The introduction of a SiO2 interfacial layer between the channel and the HfO2 reduces the detrimental mobility degradation resulting from the mobility SO phonon scattering, but increases the equivalent oxide thickness (EOT) of the gate dielectric. A possible material of choice for the first commercial introduction of high-κ gate stacks is hafnium silicate (SixHf1−xO2), being thermally stable and offering a good compromise between small EOT and large electron mobility.

http://hdl.handle.net/20.500.11768/96868 Purpose To define proangiogenic angiopoietin 2 (ANG2) expression and role(s) in human and mouse vascularised corneas. Further, to evaluate the effect of ANG2 inhibition on corneal neovascularisation (CNV). Methods CNV was induced in FVB mice by means of intrastromal suture placement. One group of animals was sacrificed 10 days later; corneas were immunostained for ANG2 and compared with (i) mouse non-vascularised corneas and (ii) human vascularised and non-vascularised corneas. A second group of CNV animals was treated systemically with an anti-ANG2 antibody. After 10 days, the corneas were whole-mounted, stained for CD31 and LYVE1 and lymphatic/blood vessels quantified. In another set of experiments, the corneal basal Bowman membrane was either (i) removed or (ii) left in place. After 2 or 10 days the corneas were removed and immunostained for collagen IV, ANG2, CD31, LYVE1, CD11b and MRC1 markers. Results In human beings and mice, ANG2 is expressed only in the epithelium, and, mildly, in the endothelium, of the avascular cornea. Instead, it is expressed in the epithelium, endothelium and stroma of vascularised corneas. Disruption of the Bowman membrane is associated with a significant increase of (i) ANG2 stromal expression and (ii) proangiogenic macrophage infiltration in the corneal stroma. Finally, blocking ANG2 significantly reduced hemangiogenesis, lymphangiogenesis and macrophage infiltration. Conclusions Balancing proper healing and good vision is crucial in the cornea, constantly exposed to potential injuries. In this paper, we suggest the existence of a mechanism regulating the onset of inflammation (and associated CNV) depending on injury severity. ZB 0 Z8 0 ZR 0 ZS 0

HfO2 based high-κ dielectrics are among the most likely candidates to replace SiO2 and the currently favoured oxinitride in the next generation of MOSFETs. High-κ materials allow the use of a thicker gate dielectric, maintaining the gate capacitance at reduced gate leakage. However, they lead to mobility degradation due to among other factors the coupling of carriers to surface soft optical phonons. Comparing the vertical field dependence of the mobility for HfO2 and SiO2, the severe degradation in mobility in the presence of high-κ becomes evident. The introduction of a SiO2 interfacial layer between the channel and the HfO2 mitigates the interaction with the SO phonons, but increases the equivalent oxide thickness (EOT) of the gate dielectric. The material of choice for the first commercial introduction of high-κ gate stacks is Hafnium Silicate (SixHf1-xO2). This alloy stands up better to the processing challenges and as a result suffers less from dielectric fluctuations.

HfO 2 -based high- κ dielectrics are among the most likely candidates to replace SiO 2 and the currently favoured oxinitride in the next generation of MOSFETs. High- κ materials allow the use of a thicker gate dielectric, maintaining the gate capacitance with reduced gate leakage. However, they lead to a fundamental mobility degradation due to the coupling of carriers to surface soft (low-energy) optical phonons. Comparing the vertical field dependence of the mobility for HfO 2 and SiO 2 , the severe degradation in mobility in the presence of high- κ becomes evident. The introduction of a SiO 2 interfacial layer between the channel and the HfO 2 mitigates this degradation, by increasing the effective distance between the carriers and the SO phonons, thus decreasing the interaction strength, this does though lead to an increase in the equivalent oxide thickness (EOT) of the gate dielectric. The material of choice for the first commercial introduction of high- κ gate stacks is Hafnium Silicate ( Si x Hf 1 - x O 2 ) . This alloy stands up better to the processing challenges and as a result suffers less from dielectric fluctuations. We show that as the fraction of Hf increases within the alloy, the inversion layer mobility is shown to decrease due to the corresponding decrease in the energy of the surface optical phonons and increase in the dielectric constant of the oxide.

The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected non-invasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20 mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation.

