Short-pulsed Q-switched fiber laser using graphene oxide quantum dots based as saturable absorber.

In this work, we report the experimental study of a Q-switched optical fiber laser based on graphene oxide quantum dots (GOQDs) as saturable absorber (SA). GOQDs are fabricated by carbonization and exfoliation electrospun polyacrylonitrile (PAN) fibers. The results of Fourier Transform Infrared Spectroscopy (FTIR) showed bands caused by the CHs and C[bond, double bond]O groups associated with the GOQDs. The Raman spectrum showed the typical G and D bands of GOQDs. The size of the GOQDs, calculated by Transmission Electron Microscopy (TEM) was 6 nm; additionally, by high resolution TEM (HRTEM), an interplanar distance of 0.19 nm corresponding to the (002) direction of the graphene oxide was calculated. The SA was achieved using the photodeposition technique of the GOQDs onto the core of a single-mode optical fiber. The nonlinear characterization (NLC) of the GOQDs was carried out using the P-scan technique with a high-gain erbium-doped fiber amplifier (EDFA) at a wavelength of 1550 nm. The obtained results showed a saturable absorption behavior with a value of ß=-1.178x10-6(m/W) and a non-linear susceptibility of Im(χ(3))≈-1.573x10-7(esu). The experimental results of the SA, based on GOQDs as a switching device in a fiber laser, showed a typical behavior of a Q-switched laser by generating a pulsed emission at a wavelength of 1599 nm, a frequency from 2 to 16 kHz, and a maximum average output power of 1.3 mW.

Nonlinear optical response of graphene oxide quantum dots fabricated from electrospun polyacrylonitrile fibers.

The nonlinear optical response of graphene oxide quantum dots (GOQDs) fabricated by the carbonization and exfoliation of electrospun polyacrylonitrile (PAN) fibers is reported. Electrospun and carbonized fibers were characterized by SEM and XPS. SEM micrograph confirmed the formation of PAN fibers of 153.44 ± 6.44 nm, while by XPS the binding energies associated with sp2 and sp3 carbon hybridizations were found, after the carbonization process. On the other hand, the GOQDs obtained were characterized by photoluminescence (PL), UV-Vis, Raman spectroscopy, and High-Resolution Transmission Electron Microscopy (HRTEM). The GOQDs size of 10 nm was estimated by HRTEM. Raman spectroscopy showed the D and G bands associated with the sp2 and sp3 hybridizations of the GOQDs, by PL two energy values of 2.67 and 2.97 eV were calculated. The UV-Vis spectrum showed two absorption bands confirming the presence of GOQDs. The nonlinear characterization was carried out using the P-scan technique, previously photodepositing GOQDs onto an optical fiber, using a coherent radiation source at a wavelength of 1550 nm. The results obtained showed a saturable absorption behavior with a value of ß = - 2.474 × 10 - 4 m / W and a nonlinear susceptibility of χ ( 3 ) ≈ - 7.749 × 10 - 4 ( e s u ) . The results of this work showed that GOQDs obtained can be used for optical switching applications.

Choosing between bad, worse and worst: what is the preferred mode of delivery for failure of the second stage of labor?

OBJECTIVE: To determine the preferred mode of delivery (vacuum, forceps or cesarean delivery) for second-stage dystocia. METHODS: Retrospective cohort study of women delivered by forceps, vacuum or cesarean delivery due to abnormalities of the second stage of labor. Primary outcome included neonatal and maternal composite adverse effects. RESULTS: A total of 547 women were included: 150 (27.4%) had forceps delivery, 200 (36.5%) had vacuum extraction, and 197 (36.1%) had cesarean section. The rate of neonatal composite outcome was significantly increased in vacuum extraction (27%) compared to forceps delivery (14.7%) or cesarean section (9.7%) (p < 0.001). There was no difference in the rate of maternal composite outcome among the groups. Both operative vaginal delivery modes were associated with significantly lower rate of postpartum infection compared to cesarean delivery (0% versus 3%, p = 0.004). CONCLUSION: Operative vaginal delivery was associated with reduced postpartum infection compared to cesarean section. Forceps delivery was associated with reduced risk for adverse neonatal outcome compared to vacuum extraction, with no increase in the risk of composite maternal complications.

Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies.

OBJECTIVE: This study aimed to examine the use of digital technology in the three-dimensional reconstruction of human placentas. STUDY DESIGN: Placentas obtained at term elective caesarean section were sampled, formalin-fixed and embedded in paraffin. Two hundred 5 µm consecutive sections were cut from each specimen and the resultant slides stained with haematoxylin and eosin. Slides were then scanned and the digitised images reconstructed using customised software. RESULTS: Three-dimensional reconstructions were successfully achieved in placentas from normal pregnancies and those complicated by pre-eclampsia, growth restriction, and gestational diabetes. Marked morphological differences were readily identifiable, most clearly in the stem villus architecture. CONCLUSION: This method is an emerging research tool for examining placental histoarchitecture at high resolution and gaining clinically relevant insight into the placental pathology allied to pregnancy complications such as PET, IUGR and GD.

Can Ultrasound Performed in Prolonged Second Stage of Labor Predict the Difficulty and Success Rates of Operative Vaginal Delivery?

OBJECTIVE: To evaluate different sonographic methods for the prediction of the difficulty and the success of operative vaginal delivery (OPD). MATERIALS AND METHODS: A prospective study was performed on 45 term singleton uncomplicated pregnancies with prolonged 2nd stage of delivery with cephalic presentation. Measurements of the fetal head, relations between the fetal head and maternal pelvic parameters during rest and during maternal pushing were taken using translabial ultrasound. RESULTS: 29 cases of OPD were successful and 4 cases failed ending in cesarean section. The passage of the biparietal diameter (BPD) of the infrapubic line (IPL) was statistically correlated with the success of OPD. Head station, passage of the BPD of the IPL, percentage of head after the IPL, circumference of head after IPL were all correlated with the difficulty of OPD. When the distance between the widest diameter of the head and the IPL is < 1.2 cm, there is a 90 % probability of success of OPD. When that distance is > 3.3 cm, there is 90 % probability of cesarean section. When the percentage of head beyond the IPL was > 54 %, there was 90 % probability of successful OPD. DISCUSSION: Translabial ultrasound is useful in the prediction of the difficulty and the success of OPD. The higher the extent of head that passed the IPL, the less difficult the OPD and the greater the success rate of the OPD.

Surface-enhanced Raman scattering of the adsorption of pesticide endosulfan on gold nanoparticles.

The absorption of pesticide endosulfan on the surface of gold nanoparticles results from the formation of micrometric structures (1-10 µm) with irregular shape because of the aggregation of individual particles. Such aggregation of gold nanoparticles after absorption of pesticide shows a surface-enhanced Raman scattering (SERS) spectrum, whose intensity depends on the concentration of endosulfan. In addition, the discoloration of the colloidal solution and a diminishing of the intensity of the surface plasmon resonance absorption from individual particles were observed by UV-visible spectroscopy. At the same time, a second band between 638 and 700 nm confirms the formation of aggregates of gold nanoparticles as the concentration of endosulfan increases. Finally, we used the SERS intensity of the S-O stretching vibration at 1239 cm(-1) from the SO3 group as a measure of concentration of pesticide endosulfan. This method could be used to estimate the level of pollution in water by endosulfan in a simple and practical form.

Differential gene expression profiles of two excitable rat cell lines after over-expression of WT- and C121W-ß1 sodium channel subunits.

