An electrically-driven GaAs nanowire surface plasmon source.

Over the past decade, the properties of plasmonic waveguides have extensively been studied as key elements in important applications that include biosensors, optical communication systems, quantum plasmonics, plasmonic logic, and quantum-cascade lasers. Whereas their guiding properties are by now fairly well-understood, practical implementation in chipscale systems is hampered by the lack of convenient electrical excitation schemes. Recently, a variety of surface plasmon lasers have been realized, but they have not yet been waveguide-coupled. Planar incoherent plasmonic sources have recently been coupled to plasmonic guides but routing of plasmonic signals requires coupling to linear waveguides. Here, we present an experimental demonstration of electrically driven GaAs nanowire light sources integrated with plasmonic nanostrip waveguides with a physical cross-section of 0.08λ(2). The excitation and waveguiding of surface plasmon-polaritons (SPPs) is experimentally demonstrated and analyzed with the help of full-field electromagnetic simulations. Splitting and routing of the electrically generated SPP signals around 90° bends are also shown. The realization of integrated plasmon sources greatly increases the applicability range of plasmonic waveguides and routing elements.

Glyburide ameliorates motor coordination and glucose homeostasis in a child with diabetes associated with the KCNJ11/S225T, del226-232 mutation.

Gain-of-function mutations of KCNJ11 can cause permanent neonatal diabetes mellitus, but only rarely after 6 months of age. Specific uncommon mutations KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and neonatal diabetes (DEND), or - more frequently - to a milder sub-type lacking epilepsy, denoted as intermediate-DEND (iDEND). Our aim was to consider a possible monogenic etiology in a 12-yr-old boy with early onset diabetes and mild neurological features. We studied a subject diagnosed with diabetes at 21 months of age, and negative to type 1 diabetes autoantibodies testing. He had learning difficulties during primary school, and a single episode of seizures at the age of 10 yr. We performed direct DNA sequencing of the KCNJ11 gene with subsequent functional study of mutated channels in COSm6 cells. The patient's clinical response to oral glyburide (Glyb) was assessed. Motor coordination was evaluated before and after 6 and 12 months of Glyb therapy. Sequencing of the KCNJ11 gene detected the novel, spontaneous mutation S225T, combined with deletion of amino acids 226-232. In vitro studies revealed that the mutation results in a K(ATP) channel with reduced sensitivity to the inhibitory action of ATP. Glyb improved diabetes control (hemoglobin A1c on insulin: 52 mmol/mol/6.9%; on Glyb: 36 mmol/mol/5.4%) and also performance on motor coordination tests that were impaired before the switch of therapy. We conclude that KCNJ11/S225T, del226-232 mutation caused a mild iDEND form in our patient. KCNJ11 should be considered as the etiology of diabetes even beyond the neonatal period if present in combination with negative autoantibody testing and even mild neurological symptoms.

Clearance of an epidemic clone of methicillin-resistant Staphylococcus aureus in a drug-use network: a follow-up study in Switzerland.

BACKGROUND: A single clone of methicillin-resistant Staphylococcus aureus (MRSA) was observed in a drug-use network starting in 1994, and was found to persist throughout 2001, with up to 19% MRSA colonization of intravenous drug users (IDUs). Recent clinical observations have shown low prevalences of this endemic drug clone among MRSA isolates. The goal of this study was to assess the evolution of MRSA carriage among IDUs. METHODS: The survey took place from November 2008 to September 2009. Ten drug dispensary facilities took part. Demographic and clinical data including sex, history of MRSA, past hospitalization, use of antibiotics, and presence of wounds were collected. Screening of the nares, throat, and wounds was done. RESULTS: Five hundred and fourteen swab specimens were obtained; 497 of them were nose/throat samples and 17 were wound swabs. MRSA was identified in 5 samples (1%). Four MRSA were found in nose/throat samples and 1 in a wound swab. Pulsed-field gel electrophoresis typing of the MRSA isolates revealed 2 different common endemic types: 4 were identified as the Zurich IDU clone and 1 as the Grison clone. CONCLUSIONS: The study shows a significant decline of MRSA colonization among IDUs. The underlying causes for this decline could not be determined fully, but we hypothesize a bundle of interventions as contributing: enhanced medical care, better wound management, isolation management, teaching IDUs basic hygiene techniques, and the national 'Four Pillars' policy. Hospital epidemiological policies such as pre-emptive isolation, length of isolation time, and screening procedures were adapted accordingly.

Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus.

Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.

P-doping mechanisms in catalyst-free gallium arsenide nanowires.

