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Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3–6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Purpose: An average parathyroid adenoma (PA) weighs < 1 g. This study aimed to characterise giant PAs ≥ 10 g (GPAs) to facilitate surgical management of primary hyperparathyroidism (PHPT). Methods: All patients with a GPA confirmed on histology were recruited from the Monash University Endocrine Surgery Unit database. Clinical and demographic data were collected and compared to a group of non-GPA patients. Results: A total of 14 GPAs were identified between 2007 and 2018 out of 863 patients (1.6%) with a single PA excised for PHPT. The GPA patients were compared to a control group of 849 non-GPA patients in the same period with similar mean age (62 ± 16 vs 63 ± 14, P= 0.66) and gender distribution (64% vs 75% female, P= 0.35). Pre-operative calcium (Ca) and parathyroid hormone (PTH) levels were significantly higher in GPA patients (P< 0.001). A higher percentage of GPA patients (79%) had concordant localisation studies (ultrasound and sestamibi) than control patients (59%), (P= 0.13), but they were significantly less likely to undergo MIP (55% vs 82%, P= 0.02). The median GPA weighed 12.5 g (IQR 10.5–24.3). Median serum Ca normalised by day 1 post-operatively, while PTH remained elevated. Both serum Ca and PTH levels were in the normal range at 3 months. All GPA lesions were benign on histopathology. Conclusion: GPAs are rare and display severe clinical and biochemical abnormalities. Despite their large size, concordant pre-operative imaging was not always achieved, and a few patients were suitable for MIP.

B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)1, and the diverse range of BCRs expressed by the total B cell population of an individual is termed the ‘BCR repertoire’. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn’s disease, Behçet’s disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and—in particular—isotype use. An increase in clonality in systemic lupus erythematosus and Crohn’s disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.

Light’s capacity to carry angular momentum is integral to our knowledge of physics and ability to probe matter. In addition to spin, photons can occupy free-space orbital angular momentum eigenstates1,2. Visible light orbital angular momentum is used in quantum information experiments, super-resolution microscopy, optical tweezers and angular momentum transfer to atoms in optical lattices3,4. Soft X-ray orbital angular momentum applications, slowed by the lack of suitable optics and the rarity of coherent X-ray sources, could enable the direct alteration of atomic states through orbital angular momentum exchange, and methods to study the electronic properties of quantum materials. We have made soft X-ray diffractive optics that generate single Laguerre–Gauss modes, observed carrying up to 30ħangular momentum per photon, or their superpositions. We also present Hermite–Gauss diffractive optics and a soft X-ray orbital angular momentum analyser. These tools could enable both the manipulation and finer characterization of topologically complex electronic matter, such as magnetic skyrmions.

We evaluated the incidence of perioperative hyperkalaemia in end-stage renal disease (ESRD) patients undergoing parathyroidectomy and investigated possible contributors to this phenomenon. This was a retrospective cohort study looking at patients who had undergone parathyroidectomy for chronic kidney disease–associated mineral bone disease (CKD-MBD) at The Alfred Hospital, Melbourne, since 2001. Baseline demographics including age, gender, aetiology of renal failure and mode of renal replacement therapy as well as anaesthetic technique and duration of surgery were studied as possible contributors. Perioperative potassium values were compared to preoperative baseline. Following stratification into normokalaemic and hyperkalaemic groups, demographic and operative data were compared. Twenty-two patients met the inclusion criteria with a median (interquartile range, IQR) age of 48.5 (42–59) years. There was a male predominance of 68%. The median (IQR) surgical time was 131 (115–164) minutes. Potassium levels rose perioperatively, with a 27.3% incidence of perioperative hyperkalaemia. Median duration of surgery was longer in the hyperkalaemic patients (167 minutes versus 125 minutes). Following the withdrawal of cinacalcet, parathyroidectomy is increasingly required in ESRD patients with CKD-MBD. Potentially life-threatening hyperkalaemia poses a significant risk in the perioperative period. Serial electrolyte monitoring is crucial to safety in this patient group. A multidisciplinary approach to perioperative management is required to ensure optimal timing of renal replacement therapy and appropriate means of serial blood sampling.