Voltage-dependent sodium channels are membrane proteins essential for cell excitability. They are composed by a pore-forming α-subunit, encoded in mammals by up to nine different genes, and four different ancillary ß-subunits. The expression pattern of the α subunit isoforms confers the distinctive functional and pharmacological properties to different excitable tissues. ß-Subunits are important modulators of channel function and expression. Mutation C121W of the ß1-subunit causes an autosomal dominant epileptic syndrome without cardiac symptoms. In neuroectoderm GH3 and cardiac H9C2 cells, the over-expression of ß1 subunit augments α subunit mRNA and protein levels as well as sodium current density. Interestingly, the introduction of the epileptogenic C121W-ß1 subunit produces additional changes in the α-subunit expression pattern of H9C2 cells, leaving unaltered the sodium channel isoform composition of GH3 cells. The challenge of the present work was to identify those genes that were differentially expressed in response to WT- or C121W-ß1 subunit over-expression in the two rat cell lines under analysis. Hence, we analyzed the total mRNA extracted from control-untransfected and from WT- and C121W-ß1-transfected GH3 and H9C2 cells by DNA-microarray. We found that, in agreement with their different embryonal origin, the over-expression of WT- and C121W-ß1 subunits modifies the expression of different gene sets in GH3 and H9C2 cells. Focusing on the effects of the C121W mutation, we found that it causes the modification of 214 genes, most of them were down-regulated (202) in GH3 cells; on the contrary, it determined the up-regulation of only five genes in H9C2 cells. Interestingly, most genes modified by the C121W ß1 subunit are involved in pivotal processes of the cell such as cellular communication and protein expression. Our results confirm the important role of the sodium channel ß1 subunit in the control of NaCh gene expression, and highlight once more the tissue-specific effect of the C121W mutation.

Head progression distance in prolonged second stage of labor: relationship with mode of delivery and fetal head station.

OBJECTIVE: To evaluate the clinical significance of fetal head progression distance (HPD), measured by transperineal ultrasound, during prolonged second stage of labor. METHODS: In this prospective study, a single operator, who was blinded to the results of the digital examination, assessed using transperineal ultrasound women at ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Patients had an empty urinary bladder and the examination was performed during maternal pushing. HPD was defined as the length of the line perpendicular to the infrapubic line that would connect it to the lowest part of the fetal bony skull. We analyzed associations between HPD and digital examination of fetal head station, fetomaternal characteristics, mode of delivery and perinatal outcome. RESULTS: Sixty-five patients in prolonged second stage of labor participated in the study. The overall mean HPD was 6.50 (± 1.35; 95% CI, 6.16-6.83) cm. No correlation was found between HPD and head position or mode of delivery, but HPD was positively correlated with fetal head station and neonatal head circumference measured after delivery. Logistic regression and receiver-operating characteristics curve analysis demonstrated no significant predictive value of HPD with respect to mode of delivery. CONCLUSION: Although HPD in prolonged second stage of labor could not predict mode of delivery, it may have a role as an ancillary tool for fetal head station assessment.

Pubic arch angle in prolonged second stage of labor: clinical significance.

OBJECTIVE: To evaluate the clinical significance of the pubic arch angle (PAA) measured by transperineal ultrasound during prolonged second stage of labor. METHODS: We evaluated prospectively 62 women ≥ 37 weeks of gestation with failure to progress in the second stage of labor. Transperineal ultrasound (transverse plane) was used to measure the pubic arch angle. Correlations with fetomaternal characteristics, mode of delivery and perinatal outcome were evaluated. RESULTS: The mean PAA was 101.1° (± 13.1°; range, 80°-135°). We found a negative correlation with maternal age. Patients with an occipitotransverse fetal position had a significantly smaller angle compared with those with occipitoanterior positions (94.3° ± 5.5° vs. 103.2° ± 14.8°, P < 0.05), as did those with operative deliveries compared with those with spontaneous vaginal delivery (97.1° ± 11.5° vs. 110.1° ± 14.0°, P < 0.05). The prediction of operative delivery in prolonged second stage of labor by receiver-operating characteristics curve using PAA alone yielded an area under the curve of 0.75. The predicted probability for operative delivery increased as PAA decreased, with an odds ratio of 0.933 for each decrease in angle of 1°. CONCLUSION: Our study suggests a correlation between the PAA and mode of delivery in prolonged second stage of labor. This may be used as an adjunctive parameter when considering delivery mode.

CFTR expression and activity from the human CFTR locus in BAC vectors, with regulatory regions, isolated by a single-step procedure.