Doped catalyst-free GaAs nanowires have been grown by molecular beam epitaxy with the gallium-assisted method. The spatial dependence of the dopant concentration and resistivity have been measured by Raman spectroscopy and four point electrical measurements. Along with theoretical considerations, the doping mechanisms have been revealed. Two competing mechanisms have been revealed: dopant incorporation from the side facets and from the gallium droplet. In the latter incorporation path, doping compensation seems to play an important role in the effective dopant concentration. Hole concentrations of at least 2.4 x 10(18) cm(-3) have been achieved, which to our knowledge is the largest p doping range obtained up to date. This work opens the avenue for the use of doped GaAs nanowires in advanced applications and in mesoscopic physics experiments.

The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy.

CONTEXT: Mutations in the Kir6.2 subunit (KCNJ11) of the ATP-sensitive potassium channel (KATP) underlie neonatal diabetes mellitus. In severe cases, Kir6.2 mutations underlie developmental delay, epilepsy, and neonatal diabetes (DEND). All Kir6.2 mutations examined decrease the ATP inhibition of KATP, which is predicted to suppress electrical activity in neurons (peripheral and central), muscle, and pancreas. Inhibitory sulfonylureas (SUs) have been used successfully to treat diabetes in patients with activating Kir6.2 mutations. There are two reports of improved neurological features in SU-treated DEND patients but no report of such improvement in adulthood. OBJECTIVE: The objective of the study was to determine the molecular basis of intermediate DEND in a 27-yr-old patient with a KCNJ11 mutation (G53D) and the patient's response to SU therapy. DESIGN: The G53D patient was transferred from insulin to gliclazide and then to glibenclamide over a 160-d period. Motor function was assessed throughout. Electrophysiology assessed the effect of the G53D mutation on KATP activity. RESULTS: The G53D patient demonstrated improved glycemic control and motor coordination with SU treatment, although glibenclamide was more effective than gliclazide. Reconstituted G53D channels exhibit reduced ATP sensitivity, which is predicted to suppress electrical activity in vivo. G53D channels coexpressed with SUR1 (the pancreatic and neuronal isoform) exhibit high-affinity block by gliclazide but are insensitive to block when coexpressed with SUR2A (the skeletal muscle isoform). High-affinity block by glibenclamide is present in G53D channels coexpressed with either SUR1 or SUR2A. CONCLUSION: The results demonstrate that SUs can resolve motor dysfunction in an adult with intermediate DEND and that this improvement is due to inhibition of the neuronal but not skeletal muscle KATP.

An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of developmental delay, epilepsy, and neonatal diabetes.

Mutations in the pancreatic ATP-sensitive K(+) channel (K(ATP) channel) cause permanent neonatal diabetes mellitus (PNDM) in humans. All of the K(ATP) channel mutations examined result in decreased ATP inhibition, which in turn is predicted to suppress insulin secretion. Here we describe a patient with severe PNDM, which includes developmental delay and epilepsy, in addition to neonatal diabetes (developmental delay, epilepsy, and neonatal diabetes [DEND]), due to a G334D mutation in the Kir6.2 subunit of K(ATP) channel. The patient was wholly unresponsive to sulfonylurea therapy (up to 1.14 mg . kg(-1) . day(-1)) and remained insulin dependent. Consistent with the putative role of G334 as an ATP-binding residue, reconstituted homomeric and mixed WT+G334D channels exhibit absent or reduced ATP sensitivity but normal gating behavior in the absence of ATP. In disagreement with the sulfonylurea insensitivity of the affected patient, the G334D mutation has no effect on the sulfonylurea inhibition of reconstituted channels in excised patches. However, in macroscopic rubidium-efflux assays in intact cells, reconstituted mutant channels do exhibit a decreased, but still present, sulfonylurea response. The results demonstrate that ATP-binding site mutations can indeed cause DEND and suggest the possibility that sulfonylurea insensitivity of such patients may be a secondary reflection of the presence of DEND rather than a simple reflection of the underlying molecular basis.

Rethinking the sGLOH Descriptor.

sGLOH (shifting GLOH) is a histogram-based keypoint descriptor that can be associated to multiple quantized rotations of the keypoint patch without any recomputation. This property can be exploited to define the best distance between two descriptor vectors, thus avoiding computing the dominant orientation. In addition, sGLOH can reject incongruous correspondences by adding a global constraint on the rotations either as an a priori knowledge or based on the data. This paper thoroughly reconsiders sGLOH and improves it in terms of robustness, speed and descriptor dimension. The revised sGLOH embeds more quantized rotations, thus yielding more correct matches. A novel fast matching scheme is also designed, which significantly reduces both computation time and memory usage. In addition, a new binarization technique based on comparisons inside each descriptor histogram is defined, yielding a more compact, faster, yet robust alternative. Results on an exhaustive comparative experimental evaluation show that the revised sGLOH descriptor incorporating the above ideas and combining them according to task requirements, improves in most cases the state of the art in both image matching and object recognition.

