Design of a suspended germanium micro-antenna for efficient fiber-chip coupling in the long-wavelength mid-infrared range.

Recent developments of photonic integrated circuits for the mid-infrared band has opened up a new field of attractive applications for group IV photonics. Grating couplers, formed as diffractive structures on the chip surface, are key components for input and output coupling in integrated photonic platforms. While near-infrared optical fibers exhibit large mode field diameters compared to the wavelength, in the long-wave regime commercially available single-mode optical fibers have mode field diameters of the order of the operating wavelength. Consequently, an efficient fiber-chip surface coupler designed for the long-wave infrared range must radiate the power propagating in the waveguide with a higher radiation strength than a conventional grating coupler in the near-infrared range. In this article, we leverage the short electrical length required for long-wave infrared couplers to design a broadband all-dielectric micro-antenna for a suspended germanium platform at 7.67 µm. The design methodology is inspired by fundamental grating coupler equations, which remain valid even when the micro-antenna has only two or three diffractive elements. A simulated coupling efficiency of ~ 40% is achieved with a 1-dB bandwidth broader than 430 nm, which is almost twice the typical fractional bandwidth of a conventional grating coupler. In addition, the proposed design is markedly tolerant to fiber tilt misalignments of ±10°. This all-dielectric micro-antenna design paves the way for efficient fiber-chip coupling in long-wavelength mid-infrared integrated platforms.

Silicon-on-insulator free-carrier injection modulators for the mid-infrared.

Experimental demonstrations of silicon-on-insulator waveguide-based free-carrier effect modulators operating at 3.8 µm are presented. PIN diodes are used to inject carriers into the waveguides, and are configured to (a) use free-carrier electroabsorption to create a variable optical attenuator with 34 dB modulation depth and (b) use free-carrier electrorefraction with the PIN diodes acting as phase shifters in a Mach-Zehnder interferometer, achieving a VπLπ of 0.052 V·mm and a DC modulation depth of 22 dB. Modulation is demonstrated at data rates up to 125 Mbit/s.

Suspended low-loss germanium waveguides for the longwave infrared.

Germanium is a material of high interest for mid-infrared (MIR) integrated photonics due to its complementary metal-oxide-semiconductor (CMOS) compatibility and its wide transparency window covering the 2-15 µm spectral region exceeding the 4 and 8 µm limit of the silicon-on-insulator platform and Si material, respectively. In this Letter, we report suspended germanium waveguides operating at a wavelength of 7.67 µm with a propagation loss of 2.6±0.3 dB/cm. To the best of our knowledge, this is the first demonstration of low-loss suspended germanium waveguides at such a long wavelength. Suspension of the waveguide is achieved by defining holes alongside the core providing access to the buried oxide layer and the underlying Si layer so that they can be wet etched using hydrofluoric acid and tetramethylammonium hydroxide, respectively. Our MIR waveguides create a new path toward long wavelength sensing in the fingerprint region.

Suspended silicon waveguides for long-wave infrared wavelengths.

In this Letter, we report suspended silicon waveguides operating at a wavelength of 7.67 µm with a propagation loss of 3.1±0.3 dB/cm. To our knowledge, this is the first demonstration of low-loss silicon waveguides at such a long wavelength, with loss comparable to other platforms that use more exotic materials. The suspended Si waveguide core is supported by a sub-wavelength grating that provides lateral optical confinement while also allowing access to the buried oxide layer so that it can be wet etched using hydrofluoric acid. We also demonstrate low-loss waveguide bends and s-bends.

New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus.

Staphylococcus aureus is a major cause of bacterial infection in humans, and has been notoriously able to acquire resistance to a variety of antibiotics. An example is methicillin-resistant S. aureus (MRSA), which despite having been initially associated with clinical settings, now is one of the key causative agents of community-acquired infections. Antibiotic resistance in S. aureus involves mechanisms ranging from drug efflux to increased expression or mutation of target proteins, and this has required innovative approaches to develop novel treatment methodologies. This review provides an overview of the major mechanisms of antibiotic resistance developed by S. aureus, and describes the emerging alternatives being sought to circumvent infection and proliferation, including new generations of classic antibiotics, synergistic approaches, antibodies, and targeting of virulence factors.

Suspended silicon mid-infrared waveguide devices with subwavelength grating metamaterial cladding.

We present several fundamental photonic building blocks based on suspended silicon waveguides supported by a lateral cladding comprising subwavelength grating metamaterial. We discuss the design, fabrication, and characterization of waveguide bends, multimode interference devices and Mach-Zehnder interferometers for the 3715 - 3800 nm wavelength range, demonstrated for the first time in this platform. The waveguide propagation loss of 0.82 dB/cm is reported, some of the lowest loss yet achieved in silicon waveguides for this wavelength range. These results establish a direct path to ultimately extending the operational wavelength range of silicon wire waveguides to the entire transparency window of silicon.