Background We report the case of monolateral corneal endotheliitis, which occurred following systemic West Nile virus (WNV) infection. Methods A 56-year-old male patient with right eye (RE) endotheliitis, diffuse arthralgias, and diagnosis of previous WNV systemic infection underwent a measurement of best spectacle corrected visual acuity (BSCVA), full ophthalmic examination, biomicroscopy, and in vivo scanning laser confocal microscopy (IVCM), before and after topical immunomodulatory treatment. In addition, a polymerase chain reaction test on aqueous humor was performed to test for WNV RNA sequences. Results Photophobia was reported at presentation. A mild corneal haze was noted at the slit lamp exam. BSCVA in RE was 0.1 LogMar, corneal thickness was 667 micron, and confocal microscopy showed stromal folds. No WNV RNA sequences were detected in the aqueous humor. The cytomegalovirus and herpes virus were not tested as the patient refused additional procedures. One month after topical corticosteroid application in the RE, the patient reported significant improvement in photophobia, BSCVA improved to −0.1 LogMar, and corneal thickness was reduced to 540 microns. In addition, IVCM showed a disappearance of stromal folds. Conclusions A presumptive diagnosis of WNV-associated endotheliitis was formulated. Improvement following topical corticosteroid treatment suggests an immune-based pathophysiology.

PURPOSE To test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG), a structure located in the brain. METHODS At 4 and 8 days after alkali burn induced in the right eyes of mice, in vivo magnetic resonance imaging (MRI) of the brain was done before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers. Interleukin-1β, TNF-α, and VEGF-A transcripts were quantified on days 1, 4, and 8, and 4 days after corneal topical anti-inflammatory treatment with 0.2% dexamethasone. The expression of Substance P and its receptor NK-1R was also measured in the TG on day 4. RESULTS Corneal alkali burn induced leukocyte infiltration, including T cells, in the right TG at 4 and 8 days. In vivo MRI showed an increased contrast uptake in the right TG, which peaked at day 8. Prussian Blue(+) USPIO(+) macrophages were observed in the right TG and exhibited an M2 phenotype. The M2-macrophage infiltration was preponderant in the TG after damage. The proinflammatory cytokines Substance P and NK-1R were significantly increased in both the TGs. The expression of IL-1β and VEGF-A was significantly reduced in the right TG with dexamethasone treatment. CONCLUSIONS We suggest, for the first time, inflammatory involvement of brain structures following ocular surface damage. Our findings support the hypothesis that the neuropeptide Substance P may be involved in the propagation of inflammation from the cornea to the TG through corneal nerves.

Background It has been recently observed that small fibre neuropathy (SFN) may present as distal symmetrical polyneuropathy and with atypical non-length-dependent pattern. Objective To describe a small series of patients with non-length-dependent SFN, investigating corneal innervation with corneal confocal microscopy (CCM). Methods Evaluation of the corneal nerve fibre density using CCM in six women with non-length-dependent SFN. The patients were characterised by sensory disturbance involving proximal regions of the limbs, face and trunks, and the diagnosis was confirmed by the findings of decreased intraepidermal nerve fibre density on skin biopsy. Results Six women, aged 35–64, had non-length-dependent SFN, related to Crohn disease, impaired glucose tolerance and Sjogren9s syndrome, or idiopathic (three cases). In all patients, CCM demonstrated decreased corneal nerve fibre density (12.5–23.4/mm 2 ; normal, >30.6/mm 2 ). Conclusion Non-length-dependent SFN may represent an intriguing diagnostic problem because of its puzzling presentation and the need for special investigations for its confirmation. In this perspective, CCM may provide a useful, non-invasive tool to complement the diagnostic workup.

The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy.To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction.Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial.Seventy-five patients with refractory DED.Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks.Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality.Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P.001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms.Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681109.

PURPOSE To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.

