Broad Defect Research Articles

Prevalence, characteristics, and pathogenesis of paravascular inner retinal defects associated with epiretinal membranes.

To investigate the prevalence, detailed characteristics, and pathogenesis of paravascular inner retinal defects (PIRDs) in eyes with epiretinal membranes (ERMs). In this prospective observational case series, we included 81 eyes of 81 patients with idiopathic ERMs, without high myopia. The retinal structure surrounding the PIRDs was assessed using sequential thin sectioning of optical coherence tomography. The PIRDs were classified into three grades. Typical defects of the inner retinal tissue were defined as grade 3. Inner retinal cleavages with openings to the vitreous cavity and no apparent defect of the inner retinal tissue were defined as grade 2. Inner retinal cleavages or cystoid spaces with no connection to the vitreous cavity were defined as grade 1. Of 81 eyes with ERMs, 31 (38.3%) had PIRDs along the temporal arcade vessels (grade 1 in six eyes, grade 2 in four eyes, and grade 3 in 21 eyes). PIRDs were frequently accompanied by broad defects of the inner retinal tissue (grade 3). Although some ERMs directly adhered to the edge of a PIRD or the retinal vessels, PIRDs were often located outside the area of adhesion to the ERM. In some OCT sections, vitreous traction on the inner retina seemed to contribute to the progression of PIRDs. Visual field abnormalities corresponded to the location of the PIRDs in 44.4% of eyes with grade 3 PIRDs. Deviation of retinal vessels due to the traction of the ERMs may contribute to the pathogenesis of PIRDs. PIRDs often cause visual field abnormalities corresponding to the location of the defect.

The fine structure of electron irradiation induced EL2-like defects in n-GaAs

Defects induced by electron irradiation in n-GaAs have been studied using deep level transient spectroscopy (DLTS) and Laplace DLTS (L-DLTS). The E0.83 (EL2) is the only defect observed prior to irradiation. Ru/n-GaAs Schottky diodes were irradiated with high energy electrons from a Sr-90 radionuclide up to a fluence of 2.45 × 1013 cm−2. The prominent electron irradiation induced defects, E0.04, E0.14, E0.38, and E0.63, were observed together with the metastable E0.17. Using L-DLTS, we observed the fine structure of a broad base EL2-like defect peak. This was found to be made up of the E0.75, E0.83, and E0.85 defects. Our study reveals that high energy electron irradiation increases the concentration of the E0.83 defect and introduces a family of defects with electronic properties similar to those of the EL2.

Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis.

The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. In contrast, in leukocytes rendered tolerant by exposure to lipopolysaccharide or after isolation from patients with sepsis and immunoparalysis, a generalized metabolic defect at the level of both glycolysis and oxidative metabolism was apparent, which was restored after recovery of the patients. Finally, the immunometabolic defects in humans were partially restored by therapy with recombinant interferon-γ, which suggested that metabolic processes might represent a therapeutic target in sepsis.

Strictly monolayer large continuous MoS2 films on diverse substrates and their luminescence properties

Despite a tremendous interest on molybdenum disulfide as a thinnest direct band gap semiconductor, single step synthesis of a large area purely monolayer MoS2 film has not yet been reported. Here, we report a CVD route to synthesize a continuous film of strictly monolayer MoS2 covering an area as large as a few cm2 on a variety of different substrates without using any seeding material or any elaborate pretreatment of the substrate. This is achieved by allowing the growth to take place in the naturally formed gap between a piece of SiO2 coated Si wafer and the substrate, when the latter is placed on top of the former inside a CVD reactor. We propose a qualitative model to explain why the MoS2 films are always strictly monolayer in this method. The photoluminescence study of these monolayers shows the characteristic excitonic and trionic features associated with monolayer MoS2. In addition, a broad defect related luminescence band appears at ∼1.7 eV. As temperature decreases, the intensity of this broad feature increases, while the band edge luminescence reduces.