We have assembled two BAC vectors containing a single fragment spanning the entire CFTR locus and including the upstream and downstream regions. The two vectors differ in size of the upstream region, and were recovered in Escherichia coli, with intact BAC DNAs prepared for structural and functional analyses. Sequence analysis allowed precise mapping of the inserts. We show that the CFTR gene was wild type and is categorized as the most frequent haplotype in Caucasian populations, identified by the following polymorphisms: (GATT)7 in intron 6a; (TG)11T7 in intron 8; V470 at position 470. CFTR expression and activity were analyzed in model cells by RT-PCR, quantitative real-time PCR, western blotting, indirect immunofluorescence and electrophysiological methods, which show the presence of an active CFTR Cl ⁻ channel. Finally, and supporting the hypothesis that CFTR functions as a receptor for Pseudomonas aeruginosa, we show that CFTR-expressing cells internalized more bacteria than parental cells that do not express CFTR. Overall, these data demonstrate that the BAC vectors contain a functional CFTR fragment and have unique features, including derivation from a single fragment, availability of a detailed genomic map and the possibility to use standard extraction procedures for BAC DNA preparations.

Binding site of activators of the cystic fibrosis transmembrane conductance regulator in the nucleotide binding domains.

The use of substances that could activate the defective chloride channels of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) has been suggested as possible therapy for cystic fibrosis. Using epithelia formed by cells stably transfected with wildtype or mutant (G551D, G1349D) CFTR, we estimated the apparent dissociation constant, K(D), of a series of CFTR activators by measuring the increase in the apical membrane current. Modification of apparent K(D) of CFTR activators by mutations of the nucleotide-binding domains (NBDs) suggests that the binding site might be in these regions. The human NBD structure was predicted by homology with murine NBD1. An NBD1-NBD2 complex was constructed by overlying monomers to a bacterial ABC transporter NBD dimer in the "head-to-tail" conformation. Binding sites for CFTR activators were predicted by molecular docking. Comparison of theoretical binding free energy estimated in the model to free energy estimated from the apparent dissociation constants, K(D), resulted in a remarkably good correlation coefficient for one of the putative binding sites, located in the interface between NBD1 and NBD2.

Leptin reverses the inhibitory effect of caloric restriction on longitudinal growth.

Caloric imbalance, particularly in critical periods of growth and development, is often the underlying cause of growth abnormalities. Serum levels of leptin are elevated in obesity and are low in malnutrition and malabsorption. The aim of the present study was to determine whether leptin integrates energy levels and growth in vivo, as shown previously in our ex vivo experiments, even in the presence of caloric restriction. In the first part of the study, mice were divided into three groups. Two groups were fed ad libitum and received leptin or vehicle only, and the third group was pair-fed with the group injected with leptin to dissociate leptin's effect on growth from its effect on food consumption. Mice given leptin had a significantly greater tibial length than untreated pair-fed animals and a similar tibial length as control mice fed ad libitum despite their lower weight. In addition, leptin significantly increased the overall size of the epiphyseal growth plate by 11%. On immunohistochemistry and in situ hybridization studies, leptin stimulated both the proliferation and differentiation of tibial growth plate chondrocytes without affecting the overall organization of the plate. There was also a marked increase in the expression and level of IGF-IR. In the second part of the study, two groups of mice were fed only 60% of their normal chow; one was injected with leptin, and the other was injected with vehicle alone. Caloric deprivation by itself reduced serum levels of IGF-I by 70% and the length of the tibia by 5%. Leptin treatment corrected the fasting-induced growth deficiency, but further reduced the level of serum IGF-I. These results indicate that leptin stimulates growth even in the presence of caloric restriction independently of peripheral IGF-I.

Leptin: obesity, diabetes and other peripheral effects--a review.

There is an increasing epidemic of obesity in the Western and developing world that has not spared children and, hence, is of great concern. Obesity presents numerous physiological and psychosocial problems for the child. Childhood obesity not only increases the risk of obesity in adulthood, it is associated with type 2 diabetes mellitus; is the leading cause of pediatric hypertension; increases the risk of coronary heart disease; and increases stress on the weight-bearing joints. Social and psychological problems are also significant consequences of obesity in children, with lowering of self-esteem and its effects on relationships with peers. Obesity is clearly associated with increased levels of the recently discovered hormone, leptin. Leptin, secreted from adipocytes, is involved in the regulation of food intake, energy expenditure, and energy balance in humans. This review focuses on the hormone, leptin, in an effort to document some of its many local and systemic effects on the body and, specifically, its potential role in obesity-induced diabetes.

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Clinical dysentery in hospitalized children.

BACKGROUND: Clinical dysentery is a severe presentation of an enteric infection. The aim of the study was to evaluate the impact of a serious bacterial etiology in clinical dysentery in hospitalized children and determine if children at high risk can be identified on the basis of clinical or laboratory parameters. PATIENTS AND METHODS: A prospective study design was used. The study population included 60 children admitted to our department with clinical dysentery over a 16-month period. Fresh stool specimens were collected on days 1, 2 and 3. The clinical and laboratory data of the children were analyzed. RESULTS: Clinical dysentery accounted for 1.7% of all pediatric hospitalizations during this period. Stool cultures were positive for Shigella spp. in 18 children (30%), and Salmonella spp. in 15 children (25%), Campylobacter jejuni was identified in one patient (2%). There were no significant differences in clinical characteristics or laboratory parameters between children with positive and negative stool cultures. CONCLUSION: 40% of the children hospitalized for clinical dysentery were eligible for antibiotic treatment. Early administration of empiric antibiotic treatment is justified in children hospitalized for clinical dysentery in Israel. Clinical or laboratory parameters were unable to differentiate those with clinical dysentery at risk of serous bacterial pathogens in stool.

Bone mineral response to a 7-month randomized controlled, school-based jumping intervention in 121 prepubertal boys: associations with ethnicity and body mass index.

We examined the effects of a 7-month jumping intervention (10 minutes, 3 times per week) on bone mineral gain in prepubertal Asian and white boys (10.3+/-0.6 years, 36.0+/-9.2 kg) at 14 schools randomized to control (n = 60) and intervention (n = 61) groups. Intervention and control groups had similar mean baseline and change in height, weight, lean mass and fat mass, baseline areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; g; dual-energy X-ray absorptiometry [DXA], QDR 4500W), and similar average physical activity and calcium intakes. Over 7 months, the intervention group gained more total body (TB) BMC (1.6%,p < 0.01) and proximal femur (PF) aBMD (1%, p < 0.05) than the control group after adjusting for age, baseline weight, change in height, and loaded physical activity. We also investigated the 41 Asian and 50 white boys (10.2+/-0.6 years and 31.9+/-4.4 kg) who were below the 75th percentile (19.4 kg/m2) of the cohort mean for baseline body mass index (BMI). Boys in the intervention group gained significantly more TB and lumbar spine (LS) BMC, PF aBMD, and trochanteric (TR) aBMD (+ approximately2%) than boys in the control group (adjusted for baseline weight, final Tanner stage, change in height, and loaded physical activity). Bone changes were similar between Asians and whites. Finally, we compared the boys in the control group (n = 16) and the boys in the intervention group (n = 14) whose baseline BMI fell in the highest quartile (10.5+/-0.6 years and 49.1+/-8.2 kg). Seven-month bone changes (adjusted as aforementioned) were similar in the control and intervention groups. In summary, jumping exercise augmented bone mineral accrual at several regions equally in prepubertal Asian and white boys of average or low BMI, and intervention effects on bone mineral were undetectable in high BMI prepubertal boys.

Activation of G551D CFTR channel with MPB-91: regulation by ATPase activity and phosphorylation.

We have designed and synthesized benzo[c]quinolizinium derivatives and evaluated their effects on the activity of G551D cystic fibrosis transmembrane conductance regulator (CFTR) expressed in Chinese hamster ovary and Fisher rat thyroid cells. We demonstrated, using iodide efflux, whole cell patch clamp, and short-circuit recordings, that 5-butyl-6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-91) restored the activity of G551D CFTR (EC(50) = 85 microM) and activated CFTR in Calu-3 cells (EC(50) = 47 microM). MPB-91 has no effect on the ATPase activity of wild-type and G551D NBD1/R/GST fusion proteins or on the ATPase, GTPase, and adenylate kinase activities of purified NBD2. The activation of CFTR by MPB-91 is independent of phosphorylation because 1) kinase inhibitors have no effect and 2) the compound still activated CFTR having 10 mutated protein kinase A sites (10SA-CFTR). The new pharmacological agent MPB-91 may be an important candidate drug to ameliorate the ion transport defect associated with CF and to point out a new pathway to modulate CFTR activity.

The phorbol ester PMA and cyclic AMP activate different Cl(-) and HCO3(-) fluxes in C127 cells expressing CFTR.

In mouse mammary epithelial C127 cells expressing wild-type cystic fibrosis transmembrane conductance regulator (CFTR), chloride efflux, measured with the Cl(-)-sensitive dye 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ), was stimulated by activation of protein kinase A with cyclic AMP elevating agents forskolin plus 3-isobutyl-1-methyl-xanthine (IBMX) and, to a less extent, by activation of protein kinase C with the phorbol 12-myristate 13-acetate (PMA). Conversely, bicarbonate influx, determined by intracellular alkalinization of cells incubated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluoresceintetraacetoxymethyl ester (BCECF-AM), was stimulated by cyclic AMP elevation, but not by PMA. Patch clamp analysis revealed that PMA activated a Cl(-) current with the typical biophysical characteristics of swelling-activated current and not of CFTR.

Skeletal muscle sodium channel is affected by an epileptogenic beta1 subunit mutation.

The syndrome of generalized epilepsy with febrile seizures plus type 1 (GEFS+) has been associated to the gene SCN1B coding for the sodium channel beta1 subunit (Wallace, R. H. et al. (1998) Nature Genetics 19, 366-370). In patients, a mutation of the cysteine 121 to trpyptophane (C121W) would cause a lack of modulatory activity of the beta1 subunit on sodium channels expressed in the brain, rendering neurons hyperexcitable. We have confirmed that the normal beta1-modulation of type-IIA adult brain alpha subunits (BIIA) expressed in frog oocytes is defective in C121W. We observed that the mixture of wild-type and mutant beta1 subunits is less effective than wild-type alone, suggesting that the mutant beta1 subunit does bind the alpha subunit. However, we also observed a similar lack of modulation by C121W of the in adult skeletal muscle alpha subunit (SkM1). This finding is in contrast with the simple idea that the mutational effect observed in the oocyte expression system is the principal physiopathological correlate of GEFS+, because no skeletal muscle symptoms have been reported in GEFS+ patients. We conclude that the manifestation of the pathological phenotype is conditioned by the presence of susceptibility genes and/or that the frog oocyte expression system is inadequate for the study of the mutant beta1 subunit physiopathology.

Molecular simulation of the interaction of kappa-conotoxin-PVIIA with the Shaker potassium channel pore.

Molecular simulation techniques were appplied to predict the interaction of the voltage-dependent Shaker potassium channel with the channel-blocking toxin kappa-conotoxin-PVIIA (PVIIA). A structural thee-dimensional model of the extracellular vestibule of the potassium channel was constructed based on structural homologies with the bacterial potassium channel Kcsa, whose structure has been solved by X-ray crystallography. The docking of the PVIIA molecule was obtained by a geometric recognition algorithm, yielding 100 possible conformations. A series of residue-residue distance restraints, predicted from mutation-cycle experiments, were used to select a small set of a plausible channel-toxin complex models among the resulting possible conformations. The four final conformations, with similar characteristics, can explain most of the single-point mutation experiments done with this system. The models of the Shaker-PVIIA interaction predict two clusters of amino acids, critical for the binding of the toxin to the channel. The first cluster is the amino acids R2, I3, Q6 and K7 that form the plug of the toxin that interacts with the entrance to the selectivity filter of the channel. The second cluster of residues, R22, F23, N24 and K25, interacts with a channel region near to the external entrance of the pore vestibule. The consistency of the obtained models and the experimental data indicate that the Shaker-PVIIA complex model is reasonable and can be used in further biological studies such as the rational design of blocking agents of potassium channels and the mutagenesis of both toxins and potassium channels.