Ultra-broad gain quantum cascade lasers tunable from 6.5 to 10.4 µm.

We present a quantum cascade laser structure with an ultra-broad gain profile that covers the wavelength range from 6.5 to 10.4 µm. In a grating-tuned external cavity, we demonstrated continuous tuning from 1027 cm(-1) to 1492 cm(-1) with this broad gain laser chip. We also fabricated distributed feedback quantum cascade laser arrays with this active region design and varied grating periods. We demonstrated single wavelength lasing from 962 (10.4) to 1542 cm(-1) (6.5 µm). The frequency coverage (580 cm(-1)) is about 46% of center frequency.

Inter-individual variability in the upper-lower limb breaststroke coordination.

The aim of the present study was to examine inter-individual variability in upper-lower limb breaststroke coordination. First, inter-individual variability was compared between recreational and comparative swimmers. Second, as recreational swimmers revealed more variable inter-limb coordination than competitive swimmers, inter-individual variability was assessed among recreational swimmers to identify coordination profiles. The elbow-knee continuous relative phase (CRP) was used to analyze upper-lower limbs coupling during a breaststroke cycle. Twenty-four recreational and twenty-four competitive swimmers swam 25 m at 80% of their maximal speed. Underwater and aerial side views were mixed and genlocked. Angular position, velocity and CRP were calculated for the knee and elbow joints by digitizing body markers from the side view. The kinematics of three cycles were filtered, averaged and normalized in terms of percentage of total cycle duration. The topography of the mean CRP curve of the recreational swimmers resembled a 'W-shape', whereas an 'inverse U-shape' was seen in the competitive swimmers. However, higher inter-individual variability was observed among the recreational swimmers than among the competitive swimmers (38.1° vs. 19.4°; p<.05), suggesting that several profiles of inter-limb coordination may exist in recreational swimmers. Coordination profiling showed that three clusters could classify the recreational swimmers.

Access of children and adolescents with type 1 diabetes to insulin pump therapy has greatly increased in France since 2001.

AIM: Insulin pump therapy is an emerging option in the management of type 1 diabetes (T1D), but it often remains unused. For this reason, in 2007, a French national survey was carried out to update the frequency of insulin pump use in the paediatric population compared with a previous survey done in 2001. METHODS: The present survey was performed in hospital departments involved in paediatric diabetes management (n = 67) and in adult departments involved in adolescent diabetes management (n = 113). The number of T1D children (age < 18 years) treated in each department, with or without the use of an insulin pump, and the number of insulin pump therapies initiated during the previous year were collected. RESULTS: A total of 60 paediatric and 28 adult centres responded, involving 9073 T1D children and adolescents (93% in paediatric departments). Of these patients, 1461 (16%) were treated by insulin pump, 89% of which were managed in paediatric centres. However, pump use was more frequent in adult than in paediatric centres (32% versus 18%, respectively). Also, 38% of insulin pumps were initiated during the year prior to the survey. In addition, in 2001, 140 children were treated with insulin pump in 13 paediatric centres (versus 56 centres in 2007). CONCLUSION: The number of centres using insulin pump therapy for diabetic children and the number of children treated by insulin pump were increased fourfold and 10-fold, respectively, from 2001 to 2007, indicating greater access to pump therapy in the French paediatric population. The present survey is still ongoing to evaluate the decision-making criteria that influence the initiation of insulin pump therapy in T1D paediatric patients.

Intra-cyclic distance per stroke phase, velocity fluctuations and acceleration time ratio of a breaststroker's hip: a comparison between elite and nonelite swimmers at different race paces.