Dissecting and Reassembling Color Correction Algorithms for Image Stitching.

This paper introduces a new compositional framework for classifying color correction methods according to their two main computational units. The framework was used to dissect fifteen among the best color correction algorithms and the computational units so derived, with the addition of four new units specifically designed for this work, were then reassembled in a combinatorial way to originate about one hundred distinct color correction methods, most of which never considered before. The above color correction methods were tested on three different existing datasets, including both real and artificial color transformations, plus a novel dataset of real image pairs categorized according to the kind of color alterations induced by specific acquisition setups. Differently from previous evaluations, special emphasis was given to effectiveness in real world applications, such as image mosaicing and stitching, where robustness with respect to strong image misalignments and light scattering effects is required. Experimental evidence is provided for the first time in terms of the most recent perceptual image quality metrics, which are known to be the closest to human judgment. Comparative results show that combinations of the new computational units are the most effective for real stitching scenarios, regardless of the specific source of color alteration. On the other hand, in the case of accurate image alignment and artificial color alterations, the best performing methods either use one of the new computational units, or are made up of fresh combinations of existing units.

Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?

BACKGROUND: Intra-islet insulin contributes to alpha-cell suppression. Akita mice carry a toxic-gain-of- function Ins2 gene mutation encoding proinsulin-C(A7)Y, similar to that described in human Mutant Ins-gene induced Diabetes of Youth, which decreases intra-islet insulin. Herein, we examined Akita mice for examination of circulating insulin and circulating glucagon levels. The possibility that loss of intra-islet suppression of alpha-cells, with increased circulating glucagon, contributes to diabetes under conditions of intra-islet insulin deficiency, raises questions about effective treatments that may be available. METHODS: Blood glucose, plasma insulin, C-peptide I, C-peptide II, and glucagon were measured at various times during development of diabetes in Akita mice. We also used Akita- like hProC(A7)Y-CpepGFP transgenic mice in Ins2+/+ , Ins2+/- and Ins2-/- genetic backgrounds (providing animals with greater or lesser defects in islet insulin production, respectively) in order to examine the relative abundance of immunostainable intra-islet glucagon-positive and insulin-positive cells. Similar measurements were made in Akita mice. Finally, the effects of treatment with insulin, exendin-4, and leptin on blood glucose were then compared in Akita mice. RESULTS: Interestingly, total insulin levels in the circulation were not frankly low in Akita mice, although they did not rise appropriately with the onset of hyperglycemia. By contrast, in severely diabetic Akita mice at 6 weeks of age, circulating glucagon levels were significantly elevated. Additionally, in Ins2+/- and Ins2-/- mice bearing the Akita-like hProC(A7)Y-CpepGFP transgene, development of diabetes correlated with an increase in the relative intra-islet abundance of immunostainable glucagon-positive cells, and a similar observation was made in Akita islets. In Akita mice, whereas a brief treatment with exendin-4 resulted in no apparent improvement in hyperglycemia, leptin treatment resulted in restoration of normoglycemia. Curiously, leptin treatment also suppressed circulating glucagon levels. CONCLUSIONS: Loss of insulin-mediated intra-islet suppression of glucagon production may be a contributor to hyperglycemia in Akita mice, and leptin treatment appears beneficial in such a circumstance. This treatment might also be considered in some human diabetes patients with diminished insulin reserve.

Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy.

Severe adipose tissue deficiency (lipoatrophy) causes insulin-resistant diabetes, elevated serum triglyceride and fatty acid levels, and massive triglyceride deposition in the liver. In lipoatrophic A-ZIP/F-1 mice, transplantation of normal adipose tissue greatly improved these parameters, whereas 1 week of leptin infusion had more modest effects. In contrast, leptin infusion was strikingly more effective in the aP2-n sterol response element binding protein 1 lipoatrophic mouse. Here we show that a longer duration of leptin infusion further improves the metabolic status of the A-ZIP/F-1 mice and that genetic background does not make a major contribution to the effect of leptin on glucose and insulin levels. Adipose transplantation using leptin-deficient ob/ob fat had no effect on the phenotype of the A-ZIP/F-1 mice. Moreover, the presence of ob/ob adipose tissue did not enhance the effects of leptin infusion. Serum adiponectin levels were 2% of control levels in the A-ZIP/F-1 mouse and increased only twofold with adipose transplantation and not at all after leptin infusion, suggesting that adiponectin deficiency is not a major contributor to the diabetic phenotype. Taken together, these results suggest that sequestration of triglycerides into fat may not be enough to restore a nondiabetic phenotype and that leptin deficiency plays a major role in causing the metabolic complications of lipoatrophy.

Impact of an outbreak of norovirus infection on hospital resources.