Colon cancer is the third leading cause of death from cancer worldwide with less than 10% survival rate at the late stage. Although mutations of certain genes have been implicated in familial colon cancer development, the etiology of the majority of colon cancer remains unknown. Herein, we identified TYRO3as a potential oncogene. Immunohistochemical staining results demonstrated that levels of TYRO3 were markedly elevated in polyps and colon cancer cells and were negatively correlated with prognosis. Overexpression of TYRO3 enhanced cell motility, invasion, anchorage-independent growth and metastatic ability, while knockdown of TYRO3 impaired all these processes. Results from meta-analysis showed that TYRO3 was associated with epithelial–mesenchymal transition (EMT) signatures. Gain-of-function and loss-of-function experiments demonstrated that expression of SNAI1, the master regulator of EMT, was regulated by TYRO3 and played a major role in mediating TYRO3-induced EMT processes. The murine model also demonstrated that Tyro3and Snai1were upregulated in the early stage of colon cancer development. To provide a proof-of-concept that TYRO3 is a druggable target in colon cancer therapy, we raised anti-TYRO3 human antibodies and showed that treatment with the human antibody abolished TYRO3-induced EMT process. More importantly, administration of this anti-TYRO3 antibody increased drug sensitivity in primary cultured colon cancer cells and xenografted mouse tumors. These findings demonstrate that TYRO3is a novel oncogene and a druggable target in colon cancer.

Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1mutants displayed senescence-associated phenotypes. OCmutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1mutants than control littermates, suggesting potential impairment of CXCR4–CXCL12-mediated HSC retention. Disruption of the CXCR4–CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated ß-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4in OBs differentially modulates HSC fate in a stage-dependent manner.

General strategies for the chemical synthesis of organic compounds, especially of architecturally complex natural products, are not easily identified. Here we present a method to establish a strategy for such syntheses, which uses network analysis. This approach has led to the identification of a versatile synthetic intermediate that facilitated syntheses of the diterpenoid alkaloids weisaconitine D and liljestrandinine, and the core of gomandonine. We also developed a web-based graphing program that allows network analysis to be easily performed on molecules with complex frameworks. The diterpenoid alkaloids comprise some of the most architecturally complex and functional-group-dense secondary metabolites isolated. Consequently, they present a substantial challenge for chemical synthesis. The synthesis approach described here is a notable departure from other single-target-focused strategies adopted for the syntheses of related structures. Specifically, it affords not only the targeted natural products, but also intermediates and derivatives in the three subfamilies of diterpenoid alkaloids (C-18, C-19 and C-20), and so provides a unified synthetic strategy for these natural products. This work validates the utility of network analysis as a starting point for identifying strategies for the syntheses of architecturally complex secondary metabolites.

Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low‐risk recipients had a normal BMI (18.5–25 kg/m2), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher‐risk. Low‐risk recipients had a predicted PGD risk of 4–7%, and high‐risk a predicted PGD risk of 15–18%. Adding a donor‐smoking lung to a higher‐risk recipient significantly increased PGD risk, although risk did not change in low‐risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables. Using three clinical prediction models based on recipient and donor factors for the development of primary graft dysfunction (PGD) after lung transplantation, the authors demonstrate that elevated mean pulmonary arterial pressures, a diagnosis other than cystic fibrosis or chronic obstructive pulmonary disease, and obesity define high‐risk recipients, and addition of a lung from a smoking donor significantly increases PGD risk in the high‐risk group.

Early epithelial injury after lung transplantation may contribute to development of bronchiolitis obliterans syndrome (BOS). We evaluated the relationship between early postoperative soluble receptor for advanced glycation end‐product (sRAGE) levels, a marker of type I alveolar cell injury and BOS. We performed a cohort study of 106 lung transplant recipients between 2002 and 2006 at the University of Pennsylvania with follow‐up through 2010. Plasma sRAGE was measured 6 and 24 h after transplantation. Cox proportional hazards models were used to evaluate the association between sRAGE and time to BOS, defined according to ISHLT guidelines. Sixty (57%) subjects developed BOS. The average time to BOS was 3.4 years. sRAGE levels measured at 6 h (HR per SD of sRAGE: 1.69, 95% CI: 1.11, 2.57, p = 0.02) and 24 h (HR per SD of sRAGE: 1.74, 95% CI: 1.14, 2.65, p = 0.01) were associated with an increased hazard of BOS. Multivariable Cox regression indicated this relationship was independent of potential confounders. Elevated plasma sRAGE levels measured in the immediate postoperative period are associated with the development of BOS. Early epithelial injury after transplantation may contribute to the development of fibrosis in BOS.

