'Off-On' Fluorescent Sensors for Physiological levels of Magnesium Ions based on Photoinduced Electron Transfer (PET) which also behave as OR Logic Gates

The fluorescence of molecules 1-3 is enhanced by factors of up to 67 in the presence of magnesium and calcium ions in neutral water which allows the selective monitoring of magnesium ions under simulated physiological conditions and permits the construction of truth tables with OR logic when these molecules are viewed as ion input-photon output molecuIar devices.

Cross-colonization of scots pine (Pinus sylvestris) seedlings by the ectomycorrhizal fungus Paxillus involutus in the presence of inhibitory levels of Cd and Zn

The effects of Cd and Zn on cross-colonization by Paxillus involutus of Scots pine seedlings was examined by using pairs of ectomycorrhizal (ECM) and non-mycorrhizal (NM) seedlings grown in the same vessel. This was done to assess, first, the ability of P. involutus to colonize NM Scots pine seedlings by growth from colonized roots of other Scots pine seedlings in the presence of Cd or Zn, and, second whether ECM colonization of Scots pine by P. involutus provided a competitive advantage over NM seedlings. Ectomycorrhizal colonization of Scots pine was shown to be more sensitive than Scots pine itself to Cd and Zn, but prior colonization did provide a competitive advantage with respect to biomass production. This beneficial effect over NM seedlings was, however, equal in the control, Cd and Zn treatments, and was due simply to growth stimulation in the presence of ECM colonization. Cross-colonization from an ECM to a NM seedling was reduced but not prevented by Cd and Zn. Cd had a more negative effect on cross-colonization than on initial colonization of seedlings, whereas Zn had an equally inhibitory effect on both parameters. These results have important implications for plant establishment on metal-contaminated sites. If cross-colonization between plants is reduced by toxic metals, plant establishment on contaminated sites might be retarded.

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

Hospitalization in Geriatric Wards: Considerations on the Evaluation of the Outcome

Within a defined law framework, the Italian central health system dictates the standards for hospitalization to local care units, which are in turn allowed to establish their own effectiveness criteria. The appropriateness of the hospitalization decision is therefore predetermined at patients admission, whereas its effectiveness relies on the ex post patient well-being as a result of the complex system of reciprocal relations between patients and healthcare agents at the ward level. We consider the outcomes in geriatric wards referring to the national health system, with respect both to patients traits at the individual level and wards/hospital settings. The risk that models the healthcare outcome is accordingly adjusted for covariates at the different levels of analysis (Goldstein & Spiegelhalter, 1996), thus allowing to differentiate among outcomes in terms of the hospitalization structure and, when appropriate, of territorial aggregation.

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD25–56 and preproIMD57–92, were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin45–92 (MRproAM45–92) in 19 patients with systolic heart failure (LVEF < 45%). In healthy subjects, plasma levels (mean + SE) of IMD (6.3 + 0.6 pg ml−1) were lower than, but correlated with those of AM (25.8 + 1.8 pg ml−1; r = 0.49, p < 0.001). Plasma preproIMD25–56 (39.6 + 3.1 pg ml−1), preproIMD57–92 (25.9 + 3.8 pg ml−1) and MRproAM45–92 (200.2 + 6.7 pg ml−1) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8 + 1.3 pg ml−1, p < 0.05), similarly to MRproAM45–92 (329.5 + 41.9 pg ml−1, p < 0.001) and AM (56.8 + 10.9 pg ml−1, p < 0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3 + 1.8 pg ml−1) than those without (6.5 + 1.0 pg ml−1; p < 0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue

β-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of Aβ peptides, proposed to drive the pathological changes found in Alzheimer’s disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in four brain regions from individuals with AD and controls. BACE1 mRNA had been previously quantified in the samples, as had glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), to track changing cell populations in the tissue. mRNA levels in the human post mortem brain tissue were assayed using quantitative real-time polymerase chain reaction (qPCR) and qbasePLUS, employing validated stably expressed reference genes. No differences in RTN3 or PPIL2 mRNA levels were found in individuals with AD, compared to controls. Both RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three showed similar disease stage-dependent changes with respect to NSE and GFAP. These findings indicated that the in vitro data demonstrating an effect of PPIL2 on BACE1 expression have functional relevance in vivo. Further research into BACE1-interacting proteins could provide a fruitful approach to the modulation of this protease and consequently Aβ production.

Effective collision strengths for forbidden transitions among the 3s23p3 fine-structure levels of Cl III

Effective collision strengths for the 10 astrophysically important fine-structure forbidden transitions among the ⁴S^o, ²D^o and ²P^o levels in the 3s²3p³ configuration of Cl III are presented. The calculation employs the multichannel R-matrix method to compute the electron-impact excitation collision strengths in a close-coupling expansion, which incorporates the lowest 23 LS target eigenstates of Cl III. These states are formed from the 3s²3p³, 3s3p⁴, 3s²3p²3d and 3s²3p²4s configurations. The Maxwellian-averaged effective collision strengths are presented graphically for all 10 fine-structure transitions over a wide range of electron temperatures appropriate for astrophysical applications [log T(K) = 3.3 - log T(K) = 5.9]. Comparisons are made with the earlier seven-state close-coupling calculation of Butler & Zeippen, and in general excellent agreement is found in the low-temperature region where a comparison is possible [log T(K) = 3.3 - log T(K) = 4.7]. However, discrepancies of up to 30 per cent are found to occur for the forbidden transitions which involve the ⁴S^o ground state level, particularly for the lowest temperatures considered. At the higher temperatures, the present data are the only reliable results currently available.

