Quantum cascade lasers monolithically integrated on germanium.

Silicon (Si) photonics can have a major impact on the development of mid-IR photonics by leveraging on the reliable and high-volume fabrication technologies already developed for microelectronic integrated circuits. Germanium (Ge), already used in Si photonics, is a prime candidate to extend the operating wavelength of Group IV-based photonic integrated circuits beyond 8 µm, and potentially up to 15 µm. High performance quantum cascade lasers (QCLs) and interband cascade lasers grown on Si have been demonstrated, whereas no QCLs monolithically integrated on Ge have been reported yet. In this work, we present InAs-based QCLs directly grown on Ge by molecular beam epitaxy. The lasers emitting near 14 µm exhibited threshold current densities as low as 0.8-0.85 kA/cm2 at room temperature.

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.

Localized surface plasmon resonance frequency tuning in highly doped InAsSb/GaSb one-dimensional nanostructures.

We report a detailed analysis of the influence of the doping level and nanoribbon width on the localized surface plasmon resonance (LSPR) by means of reflectance measurements. The plasmonic system, based on one-dimensional periodic gratings of highly Si-doped InAsSb/GaSb semiconductor nanostructures, is fabricated by a simple, accurate and large-area technique fabrication. Increasing the doping level blueshifts the resonance peak while increasing the ribbon width results in a redshift, as confirmed by numerical simulations. This provides an efficient means of fine-tuning the LSPR properties to a target purpose of between 8-20 µm (1250-500 cm(-1)). Finally, we show surface plasmon resonance sensing to absorbing polymer layers. We address values of the quality factor, sensitivity and figure of merit of 16 700 nm RIU(-1) and 2.5, respectively. These results demonstrate Si-doped InAsSb/GaSb to be a low-loss/high sensitive material making it very promising for the development of biosensing devices in the mid-infrared.

Silicon-on-insulator shortwave infrared wavelength meter with integrated photodiodes for on-chip laser monitoring.

This paper demonstrates a very compact wavelength meter for on-chip laser monitoring in the shortwave infrared wavelength range based on an optimized arrayed waveguide grating (AWG) filter with an integrated photodiode array. The AWG response is designed to obtain large nearest neighbor crosstalk (i.e. large overlap) between output channels, which allows accurately measuring the wavelength of a laser under test using the centroid detection technique. The passive AWG is fabricated on a 220 nm silicon-on-insulator (SOI) platform and is combined with GaInAsSb-based photodiodes. The photodiodes are heterogeneously integrated on the output grating couplers of the AWG using DVS-BCB adhesive bonding. The complete device with AWG and detectors has a footprint of only 2 mm(2) while the measured accuracy and resolution of the detected wavelength is better than 20pm.

Silicon-on-insulator spectrometers with integrated GaInAsSb photodiodes for wide-band spectroscopy from 1510 to 2300 nm.

We present a silicon-on-insulator (SOI) based spectrometer platform for a wide operational wavelength range. Both planar concave grating (PCG, also known as echelle grating) and arrayed waveguide grating (AWG) spectrometer designs are explored for operation in the short-wave infrared. In addition, a total of four planar concave gratings are designed to cover parts of the wavelength range from 1510 to 2300 nm. These passive wavelength demultiplexers are combined with GaInAsSb photodiodes. These photodiodes are heterogeneously integrated on SOI with benzocyclobutene (DVS-BCB) as an adhesive bonding layer. The uniformity of the photodiode characteristics and high processing yield, indicate a robust fabrication process. We demonstrate good performance of the miniature spectrometers over all operational wavelengths which paves the way to on-chip absorption spectroscopy in this wavelength range.

Carrier dynamics in (Ga,In)(Sb,Bi)/GaSb quantum wells for laser applications in the mid-infrared spectral range.

We present experimental studies on low-temperature ([Formula: see text]) carrier dynamics in (Ga,In)(Sb,Bi)/GaSb quantum wells (QWs) with the nominal In content of 3.7% and the Bi ranging from 6 to 8%. The photoreflectance experiment revealed the QW bandgap evolution with [Formula: see text] % Bi, which resulted in the bandgap tunability roughly between 629 and [Formula: see text], setting up the photon emission wavelength between 1.97 and [Formula: see text]. The photoluminescence experiment showed a relatively small 3-10[Formula: see text] Stokes shift regarding the fundamental QW absorption edge, indicating the exciton localisation beneath the QW mobility edge. The localised state's distribution, being the origin of the PL, determined carrier dynamics in the QWs probed directly by the time-resolved photoluminescence and transient reflectivity. The intraband carrier relaxation time to the QW ground state, following the non-resonant excitation, occurred within 3-25[Formula: see text] and was nearly independent of the Bi content. However, the interband relaxation showed a strong time dispersion across the PL emission band and ranging nearly between 150 and [Formula: see text], indicating the carrier transfer among the localised state's distribution. Furthermore, the estimated linear dispersion variation parameter significantly decreased from [Formula: see text] to [Formula: see text] with increasing the Bi content, manifested the increasing role of the non-radiative recombination processes with Bi in the QWs.