With an increase in the number of electrical systems installed in vehicles, the wire harness design has become increasingly complicated and, accordingly, it has become essential that it is validated. Simulation is a good method of validation but it requires models of the installed electrical systems as well as wire harness design tools to support the simulation function. An electronic control unit (ECU) is a particularly important electrical system because it is connected to many other electrical systems through the wire harness and controls their operations. In this study, a method for modelling ECUs is developed, using the Capital Harness system design tool. The model parameters of the ECU are categorized into system parameters, external parameters, network parameters, and power parameters. The electrical structure of an ECU is built on the basis of the types and default states of the parameters. The behaviour of the ECU is defined in terms of simplified combinational logics in a state-machine-based structure since the target of the modelling is to simulate the logical connection conformity of the wire harness. A power-seat ECU model is developed, using the proposed method, and the feasibility of the simulation for wire harness validation is described.

The use of ultrasound in the diagnosis and management of disorders of the tendo Achillis is discussed. Some of the pathological processes which occur in Achilles tendinopathy can be identified by ultrasound, which may also be used to direct local treatment.

Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis MS and Crohn disease) clearance and 4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood–brain barrier (ivBBB).

BACKGROUND: Recently, it was reported that the 4‐week exposure of rats to a concrete building environment under cool temperatures (11.7–12.1°C) had adverse effects on the general health parameters. This study examined the potential effects of concrete and hwangto building environments on pregnant dams and embryo‐fetal development in Sprague‐Dawley rats. METHODS: Groups of 10 mated females were exposed to polycarbonate (control), concrete, or hwangto cages from gestational days (GD) 0 to 20 under cool temperatures (11.9–12.5°C). All the females underwent a caesarean section on GD 20, and their fetuses were examined for any morphological abnormalities. RESULTS: The temperatures in the cages were similar in all groups but the relative humidity in the concrete and hwangto groups were higher than in the control group. The concentration of volatile organic compounds in the hwangto group during the study period was lower than in the control group. In the concrete group, maternal effects manifested as an increase in the incidence of clinical signs, a lower body weight, and a decrease in the thymus and ovary weights. Developmental effects included increased post‐implantation loss and decreased litter size. In contrast, in the hwangto group, there were no exposure‐related adverse effects on the maternal and developmental parameters. CONCLUSIONS: Overall, the exposure of pregnant rats to a concrete building environment under cool temperatures has adverse effects on the clinical signs, body weight, organ weight, and embryo‐fetal development. On the other hand, exposure to a hwangto building environment does not have any adverse effects on pregnant dams or on embryo‐fetal development in rats. Birth Defects Res (Part B), 2008. © 2008 Wiley‐Liss, Inc.

Many bovine Staphylococcus aureus isolates from Argentina are nontypeable (NT), i.e., they do not produce serotype 5 or 8 capsular polysaccharides (CPs). Some of these NT strains have a deletion of the cap5(8) gene cluster mediated by a variant of IS257, now designated IScap. IScap showed 93% amino acid identity to S. aureus ORF49 but only 85% identity to IS431 from S. aureus N315 and 88% identity to an IS257-like element from bovine strain RF122. Thirty-six (53%) of 68 bovine isolates, drawn from a previously described S. aureus strain collection, carried some variant of IS257, including IScap. Of these 36 IS+isolates, 6 were CP5+, 1 was CP8+, and 29 were NT. Forty-four of the 68 isolates were NT, and 24 of these 44 NT isolates (55%) exhibited IScap-mediated deletion of the cap5(8) gene cluster. IScap was not found among 20 human NT S. aureus isolates bearing the cap5HIJK genes, which suggests that IScap-mediated deletion of the capsule locus is restricted to bovine strains of S. aureus. We were unable to identify a precursor strain in which IScap flanked the cap5(8) capsule locus, nor were we able to select for deletion of the cap5(8) locus in vitro. Our results support the hypothesis that deletion of the cap5 locus occurred in the distant past and that the relative abundance of these NT strains may be a result of their ability to persist in subclinical mastitis infection in cows.

