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Repeats of the disaccharide unit N -acetyllactosamine (LacNAc) occur as type 1 (Galβ1, 3GlcNAc) and type 2 (Galβ1, 4GlcNAc) glycosylation motifs on glycoproteins and glycolipids. The LacNAc motif acts as binding ligand for lectins and is involved in many biological recognition events. To the best of our knowledge, we present, for the first time, the synthesis of LacNAc type 1 oligomers using recombinant β1,3-galactosyltransferase from Escherichia coli and β1,3- N -acetylglucosaminyltranferase from Helicobacter pylori . Tetrasaccharide glycans presenting LacNAc type 1 repeats or LacNAc type 1 at the reducing or non-reducing end, respectively, were conjugated to bovine serum albumin as a protein scaffold by squarate linker chemistry. The resulting multivalent LacNAc type 1 presenting neo-glycoproteins were further studied for specific binding of the tumor-associated human galectin 3 (Gal-3) and its truncated counterpart Gal-3∆ in an enzyme-linked lectin assay (ELLA). We observed a significantly increased affinity of Gal-3∆ towards the multivalent neo-glycoprotein presenting LacNAc type 1 repeating units. This is the first evidence for differences in glycan selectivity of Gal-3∆ and Gal-3 and may be further utilized for tracing Gal-3∆ during tumor progression and therapy., Competing Interests: The authors declare no conflict of interest.

This study evaluates height loss during the day in light of variables assessable through participant self-report. Participants were 19 female and 15 male staff and students who met with us twice with a mean interval between measurement sessions of 6.96h (SD=0.86). Hypotheses were evaluated using two-stage least squares regression analysis (SYSTAT 10). Males and females lost similar amounts of height between sessions (male,x¯=6.9mm;female,x¯=7.4mm). Among factors considered to impact overall height loss, sleep duration (Adj. R 2 =0.181, p=0.022) and height (Adj. R 2 =0.121, p=0.048) were useful in univariate analyses, though they were not significant in any models that included variables other than sex. Judging from log-transformed BMI variation, heavier males and females lost more height (F (2, 31) =4.59, Adj. R 2 =0.179, p=0.018). Among factors anticipated to reduce height loss by acting prior to morning measurements, only time spent walking was significantly associated (β=2.6±0.8mm, t=3.16, p=0.004) when included as a predictor along with sex (p=0.17) and log-BMI (p=0.003). This model explained about 38% of height loss variance. None of the factors considered as potentially acting between measurement sessions showed statistically significant influences when included in the model just described, though predictor coefficients were in the anticipated direction. Results suggest that self-reported activities may be an important supplement to anthropometric studies, both for planning and later evaluation, particularly in large studies., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

A novel type of hypervalent iodine(III) reagents, vinylbenziodoxolones (VBX), has been synthesized in a one-pot reaction from 2-iodobenzoic acid. VBX is bench stable, has been thoroughly characterized and the cyclic structure is supported by X-ray analysis. The reactivity of VBX was investigated in vinylation of nitrocyclohexane, and delivered vinylated products with opposite regioselectivity compared to acyclic vinyl(aryl)iodonium salts. The reagents could become a powerful tool in vinylation reactions under both metal-free and metal-catalyzed conditions., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The majority of neuroendocrine tumors originate in the digestive system and incidence is increasing within Canada and globally. Due to rapidly evolving evidence related to diagnosis and clinical management, updated guidance on the diagnosis and treatment of gastrointestinal neuroendocrine tumors (GI-NETs) are of clinical importance. Well-differentiated GI-NETs may exhibit indolent clinical behavior and are often metastatic at diagnosis. Some NET patients will develop secretory disease requiring symptom control to optimize quality of life and clinical outcomes. Optimal management of GI-NETs is in a multidisciplinary environment and is multimodal, requiring collaboration between medical, surgical, imaging and pathology specialties. Clinical application of advances in pathological classification and diagnostic technologies, along with evolving surgical, radiotherapeutic and medical therapies are critical to the advancement of patient care. We performed a systematic literature search to update our last set of published guidelines (2010) and identified new level 1 evidence for novel therapies, including telotristat etiprate (TELESTAR), lanreotide (CLARINET), everolimus (RADIANT-2; RADIANT-4) and peptide receptor radionuclide therapy (PRRT; NETTER-1). Integrating these data with the clinical knowledge of 16 multi-disciplinary experts, we devised consensus recommendations to guide state of the art clinical management of GI-NETs., (Copyright © 2016. Published by Elsevier Ltd.)