Amorphous calcium carbonate biomineralization in the earthworm's calciferous gland: pathways to the formation of crystalline phases.

In this study, we investigated the microstructural transformations that take place during carbonate formation in the earthworm's calciferous gland by analysing the evolution from the precursor fluid of the solid phases (spherulites) to the final carbonate concretions released by the gland. Results from HREM and electron diffraction showed that the spherulithic deposits merely consisted of ACC partially transformed to vaterite. Furthermore, comparisons of the diffraction spectra and microstructural analyses allowed the identification of the transition sequences to more stable carbonates. And thus, transformations of ACC to calcite were observed on the surfaces of these amorphous globular aggregates as their smooth characteristic surface became rougher with time. This transition path was not unique, and the presence of aragonite, as an intermediate phase, has also been found. In this particular case, the transition process followed a completely different pathway with the crystallization starting in the centre of the sphere and progressively extending to the periphery, leading to the formation of radial aggregates. In situ experiments performed on the freshly extracted precursor fluid and analysed by FT-IR spectroscopy showed that ACC is the main constituent and is probably stabilised by macromolecules such as proteins and sugars. Furthermore, the Debye-Scherrer diffraction experiments showed that the carbonate phase present in this fluid remains stable as ACC for more than a week. All these features are indicative of this entire process being biologically controlled by the earthworms. The analysis of the amorphous structure factor of this ACC indicates that these transformations are preceded by short-range order modifications of the amorphous precursor phase.

Specific molecular targets to control tropical diseases.

Chagas' disease or American trypanosomiasis is considered by the Word Health Organization to be one of the important tropical parasitic diseases worldwide together with malaria and schistosomiasis. The etiologic agent of this illness is the kinetoplastid protozoon Trypanosoma cruzi. The present chemotherapy for the treatment of Chagas' disease remains unsolved. The drugs currently in use are old, ineffective and toxic. Bearing in mind the metabolic differences between the parasite and the mammalian host, some attractive interesting molecular targets for drug design are presented.

Design, synthesis, and biological evaluation of new growth inhibitors of Trypanosoma cruzi (epimastigotes).

As a continuation of our project aimed at the search for new chemotherapeutic agents against Chagas' disease, several drugs structurally related to the insect growth regulator Fenoxycarb and the naturally occurring juvenile hormone of insects were designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible of this disease. Isoprenoid derivatives (compounds 33, 34, 36, and 37) were potent growth inhibitors of Trypanosoma cruzi epimastigotes. In addition, taking into account the high activity observed for compound 30 and the inhibitory action of related compounds, the allyl ether moiety bonded at the polar extreme of these inhibitors proved to be a promising group for the design of new drugs.

Design and synthesis of aryloxyethyl thiocyanate derivatives as potent inhibitors of Trypanosoma cruzi proliferation.

As a part of our project directed at the search of new chemotherapeutic agents against American trypanosomiasis (Chagas' disease), several drugs possessing the 4-phenoxyphenoxy skeleton and other closely related structures employing the thiocyanate moiety as polar end group were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for this disease. These thiocyanate analogues were envisioned bearing in mind the potent activity shown by 4-phenoxyphenoxyethyl thiocyanate (compound 8) taken as lead drug. This compound had previously proved to be an extremely active growth inhibitor against T. cruzi with IC(50) values ranging from the very low micromolar level in epimastigotes to the low nanomolar level in the intracellular form of the parasite. Of the designed compounds, the ethyl thiocyanate drugs connected to nonpolar skeletons, namely, arylthio, 2,4-dichlorophenoxy, ortho-substituted aryloxy, and 2-methyl-4-phenoxyphenoxy (compounds 15, 34, 47, 52, 72, respectively), were shown to be very potent antireplicative agents against T. cruzi. On the other hand, conformationally restricted analogues as well as branched derivatives at the aliphatic side chain were shown to be moderately active against T. cruzi growth. The biological activity of drugs bearing the thiocyanate group correlated quite well with the activity exhibited by their normal precursors, the tetrahydropyranyl ether derivatives, when bonded to the same nonpolar skeleton. Compounds having the tetrahydropyranyl moeity as polar end were proportionally much less active than sulfur-containing derivatives in all cases. Drugs 47 and 72 also resulted to be very active against the amastigote form of the parasite growing in myoblasts; however, they were slightly less active than the lead drug 8. On the other hand, compounds 34 and 52 were almost devoid of activity against myoblasts. Surprisingly, the dithio derivative 15 was toxic for myoblasts.