ABSTRACTMany bovine Staphylococcus aureusisolates from Argentina are nontypeable (NT), i.e., they do not produce serotype 5 or 8 capsular polysaccharides (CPs). Some of these NT strains have a deletion of the cap5(8) gene cluster mediated by a variant of IS257, now designated IScap. IScapshowed 93% amino acid identity to S. aureusORF49 but only 85% identity to IS431from S. aureusN315 and 88% identity to an IS257-like element from bovine strain RF122. Thirty-six (53%) of 68 bovine isolates, drawn from a previously described S. aureusstrain collection, carried some variant of IS257, including IScap.Of these 36 IS+isolates, 6 were CP5+, 1 was CP8+, and 29 were NT. Forty-four of the 68 isolates were NT, and 24 of these 44 NT isolates (55%) exhibited IScap-mediated deletion of the cap5(8) gene cluster. IScapwas not found among 20 human NT S. aureusisolates bearing the cap5HIJKgenes, which suggests that IScap-mediated deletion of the capsule locus is restricted to bovine strains of S. aureus. We were unable to identify a precursor strain in which IScapflanked the cap5(8) capsule locus, nor were we able to select for deletion of the cap5(8) locus in vitro. Our results support the hypothesis that deletion of the cap5locus occurred in the distant past and that the relative abundance of these NT strains may be a result of their ability to persist in subclinical mastitis infection in cows.

Our aim was to determine whether abnormalities noted on MRI immediately after reduction for developmental dysplasia of the hip could predict the persistance of dysplasia and aid surgical planning. Scans of 13 hips in which acetabular dysplasia had resolved by the age of four years were compared with those of five which had required pelvic osteotomy for persisting dysplasia. The scans were analysed by two consultant musculoskeletal radiologists who were blinded to the outcome in each child.The postreduction scans highlighted a number of anatomical abnormalities secondary to developmental dysplasia of the hip, but statistical analysis showed that none were predictive of persisting acetabular dysplasia in the older child, suggesting that the factors which determine the long-term outcome were not visible on these images.

The total organic carbon (TOC) disappearance kinetics of the model organic sulfur heteroatom, thiodiglycol [TDG, (HOC2H4)2S], was investigated in an isothermal continuous tubular reactor under supercritical water oxidation (SCWO) conditions. The experiments were conducted at a temperature of 397−617 °C and a fixed pressure of 25 MPa, with a residence time that ranged from 9 s to 40 s. The initial TOC concentrations of TDG were varied from 1.75 mmol/L to 21.04 mmol/L and the oxygen concentrations were varied from 110% to 440% of the stoichiometric requirement. All the TOC conversions were >90% under the above experimental conditions. The major sulfur-containing products of the reaction were sulfuric acid and hydrogen sulfide, whereas the carbon-containing products included carbon monoxide, methane, and carbon dioxide. By taking into account the dependence of the oxidant and TOC concentration on the reaction rate, a global TOC disappearance rates expression was regressed from the data of 58 experiments, to a 95% confidence level. The resulting activation energy was determined to be 41.53 ± 1.65 kJ/mol, and the pre-exponential factor was (1.64 ± 0.55) × 10² L^1.12 mmol^-0.12 s^-1. The reaction orders for the TOC and the oxidant were 1.02 ± 0.01 and 0.10 ± 0.01, respectively.

The preparation and characterization of a novel dicobalt-containing monophosphine ligand, 4a, is presented. Palladium-catalyzed Suzuki−Miyuara reactions employing 4a/Pd(OAc)2 were pursued. The optimized reaction conditions were found to start with 1 molar equiv of arylhalides, 1.5-fold of phenylbronic acid, 3-fold of KF in 1 mL of THF, and 1 mol % of 4a/Pd(OAc)2 as catalytic precursor. The ³¹P NMR studies reveal moderate reductive capacity of 4a toward Pd(OAc)2. The unique bonding mode of 4a toward Pd ensures that the ratio of 4a/Pd is equal to 1:1. Two plausible active species, I and [I-OAc]^-, were proposed as the catalytically active species in the Suzuki−Miyaura cross-coupling reaction. The validity of this assumption was examined by ³¹P NMR spectra and density functional theory (DFT) means. In addition, we have demonstrated theoretically that the dicobalt moiety of 4a acts as an effective auxiliary in stabilizing the Pd(0) center during catalytic reaction.

Abstract

Bi-substituted YIG (Bi1.8Y1.2Fe5O12) nanoparticles were prepared by ultrasonic irradiation-assisted coprecipitation and annealing processes. The nanoparticles were dispersed in a plastic epoxy binder with a dispersing agent to induce polymerization by the solidifying agent. The magnetic and magneto-optical properties of the nanoparticles and the Bi-YIG/epoxy hybrid materials were investigated. The particles heat treated at 650 °C show a spherical shape and its size is smaller than 20 nm. The saturation magnetization of the Bi-YIG nanoparticles is 17 emu/g. As the particle content in the hybrid materials increases from 0.01 to 0.20 wt%, both the Faraday rotation (θF) and the Verdet constant of the hybrid materials at the wavelength 525 nm increase from 2.4 to 52.8 deg/cm, and from 0.02 × 10−2 to 2.63 × 10−2 deg/Oe cm, respectively. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