Influence of laser repetition rate on the structural and optical properties of GaN layers grown on sapphire (0001) by laser molecular beam epitaxy

High-quality GaN layers were grown on sapphire (0001) substrates using laser molecular beam epitaxy (LMBE) by laser ablating a solid GaN target at different laser repetition rates (10–40 Hz) under a constant supply of r.f. nitrogen plasma. The effect of laser repetition rate on the structural and optical properties of GaN layers was systematically studied using high-resolution X-ray diffraction (HRXRD), field emission scanning electron microscopy, atomic force microscopy, Raman spectroscopy and photoluminescence (PL) spectroscopy. High-resolution X-ray rocking curve measurements revealed highly c-axis oriented GaN layers on sapphire grown at 30 Hz with a calculated screw dislocation density of ~1.42 × 107 cm−2, whereas the GaN layers grown at 10 or 40 Hz consisted the screw dislocation density in the range of 108–109 cm−2. Surface morphological analysis revealed a change in grain size as well as surface roughness as a function of laser repetition rate and is explained on the basis of growth kinetics. Vibrational Raman spectroscopy revealed that the GaN layer grown at 10 Hz shows an in-plane compressive stress of ~1 GPa, while the film grown at 30 Hz exhibits a minimum stress of ~0.3 GPa. The PL measurements show a highly luminescent band-to-band emission of GaN at 3.44 eV for the 10 Hz grown highly strained GaN layer and at 3.41 eV for the less strained film grown at 30 Hz along with a broad defect band emission centered around 2.28 eV. It is found that the GaN layers grown at 30 Hz have excellent structural and optical properties. We expect that the less strained thin and highly oriented GaN film grown by LMBE can further be utilized for developing prodigious low-temperature-grown nitride-based multilayer structures and devices.

The Usefulness of Laparoscopy in the Treatment of Incarcerated Internal Hernia through a Defect in the Broad Ligament

Hernias through the broad ligament are rare with a reported incidence of only 4-7% of cases of internal hernias. Here, we report on a rare case of incarcerated internal hernia through a spontaneous defect in the broad ligament which was repaired using a laparoscopic technique. A 41-year-old female was admitted with colic abdominal pain. Laparoscopic exploration was performed for the diagnosis of intestinal obstruction. Laparoscopic examination confirmed an approximately 10-㎝-long ileal loop herniated in the anterior to posterior direction through a left broad ligament defect. A large defect in the broad ligament was closed by an intracorporeal continuous running suture. The patient was highly satisfied with the cosmetic result. In conclusion, laparoscopy could be particularly helpful during pelvic surgery, which usually requires large skin incisions to ensure a good field of view. This approach was cosmetically effective, decreased the postoperative complications, and promoted early recovery to usual activity.

Enhanced UV Emission From Silver/ZnO And Gold/ZnO Core-Shell Nanoparticles: Photoluminescence, Radioluminescence, And Optically Stimulated Luminescence.

The optical properties of core-shell nanoparticles consisting of a ZnO shell grown on Ag and Au nanoparticle cores by a solution method have been investigated. Both the ZnO/Ag and ZnO/Au particles exhibit strongly enhanced near-band-edge UV emission from the ZnO when excited at 325 nm. Furthermore, the UV intensity increases with the metal nanoparticle concentration, with 60-fold and 17-fold enhancements for the ZnO/Ag and ZnO/Au, core-shell nanoparticles respectively. Accompanying the increase in UV emission, there is a corresponding decrease in the broad band defect emission with nanoparticle concentration. Nonetheless, the broad band luminescence increases with laser power. The results are consistent with enhanced exciton emission in the ZnO shells due to coupling with surface plasmon resonance of the metal nanoparticles. Luminescence measurements during and after exposure to X-rays also exhibit enhanced UV luminescence. These observations suggest that metal nanoparticles may be suitable for enhancing optical detection of ionizing radiation.

Broad ligament defects as a cause of chronic pelvic pain

We report a case of a woman with chronic right-sided pelvic pain with an unusual combination of broad ligament defects and associated terminal ileum and caecum herniation. Reduction of the hernia and closure of the defects at laparoscopy resulted in resolution of the patient’s painful symptoms. Review of the literature suggests that, although rare, such defects should be considered in the differential diagnosis of persistent pelvic pain. Where found incidentally, broad ligament defects should be repaired in order to prevent sinister complications such as bowel obstruction and strangulation.

