From Stem Cells to Bone-Forming Cells

Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. In this review, we briefly define the cellular identity and function of osteoblasts and discuss the main populations of osteoprogenitor cells identified to date. We also provide examples of long-known and recently recognized regulatory pathways and mechanisms involved in the specification of the osteogenic lineage, as assessed by studies on mice models and human genetic skeletal diseases.     

Effects of L-arginine and N omega-nitro-L-arginine methyl ester on cardiac perfusion and function after 1-day cold preservation of isolated hearts

BACKGROUND: Coronary flow responses to endothelium-dependent (acetylcholine [ACh] or 5-hydroxytryptamine [5-HT]) and endothelium-independent (adenosine [ADE] or nitroprusside [NP]) vasodilators may be altered before and after 1-day hypothermia during the perfusion of arginine vasopressin (AVP), D-arginine (D-ARG), L-arginine (L-ARG), or nitro-L-arginine methyl ester (L-NAME). METHODS AND RESULTS: Four groups of guinea pig hearts (37.5 degrees C [warm]) were perfused for 6 hours with AVP, L-ARG, L-NAME, or nothing (control). Five heart groups (cold) were perfused with AVP, D-ARG, L-ARG, L-NAME, or nothing (control), but after 2 hours they were perfused at low flow for 22 hours at 3.7 degrees C and again for 3 hours at 37.5 degrees C. ADE, butanedione monoxime, and NP were given for cardioprotection before, during, and after hypothermia. In warm groups, L-ARG did not alter basal flow or ADE, ACh, 5-HT, or NP responses, whereas L-NAME and AVP reduced basal flow and the ADE response, abolished ACh and 5-HT responses, and increased the NP response. In cold groups after hypothermia. L-ARG did not alter basal flow, but L-NAME, AVP, D-ARG, and control reduced flow. In the postcold L-ARG group, ACh increased peak flow, but NP did not increase flow in other cold groups. Effluent L-ARG and L-CIT in the cold control group fell from 64 +/- 9 and 9 +/- 1 micrograms/L at 1 hour to 36 +/- 5 and 5 +/- 1 micrograms/L at 25 hours, respectively. Left ventricular pressure and cardiac efficiency improved more in the postcold L-ARG group than in the postcold D-ARG, AVP, and L-NAME groups. CONCLUSIONS: Endogenous effluent levels of L-ARG and L-CIT decrease after 24 hours in isolated hearts, whereas perfusion of L-ARG improves cardiac performance, basal coronary flow, and vasodilator responses. In contrast, L-NAME, L-ARG, and AVP limit flow and performance but maintain a partial vasodilatory response to NP. Sustained release of NO may account for improved performance after L-ARG after hypothermia.     

Synthesis and evaluation of phorboid 20-homovanillates: discovery of a class of ligands binding to the vanilloid (capsaicin) receptor with different degrees of cooperativity

A number of phorboid 20-homovanillates were prepared by condensation of phorbol 12,13-diesters and 12-dehydrophorbol 13-esters with Mem-homovanillic acid followed by removal of the protecting group with SnCl4 in THF. These compounds were evaluated for their ability to inhibit [3H]resiniferatoxin (RTX) binding to rat spinal cord membranes. Compounds bearing a lipophilic ester group on ring C were considerably active, but a surprising tolerance of the vanilloid receptor toward the location and the orientation of this ester group was disclosed. Unexpectedly, these ligands could also diminish, to a variable degree, the positive cooperativity which characterizes RTX binding to the vanilloid receptor. Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assay used to characterize vanilloid-like activity. PPAHV showed only a marginal pungency and failed to induce a measurable hypothermia response at doses (up to 200 mg/kg) at which it effectively desensitized against neurogenic inflammation. These data suggest that the peculiar binding behavior of these ligands might be associated with a distinct spectrum of biological activity.     

Proteomics and Leishmaniasis: Potential Clinical Applications

Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. They are endemic in 98 countries, affect around 12 million people worldwide and may present several distinct clinical forms. Unfortunately, there are only a few drugs available for treatment of leishmaniasis, which are toxic and not always effective. Different parasite species and different clinical forms require optimization of the treatment or more specific therapies, which are not available. The emergence of resistance is also a matter of concern. Besides, diagnosis can sometimes be complicated due to atypical manifestations and associations with other pathologies. In this review, proteomic data are presented and discussed in terms of their application in important issues in leishmaniasis such as parasite resistance to chemotherapy, diagnosis of active disease in patients and dogs, markers for different clinical forms, identification of virulence factors, and their potential use in vaccination. It is shown that proteomics has contributed to the discovery of potential biomarkers for prognosis, diagnosis, therapeutics, monitoring of disease progression, treatment follow‐up and identification of vaccine candidates for specific diseases. However, the authors believe its capabilities have not yet been fully explored for routine clinical analysis for several reasons, which will be presented in this review.     

