Applications of Isothermal Titration Calorimetry in Biophysical Studies of G-quadruplexes

G-quadruplexes are higher-order nucleic acids structures formed by G-rich sequences that are stabilized by tetrads of hydrogen-bonded guanine bases. Recently, there has been growing interest in the study of G-quadruplexes because of their possible involvement in many biological processes. Isothermal titration calorimetry (ITC) has been proven to be a useful tool to study the energetic aspects of G-quadruplex interactions. Particularly, ITC has been applied many times to determine the thermodynamic properties of drug-quadruplex interactions to screening among various drugs and to address drug design. In the present review, we will focus on the ITC studies of G-quadruplex structures and their interaction with proteins and drugs and the most significant results will be discussed.     

Low prevalence of microalbuminuria in young Italian insulin-dependent diabetic patients with short duration of disease: a population-based study. Piedmont Study Group for Diabetes Epidemiology

Objectives of this study were to determine the prevalence of microalbuminuria and the level of glycaemic control obtained in a young Italian population-based cohort of subjects with short duration of insulin-dependent diabetes mellitus (IDDM). Out of 298 subjects with onset of IDDM in the period 1984-88, 211 were examined (71%) in 1991-92 (duration of disease 3-9 years). Microalbuminuria was defined as albumin excretion rate (AER) 20-200 micrograms min-1 in an overnight urine collection or alb/creat > 2.5 mg mmol-1 in men and > 4.5 mg mmol-1 in women in one first morning urine sample. Twelve subjects had AER 20-200 micrograms min-1 and 4 had elevated alb/creat ratio. Prevalence of microalbuminuria was 7% (95% Cl 4.0-11.1) in subjects with duration of IDDM 3-9 years and 4% (0.3-7.7) in subjects with duration 3-5 years. Only 1 microalbuminuric subject was found out of 52 aged < or = 14 years. Duration of IDDM was significantly higher (6.9 +/- 1.9 years vs 5.7 +/- 1.6, p = 0.007) and HDL-cholesterol lower (1.22 +/- 0.21 mM vs 1.42 +/- 0.34, p = 0.025) in micro- than in normoalbuminuric subjects, even after adjustment for age, systolic and diastolic blood pressure, BMI, and HbA1c. In almost 50% of the cohort, HbA1c levels were over 9%, whereas only in 10.9% HbA1c levels were lower than 6.6% (mean +3 SD). In conclusion, this Italian population-based study showed low prevalence of microalbuminuria in young subjects with short duration of IDDM, even if the glycaemic control obtained was far from ideal.     

New Raman pump module for reducing pump-signal four-wave-mixing interaction in co-pumped distributed Raman amplifiers

We propose a new Raman pump module that effectively reduces four-wave-mixing (FWM) nonlinear interaction among longitudinal pump modes and wavelength-division-multiplexed (WDM) signals in co-pumped distributed Raman amplifiers based on nonzero dispersion-shifted fibers (NZ-DSFs). Theory and experiments confirm that the proposed pump module structure, based on polarization- and wavelength-multiplexed Fabry-Perot lasers, allows distributed amplification with high co-propagating on-off Raman gain, providing a key technology for all-Raman-based dense-WDM ultralong-haul transmission.     

An ADC histogram test based on small-amplitude waves

This paper deals with a new method improving the static test for analogue-to-digital converters. The method is based on a histogram procedure using as test signals small-amplitude triangular waves superimposed on suitable constant offset values. The histogram is built over the converter fullscale by varying the offset step by step systematically. A small amplitude and a reduced time slope in comparison to the converter range and slew rate, respectively, lead to static test conditions. This procedure allows inexpensive function generators to be used and the test duration to be dramatically reduced. Experimental results of tests aimed at validating, characterizing, and comparing the proposed method on two different converter architectures are presented.     

A schedulability condition for deadline-ordered service disciplines

In a deadline-ordered service discipline, packets are assigned transmission deadlines and eligibility times and are transmitted in increasing order of deadlines. Different deadline-ordered service disciplines are distinguished by how they calculate deadlines and eligibility times. One of the more difficult analytical problems one faces when designing a new deadline-ordered service discipline is to prove that one can bound the end of transmission times of packets relative to their assigned deadlines, which we call schedulability. We show that, no matter how one calculates deadlines, there is a simple schedulability condition for deadline-ordered service disciplines. This schedulability condition is necessary and sufficient for preemptive deadline-ordered service disciplines, and for a server that allows the presence of nonreal-time packets (i.e., packets with no deadlines), it is also necessary and sufficient for nonpreemptive deadline-ordered service disciplines. We also address the schedulability problem for service disciplines in general, and show the optimality of deadline-ordered service disciplines. To demonstrate how our results simplify schedulability determination, we use them to prove the known schedulability conditions of VirtualClock, Packet-by-Packet Generalized Processor Sharing (PGPS), Stop-and-Go, and Delay-Earliest-Due-Date (Delay-EDD), and to provide a new result, the necessary schedulability condition of VirtualClock     

Percutaneous blind needle biopsy versus combined laparoscopic excisional and guided needle biopsy in the diagnosis of liver disorders in pediatric patients

A special interest, both in scientific publications and in the mass media, is recently emerged about the use of hormone replacement therapy (HRT) in post-menopausal women. Beside, in fact, the specific indication for the relief of menopausal symptoms, hypotheses are debated about a possible role of HRT in the reduction of risk of osteoporosis and cardiovascular diseases, and in the increased risk of breast cancer. This situation emphasizes the need for assessing the benefit/risk profile for HRT in order to ensure that strategies of proven clinical effectiveness, based on large randomized clinical trials, will be adopted in the population.     

Università di Roma Tre, 1995-2005: Architecture and Mathematics

Andrea Pagano and Laura Tedeschini Lalli present a brief note on what has to be considered a teaching success story. They tell of ten years of teaching mathematics at the Faculty of Architecture of the Università di Roma Tre, describing some new course content that has been introduced, the methods used and, above all, the spirit that has driven the ideas about teaching mathematics to future architects. The experience covers the full curriculum of the student: from first year courses to individual projects.     

The Fight against the Influenza A Virus H1N1: Synthesis,Molecular Modeling,and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors

The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA–PB1 inhibitors.