Case Report of GNAS Epigenetic Defect Revealed by a Congenital Hypothyroidism

Pseudohypoparathyroidism (PHP) is a group of disorders characterized by end-organ resistance to the parathyroid hormone (PTH). PHP type 1A includes multihormone resistance syndrome, Albright's hereditary osteodystrophy, and obesity and is caused by mutations in GNAS exon 1 through 13. PHP type 1B (PHP1B), caused by epigenetic changes in the GNAS locus, was initially described as an isolated resistance to PTH. Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS. Here we report a case of PHP caused by epigenetic changes in GNAS in a patient with congenital hypothyroidism. The patient was referred for a positive newborn screening for hypothyroidism (TSH 50 mIU/L). She exhibited severe clinical features of congenital hypothyroidism. The thyroid was in place, and etiologic explorations were negative. TSH was normalized under L-thyroxin, and the symptoms disappeared, except for a macroglossia. In childhood, PHP was suspected in addition to elevated PTH, obesity, brachydactyly, and a rounded face. Sequencing, methylation analysis, and large deletion research were performed in GNAS. No genetic mutations were found. Methylation analysis revealed a broad epigenetic defect without deletion in GNAS consistent with sporadic PHP1B. The multilocus methylation analysis were negative. This finding expands the known onsets of PHP1B and emphasizes the need for a new PHP classification system. This case report has important consequences for the etiologic diagnosis of congenital hypothyroidism because it adds a new cause of the disease.

A-T flap for the reconstruction of an operative wound in the malar region

The malar region is the site of skin tumors and sometimes a primary closure is not possible after the excision of the lesion. The A-T flap is a good method for reconstructing an broad and deep defect in which the local surrounding tissue does not allow direct closure. The present study describes the implementation of an A-T flap as an option for the reconstruction of an operative wound secondary to the excision of a basal cell carcinoma.

Regulation of C. elegans neuronal differentiation by the ZEB-family factor ZAG-1 and the NK-2 homeodomain factor CEH-28.

The C. elegans pharyngeal neuron M4 is a multi-functional cell that acts as a cholinergic motor neuron to stimulate peristaltic pharyngeal muscle contraction and as a neuroendocrine cell secreting neuropeptides and growth factors to affect other cells both inside and outside the pharynx. The conserved transcription factors ZAG-1 and CEH-28 are co-expressed in M4 through most of development, and here we examine how these factors contribute to M4 differentiation. We find ZAG-1 functions upstream of CEH-28 in a branched pathway to activate expression of different sets of M4 differentiation markers. CEH-28 activates expression of the growth factor genes dbl-1 and egl-17, and the neuropeptide genes flp-5 and flp-2, while ZAG-1 activates expression of the serotonin receptor ser-7, as well as expression of ceh-28 and its downstream targets. Other markers of M4 differentiation are expressed normally in both zag-1 and ceh-28 mutants, including the neuropeptide gene flp-21 and the acetylcholine biosynthetic gene unc-17. Unlike ceh-28 mutants, zag-1 mutants completely lack peristaltic muscle contractions resulting from broader defects in M4 differentiation. Despite these defects, neither ZAG-1 nor CEH-28 are terminal selectors of the M4 phenotype, and we suggest they function in a hierarchy to regulate different aspects of M4 differentiation.

Depletion of the Central Metabolite NAD Leads to Oncosis-mediated Cell Death

Depletion of the central metabolite NAD in cells results in broad metabolic defects leading to cell death and is a proposed novel therapeutic strategy in oncology. There is, however, a limited understanding of the underlying mechanisms that connect disruption of this central metabolite with cell death. Here we utilize GNE-617, a small molecule inhibitor of NAMPT, a rate-limiting enzyme required for NAD generation, to probe the pathways leading to cell death following NAD depletion. In all cell lines examined, NAD was rapidly depleted (average t½ of 8.1 h) following NAMPT inhibition. Concurrent with NAD depletion, there was a decrease in both cell proliferation and motility, which we attribute to reduced activity of NAD-dependent deacetylases because cells fail to deacetylate α-tubulin-K40 and histone H3-K9. Following depletion of NAD by >95%, cells lose the ability to regenerate ATP. Cell lines with a slower rate of ATP depletion (average t½ of 45 h) activate caspase-3 and show evidence of apoptosis and autophagy, whereas cell lines with rapid depletion ATP (average t½ of 32 h) do not activate caspase-3 or show signs of apoptosis or autophagy. However, the predominant form of cell death in all lines is oncosis, which is driven by the loss of plasma membrane homeostasis once ATP levels are depleted by >20-fold. Thus, our work illustrates the sequence of events that occurs in cells following depletion of a key metabolite and reveals that cell death caused by a loss of NAD is primarily driven by the inability of cells to regenerate ATP.