24-GHz ultra-wideband transmitter for vehicular short-range radar applications

This paper presents a 24-GHz transmitter for ultra-wideband short-range radar applications fabricated in a 0.13-μm SiGe:C BiCMOS technology. The circuit is composed of a frequency synthesiser, based on 24-GHz voltage-controlled oscillator in an N-integer phase-locked loop (PLL), a RF switch delivering a 0-dBm output power, and a tunable rectangular pulse generator, whose pulse width covers a range between 0.5 and 1.2 ns. The transmitter has been developed for a flip-chip bumping assembly on a module with an UWB antenna. Assuming a 10.5-dBi antenna gain, it is compliant with European Telecommunications Standards Institute (ETSI) transmission mask and is able to cover the main automotive applications addressing both a resolution better than 0.1 m and maximum unambiguous range of 15 m.     

A System Design Methodology for Analog Feed Forward Artificial Neural Networks

Today Feed Forward Neural Networks (FFNs) use paradigms tied to mathematical frameworks more than to actual electronic devices. This fact makes analog neural integrated circuits heavy to design. Here we propose an alternative model that can use the native computational properties of the basic electronic circuits. A practical framework is described to train analog FFNs in compliance with the model. This is especially useful whenever the weight storage elements cannot be re-programmed on the fly at a high rate. To show how the capability of such framework can be applied to neural systems with non conventional architectures two cases are presented. The first one is a neural signal processor named NESP which has sigmoidal neurons and the other is an innovative architecture named N-LESS.     

Low-power broadband quadrature signal generator based on phase-tunable dividers

This paper presents the design and experimental results of a low-power 300–960 MHz I/Q signal generator for low-IF receivers. The circuit is based on phase-tunable dividers and uses delay-locked loops, which provide phase accuracy for the quadrature signals as well as low-sensitivity of the phase error against temperature and power supply variations. Thanks to the adopted technique, the phase error can be further reduced by trimming the reference voltage of the delay-locked loops through a calibration digital word, which can be stored in a non-volatile memory during manufacturing. The I/Q generator exhibits an absolute phase error before calibration that is lower than 1.5°. The I/Q phase drift due to temperature variations from ?40 to 85 °C and power supply variations from 1.1 to 1.3 V is 0.3° and 0.2°, respectively. By dividing the overall frequency range into four 165-MHz wide sub-bands and using only four 5-bit calibration words, the I/Q phase variation with respect to frequency, temperature, and power supply is lower than 1° in the 300–960 MHz operating band. The I/Q generator is implemented in a 90-nm CMOS technology and exhibits a current consumption as low as 0.5 mA.     

Optimization of pump absorption in MOF lasers via multi-long-period gratings: design strategies

Different strategies for designing optical couplers, optimized to enhance the pump absorption in the rare-earth-doped core of microstructured fiber lasers, are illustrated. Three kinds/configurations of optical couplers have been designed and compared as examples of the different design strategies which can be followed. Their effectiveness to enhance the performance of an ytterbium-doped, double cladding, microstructured optical fiber laser has been accurately simulated. They consist of a suitable cascade of multiple long-period gratings (MLPGs) inscribed in the fiber core region. The characteristics of the MLPG couplers have been simulated via a homemade computer code based on both rate equations and an extended coupled mode theory. The proposed MLPG couplers seem particularly useful in the case of low rare-earth concentration but, even for a middle-high ytterbium concentration, as N(Yb)=5×10(25) ions/m(3), the slope efficiency S can be increased up to 20%, depending on the fiber length.     

Low-voltage dynamic biasing technique for CMOS class ABcurrent-mode circuits

A novel dynamic biasing technique that can be used for the design of CMOS class AB current-mode circuits is presented. The approach takes advantage of the switched capacitor (SC) technique and enables extremely low voltage operations. An application of the proposed technique to the design of a basic input stage is given and simulations showing good agreement with the expected results are provided