Collagen crosslinking (CXL) has been proposed as a treatment for infectious keratitis. Given the insurgence of antibiotic-resistant microorganisms and frequent toxicity of topical medications, CXL may be a potential treatment for corneal infections. However, corneal infection is itself a possible complication of this treatment. We describe a case of severe corneal thinning and melting in a woman who had a CXL procedure as a treatment for herpetic keratitis. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Background Goldenhar Syndrome is characterized by malformations of multiple anatomical districts. Between these, bulbar dermoids are common and represent a significant clinical problem as they can affect both ocular function and aesthetic comfort. Histologic characterization of dermoids has been extensively performed; however, no reports exist describing in vivo confocal microscopy (IVCM) of these lesions. We aimed to (i) describe the in vivo confocal morphology of limbal dermoids in Goldenhar syndrome and (ii) compare these findings with standard light microscopy. Case presentation A 15-year-old Caucasian female affected by Goldenhar Syndrome showed a left, infero-temporal, limbal neoformation, with extension to the left orbital region. Prior to surgical removal, IVCM was performed with the Heidelberg Retina Tomograph II, Cornea Module, using the “section” modality. The IVCM sections showed structures resembling corneal epithelium and vascular structures. Surgical removal of the lesion was decided as it caused poor eyelid closure. After surgical removal, sectioning and standard optical microscopy were performed. The comparison between IVCM imaging and standard microscopy sections were highly correlated in the detection of the pilar and vascular structures. Conclusions This study showed that IVCM may be a useful technique to study limbal dermoids, given its ability to detect typical microscopic features and its comparability to optical microscopy, which is the current standard.

The effective potential originated by the nonplanar geometry of a two-dimensional electron gas (2DEG) modifies its coherent transport properties. To date no direct evidence of such purely geometric potential has been revealed. Here we expose its effects by computing the transmission characteristics of a semiconductor cylindrical 2DEG forming a Y junction. For some cylinder radii, we find that the activation thresholds of the transmission channels in the two drain leads are exchanged, with this effect being robust against the geometrical details of the three-terminal junction.

We study the electronic states of core multi-shell semiconductor nanowires, including the effect of strong magnetic fields. We show that the multi-shell overgrowth of a free-standing nanowire, together with the prismatic symmetry of the substrate, may induce quantum confinement of carriers in a set of quasi-1D quantum channels corresponding to the nanowire edges. Localization and inter-channel tunnel coupling are controlled by the curvature at the edges and the diameter of the underlying nanowire. We also show that a magnetic field may induce either Aharonov-Bohm oscillations of the energy levels in the axial configuration, or a dimensional transition of the quantum states from quasi-1D to Landau levels for fields normal to the axis. Explicit predictions are given for nanostructures based on GaAs, InAs, and InGaN with different symmetries., Comment: 13 pages, 4 figures, To be published in Nano Letters

In the past years a strong attention has been focused on the optical and transport properties of semiconductor hetero-structures owing to the possibility of tailoring material parameters such as the electron effective mass and the band gap, by changing the structure parameters. Recent experimental results on InxGa1−xAs structures cannot be explained in the framework of standard theoretical and simulative approaches for the description of carrier transport in quantum wells. In order to get a better insight on the effect of the surface roughness on the conductance, we have considered meandering quantum wires and have computed their coherent transport characteristics. We find that, at low energies, the transmission coefficient is strongly dependent on the SR parameters. The dependence of conductance upon length of the device is also analyzed.

Publisher Summary This chapter explains the concepts behind the invention, programming, and behavior of the LEGO Turing Machine. The Turing Machine is a very primitive sort of computer; the simplest possible machine that could perform computation, and an ancestor of any modern computer. It can be considered as a grandparent of RCX. The first and main part of the original Turing Machine consists of a tape of infinite length, divided into cells. Each cell has just enough space for a single symbol to be written. A head reads and writes on the tape, and can move one cell at a time, moving to either the left or to the right. The device itself is always in one of a finite number of states. These states determine what action the machine should perform via a special programming feature called a state transition table (or action table). The state transition table tells the Turing Machine what to do when it is in a certain state and encounters a specific symbol. Finally, the chapter illustrates the programming of LEGO Turing Machine using NQC.