With the aim of investigating the effect of the side-chain length on the order and structure of thin films of side-chain liquid crystalline polymers, poly(oxyethylene)s containing various lengths of n-alkylsulfonylmethyl side chains (CH2SO2(CH2)m-1CH3; m = 5, 7, 10, and 16) were synthesized. The inner structure, surface structure, and adhesion behavior of thin films of these polymers were investigated. An X-ray reflectivity study of a polymer film spin-coated onto a silicon wafer showed that upon annealing above the glass transition temperature, the film has a lamellar structure in which the ordered layers are parallel to the substrate surface. When alkyl chain length in the side group is longer than the critical length, the layered structure is less perfect. Also, the air−polymer surface and the interface between layers are not smooth. This result implies that side chains are presumably loosely oriented. It can be expected that the critical length of the side chain is between m = 11 and m = 16. Near-edge X-ray absorption fine structure spectroscopy results also confirm that side chains near the top surface are loosely oriented when m is larger than the critical value. Force−displacement curves measured with atomic force microscopy also show an abrupt change in the adhesion force when the alkyl side chain length in the side group is longer than the critical length, which results from the side-chain conformation.

With the aim of developing a material with switchable tack properties, a side-chain liquid crystalline polymer containing a poly(oxyethylene) backbone and n-heptylsulfonylmethyl side chains was synthesized. The inner structure, surface properties, and tack behavior of this polymer film were investigated. An X-ray reflectivity study of a film of the polymer coated onto a silicon wafer showed that, upon annealing above the glass transition temperature, the film has a lamellar structure in which the ordered layers are parallel to the substrate surface. The layer thickness is roughly twice the length of the fully extended side chain, indicating a double-layered structure of the polymer with side chains normal to the polymer backbone having an almost all-trans conformation. The contact angle decreases abruptly at the isotropic transition temperature, which results from the disappearance of the smectic order. The coiling of the polymer backbone and disordering of side chains occur above the isotropic transition temperature. NEXAFS spectroscopy and AFM results confirmed that at temperatures below the isotropic transition temperature the side chains in the top layer are oriented such that they are almost perpendicular to the surface, which results in the packing of the CH3 groups at the surface and hence a very low surface energy. A remarkable change in tack properties is observed at the smectic-to-isotropic transition temperature. The dramatic change in tack properties, which occurs within a narrow temperature range, is due to the change in the surface energy and viscoelastic behavior of the film. This reversible and dramatic change in the tack force over a narrow temperature range could potentially be exploited in applications that require materials with switchable tackiness.

AbstractWhile the effectiveness of autogenous fat augmentation after microsurgical removal (FAMSR) of the vocal nodules (VN) has been previously shown in patient treatment programs, relatively little information is available regarding the long-term effectiveness of such a procedure. This paper examines, in retrospect, the long-term effectiveness of FAMSR in patients with VN (n = 41) using pre- and post-FAMSR perceptual acoustic and phonatory function data and videolaryngostroboscopic findings for 33 patients. The mean follow-up time was 18 months. Thirty-three (80.4%) patients displayed excellent results; 4 (9.8%) experienced improvement, and 4 (9.8%) postprocedure failure. Patient phonatory functions showed significant improvements in shimmer, harmonic-to-noise ratio, phonation time (p &lt; 0.05), grade, roughness and breathiness (p &lt; 0.001). The videolaryngostroboscopic rating showed significant improvements in vocal fold edge linearity, vocal fold vibration amplitude, and mucosal wave excursion (p &lt; 0.001). Improvements observed through long-term follow-up tended to be less dramatic in patients with recurrent VN than those with nonrecurrent VN. FAMSR is an easy, safe, and fast procedure which should be considered as an option in treating VN patients who either require surgery or do not have the time or perseverance to complete a lengthy program of speech therapy.Copyright © 2003 S. Karger AG, Basel

To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression.

The electrochemical behaviour of palladium in dilute acidic chloride solution was investigated using a rotating disc electrode system and the electrowinning of palladium using a modified electrochemical cyclone cell was also carried out. The effect of several variables such as applied voltage, hydrochloric acid concentration and electrolyte flow rate were studied to obtain the optimum conditions for electrowinning. More than 99% of the palladium in solution was recovered within an hour under the optimum conditions using the cyclone cell and grey powdery deposits were observed at a high applied voltage. The purity of palladium electrowon from the leach liquor was at least 99%.