Effective collision strengths for fine-structure forbidden transitions among the 2s22p3 levels of S x

Effective collision strengths for electron-impact excitation of the N-like ion S x are calculated in the close-coupling approximation using the multichannel R-matrix method. Specific attention is given to the 10 astrophysically important fine-structure forbidden transitions among the ⁴S^O, ²D^o and ²P^o levels in the 2s²2p³ ground configuration. The total (e^- + ion) wavefunction is expanded in terms of the 11 lowest LS eigenstates of S x, and each eigenstate is represented by extensive configuration-interaction wavefunctions. The collision strengths obtained are thermally averaged over a Maxwellian distribution of velocities, for all 10 fine-structure transitions, over the range of electron temperatures log T(K) = 4.6-6.7 (the range appropriate for astrophysical applications). The present effective collision strengths are the only results currently available for these fine-structure transition rates.

Effective collision strengths for fine-structure forbidden transitions among the 2s22p3 levels of Ne IV

Effective collision strengths for electron-impact excitation of the N-like ion NeIV are calculated in the close-coupling approximation using the multichannel R-matrix method. Specific attention is given to the 10 astrophysically important fine-structure forbidden transitions among the ⁴S^o, ²D^o and ²P^o levels in the 2s²2p³ ground-state configuration. The expansion of the total wavefunction incorporates the lowest 11 LS eigenstates of NeIV, consisting of eight n = 2 terms with configurations 2s²2p³, 2s2p⁴ and 2p⁵, together with three n = 3 states of configuration 2s²2p²3s. We present in graphical form the effective collision strengths obtained by thermally averaging the collision strengths over a Maxwellian distribution of velocities, for all 10 fine-structure transitions, over the range of electron temperatures log T(K) = 3.6 to log T(K) = 6.1 (the range appropriate for astrophysical applications). Comparisons are made with the earlier, less sophisticated close-coupling calculation of Giles, and excellent agreement is found in the limited temperature region where a comparison is possible [log T(K) = 3.7 to log 7(K) = 4.3]. At higher temperatures the present data are the only reliable results currently available.

Effective collision strengths for fine-structure forbidden transitions among the 3s 23p 3 levels of Ar IV

The multichannel R-matrix method is used to compute electron impact excitation collision strengths in Ar IV for all fine-structure transitions among the ⁴S°, ²D° and ²P° levels in the 3s ²3p ³ ground configuration. Included in the expansion of the total wavefunction are the lowest 13 LS target eigenstates of Ar iv formed from the 3s ²3p ³, 3s3p ⁴ and 3s ²3p ²3d configurations. The effective collision strengths, obtained by averaging the electron collision strengths over a Maxwellian distribution of electron velocities, are presented for all 10 fine-structure transitions over a wide range of electron temperatures of astrophysical interest (T _e = 2000-100 000 K). Comparisons are made with an earlier 7-state close-coupling calculation by Zeippen, Butler & Le Bourlot, and significant differences are found to occur for many of the forbidden transitions considered, in particular those involving the ⁴S° ground state, where discrepancies of up to a factor of 3 are found in the low-temperature region. © 1997 RAS.

Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by 1H-MRS

We used1H-magnetic resonance spectroscopy to noninvasively determine total creatine (TCr), choline-containing compounds (Cho), and intracellular (IT) and extracellular (between-muscle fibers) triglycerides (ET) in three human skeletal muscles. Subjects' (n = 15 men) TCr concentrations in soleus [Sol; 100.2 ± 8.3 (SE) mmol/kg dry wt] were lower (P < 0.05) than those in gastrocnemius (Gast; 125.3 ± 9.2 mmol/kg dry wt) and tibialis anterior (TA; 123.7 ± 8.8 mmol/kg dry wt). The Cho levels in Sol (35.8 ± 3.6 mmol/kg dry wt) and Gast (28.5 ± 3.5 mmol/kg dry wt) were higher (P < 0.001 andP < 0.01, respectively) compared with TA (13.6 ± 2.4 mmol/kg dry wt). The IT values were found to be 44.8 ± 4.6 and 36.5 ± 4.2 mmol/kg dry wt in Sol and Gast, respectively. The IT values of TA (24.5 ± 4.5 mmol/kg dry wt) were lower than those of Sol (P < 0.01) and Gast (P < 0.05). There were no differences in ET [116.0 ± 11.2 (Sol), 119.1 ± 18.5 (Gast), and 91.4 ± 19.2 mmol/kg dry wt (TA)]. It is proposed that the differences in metabolite levels may be due to the differences in fiber-type composition and deposition of metabolites due to the adaptation of different muscles during locomotion.

Developing Science Gateways at Various Levels of Granularity Using WS-PGRADE/gUSE

Science gateways can provide access to distributed computing resources and applications at very different levels of granularity. Some gateways do not even hide the details of the underlying infrastructure, while on the other end some provide completely customized high-level interfaces to end-users. In this chapter the different granularity levels at which science gateways can be developed with WS-PGRADE/gUSE are analysed. The differences between these various granu-larity levels are also illustrated via the example of a molecular docking gateway and its four different implementations.