orneal nerves are known to con-tribute significantly to ocularsurface integrity. A normal cornealinnervation is required for a normaltear secretion and flow. In fact, dryeye disease is defined as a disorder ofthe lacrimal functional unit, an inte-grated system comprising the sensoryand motor nerves (DEWS 2007). Cor-neal nerve depletion reduces tearsecretion by decreasing reflex-inducedlacrimal secretion and by reducing theblink rate. Moreover, corneal nervessecrete up to 17 different mediatorssuch as nerve growth factor and oth-ers, which have profound effects oncorneal surface homoeostasis (Mu¨lleret al. 2003).Damage to the sensory nerves in theocular surface, particularly the cornea,is common in a number of conditions,including refractive surgery, keratopl-asty and even normal ageing (He et al.2010). Corneal nerve damage oftenoccurs in concomitance with inflam-mation elicited by surgery or drugs;hence, it is difficult to precisely dissectthe role of corneal nerves in dry eye.We recently developed a murinemodel of corneal denervation (TSE,Trigeminal Stereotactic Electrolysis)where we selectively ablate the oph-thalmic branch of the trigeminal nerve(Ferrari et al. 2011). We used thismodel to test whether and to whichextent selective sensory nerve ablationcould induce dry eye in terms of (i)tear secretion and (ii) corneal fluores-cein staining.Eight eyes of eight C57BL⁄6 micewere used. Animals were examinedbefore and 7 days after TSE. Theeffectiveness of the procedure wasconfirmed by the absence of blinkreflex (Ferrari et al. 2011). At the endof the procedure, a complete tars-orrhaphy was performed to minimizethe effect of absent blink reflex. Theanimals were examined using a biomi-croscope, and tear production wasquantified with phenol red thread test.Finally, the corneas were stained withfluorescein and scored according tothe National Eye Institute GradingSystem.Before TSE was performed, biomi-croscopy revealed a normal cornea.Corneal fluorescein staining was nega-tive before TSE (score, 0) and phenoltest was 2.59 ± 0.44 mm (mean ±SD). Corneal reflex was tested with acotton thread and found to be presentin all the eyes. Following TSE, corneafluorescein staining score was10.39 ± 2.20 (mean ± SD), phenoltest decreased to 0.52 ± 0.36 mm(mean ± SD) and corneal reflex wasabsent in all the eyes (Fig. 1). AfterTSE, we found significant differencesin both the fluorescein score (p

Publisher Summary The most known characteristic creation of Logo is the Turtle; it is a symbolic turtle that moves across the computer screen according to the instruction it receives. With simple instructions like “forward 10” the turtle moves straight ten units, and with “right 90” it turns clockwise to 90 degrees. The statements “pen-up” and “pen-down” specify whether the turtle leaves a track behind it, thus producing drawings or rather just moving to a different location. The language includes many other commands, but these are enough to understand the principles of the Turtle Graphics that made Logo so famous. The idea behind building the turtle is about building a small robotic platform that is able to go forward and backward, turn in place, and lower and raise a pen. Despite this apparent simplicity, if one wants a turtle that works as expected, the task has many stringent requirements that must be adhered to. For instance, the robot must go absolutely straight, the pen must be exactly in the pivoting point of the robot, because it must stay in the same place on the floor while the robot turns, and one needs a tracking system to measure both the traveled distances and angles.

The ability to find a way through a maze is considered a good test of intelligence, and has been used with mice and other animals to measure their capacities. This chapter briefly provides an overview of solving a maze. In addition, it explains what knowledge and skills are necessary to find the way out. Analysis is important to implement maze solving: one requires a strategy and it has to be detailed enough to be translated into program instructions for a robot. Finding one's way in a labyrinth is a special case of navigation and requires some abilities, with the addition of some memory to remember. There are several techniques discussed to find a way, such as using the left side–right side strategy. This technique solves an incredibly large class of mazes, its rule being quite simple to remember and apply. It states that, when applicable, if one follows the left wall and turns left whenever possible, one will find the exit. To be more precise, if following the right wall then one should use the same route or follow the left wall from the exit to the entrance.

Publisher Summary This chapter illustrates some ways to build arms, hands, clamps, pliers, and other tools to grab and handle objects. One of the basic measurements of movement explored in this chapter is the degree of freedom (DOF), or the number of directions in which an object (like a robotic arm) has a range of motion. Every independent movement represents a degree of freedom (DOF), something that can happen without affecting and being affected by other movements in the same device. The DOF concept helps in understanding the terms of numbers why simple hands diverged so widely from the flexibility a human hand has. This chapter explains that finding the object is the hardest part of the job, but there are cases where one can use a random search pattern, or where the object sits on the robot's path, as in the line following example.

Publisher Summary This chapter discusses some projects that could be considered “classic,” because almost everybody with a MINDSTORMS kit tries them sooner or later. With exploring the room, the task is to build a robot with the basic ability to move around, detect obstacles, and change its route accordingly. If a room has a flight of stairs going down, one can equip the robot with a kind of detector to sense the edge and avoid a bad fall. There is a theme that pervades this chapter concerns the care one should put into the particulars: building a robot that works roughly as expected, compared to looking for optimal performance are two very different approaches. The concept behind the design of a robot is an important element in regard to its functioning; this chapter explains how shifting from the differential drive to the steering drive can have an impressive effect on the resulting efficiency.