Structural, compositional, and photoluminescence characterization of thermal chemical vapor deposition-grown Zn3N2 microtips

The catalytic growth of Zn3N2 using guided-stream thermal chemical vapor deposition has been investigated within the parameter range of acicular growth to obtain uniform microtips with a high crystalline quality. The cubic anti-bixbyite crystal structure of Zn3N2 microtips and its related phonon mode are revealed by X-ray diffraction and Raman spectroscopy, respectively. The surface morphologies of pure and surface-oxidized Zn3N2 microtips are depicted by scanning electron microscopy and show the crack formation on the surface-oxidized Zn3N2 microtips. The spatial element distribution map confirms the VLS growth mechanism for Zn3N2 microtips and reveals the depth profile of zinc, nitrogen, oxygen, and nickel elements. Photoluminescence (PL) spectra of Zn3N2 microtips show a sharp infrared band-to-band emission peak at 1.34 eV with a full width at half maximum of ∼100 meV and a very broad oxygen-related defect band emission peak centered at ∼0.85 eV.

Operative Interventions for Clivus Osteoradionecrosis with CSF Leak following Stereotactic Radiosurgery for Nasopharyngeal Carcinoma

Objectives: Nasopharyngeal carcinoma (NPC) local recurrence still represents a major clinical challenge and a high mortality and morbidity cause. The authors report a case of a 44-year-old male with clivus osteoradionecrosis (ORN) and dural radionecrosis who presented with cerebrospinal fluid (CSF) leak, 6 months after a boost of stereotactic radiosurgery using gamma knife for the treatment of locally recurrent NPC, following conventional external beam radiotherapy (EBRT) with chemotherapy. Methods: A direct transnasal endoscopic-assisted approach with multiple reconstructive pedicled flap technique was used to achieve watertight dural reconstruction. Results: Despite CSF leak recurrence, after the second attempt we achieved a successful clivus reconstruction using a bilateral posterior pedicle inferior turbinate flap (PPITF). The reconstruction withstood a watertight seal for 1 month, until patient death from cardiopulmonary arrest as a result of ventilator-associated pneumonia. Conclusions: We recommend an early diagnosis and surgical intervention in the setting of clivus ORN. Local debridement of necrotic bone is critical for local nasal graft adherence and survival. The evidence of dural radionecrosis is a predictor of bad prognosis. As a result, broad dural defect exposition should be the standard procedure with the use of a multi-layered technique combined with vascularized pedicle flaps regardless of the dural tear dimension.

Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3.

Insulinoma associated 1 (Insm1) plays an important role in regulating the development of cells in the central and peripheral nervous systems, olfactory epithelium and endocrine pancreas. To better define the role of Insm1 in pancreatic endocrine cell development we generated mice with an Insm1GFPCre reporter allele and used them to study Insm1-expressing and null populations. Endocrine progenitor cells lacking Insm1 were less differentiated and exhibited broad defects in hormone production, cell proliferation and cell migration. Embryos lacking Insm1 contained greater amounts of a non-coding Neurog3 mRNA splice variant and had fewer Neurog3/Insm1 co-expressing progenitor cells, suggesting that Insm1 positively regulates Neurog3. Moreover, endocrine progenitor cells that express either high or low levels of Pdx1, and thus may be biased towards the formation of specific cell lineages, exhibited cell type-specific differences in the genes regulated by Insm1. Analysis of the function of Ripply3, an Insm1-regulated gene enriched in the Pdx1-high cell population, revealed that it negatively regulates the proliferation of early endocrine cells. Taken together, these findings indicate that in developing pancreatic endocrine cells Insm1 promotes the transition from a ductal progenitor to a committed endocrine cell by repressing a progenitor cell program and activating genes essential for RNA splicing, cell migration, controlled cellular proliferation, vasculogenesis, extracellular matrix and hormone secretion.

A facile route towards the preparation of ZnSe nanocrystals

Zinc selenide (ZnSe) nanocrystals (NCs) have been synthesized using oleic acid (OA) as capping agent via a simple chemical route. The zinc blende phase of ZnSe NCs has been predicted form the X-ray diffraction (XRD) analysis. The results of transmission electron microscopy (TEM) demonstrated the spherical shape of ZnSe NCs with the diameters in the range of 3 to 6nm. Fourier transform infrared (FTIR) spectroscopy indicates that OA ligands were bound strongly on the ZnSe nanocrystal surface as a carboxylate. The optical absorption of ZnSe NCs displays blue shift with respect to bulk due to size quantization effect. Photoluminescence (PL) of the ZnSe NCs shows a broad defect level emission between 400 and 700nm.