The aim of this study was to compare the intra-cyclic velocity graphs of breaststroke swimmers at two skill levels in relation to their movement phases. Two groups of nine male swimmers were videotaped underwater at three swimming race paces corresponding to their actual competitive times for the 200-m, 100-m and 50-m breaststroke. Their forward intra-cyclic hip velocity was recorded with a velocity-meter. The breaststroke cycle was divided into four phases: leg propulsion, leg-arm lag phase, arm propulsion, and arm and leg recovery. From the velocity-time data, the following parameters were computed: an index of velocity fluctuations (IVF), the distance covered during each stroke phase, and an acceleration-deceleration time ratio (ADTR). The main results showed that in both groups of swimmers, when the race pace increased, the distance covered during the leg-arm lag phase decreased, while the other swimming phases remained stable. When expressed in relative values, the percentage of distance covered during the leg-arm lag phase decreased. In nonelite swimmers, the percentage of distance covered in the other stroke phases increased significantly, while only a tendency was noted in the elite group. Elite swimmers demonstrated a higher ADTR at the 50-m pace than at their 100-m and 200-m paces. An inter-group comparison showed that elite swimmers had higher values for the IVF and ADTR, which indicated their capacity to accelerate to boost the swim and highlighted the relevancy of these factors to discriminate skill level.

Arm-leg coordination in flat breaststroke: a comparative study between elite and non-elite swimmers.

The aim of this study was to compare the arm-leg coordination in flat breaststroke among four groups of swimmers (elite males, elite females and non-elite males, non-elite females) of two different competitive levels. Using a velocity-video system, both forward acceleration and deceleration phases of the hip were first identified. Based on these phases, four temporal gaps indicated the time duration between arm and leg actions throughout three race paces (200, 100, and 50 m). For both groups, a velocity increase was combined with an increase of stroke rate, a decrease of stroke length, and an increase of the propulsive phases and a decrease of the glide phases. However, when the relative duration of one stroke cycle was considered, the elite swimmers had significant shorter time of the glide phase than lower competitive level swimmers (18.80 % vs. 31.04 % for females and 11.89 % vs. 19.60 % for males) combined with a longer stroke length (respectively 2.05 m vs. 1.73 m and 2.03 m vs. 1.82 m). Furthermore, the temporal gaps of the elite swimmers showed a greater continuity in the arm and leg actions, which indicates a better timing than non-elite swimmers. It was concluded that elite breaststroke swimmers are able to optimise their propulsion by reducing their glide phase and using a more continuous timing between arm and leg coordination.

Evaluation of arm-leg coordination in flat breaststroke.

This study proposes a new method to evaluate arm-leg coordination in flat breaststroke. Five arm and leg stroke phases were defined with a velocity-video system. Five time gaps quantified the time between arm and leg actions during three paces of a race (200 m, 100 m and 50 m) in 16 top level swimmers. Based on these time gaps, effective glide, effective propulsion, effective leg insweep and effective recovery were used to identify the different stroke phases of the body. A faster pace corresponded to increased stroke rate, decreased stroke length, increased propulsive phases, shorter glide phases, and a shorter T1 time gap, which measured the effective body glide. The top level swimmers showed short time gaps (T2, T3, T4, measuring the timing of arm-leg recoveries), which reflected the continuity in arm and leg actions. The measurement of these time gaps thus provides a pertinent evaluation of swimmers' skill in adapting their arm-leg coordination to biomechanical constraints.

Marital status and family size of type 1 diabetic patients in a French cohort.

OBJECTIVE: To compare the marital status, the number of offspring and the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women. METHODS: From the database of patients attending our department, we reviewed the files of all the 352 subjects aged >=40 years with type 1 diabetes and compared male and female patients for whom age, age at diagnosis of diabetes, marital status, socio-economic status, number and age of offspring, diagnosed type 1 diabetes in the offspring could be obtained from patient's record and/or direct interview (86 males and 78 females). RESULTS: In this population, 73% of women and 81% of men were married or living a marital life (NS), and 35% of women versus 8% of men had no offspring (P<0.0001). The proportion of parents with 2 offspring or more was 43% in females and 61% in males (p=0.03) and was not related to the socio-economic status. The number of offspring with diagnosed type 1 diabetes was small (8/229) and did not show significant association with gender of the parent, with a cumulative incidence of 3.2 and 3.7% in offspring of type 1 diabetic mothers and fathers respectively. CONCLUSION: Type 1 diabetic women born before 1960 had fewer children than men. In this cohort, there was no difference in the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women despite reduced family size in women.