OBJECTIVE: To describe a nosocomial norovirus outbreak, its management, and its financial impact on hospital resources. DESIGN: A matched case-control study and microbiological investigation. METHODS: We compared 16 patients with norovirus infection with control-patients matched by age, gender, disease category, and length of stay. Bed occupancy-days during the peak incidence period of the outbreak were compared with the corresponding periods in 2001 and 2002. Expenses due to increased workload were calculated based on a measuring system that records time spent for nursing care per patient per day. RESULTS: The attack rates were 13.9% among patients and 29.5% among healthcare workers. The median number of occupied beds was significantly lower due to bed closure during the peak incidence in 2003 (29) compared with the median number of occupied beds in 2001 and 2002 combined (42.5). Based on this difference and a daily charge of 562.50 dollars per patient, we calculated a revenue loss of 37,968 dollars. Additional expenses totaled 10,300 dollars for increased nursing care. Extra costs for microbiological diagnosis totaled 2707 dollars. Lost productivity costs due to healthcare workers on sick leave totaled 12,807 dollars. The expenses for work by the infection control team totaled 1408 dollars. The financial impact of this outbreak on hospital resources comprising loss of revenue and extra costs for microbiological diagnosis but without lost productivity costs, increased nursing care, and expenses for the infection control team totaled 40,675 dollars. CONCLUSIONS: Nosocomial norovirus outbreaks result in significant loss of revenue and increased use of resources. Bed closures had a greater impact on hospital resources than increased need for nursing care

Metric 3D reconstruction and texture acquisition of surfaces of revolution from a single uncalibrated view.

Image analysis and computer vision can be effectively employed to recover the three-dimensional structure of imaged objects, together with their surface properties. In this paper, we address the problem of metric reconstruction and texture acquisition from a single uncalibrated view of a surface of revolution (SOR). Geometric constraints induced in the image by the symmetry properties of the SOR structure are exploited to perform self-calibration of a natural camera, 3D metric reconstruction, and texture acquisition. By exploiting the analogy with the geometry of single axis motion, we demonstrate that the imaged apparent contour and the visible segments of two imaged cross sections in a single SOR view provide enough information for these tasks. Original contributions of the paper are: single view self-calibration and reconstruction based on planar rectification, previously developed for planar surfaces, has been extended to deal also with the SOR class of curved surfaces; self-calibration is obtained by estimating both camera focal length (one parameter) and principal point (two parameters) from three independent linear constraints for the SOR fixed entities; the invariant-based description of the SOR scaling function has been extended from affine to perspective projection. The solution proposed exploits both the geometric and topological properties of the transformation that relates the apparent contour to the SOR scaling function. Therefore, with this method, a metric localization of the SOR occluded parts can be made, so as to cope with them correctly. For the reconstruction of textured SORs, texture acquisition is performed without requiring the estimation of external camera calibration parameters, but only using internal camera parameters obtained from self-calibration.

Genetic background (C57BL/6J versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice.

We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important.

Functional characterization of a novel KCNJ11 in frame mutation-deletion associated with infancy-onset diabetes and a mild form of intermediate DEND: a battle between K(ATP) gain of channel activity and loss of channel expression.

ATP-sensitive potassium (K(ATP)) channels are widely distributed in various tissues and cell types where they couple cell metabolism to cell excitability. Gain of channel function (GOF) mutations in the genes encoding Kir6.2 (KCNJ11) or the associated regulatory ssulfonylurea receptor 1 subunit (ABCC8), cause developmental delay, epilepsy and neonatal diabetes (DEND) due to suppressed cell excitability in pancreatic ß-cells and neurons. The objective of this study was to determine the molecular basis of infancy-onset diabetes and a mild form of intermediate DEND, resulting from a novel KCNJ11 in frame mutation plus deletion. The naturally occurring Kir6.2 mutation plus deletion (Ser225Thr, Pro226_Pro232del) as well as the isolated S225T mutation or isolated del226-232 deletion were coexpressed with SUR1 in COS cells in homozygous or heterozygous states. The protein expression and gating effects of the resulting channels were assessed biochemically and electrophysiologically. For both the deletion and point mutations, simulated heterozygous expression resulted in overall increased conductance in intact cells in basal conditions and rightward shifted ATP dose-response curves in excised patches, due to increased intrinsic open probability. Interestingly, homomeric channels for the combined deletion/mutation, or for the deletion alone, showed dramatically reduced channel expression at the cell membrane, which would underlie a reduced function in vivo. These results demonstrate that both the mis-sense mutation and the deleted region in the Kir6.2 subunit are important for control of the intrinsic channel gating and suggest that the clinical presentation could be affected by the competition between loss-of-function by reduced trafficking and enhanced channel gating.

Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?

Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter's syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR.