Room temperature mid-infrared fiber lasing beyond 5 µm in chalcogenide glass small-core step index fiber.

This Letter, to the best of our knowledge, reports mid-infrared fiber lasing beyond 5 µm at room temperature for the first time, Ce3+-doped, chalcogenide glass, step index fiber employed in-band pumping with a 4.15 µm quantum cascade laser. The lasing fiber is was 64 mm long, with a calculated numerical aperture of 0.48 at the lasing wavelengths. The core glass was Ge15As21Ga1Se63 atomic % (at. %), doped with 500 parts-per-million-by-weight Ce, with a 9 µm core diameter. The cladding glass was Ge21Sb10Se69 at. % with a 190 µm outer diameter. As pump power increases continuous wave lasing corresponding to the 2F7/2→2F5/2, transition in the Ce3+ ion occurs at 5.14 µm, 5.17 µm, and 5.28 µm.

Superior photoluminescence (PL) of Pr³âº-In, compared to Pr³âº-Ga, selenide-chalcogenide bulk glasses and PL of optically-clad fiber.

The photoluminescent-(PL)-properties of Pr³âº-ions in indium-containing selenide-chalcogenide bulk-glasses are found to be superior when compared with gallium-containing analogues. We observe circa doubling of mid-infrared (MIR) PL intensity from 3.5 to 6 µm for bulk glasses, pumped at 1.55 µm wavelength, and an increased excited state lifetime at 4.7 µm. PL is reported in optically-clad fiber. Ga addition is well known to enhance RE³âº solubility and PL behavior, and is believed to form ([RE³âº]-Se-[Ga(III)]) in the glasses. Indium has the same outer electronic-structure as gallium for solvating the RE-ions. Moreover, indium is heavier and promotes lower phonon energy locally around the RE-ion, thereby enhancing the RE-ion PL behavior, as observed here.

Structural study of Al2O3-Na2O-CaO-P2O5 bioactive glasses as a function of aluminium content.

Calcium phosphate based biomaterials are extensively used in the context of tissue engineering: small changes in composition can lead to significant changes in properties allowing their use in a wide range of applications. Samples of composition (Al(2)O(3))(x)(Na(2)O)(0.11-x)(CaO)(0.445)(P(2)O(5))(0.445), where x = 0, 0.03, 0.05, and 0.08, were prepared by melt quenching. The atomic-scale structure has been studied using neutron diffraction and solid state (27)Al MAS NMR, and these data have been rationalised with the determined density of the final glass product. With increasing aluminium concentration the density increases initially, but beyond about 3 mol. % Al(2)O(3) the density starts to decrease. Neutron diffraction data show a concomitant change in the aluminium speciation, which is confirmed by (27)Al MAS NMR studies. The NMR data reveal that aluminium is present in 4, 5, and 6-fold coordination and that the relative concentrations of these environments change with increasing aluminium concentration. Materials containing aluminium in 6-fold coordination tend to have higher densities than analogous materials with the aluminium found in 4-fold coordination. Thus, the density changes may readily be explained in terms of an increase in the relative concentration of 4-coordinated aluminium at the expense of 6-fold aluminium as the Al(2)O(3) content is increased beyond 3 mol. %.

Increased antibodies for the alpha7 subunit of the nicotinic receptor in schizophrenia.

One of the etiological theories of schizophrenia is dysregulation of the immune system. Autoantibodies specific for the alpha7 subunit of the nicotinic receptor could potentially contribute to the pathophysiology of the disease. In this study, positive antibodies specific for the receptor were found to exist in 23% of the patients diagnosed with schizophrenia (n=21). On the average, levels for the antibody were elevated in the schizophrenia patient population than in controls. The data also suggests that there is a significant correlation between antibody titer and age, lending support to the neurodegenerative nature of the disease.

Iron: A Pathological Mediator of Alzheimer Disease?