Publisher Summary This chapter provides a brief discussion of various electronic games, such as pinball machine, Simon-says games, and other electronic games. The pinball machine is probably the only survivor in the gaming arcade's evolution to electronics. To build a pinball machine, an incredible amount of parts are used: most of the parts are plain 2 x n bricks. The surface of the pinball is built with bricks turned on their side. This technique allows achieving a smooth surface without using tiles, and makes it easy to insert sensors, axle pegs, and anything else that needs a vertical mount over the surface. Programming a pinball is not very complicated. When the game starts, the score is reset to zero, and the ball counts to the initial number. Furthermore, the Simon says game is inspired by Milton Bradley's commercial product Simon, which has had great success among families. It is not an arcade game, but is still very challenging and devised for players to compete against themselves or others. The purpose of the game is to copy the sequence performed by the machine. It starts with just one light, then the sequence of lights becomes longer and longer as the game proceeds. Every time the user successfully reproduces the series, the machine plays it again, adding one more light to the end of the sequence.

Publisher Summary This chapter focuses on designing and constructing a LEGO robot and mainly focuses on two projects that are of a mouse and turtle. Mouse is a simple project, which uses one motor and two touch sensors, and it's easy to replicate using only the parts contained in the Robotic Invention System. The turtle, on the contrary, is a bit more sophisticated and requires a few additional parts. The LEGO turtle project is ambitious than the mouse project. The most relevant parts in turtles are the legs. In contrast to mouse, the turtle robot walks on feet and uses leg geometry. The turtle does not only employ its legs to support its weight, but it helps itself along with the rest of the body. In describing the mouse, the goal was to limit its size. This led to use a variant of the steering drive configuration, which, at the price of reduced control regarding direction, works with a single motor. Another goal was to make the robot very fast, which resulted in the use of wheels instead of true legs. The turtle project started with a different premise: the robot could be slow or had to be slow, thus a legged configuration was quite appropriate.

Publisher Summary Pneumatics is the discipline that describes gas flows and how to use its properties to transmit energy or convert the same into force and motion. Most pneumatic applications use that gaseous mixture most widely available—air—and the LEGO world is no exception. Pneumatics is a great tool for robotics, and is especially useful when mechanisms need linear motion or an elastic behavior. It is also very useful as a way to store energy for subsequent uses. The most important property of pneumatics is that they have neither specific shape nor volume, because they expand and fill all available space within a container. This means that the quantity of gas inside a tank does not solely depend on the tank's volume. The greater the quantity of gas in a given volume, the higher is its pressure. The fact that gases are so easy to compress is what makes pneumatics different from hydraulics (the science of liquid flow). Essentially, liquids are uncompressible. When an individual compresses a gas into a tank, increasing its pressure, he is storing energy. Pressure can be interpreted also as a density of energy, that is, the quantity of energy per unit volume. This leads to a very interesting application of pneumatics: one can use tanks to accumulate energy, which can then be later released when needed.

Publisher Summary This chapter deals with competitions where the rival robots fight face-to-face in a spectacular way. The technical aspects of building a successful Sumo robot are important, the design requires much more than simply putting together a few mechanical solutions: it requires a strategy. The process starts before building a robot. It begins by examining the rules carefully, understanding what one can and cannot do, and deciding a line of action. Also, one must try to imagine what the opponents strategy can be, plan the robot to be able to resist their attacks, and then take advantage of their weak points. The making of a strong Sumo robot requires much more than just brute force. When optimizing the pushing power of a robot, the first thing required is an objective way to measure it. Without measuring the force, the improvements one make are subjective and as a result are very inaccurate. While building and programming a robot, one should make reliability the first priority.

Publisher Summary This chapter briefly discusses the gears and discovers the powerful qualities they offer, transforming one force into another almost magically. A single gear wheel alone is not very useful, unless there is a different usage from what it was conceived for. One of the finest properties of gears is that this conversion is symmetrical: one can convert torque into velocity or vice versa. And the math required to manage and understand the process is as simple as doing division. Gears are not the only way to transfer power the present that pulley–belt systems, as well as chains, serve the same purpose and helps in connecting distant systems. Belts provide an intrinsic torque-limiting function, and do well in high-speed low-torque situations. Chains, on the other hand, don't limit torque but do increase friction, so they are more suitable for transferring power at slow speeds.