Apo2L/TRAIL and its death and decoy receptors.

Apo2 ligand or tumour necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is one of the several members of the tumour necrosis factor (TNF) gene superfamily that induce apoptosis through engagement of death receptors (DRs). Apo2L/TRAIL interacts with an unusually complex receptor system of two DRs and three decoys. This protein has garnered intense interest as a potential candidate for cancer therapy because as a trimer it selectively induces apoptosis in many transformed cells but not in normal cells. While much of the early characterisation of Apo2L/TRAIL and its receptors relied on overexpression studies, recent work using untransfected cells has clarified how endogenous proteins transmit apoptotic signals from this ligand. In this review, we focus on the apoptotic signalling pathways stimulated by Apo2L/TRAIL and summarise what is known about its physiological role.

Metabolic and immunogenetic prediction of long-term insulin remission in African patients with atypical diabetes.

AIMS: We aimed to characterize a cohort of 'atypical' diabetic patients of sub-Saharan African origin and to analyse possible determinants of long-term remission. METHODS: Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti-GAD, anti-ICA and HLA class II) markers of Type 1 diabetes were compared with a 90-non-diabetic unrelated adult African population. RESULTS: Twenty-one ketonuric patients (age 42 +/- 9 (sd) years; body mass index (BMI) 26 +/- 3 kg/m2) were initially insulin-treated (IT), and 21 non-ketonuric patients (age 38 +/- 8 years; BMI 26 +/- 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 +/- 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3-64.4) and stimulated C-peptide (OR 8.17, 95% CI 1.5-44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin-treated NIT. Anti-GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P < 0.001) without significant difference between the subgroups. CONCLUSION: Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long-term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long-term remission.

Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8.

Caspase-8 is believed to play an obligatory role in apoptosis initiation by death receptors, but the role of its structural relative, caspase-10, remains controversial. Although earlier evidence implicated caspase-10 in apoptosis signaling by CD95L and Apo2L/TRAIL, recent studies indicated that these death receptor ligands recruit caspase-8 but not caspase-10 to their death-inducing signaling complex (DISC) even in presence of abundant caspase-10. We characterized a series of caspase-10-specific antibodies and found that certain commercially available antibodies cross-react with HSP60, shedding new light on previous results. The majority of 55 lung and breast carcinoma cell lines expressed mRNA for both caspase-8 and -10; however, immunoblot analysis revealed that caspase-10 protein expression was more frequently absent than that of caspase-8, suggesting a possible selective pressure against caspase-10 production in cancer cells. In nontransfected cells expressing both caspases, CD95L and Apo2L/TRAIL recruited endogenous caspase-10 as well as caspase-8 to their DISC, where both enzymes were proteolytically processed with similar kinetics. Caspase-10 recruitment required the adaptor FADD/Mort1, and caspase-10 cleavage in vitro required DISC assembly, consistent with the processing of an apoptosis initiator. Cells expressing only one of the caspases underwent ligand-induced apoptosis, indicating that each caspase can initiate apoptosis independently of the other. Thus, apoptosis signaling by death receptors involves not only caspase-8 but also caspase-10, and both caspases may have equally important roles in apoptosis initiation.

Transcript cleavage, attenuation, and an internal promoter in the Rhodobacter capsulatus puc operon.

The stoichiometry of the structural proteins of the photosynthetic apparatus in purple photosynthetic bacteria is achieved primarily by complex regulation of the levels of mRNA encoding the different proteins, which has been studied in the greatest detail in the puf operon. Here we investigated the transcriptional and posttranscriptional regulation of the puc operon, which encodes the peripheral light harvesting complex LHII. We show that, analogous to the puf operon, a primary transcript encoding five puc genes is rapidly processed to generate more stable RNA subspecies. Contrary to previous hypotheses, translational coupling and regulation of puc transcription by puc gene products were found not to occur. A putative RNA stem-loop structure appears to attenuate transcription initiated at the puc operon major promoter. We also found that a minor pucD-internal promoter contributes to the levels of a message that encodes the LHII 14-kDa gamma (PucE) protein.

The mitotic centromeric protein MEI-S332 and its role in sister-chromatid cohesion.

Faithful segregation of sister chromatids during cell division requires properly regulated cohesion between the sister centromeres. The sister chromatids are attached along their lengths, but particularly tightly in the centromeric regions. Therefore specific cohesion proteins may be needed at the centromere. Here we show that Drosophila MEI-S332 protein localizes to mitotic metaphase centromeres. Both overexpression and mutation of MEI-S332 increase the number of apoptotic cells. In mei-S332 mutants the ratio of metaphase to anaphase figures is lower than wild type, but it is higher if MEI-S332 is overexpressed. In chromosomal squashes centromeric attachments appear weaker in mei-S332 mutants than wild type and tighter when MEI-S332 is overexpressed. These results are consistent with MEI-S332 contributing to centromeric sister-chromatid cohesion in a dose-dependent manner. MEI-S332 is the first member identified of a predicted class of centromeric proteins that maintain centromeric cohesion.

Run-on gene transcription in human neocortical nuclei. Inhibition by nanomolar aluminum and implications for neurodegenerative disease.

The incorporation of [alpha-32P]-uridine triphosphate into DNA transcription products was examined in short post-mortem interval (PMI) human brain neocortical nuclei (n, 22; PMI, 0.5-24 h) using run-on-gene transcription. Reverse Northern dot-blot hybridization of newly synthesized RNA against either total cDNA or Alu repetitive DNA indicated that human brain neocortical nuclei of up to 4-h PMI were efficient in incorporating radiolabel into new transcription products, after which there was a graded decline in de novo RNA biosynthetic capacity. To test the effects of 0-3000 nM concentrations of ambient aluminum on RNA polymerase I (RNAP I) and RNA polymerase II (RNAP II) transcription, dot blots containing 0.5, 1.0, 2.0, and 5.0 micrograms of DNA for (1) the human-specific Alu repetitive element (2) the neurofilament light (NFL) chain, and (3) glial fibrillary acidic protein (GFAP) were Northern hybridized against newly synthesized radiolabeled total RNA. These DNAs represent heterogeneous nuclear RNA (hnRNA), neuronal-, and glial-specific markers, respectively. We report here a dose-dependent repression in the biosynthetic capabilities of brain RNAP II in the range of 50-100 nM aluminum, deficits similar to those previously described using a rabbit neocortical nuclei transcription system and at concentrations that have been reported in Alzheimer's disease (AD) euchromatin. Transcription from RNAP II and the neuron-specific NFL gene in the presence of aluminum was found to be particularly affected. These findings support the hypothesis that brain gene transcription in the presence of trace amounts of ambient aluminum impairs mammalian brain DNA to adequately read out genetic information.

Multicentre evaluation of the DCA 2000 system for measuring glycated haemoglobin. DCA 2000 Study Group.

The recommended method for assessing long-term blood glucose control in diabetic patients is the measurement of glycated haemoglobin (Hb). The Ames DCA 2000 system for assaying glycated Hb uses an immunoassay with a monoclonal antibody specific for an aminoacid sequence within the HblAc molecule. This study compared the performance of the DCA 2000 system for HblAc measurement with that of high-performance liquid chromatography (HPLC). A total of 1.016 insulin-dependent and non-insulin-dependent diabetic patients from 5 outpatient clinics took part. The correlation coefficients between DCA 2000 and HPLC data ranged between 0.94 and 0.98, depending on site. The mean variations and 95% confidence intervals for the differences between the results for each sample were: site A 0.172 (-1.186 to 1.53), site B -0.275 (-1.317 to 0.767), site C -0.146 (-0.868 to 0.576), site D -0.088 (-0.864 to 0.688), and site E -0.251 (-1.099 to 0.597). The sensitivity of the DCA 2000 assay ranged between 80 and 94%, and the specificity between 88 and 100%, depending on site. For pooled results, the correlation coefficient assayed by the two methods was 0.95. The mean variation was -0.116 and the 95% confidence interval -1.23 to 0.998. The sensitivity of DCA 2000 was 91%, and the specificity 94%. DCA tended to underestimate HbAlc slightly as compared to HPLC. This study confirms the reliability of DCA 2000 for measuring glycated Hb. The system is easy to use and provides valuable information for the care of the diabetic patients.