Metal-catalyzed oxidation and free radical formation are potent mediators of cellular injury to every category of macromolecule found in vulnerable neuronal populations and are thought to play an early and central role in Alzheimer disease (AD) pathogenesis. While metal-binding sites are present in proteins that accumulate in AD, metal-associated redox activity is primarily noted with nucleic acids, specifically with cytoplasmic RNA. Iron dyshomeostasis in AD is thought to arise from haem breakdown and mitochondrial turnover, and a reduction in microtubule density in vulnerable neurons increases redox-active metals, initiating a cascade of events culminating in characteristic pathologic features. Increased understanding of these early changes may be translated into more effective therapeutic modalities for AD than those currently in use.

Adulthood olanzapine treatment fails to alleviate decreases of ChAT and BDNF RNA expression in rats quinpirole-primed as neonates.

Neonatal quinpirole (dopamine D(2)/D(3) agonist) treatment to rats has been shown to increase dopamine D(2) receptor sensitivity throughout the animal's lifetime. Male and female Sprague-Dawley rats were neonatalally treated with quinpirole (1 mg/kg) from postnatal days (P) 1-21 and raised to adulthood. Beginning on P62, rats were administered the atypical antipsychotic olanzapine (2.5 mg/kg) twice daily for 28 days. Starting 1 day after the end of olanzapine treatment, animals were behaviorally tested on the place and match-to-place version of the Morris water maze (MWM) over seven consecutive days, and a yawning behavioral test was also performed to test for sensitivity of the D(2) receptor 1 day following MWM testing. Similar to results from a past study, olanzapine alleviated cognitive impairment on the MWM place version and increases in yawning produced by neonatal quinpirole treatment. Brain tissue analyses showed that neonatal quinpirole treatment resulted in a significant decrease of hipppocampal ChAT and BDNF RNA expression that were unaffected by adulthood olanzapine treatment, although adulthood olanzapine treatment produced a significant increase in cerebellar ChAT RNA expression. There were no significant effects of drug treatment on NGF RNA expression in any brain area. These results show that neonatal quinpirole treatment produced significant decreases of protein RNA expression that is specific to the hippocampus. Although olanzapine alleviated cognitive deficits produced by neonatal quinpirole treatment, it did not affect expression of proteins known to be important in cognitive performance.

A homolog of the vaccinia virus D13L rifampicin resistance gene is in the entomopoxvirus of the parasitic wasp, Diachasmimorpha longicaudata.

The parasitic wasp, Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae), introduces an entomopoxvirus (DlEPV) into its Caribbean fruit fly host, Anastrepha suspensa. (Loew) (Diptera: Tephritidae), during oviposition. DlEPV has a 250-300 kb unipartite dsDNA genome, that replicates in the cytoplasm of the host's hemocytes, and inhibits the host's encapsulation response. The putative proteins encoded by several DlEPV genes are highly homologous with those of poxviruses, while others appear to be DlEPV specific. Here, a 2.34 kb sequence containing a 1.64 kb DlEPV open reading frame within a cloned 4.5 kb EcoR1 fragment (designated R1-1) is described from a DlEPV EcoRI genomic library. This open reading frame is a homolog of the vaccinia virus rifampicin resistance (rif) gene, D13L, and encodes a putative 546 amino acid protein. The DlEPV rif contains two EcoRV, two HindIII, one XbaI, and one DraII restriction sites, and upstream of the open reading frame the fragment also contains EcoRV, HindII, SpEI, and BsP106 sites. Early poxvirus transcription termination signals (TTTTTnT) occur 236 and 315 nucleotides upstream of the consensus poxvirus late translational start codon (TAAATG) and at 169 nucleotides downstream of the translational stop codon of the rif open reading frame. Southern blot hybridization of HindIII-, EcoRI-, and BamH1-restricted DlEPV genomic DNA probed with the labeled 4.5 kb insert confirmed the fidelity of the DNA and the expected number of fragments appropriate to the restriction endonucleases used. Pairwise comparisons between DlEPV amino acids and those of the Amsacta moorei, Heliothis armigera, and Melanoplus sanguinipes entomopoxviruses, revealed 46, 46, and 45 % similarity (identity + substitutions), respectively. Similar values (41-45%) were observed in comparisons with the chordopoxviruses. The mid portion of the DlEPV sequence contained two regions of highest conserved residues similar to those reported for H. armigera entomopoxvirus rifampicin resistance protein. Phylogenetic analysis of the amino acid sequences suggested that DlEPV arose from the same ancestral node as other entomopoxviruses but belongs to a separate clade from those of the grasshopper-infecting M. sanguinipes entomopoxvirus and from the Lepidoptera-infecting (Genus B or Betaentomopoxvirus) A. moorei entomopoxvirus and H. armigera entomopoxvirus. Interestingly, the DlEPV putative protein had only 3-26.4% similarity with RIF-like homologs/orthologs found in other large DNA non-poxviruses, demonstrating its closer relationship to the Poxviridae. DlEPV remains an unassigned member of the Entomopoxvirinae (http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm) until its relationship to other diptera-infecting (Gammaentomopoxvirus or Genus C) entomopoxviruses can be verified. The GenBank accession number for the nucleotide sequence data reported in this paper is EF541029.

Bistability in doped organic thin film transistors.

Organic thin film transitors (TFTs) with the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonic acid), PEDOT:PSS, as the active layer and cross-linked, layer-by-layer assembled poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA) multilayers as the gate dielectric layer were investigated. A combination of spectroscopic data and device performance characteristics was used to study the behavior of these TFT devices under a variety of controlled environmental test conditions. It was shown that depletion and recovery of the device can be induced to occur by a means that is consistent with the electrochemical oxidation and reduction of water contained in the film. In addition to acting as a reactant, moisture also acts as a plasticizer to control the mobility of other species contained in the film and thereby permits bistable operation of these devices. Raman spectroscopy was used to show that the observed device switching behavior is due to a change in the PEDOT doping level.

Fabrication of organic thin-film transistors using layer-by-layer assembly.

Layer-by-layer assembly is presented as a deposition technique for the incorporation of ultrathin gate dielectric layers into thin-film transistors utilizing a highly doped organic active layer. This deposition technique enables the fabrication of device structures with a controllable gate dielectric thickness. In particular, devices with a dielectric layer comprised of poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA) bilayer films were fabricated to examine the properties of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as the transistor active layer. The transistor Ion/off ratio and switching speed are shown to be controlled by the gate bias, which is dependent upon the voltage applied and the number of bilayers deposited for the gate dielectric. The devices operate in the depletion mode as a result of dedoping of the active layer with the application of a positive gate bias. The depletion and recovery rate are highly dependent on the level of hydration in the film and the environment under which the device is operated. These observations are consistent with an electrochemical dedoping of the conducting polymer during operation.

Initial experience with the adjustable gastric band in morbidly obese US adolescents and recommendations for further investigation.

BACKGROUND: The public health crisis of obesity has spread to the pediatric population. In morbidly obese (MO) adolescents, early weight loss intervention can reduce and prevent obesity-related comorbidities and mortality and improve quality of life. The present study was performed to evaluate weight loss efficacy and safety of "off-label" laparoscopic adjustable gastric banding (LAGB) procedures performed in MO adolescents by our adult bariatric program. PATIENTS AND METHODS: We retrospectively reviewed data from 716 LAGB procedures performed on an off-label basis in adults and 24 adolescent patients ages 14 to 20 years by the adult bariatric program at our institution between 2001 and 2006. RESULTS: There was no mortality. Average operative time was 45 minutes, length of stay for adolescents was 15 hours, and weight loss outcome and overall surgical complication rates are comparable between adolescents and adults. For adolescent subjects, baseline mean preoperative body mass index was 49 kg/m and average excess weight loss rates were 22%, 34%, 52%, 42%, and 42% at 3, 6, 12, 24, and 36 months, respectively. The overall complication rate was 29%, with a 25% incidence of pouch enlargement in adolescents (vs 18% in adult patients; P = ns). Two of 24 adolescent patients (8.4%) required laparoscopic band repositioning (vs 1.5% of adult patients; P = 0.06). CONCLUSIONS: LAGB is an effective and safe surgical weight loss modality for MO adolescent subjects. Vigilant follow-up for LAGB-related complications and intensive postoperative behavioral management are important for improving long-term success. We recommend continued investigation of long-term efficacy and safety of LAGB in this population.

Short-term outcome in the first 10 morbidly obese adolescent patients in the FDA-approved trial for laparoscopic adjustable gastric banding.

BACKGROUND: We received the LAP-BAND Investigational Device Exemption (IDE) from the US Food and Drug Administration in December 2004 to conduct a prospective longitudinal trial examining the safety and efficacy of laparoscopic adjustable gastric banding (LAGB) in morbidly obese adolescents ages 14 to 17 years. OBJECTIVES: To report the short-term results of LAGB in the first 10 adolescents with complete 9 months of follow-up. PATIENTS AND METHODS: Baseline characteristics and outcome data were analyzed in 10 patients enrolled between March 2005 and February 2006. RESULTS: All of the patients were girls. Their mean body mass index (+/-SD) was 50 +/- 13 kg/m, and excess weight was 171 +/- 79 pounds. Comorbidities included depression (3 patients), sleep apnea (3), hypertension (6), dyslipidemia (7), insulin resistance (9), metabolic syndrome (9), and steatohepatitis (in 4 of 5 patients with liver biopsy). Operative time was 45 +/- 9 minutes, and discharges were within 23 hours of surgery. Band-related complications were as follows: 2 dehydration, 1 pouch dilation, and 1 port revision. All of the patients lost weight, with a 9-month excess weight loss of 30% +/- 16% (range 14%-57%). Hypertension and the metabolic syndrome were resolved in 100% of patients (P = 0.04) and 80% of the patients (P = 0.01), respectively, along with significant improvement in the Pediatric Quality of Life and Beck Depression Inventory scores and a trend toward improvement in high-density lipoprotein cholesterol abnormalities (P = 0.08). CONCLUSIONS: At short-term follow-up, weight loss occurred with minimal complications, leading to early resolution of major obesity-related comorbidities. Continued evaluation of the long-term safety and efficacy of LAGB as a surgical adjunct to a comprehensive obesity treatment program is warranted.

Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC).

This study examines the effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (PROZAC), on the ontogeny of spontaneous swimming activity (SSA) in developing zebrafish. The development of zebrafish motor behavior consists of four sequential locomotor patterns that develop over 1-5 days post fertilization (dpf), with the final pattern, SSA, established at 4-5 dpf. In stage specific experiments, larvae were exposed to 4.6 microM fluoxetine for 24 h periods beginning at 24 h post fertilization (hpf) and extending through 5 dpf. From 1-3 dpf, there was no effect on SSA or earlier stages of motor development, i.e., spontaneous coiling, evoked coiling and burst swimming. Fluoxetine exposure at 3 dpf for 24 h resulted in a transient decrease in SSA through 7 dpf with a complete recovery by 8 dpf. Larvae exposed to 4.6 microM fluoxetine for 24 h on 4 or 5 dpf showed a significant decrease in SSA by day 6 with no recovery through 14 dpf. Although SSA was significantly affected 24 h after fluoxetine exposure, there was little or no effect on pectoral fin movement. These results demonstrate both a stage specific and a long term effect of 4.6 microM fluoxetine exposure in 4 and 5 dpf larvae. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the relative levels of a serotonin transporter protein (SERT) transcript and the serotonin 1A (5-HT(1A)) receptor transcript in developing embryos/larvae over 1-6 dpf. Both transcripts were present at 24 hpf with the relative concentration of SERT transcript showing no change over the developmental time range. The relative concentration of the 5-HT(1A) receptor transcript, however, showed a two-tiered pattern of concentration. RT-PCR was also used to detect potential changes in the SERT and 5-HT(1A) receptor transcripts in 6 dpf larvae after a 24 h exposure to 4.6 microM fluoxetine on 5 dpf. Three separate regions of the CNS were individually analyzed, two defined brain regions and spinal cord. The two brain regions showed no effect on transcript levels subsequent to fluoxetine exposure, however, the spinal cord showed a significant decrease in both transcripts. These results suggest a correlation between decreased concentration of SERT and 5-HT(1A) receptor transcripts in spinal cord and decreased SSA subsequent to fluoxetine exposure.

Structural and physico-chemical analysis of calcium/strontium substituted, near-invert phosphate based glasses for biomedical applications.

Neutron diffraction, 23Na and 31P NMR, and FTIR spectroscopy have been used to investigate the structural effects of substituting CaO with SrO in a 40P2O5·(16-x)CaO·20Na2O·24MgO·xSrO glass, where x is 0, 4, 8, 12 and 16mol%. The 31P solid-state NMR results showed similar amounts of Q1 and Q2 units for all of the multicomponent glasses investigated, showing that the substitution of Sr for Ca has no effect on the phosphate network. The M-O coordinations (M=Mg, Ca, Sr, Na) were determined for binary alkali and alkaline earth metaphosphates using neutron diffraction and broad asymmetric distributions of bond length were observed, with coordination numbers that were smaller and bond lengths that were shorter than in corresponding crystals. The Mg-O coordination number was determined most reliably as 5.0(2). The neutron diffraction results for the multicomponent glasses are consistent with a structural model in which the coordination of Ca, Sr and Na is the same as in the binary metaphosphate glass, whereas there is a definite shift of Mg-O bonds to longer distance. There is also a small but consistent increase in the Mg-O coordination number and the width of the distribution of Mg-O bond lengths, as Sr substitutes for Ca. Functional properties, including glass transition temperatures, thermal processing windows, dissolution rates and ion release profiles were also investigated. Dissolution studies showed a decrease in dissolution rate with initial addition of 4mol% SrO, but further addition of SrO showed little change. The ion release profiles followed a similar trend to the observed dissolution rates. The limited changes in structure and dissolution rates observed for substitution of Ca with Sr in these fixed 40mol% P2O5 glasses were attributed to their similarities in terms of ionic size and charge. STATEMENT OF SIGNIFICANCE: Phosphate based glasses are extremely well suited for the delivery of therapeutic ions in biomedical applications, and in particular strontium plays an important role in the treatment of osteoporosis. We show firstly that the substitution of strontium for calcium in bioactive phosphate glasses can be used to control the dissolution rate of the glass, and hence the rate at which therapeutic ions are delivered. We then go on to examine in detail the influence of Sr/Ca substitution on the atomic sites in the glass, using advanced structural probes, especially neutron diffraction. The environments of most cations in the glass are unaffected by the substitution, with the exception of Mg, which becomes more disordered.

Ferric cycle activity and Alzheimer disease.

Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.

Theoretical study of population inversion in active doped MIR chalcogenide glass fibre lasers (invited).

We study the mechanism of the population inversion in mid-infrared fibre lasers based on a chalcogenide glass host doped with active lanthanide ions. Three lanthanide dopant ions are considered: terbium, dysprosium and praseodymium. We predict the relevant trivalent ion level populations and gain. The simulation parameters were obtained by fabricating and optically characterising a series of trivalent ion doped chalcogenide glass samples. We also provide simple analytical expressions that aid the design of the cascade lasing process.

Homocysteine and Alzheimer's disease: a modifiable risk?

A hypothesis is proposed that reconciles the epidemiological observation of elevated homocysteine in Alzheimer's disease (AD) with clinical features of the disease, particularly evidence of increased oxidative stress. We propose homocysteine is involved in an iron dysregulation/oxidative stress cycle that has a central role in the pathogenesis of AD. The implications of the hypothesis and some strategies for testing it are discussed.

Heme catabolism and heme oxygenase in neurodegenerative disease.

Heme oxygenase, the rate-limiting step in heme catabolism, appears to play an important role in a number of neurodegenerative disorders, such as Alzheimer disease. Interestingly, the spatial distribution of heme oxygenase-1 expression in diseased brain is essentially identical to that of the pathological expression of tau, suggesting a key role for both in disease progression. Like heme oxygenase, the expression, phosphorylation, and aggregation of tau are regulated through signal cascades, including the extracellular signal-regulated kinases, whose activities are modulated by oxidative stress. Therefore, the expression of tau and heme oxygenase-1 in a coordinated manner likely plays a pivotal role in the cytoprotection of neuronal cells. This places heme oxygenase at the center of disease pathogenesis and offers a novel therapeutic approach targeted at either the causes or consequences of enzyme induction.

Hematoma removal, heme, and heme oxygenase following hemorrhagic stroke.

The hemorrhagic strokes, intracerebral (ICH) and subarachnoid hemorrhage (SAH), often have poor outcomes. Indeed, the most common hemorrhagic stroke, ICH, has the highest mortality and morbidity rates of any stroke subtype. In this report, we discuss the evidence for the staging of red blood cell removal after ICH and the significance of control of this process. The protective effects of clinically relevant metalloporphyrin heme oxygenase inhibitors in experimental models of ICH and in superficial siderosis are also discussed. We also examine literature paradoxes related to both heme and heme oxygenase in various disorders of the central nervous system. Last, new data are presented that support the concept that heme, although primarily a pro-oxidant, can also have antioxidant properties.

A clinical practice model for treatment of college-aged incest survivors.

Adult incest survivors frequently exhibit signs and symptoms of posttraumatic stress disorder. Many clinicians have geared their group treatment of incest survivors to address these manifestations. Given the nature of the sexual abuse, the early developmental periods in which some trauma occurs, the past and current relationship between the victim and the perpetrator, and the dynamics inherent in this violation and betrayal of trust, love, and power within the family unit, additional clinical concerns and safeguards must be considered. In addition, the struggles of college-aged incest survivors to come to terms with their history of sexual abuse often mirror the developmental tasks faced by their peers--autonomy, intimacy, sexuality, and formation of personal values and ethics. To focus solely on the incest without also considering these developmental issues may solidify a gridlock between inadequate resolution of the developmental issues and the continued victimization of the student incest survivor. The author discusses a time-limited group treatment for college-aged incest survivors that uses a modified posttraumatic stress disorder model as a conceptual framework and addresses both sets of concerns.

Structure of iron phosphate glasses modified by alkali and alkaline earth additions: neutron and x-ray diffraction studies.

The structure of iron phosphate glasses modified by additions of K(2)O and BaO, with nominal molar compositions [(1 - x)(0.6P(2)O(5)-0.4Fe(2)O(3))]xMe(y)O, where x = 0-0.4 in increments of 0.1; Me=K or Ba; and y = 1 or 2, has been investigated using neutron diffraction and x-ray diffraction techniques. Fitted coordination numbers for P-O and Fe-O showed a notable change in the P-O(NBO) and P-O(BO) contributions at greater than 20 mol% modifier addition, with barium producing a markedly larger increase in P-O(NBO) contribution than potassium. Fitting of T(N)(r) and T(X)(r) provided average n(BaO) = 9 and n(KO) = 6. Iron occurs in a range of coordination sites in these glasses: ([6])Fe(2+), ([4])Fe(3+), ([5])Fe(3+) and ([6])Fe(3+). The partitioning between these sites gives average n(FeO) = 5.2-5.8, with barium-doped glasses exhibiting higher average n(FeO) than potassium-doped glasses. The stronger depolymerizing effect of Ba(2+) than K(+) on the phosphate network, coupled with its greater ionic charge and higher Me-O, Fe-O and O···O coordination numbers, explain previously observed divergences in physical properties between the barium-doped and the potassium-doped glasses.