Conformationally locked nucleoside analogues. Synthesis of dideoxycarbocyclic nucleoside analogues structurally related to neplanocin C.

The glycon moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme northern and southern conformations as defined by the pseudorotation cycle. The concept of preparing rigid nucleoside analogues with the glycon conformation locked in one of these two extremes was tested with the synthesis of some cyclopropane-fused dideoxycarbocyclic nucleosides, similar to the well-known class of anti-HIV active dideoxynucleosides. The new compounds described here are dideoxynucleoside analogues of the fermentation product neplanocin C (6) which exhibits a typical northern geometry for its 6-oxabicyclo[3.1.0]hexane pseudosugar moiety. However, in view of the lability of the epoxide ring in this system, the equivalent cyclopropane-fused bicyclo[3.1.0]hexane system was used instead to prepare the corresponding dideoxynucleoside analogues bearing all the common bases [(+/-)-9-13]. Due to the well-documented preference of unrestricted bicyclo[3.1.0]hexane systems to exist exclusively in a boat conformation, the resulting nucleosides are structurally locked in a typical northern conformation similar to that of neplanocin C. The locked northern conformation in these nucleosides remained unchanged in solution in the 20-80 degrees C temperature range according to variable temperature 1H NMR studies. For the synthesis of these compounds, racemic trans-1-[(benzyloxy)methyl]-4-hydroxybicyclo[3.1.0]hexane [(+/-)-18] was prepared by a samarium-promoted cyclopropanation reaction with the antecedent cyclopentenol. All of the bases were incorporated under Mitsunobu conditions and converted to the desired final products following a standard methodology. Anti-HIV evaluation revealed that only the adenosine analogue (+/-)-9 possessed enough activity to warrant resolution into its optical antipodes. This was realized by chiral HPLC chromatography to give the individual enantiomers (-)-32 and (+)-33. Adenosine deaminase was used to identify isomer (+)-33 as the enantiomer with the "natural" configuration which was solely responsible for the observed biological activity and toxicity of (+/-)-9. It is possible that the exclusive northern conformation adopted by these nucleosides reduces their substrate affinity for the various activating kinases, except in the case of the adenosine analogue.

Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi.

Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at the polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC50 of 2.2 microM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.

Gas chromatographic-mass spectrometric method for the assessment of oxidative damage to double-stranded dna by quantification of thymine glycol residues.

A technique for the measurement of thymine glycol at parts per million concentrations in double-stranded polymeric DNA is described. The procedure utilizes base to ring-open DNA-bound thymine glycol in the presence of monomeric [(2)H4]thymine glycol as an internal standard, followed by reduction, solvolytic cleavage, and quantification of the characteristic methyl-2-methylglycerate released from polymeric DNA. Methyl-2-methyl-glycerate is derivatized to form the di-tert-butyldimethylsilyl [(TBDMS)2] ether to enhance its gas chromatographic properties and electron ionization detection. This assay was tested by measuring thymine gIyco1 levels in native, undamaged DNA (not purposefully oxidized). The measured quantities of thymine glycol are proportional to the amount of DNA analyzed. Components of DNA not containing oxidizable thymine do not contribute to the measured signal from methyl-2-methylglycerate-(TBDMS)2. These results indicate that there is approximately one thymine glycol per lo6 bases in undamaged DNA and that this value increases with storage of DNA in refrigerated aqueous solutions.

Effects of juvenile hormone on mammalian steroidogenesis.

The effects of juvenile hormone-III (JH-III) and the JH analogue 2-(4-phenoxyphenoxy)-ethoxyte-trahydropiran on testicular steroidogenesis were studied. By using cultured MA-10 Leydig tumor cells as a model, these compounds were found to be potent inhibitors of LH/hCG steroidogenic action in a dose-dependent manner. Scatchard plot analysis of the binding data indicated that the JH analogue did not significantly alter the affinity nor the number of hCG binding sites, as well as GTP binding to plasma membranes. JH analogue inhibited the stimulatory action of both cholera toxin and forskolin on cAMP production and the concomitant steroidogenic response. JH analogue inhibited (Bu)2cAMP-stimulated progesterone synthesis, indicating that a process downstream to the adenylyl cyclase in the steroidogenic pathway is also affected.