Are the implications of the Diabetes Control and Complications Trial (DCCT) feasible in daily clinical practice?

The Diabetes Control and Complications Trial was conducted in heavily-equipped centres on a selected and motivated patient cohort. The aim of the present study was to evaluate at one-year follow-up the results of intensive insulin therapy in patients with insulin-dependent diabetes mellitus attending a department of diabetology. From October 1, 1993, to December 31, 1994, all our hospitalised patients under 55 years of age with HbA1c levels above 8% and receiving 2 daily insulin injections were offered the opportunity to shift to 3 daily injections (short-acting insulin in the morning and at midday, and a mixture of short-acting and intermediate insulin in the evening). Patients were instructed to increase blood glucose self-monitoring and to see their diabetologist more often (once every two months). Five patients refused and 45 accepted this proposal: 22 women and 23 men (mean age 31.8 +/- 10.9 yr), BMI 23.5 +/- 2.9 kg/m2, duration of diabetes 12.8 +/- 10.1 yr, HbA1c 10.0 +/- 2.0%. Five patients were lost to follow-up, 2 asked to have their medical file transferred, 3 returned to 2 daily injections, and 5 consulted only once during the year of follow-up. For the 29 patients seen after one-year follow-up, the decrease in HbA1c levels from 10.0 +/- 1.9% to 9.5 +/- 1.8% was not statistically significant. Sixteen patients complained of increased occurrence of hypoglycaemia (3 comas). In routine clinical practice, the prescription of intensive insulin therapy to non-selected insulin-dependent diabetic patients can be associated with a high number of patients lost to follow-up (17% in our study). An increase in the number of daily insulin injections will improve glycaemic control only if self-monitoring and medical surveillance are also intensified. However, many long-term poorly-controlled insulin-dependent diabetic patients are reluctant to comply with these recommendations.

Topological analysis of the Rhodobacter capsulatus PucC protein and effects of C-terminal deletions on light-harvesting complex II.

A theoretical model for the cytoplasmic membrane topology of the Rhodobacter capsulatus PucC protein was derived and tested experimentally with pucC'::pho'A gene fusions. The alkaline phosphatase (AP) activities of selected fusions were assayed, and the resultant pattern of high and low activity was compared with that of the theoretical model. High AP activity correlated well with fusion joints located in regions predicted to be periplasmic, and most fusions in predicted cytoplasmic loops yield approximately 1/20th as much activity. Replacement of pho'A with lac'Z in nine of the fusions confirmed the topology, as beta-galactosidase activities were generally reciprocal to the corresponding AP activity. On the basis of the theoretical analysis and the information provided by the activities of fusions, a model for PucC topology in which there are 12 membrane-spanning segments and both the N and C termini are located in the cytoplasm is proposed. Translationally out-of-frame pucC::phoA fusions were expressed in an R. capsulatus delta pucC strain. None of the fusions missing only one or two of the proposed C-terminal transmembrane segments restored the wild-type phenotype, suggesting that the C terminus of PucC is important for function.

Detection of coronary artery disease in diabetic patients.