Low Temperature Mn Doped ZnO Nanorod Array: Synthesis and Its Photoluminescence Behavior

The present study focused on low temperature synthesis of Mn doped ZnO nanorod array film via chemical bath deposition method on glass substrates. Microstructural, morphological, and optical properties of Mn doped ZnO nanorods were investigated. X-ray diffraction patterns showed sharp and intense peaks, indicating the highly crystalline nature of the film. Energy dispersive X-ray (EDAX) results confirmed the presence of Mn ions in ZnO nanorods. Scanning electron microscopy (SEM) pictures suggested Mn doped ZnO nanorods were well aligned and distributed throughout the surface. Vibrational analysis has been carried out by Fourier transform infrared and Raman spectroscopy. Room temperature photoluminescence (PL) exhibited the presence of one broad defects related band in the visible region ranging 440–640 nm. Blue shifting in the absorption edge with Mn doping was observed in absorption spectra.

Targeted modification of complex N-glycosylation results in a spontaneous CVID-like immunodeficiency with anti-lymphocyte autoimmunity (BA14P.204)

Abstract Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency affecting humans. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG antibody production to infection or vaccination. Many patients also exhibit symptoms of abnormal T cell function, including an apparent lack of naïve T cells which correlates with clinical severity. We describe here one of the first animal models of spontaneous CVID that incorporates aspects of both humoral and T cell dysfunction. The CVID mice exhibit characteristic deficiencies in IgG responses to both protein and polysaccharide vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity due to a persistent autoimmune response depleting naïve T cells, which appears to be mechanistically linked to changes in erythrocyte surface N-glycosylation. The N-glycosylation dependent auto-epitopes that emerge on erythrocytes were found to cross-react with naïve T cells independent of changes to the latter’s glycosylation profile. While the use of Ig replacement therapy and antibiotics has reduced the number of infections in CVID, the major inflammatory complications such as lung disease, cancer, and autoimmunity still develop; thus our findings provide potential insight into human CVID beyond hypogammaglobulinemia by addressing the mechanisms that may contribute to the more broad defects in adaptive immunity linked to clinical severity.

Rhythmic U2af26 Alternative Splicing Controls PERIOD1 Stability and the Circadian Clock in Mice

The circadian clock drives daily rhythms in gene expression to control metabolism, behavior, and physiology; while the underlying transcriptional feedback loops are well defined, the impact of alternative splicing on circadian biology remains poorly understood. Here we describe a robust circadian and light-inducible splicing switch that changes the reading frame of the mouse mRNA encoding U2-auxiliary-factor 26 (U2AF26). This results in translation far into the 3' UTR, generating a C terminus with homology to the Drosophila clock regulator TIMELESS. This new U2AF26 variant destabilizes PERIOD1 protein, and U2AF26-deficient mice show nearly arrhythmic PERIOD1 protein levels and broad defects in circadian mRNA expression in peripheral clocks. At the behavioral level, these mice display increased phase advance adaptation following experimental jet lag. These data suggest light-induced U2af26 alternative splicing to be a buffering mechanism that limits PERIOD1 induction, thus stabilizing the circadian clock against abnormal changes in light:dark conditions.

Generation of vacancy cluster-related defects during single MeV silicon ion implantation of silicon

Deep Level Transient Spectroscopy (DLTS) has been used to study defects formed in bulk silicon after implantation of 8.3MeV 28Si3+ ions at room temperature. For this study, Schottky diodes prepared from n-type Czohralski-grown silicon wafers have been implanted in the single ion regime up to fluence value of 1×1010cm−2 utilizing the scanning focused ion microbeam as implantation tool and the Ion Beam Induced Current (IBIC) technique for ion counting.Differential DLTS analysis of the vacancy-rich region in self-implanted silicon reveals a formation of the broad vacancy-related defect state(s) at Ec −0.4eV. Direct measurements of the electron capture kinetics associated with this trap at Ec −0.4eV, prior to any annealing do not show an exponential behaviour typical for the simple point-like defects. The logarithmic capture kinetics is in accordance with the theory of majority carrier capture at extended or cluster-related defects. We have detected formation of two deep electron traps at Ec −0.56eV and Ec −0.61eV in the interstitial-rich region of the self-implanted silicon, before any annealing. No DLTS signal originating from vacancy-oxygen trap at Ec −0.17eV, present in the sample irradiated with 0.8MeV neutrons, has been recorded in the self-implanted sample.