Sulphur-containing derivatives structurally related to fenoxycarb are potent growth inhibitors against the intracellular form of Trypanosoma cruzi.

Sulphur-containing derivatives structurally related to the insect growth regulator fenoxycarb were shown to be extremely active antiproliferative agents against the amastigote form of Trypanosoma cruzi in in vitro assays. All of these drugs had previously been proved to be remarkably potent growth inhibitors against the epimastigote form of the parasite.

The sterols of Cucurbita moschata ("calabacita") seed oil.

From the sterol fraction of seed oil from commercial Cucurbita moschata Dutch ("calabacita") delta 5 and delta 7 sterols having saturated and unsaturated side chain were isolated by chromatographic procedures and characterized by spectroscopic (1H and 13C-nuclear magnetic resonance, mass spectrometry) methods. The main components were identified as 24S-ethyl 5 alpha-cholesta-7,22E-dien-3 beta-ol (alpha-spinasterol); 24S-ethyl 5 alpha-cholesta-7,22E,25-trien-3 beta-ol (25-dehydrochondrillasterol); 24S-ethyl 5 alpha-cholesta-7,25-dien-3 beta-ol; 24R-ethyl-cholesta-7-en-3 beta-ol (delta 7-stigmastenol) and 24-ethyl-cholesta-7, 24(28)-dien-3 beta-ol (delta 7,24(28)-stigmastadienol).

Arterial microanastomosis technique by using only one stitch.

The starting point of this work is the description of a microsurgical technique designed to carry out termino-terminal arterial anastomosis in rats. The technique is based on the intussusception of the afferent vessel of the anastomosis in the efferent vessel, both of which are fixed by a horizontal U-shaped stitch. Of the twelve cases which make up this series, haemorrhage appeared in two, and a postanastomotic aneurysm developed in one. The lack of complications both before and after operating, even in the long term, in the balance of the cases (75%), together with the simple and quick procedure of this kind of anastomosis, makes this technique a possible alternative to the classical techniques of vascular microanastomosis in experimental surgery.

Effects of juvenile hormone analogues (JHA) on the development of Trypanosoma cruzi.

Juvenile hormone analogues were tested for their lytic activity on Trypanosoma cruzi Chagas, 1909 blood tripomastigotes cultivated in vitro. The results indicated that the carbamate 4 and the phenoxyphenol derivative 1 are considered good candidates for blood sterilization. The compounds were also assayed for inhibition of development of parasites in infected mice showing a moderated degree of activity.

[Triage area. Use and effectiveness of a protocol]. / Area de "triage". Utilidad y eficacia de un protocolo.

In the Organization of the urgency services, there's a general agreement about need to have a triage system or a first classification of the patient at their arrival, for a quick, ordered, and directed access, attending the dangerously wounded patient with priority, acting like a true filter of the dangerously wounded patient. This is a function realized in The Juan Ramon Jimenez Hospital by nurses in the triage area. Patient is classified into these groups, determining of this way the priority of their attention, basing in the triage protocol: I: emergency or vital risks. II: acute processes, critical. III: acute processes, no critical. IV: banal processes, no urgent. The objective of this study is to evaluate the utility and efficacy of the nurse triage protocol from the valuation of different nurses, compiling data of 300 clinic histories, taking as indicative or evaluations, the degree of homogeneity of the differents triages realized. We take from a comparative description study of a total of 300 cases, being cassified in a continuous way by two nurses in different areas. To emphasize, that of the total of the studied population, the percentage of patients that have been classified with the same gravity level by both nurses, is about the 95.9%, being located the not coincidences, always in levels iii and iv. the 99.7% of these patients have been derived to the same speciality atter their triage. The specialities that sustain greater assistance demand are internal medicine and traumatology, with a 41.7% and a 34.3% respectively. The total of studied cases, 75% attend to the urgency service by own petition, which 86% are catalogued as level iv (banal processes), 23.4% are transmitted by urgency services or provide p10, being only a 20% of theses cases considered as acute processes, that it supposes a 4.6% of the total and a 1.3% are transferred by e.p.e.s 061, being the 100% defined as acute processes. The group of age that demand more sanitary assistance is between 20 and 40 years, prevailed the masculine sex in all the groups, except in those greater of 60 years, where the women exceed them in a 23.6%.

Rat vas deferens SERCA2 is modulated by Ca2+/calmodulin protein kinase II-mediated phosphorylation.

Ca2+ pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca2+-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca2+ (Ca0.5 = 780 nM) and a low sensitivity to vanadate (IC50 = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca2+/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca2+ and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca2+ accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca2+ and CaM, possibly via CaMKII, in a process that results in stimulation of Ca2+ pumping activity.