Coronary artery disease may be difficult to detect in diabetic patients. This study was designed to determine the specificity and sensitivity of three noninvasive tests. Accordingly, the results of 48-h ambulatory electrocardiogram (ECG) monitoring, maximal ECG exercise test, and intravenous dipyridamole myocardial thallium scintigraphy were compared in 59 middle-aged diabetic patients who were consecutively selected for suspected coronary artery disease. All patients also underwent coronary angiography, which was performed regardless of the results of the non-invasive tests. Twenty patients (34%) had significant coronary lesions, i.e. stenosis equal to or greater than 70%, and 16 of these 20 patients (80%) had double or triple vessel disease. Sensitivity and specificity were, respectively, 25% and 88% for ambulatory ECG monitoring, 75% and 77% for the exercise test and 80% and 87% for thallium myocardial scintigraphy. This observation strongly supports the use of non-invasive tests for the detection of coronary artery disease in those diabetic patients at high risk of such disease. As the exercise test is cheaper and more widely available than thallium myocardial scintigraphy it should be used as a first line examination. Dipyridamole myocardial scintigraphy may provide an alternative solution for those patients who cannot perform maximal exercise, or with atypical clinical presentation.

Immunoradiometric assay of human intact proinsulin applied to patients with type 2 diabetes, impaired glucose tolerance, and hyperandrogenism.

We describe an immunoradiometric assay for human intact proinsulin in serum. In this method, one monoclonal antibody, coated onto polyacrylamide beads, cross-reacts with proinsulins and insulin. A sandwich is formed with intact proinsulin, split (65-66) proinsulin, and des (64-65) proinsulin binding with an 125I-labeled monoclonal antibody specific for an epitope at the intact B-C junction of proinsulin. Because split (65-66) and des (64-65) proinsulin concentrations are very low in serum, this assay essentially measures intact proinsulin. When we used 1-mL serum samples, the mean detection limit was 0.4 pmol/L. Mean proinsulin concentrations (pmol/L) were 3.4 (range 1-9.1) in healthy fasting subjects, 28.5 (9.7-101) in patients with type 2 diabetes (treated with metformin and sulfonylureas), 5.0 (1.6-9.3) in women with hyperandrogenism and normal insulinemia, 10.3 (2.6-36) in women with hyperandrogenism and hyperinsulinemia, and 8.5 (4.8-21.3) in patients with impaired glucose tolerance.

Hepatic glucose production during intraperitoneal and intravenous closed-loop insulin regulation of blood glucose in type 1 (insulin-dependent) diabetic patients.

Intraperitoneal infusion of insulin should be more physiological than intravenous insulin since part of the insulin is directed toward the portal vein, which allows the liver to retain its major role in glucose homeostasis. The regulation of hepatic glucose production during the intraperitoneal and intravenous infusions of insulin were compared in eight Type 1 (insulin-dependent), C-peptide-deficient diabetic patients. Primed, continuous infusions of [6,6-2H]glucose were given in the postabsorptive state and during continuous infusion of unlabelled glucose at 1.5 and 4 mg/kg.min, while normoglycaemia was maintained by closed-loop intraperitoneal and intravenous insulin delivery. During all three periods, plasma glucose concentrations remained near normal (variations 3.8-6.1%). The insulin infusion rates required for normal plasma glucose concentrations were essentially the same for the intravenous and intraperitoneal routes in all cases, although the variations were greater with intraperitoneal insulin. Plasma free-insulin levels were only slightly, non-significantly lower with intraperitoneal infusion than with intravenous infusion. Hepatic glucose production was significantly lower with intraperitoneal insulin during all three conditions: basal: 1.71 +/- 0.14, i.p. vs 2.37 +/- 0.26 mg/kg.min, i.v.; 1.5 mg/kg.min glucose infusion: 0.49 +/- 0.23, i.p. vs 0.88 +/- 0.18 mg/kg.min, i.v.; 4 mg/kg.min glucose infusion: 0.31 +/- 0.10, i.p. vs 0.56 +/- 0.12 mg/kg.min, i.v.. These results, obtained with steady-state conditions for plasma glucose, isotopic plasma glucose enrichments and unlabelled glucose infusion rates, suggest that better control of hepatic glucose production leading to normoglycaemia was achieved with the intraperitoneal infusion.