III-V-on-silicon integrated micro - spectrometer for the 3 µm wavelength range.

A compact (1.2 mm2) fully integrated mid-IR spectrometer operating in the 3 µm wavelength range is presented. To our knowledge this is the longest wavelength integrated spectrometer operating in the important wavelength window for spectroscopy of organic compounds. The spectrometer is based on a silicon-on-insulator arrayed waveguide grating filter. An array of InAs0.91Sb0.09 p-i-n photodiodes is heterogeneously integrated on the spectrometers output grating couplers using adhesive bonding. The spectrometer insertion loss is less than 3 dB and the waveguide-referred responsivity of the integrated photodiodes at room temperature is 0.3 A/W.

Optical detection and modulation at 2µm-2.5µm in silicon.

Recently the 2µm wavelength region has emerged as an exciting prospect for the next generation of telecommunications. In this paper we experimentally characterise silicon based plasma dispersion effect optical modulation and defect based photodetection in the 2-2.5µm wavelength range. It is shown that the effectiveness of the plasma dispersion effect is dramatically increased in this wavelength window as compared to the traditional telecommunications wavelengths of 1.3µm and 1.55µm. Experimental results from the defect based photodetectors show that detection is achieved in the 2-2.5µm wavelength range, however the responsivity is reduced as the wavelength is increased away from 1.55µm.

Suspended SOI waveguide with sub-wavelength grating cladding for mid-infrared.

We present a new type of mid-infrared silicon-on-insulator (SOI) waveguide. The waveguide comprises a sub-wavelength lattice of holes acting as lateral cladding while at the same time allowing for the bottom oxide (BOX) removal by etching. The waveguide loss is determined at the wavelength of 3.8 µm for structures before and after being underetched using both vapor phase and liquid hydrofluoric acid (HF). A propagation loss of 3.4 dB/cm was measured for a design with a 300 nm grating period and 150 nm holes after partial removal (560 nm) of BOX by vapor phase HF etching. We also demonstrate an alternative design with 550 nm period and 450 nm holes, which allows a faster and complete removal of the BOX by liquid phase HF etching, yielding the waveguide propagation loss of 3.6 dB/cm.

Demonstration of Silicon-on-insulator mid-infrared spectrometers operating at 3.8 µm.

The design and characterization of silicon-on-insulator mid-infrared spectrometers operating at 3.8 µm is reported. The devices are fabricated on 200 mm SOI wafers in a CMOS pilot line. Both arrayed waveguide grating structures and planar concave grating structures were designed and tested. Low insertion loss (1.5-2.5 dB) and good crosstalk characteristics (15-20 dB) are demonstrated, together with waveguide propagation losses in the range of 3 to 6 dB/cm.

Dipyridamole-dobutamine echocardiography: a novel test for the detection of milder forms of coronary artery disease.

OBJECTIVES: This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography. BACKGROUND: Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine). METHODS: One hundred fifty patients (mean [+/- SD] age 51 +/- 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamole-dobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 micrograms/kg body weight per min) was performed on a separate day. RESULTS: Significant coronary artery disease (> 50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamole-dobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 +/- 30) and was comparable during the dobutamine (186 +/- 59) and dipyridamole-dobutamine tests (179 +/- 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all). CONCLUSIONS: Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.

High dose adenosine stress echocardiography for noninvasive detection of coronary artery disease.

OBJECTIVES: The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD). BACKGROUND: In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has sub-optimal sensitivity for detecting milder forms of CAD. METHODS: Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 micrograms/kg body weight per min over 3 min followed by 140 micrograms/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 micrograms/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as > or = 50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients. RESULTS: The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617). CONCLUSIONS: We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology.

OBJECTIVES: The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND: Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS: Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

Diapedesis of thrombocytes from capillary into the intercellular space of interscapular brown adipose tissue and their increase by Ca-Sandoz.

Diapedetic capacity of the rat thrombocytes to leave capillaries of the interscapular brown adipose tissue (IBAT) and infiltrate the interstitium has been observed by conventional electron-microscopy. Thrombocytes that reach IBAT interstitium are morphologically completely different from lumenary ones. The interstitial thrombocyte has a prominet head region (1.51 x 2.12 microns) and very long phylopodium (3.43 microns). Experimental conditions which induced drastic changes in morphology of interstitial thrombocytes were: sucrose overfeeding (10% over 2 days); a 24 hour starving after sucrose overfeeding and Ca-Sandoz drinking (480 mg/L Ca2+ during 2 days). The thrombocytes in the IBAT interstitium can be classified as activated according to: a) pseudopode extension; b) swollen open canalicullar system (OCS); c) endocytosis via coated pits and vesicles; and d) structural changes in alpha granules excreted to the interstitium through OCS. In the IBAT interstitium of 24-hour starved rats after sucrose overfeeding, a thrombocytic layer was observed. It was suggested that thrombocyte adrenalin, stored in dense bodies, was selectively included in the IBAT supply without mediation of the central nervous system.

Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection.

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide radical production in the rat brain was examined after injection of kainate, non-NMDA receptor agonist, kainate plus 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), selective AMPA/kainate receptor antagonist, or kainate plus 2-amino-5-phosphonopentanoic acid (APV), selective NMDA receptor antagonist. Competitive glutamate receptor antagonists were injected with kainate unilaterally into the CA3 region of the rat hippocampus. We investigated superoxide production and mitochondrial MnSOD activity after injection. The measurements took place at different times (5, 15 min, 2, 48 h and 7 days) in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. Used glutamate antagonists APV and CNQX both expressed sufficient neuroprotection in sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. Following intrahippocampal antagonists injection they, also, interpose different neuroprotection effect on the induction of MnSOD activity in distinct brain regions affected by the injury, which are functionally connected via afferents and efferents. It suggests that MnSOD protects the cells in these regions from superoxide-induced damage and therefore may limit the retrograde and anterograde spread of neurotoxicity.

Direct determination of lead in blood by differential pulse stripping voltammetry.

A simple and rapid method for determination of lead in blood by differential pulse stripping voltammetry (DPS) without preliminary mineralization of the sample, is described. Lead determination was performed in native samples of blood in the electrolyte of Britton-Robinson buffer (pH 5-5.5). The proposed method is shown to be reproducible and in good agreement with the reference technique AAS used on mineralized blood samples. Our results indicate that differential pulse stripping voltammetry is a reliable, rapid and highly sensitive method for blood lead analysis.

Prognostic value of myocardial viability determined by a 201Tl SPECT study in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58+/-9 years) by 201Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43+/-10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functional improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P <0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P =0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P =0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

Pancreatic polypeptide cells of rat pancreas after chronic ethanol feeding.

Male Wistar rats, (2 months old) were randomly divided into two groups according to the diet offered (C-control and E-ethanol treated rats). Final body weight was significantly increased but pancreatic weight as a percentage of body weight was decreased in ethanol treated rats. Volume density, number of pancreatic poly peptide (PP)-cells per islet and per micron 2 of islet were significantly increased. PP-cells were abundant and occupied the whole periphery of islets in the splenic part of the pancreas. Those cells showed strong immunopositivity. At the ultrastructural level PP granules had predominantly less electron density. The mean diameter of PP granules was significantly increased and the number of granules of larger diameter was greater in the E group of rats, than in the controls.

Gastrin producing G-cells after chronic ethanol and low protein nutrition.

Male Wistar rats, (2 months old), randomly divided according to the diet offered to four groups (C-control; A- alcoholized, PD-protein-deprived, A-PD- alcoholized protein-deprived). In group A and A-PD rats, the number of gastrin producing G-cells was significantly lower. The volume density of G-cells was significantly decreased in alcoholic rats. Fasting serum gastrin level (FSGL) significantly raised due to combined effect of alcohol consumption and protein malnutrition. In group A rats, the profile area of G-cells and their nuclei increased. In PD rats, the profile area of G cells also increased. There were no differences in nucleus/cell ratio due to alcohol ingestion alone, but it decreased significantly in PD and A-PD rats. Pale and lucent types of granules were predominantly seen in G-cells of animals of group A and A-PD. Mean diameter of granules increased in A, PD and A-PD rats. Other endocrine cells (ECL, D, EC) also decreased in number in A rats. Somatostatin producing D-cells decreased significantly in A-PD rats, both in fundic and pyloric mucosa.

Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dipyridamole.

BACKGROUND: Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. METHODS: The study group consisted of 20 consecutive patients (52 +/- 10 years, 17 male, 3 female) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for > 5% (inferoapical and posterolateral regions) or > 10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the followup period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. RESULTS: Out of the 180 analyzed segments (20 x 9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34 +/- 12% to 42 +/- 14% in the follow-up period (p = 0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51%), whereas 32 segments were responders (36%, p = 0.05 vs. dobutamine) during low dose dipyridamole. Positive predictive value of dobutamine and dipyridamole for predicting functional recovery was 72% and 75% (p = ns), respectively. Negative predictive value of dobutamine and dipyridamole was 48% and 69% (p = 0.05), respectively. In the group of patients with most severe dyskinesia (regional ejection fraction < 35%, 42 segments) positive predictive value was 73% and 82%, while negative predictive value was 42% and 64% for low dose dobutamine and low dose dipyridamole respectively (p = ns). CONCLUSION: Although low dose dobutamine induced higher rate of positive responses during radionuclide ventriculography imaging, dipyridamole radionuclide ventriculography has shown superior, particularly negative, prognostic value for predicting functional recovery of infarcted regions.