A numerical program, which calculates the temperature profiles of electric arc spray formed (EASF) preforms, is coded on the basis of a shape forming model, droplet flight dynamics, and the boundary fitted coordinate (BFC) method for the calculation of heat transfer equations. Some thermophysical input data for the calculations, such as average droplet temperature impinging on the deposit surface, effective thermal conductivity of the deposit, and heat transfer coefficient at the interface and surface, are given by matching the experimental results with the numerical calculation results. Using the program, the temperature changes of the Fe-0 06%C steel ring deposit during the EASF process are calculated. The effects of the EASF parameters, such as substrate rotation velocity, average droplet temperature, and wire feedrate, on the temperature changes of the Fe-0.06%C steel ring preforms are also estimated.

Abstract: Haplotype frequencies of nine Y-chromosome STR loci (DYS19, DYS385, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393) in the Taiwanese Han population were established. A total of 183 unrelated individuals produced 162 haplotypes, of which 146 were unique, 1 was found in 5 individuals, 2 were found in 3 individuals and 13 were found in 2 individuals. The haplotype diversity (99.99%) and discrimination capacity (88.5%) were calculated. A family study of 109 father/son pairs in 100 families showed 2 mutational events in the DYS389II locus and 1 in the DYS392 locus.

Partial replacement of ethoxide ligands with N-alkoxo-β-ketoiminates in the tantalum or niobium ethoxides resulted in M(N-alkoxo-β-ketoiminate)(OEt)3 (M = Ta and Nb) complexes. Most of these complexes are liquid and showed enhanced thermal and chemical stability, especially toward moisture. These complexes have octahedral geometry with a meridional N-alkoxo-β-ketoiminate ligand and showed fluxional behaviors. All of these precursors, especially the ones with methyl groups on both the N-alkoxo and β-ketoiminate backbones, demonstrate considerably higher deposition rates than M2(OEt)10 (M = Ta and Nb), one of the most popular precursors for Ta2O5 and Nb2O5 films. Thermogravimetric analysis experiments showed that successive decomposition of ethoxide ligands is followed by decomposition of N-alkoxo-β-ketiminate in the pyrolysis process. Introduction of a methyl group onto the N-hydroxyethyl backbone enhanced the thermal stability at lower temperatures and the pyrolysis rate at higher temperatures. X-ray diffraction patterns indicate that the deposited films are not crystallized until the substrate temperature goes over 650 °C. Well-crystallized longish grains were formed in the Ta2O5 film deposited at 700 °C, but it was found from the depth profile spectra by Auger electron spectroscopy (AES) that the nitrogen and carbon impurities are 2.3% and 4.2%, respectively, for the Ta2O5 film deposited at 550 °C. Heat treatment at 700 °C in oxygen removed the nitrogen impurity in this Ta2O5 completely, and the residual carbon was proved to be negligible from the AES and X-ray photoelectron spectroscopy results.

ABSTRACTDuring the first 45 days after intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are closely related to the sites of virus gene expression and tissue inflammation. In the present study, these chemokines were monitored during the latter 135 days of a 6-month course of TMEV-induced disease in susceptible (PLJ) or resistant (C57BL/6) mice that possessed or lacked either CD4+or CD8+T cells. These data were additionally correlated to mouse genotype, virus persistence in the CNS, antiviral antibody titers, mortality, and the severity of neurological disease. Surprisingly, the major determinant of chemokine expression was virus persistence: the factors of susceptible or resistant genotype, severity of neuropathology, and presence or absence of regulatory T cells exerted minimal effects. Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.

( n -Hexadecylsulfonyl)methyl-substituted poly(oxyethylene) (16SP), ( n -hexadecylthio)methyl-substituted poly(oxyethylene) (16TP), [(6- n -nonylsulfonyl)hexylthio]methyl-substituted poly(oxyethylene) (9S6TP), and [(6- n -nonylsulfonyl)hexylsulfonyl]methyl-substituted poly(oxyethylene) (9S6SP) were synthesized. 9S6SP and 16SP containing sulfonylmethyl side groups showed highly ordered smectic layer structures at room temperature and liquid crystalline behavior at higher temperatures, while 9S6TP and 16TP containing thiomethyl side groups did not show any liquid crystalline behavior. The ordered phases of the polymers were studied using differential scanning calorimetry, cross-polarizing optical microscopy, and X-ray diffraction. The unusual liquid crystallinity of 16SP and 9S6SP was ascribed to the amphiphilic character of these polymers.