Aims: The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug., Main Methods: Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1., Key Findings: In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3., Significance: Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Conjugated nitroalkenes and nitrodienes undergo smooth α-hydrazination with azodicarboxylates through an imidazole catalyzed carbon-heteroatom bond formation under Morita-Baylis-Hillman conditions. The resulting hydrazinonitroalkenes take part in 1,3-dipolar cycloaddition with azide under mild conditions to give hydrazinotriazoles. A [3 + 2] annulation with phenols and naphthols involving Michael addition and cyclization as the key steps lead to arenodihydrofurans bearing a key hydrazinodicarboxylate moiety. Both regioisomers of naphthodihydrofurans could be synthesized by our methodology by employing the appropriate naphthol.

Background: A critical source of variability in dynamic perfusion computed tomography (DPCT) is the arterial input function (AIF). However, the impact of the AIF location in lung DPCT has not been investigated yet. The purpose of this study is to determine whether the location of the AIF within the central pulmonary arteries influences the accuracy of lung DPCT maps., Methods: A total of 54 lung DPCT scans were performed in three pigs using different rates and volumes of iodinated contrast media. Pulmonary blood flow (PBF) perfusion maps were generated using first-pass kinetics in three different AIF locations: the main pulmonary trunk (PT), the right main (RM) and the left main (LM) pulmonary arteries. A total of 162 time density curves (TDCs) and corresponding PBF perfusion maps were generated. Linear regression and Spearman's rank correlation coefficient were used to compare the TDCs. PBF perfusion maps were compared quantitatively by taking twenty six regions of interest throughout the lung parenchyma. Analysis of variance (ANOVA) was used to compare the mean PBF values among the three AIF locations. Two chest radiologists performed qualitative assessment of the perfusion maps using a 3-point scale to determine regions of perfusion mismatch., Results: The linear regression of the TDCs from the RM and LM compared to the PT had a median (range) of 1.01 (0.98-1.03). The Spearman rank correlation between the TDCs was 0.88 (P<0.05). ANOVA analysis of the perfusion maps demonstrated no statistical difference (P>0.05). Qualitative comparison of the perfusion maps resulted in scores of 1 and 2, demonstrating either identical or comparable maps with no significant difference in perfusion defects between the different AIF locations., Conclusions: Accurate PBF perfusion maps can be generated with the AIF located either at the PT, RM or LM pulmonary arteries.

An efficient, mild, and metal-free arylation of nitroalkanes with diaryliodonium salts has been developed, giving easy access to tertiary nitro compounds. The reaction proceeds in high yields without the need for excess reagents and can be extended to α-arylation of nitroesters. Nitroalkanes were selectively C-arylated in the presence of other easily arylated functional groups, such as phenols and aliphatic alcohols.

Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers.

Lipid classes and fatty acid compositions of a digenetic trematode, Isoparorchis hypselobagri inhabiting swim bladder of Wallago attu were analyzed by TLC and GLC. The total lipid (TL) and percent content of neutral lipid (NL, 61.59), glycolipid (GL, 19.78) and phospholipid (PL, 18.62) were recorded. The total lipid is 3.81 % of the wet weight of the body tissue. The total percent of saturates, monoenes, dienes and polyenes in TL, NL, GL, and PL of the parasite were 52.0, 49.7, 57.9, 61.5; 31.7, 31.8, 33.1, 26.3; 5.7, 5.7, 4.7, 4.2; as well as 10.33, 12.6, 4.3, 7.4 respectively. Diunsaturated fatty acids were present in low amount. Palmitic 16:0 (among all saturates) and oleic 18:1ω9 (among all unsaturates) acids were the predominant fatty acids in the parasite recorded.

Many animals use coloration to communicate with other individuals. Although the signalling role of avian plumage colour is relatively well studied, there has been much less research on coloration in avian bare parts. However, bare parts could be highly informative signals as they can show rapid changes in coloration. We measured bill colour (a ubiquitous bare part) in over 1600 passerine species and tested whether interspecific variation in carotenoid-based coloration is consistent with signalling to potential mates or signalling to potential rivals in a competitive context. Our results suggest that carotenoid bill coloration primarily evolved as a signal of dominance, as this type of coloration is more common in species that live in social groups in the nonbreeding season, and species that nest in colonies; two socio-ecological conditions that promote frequent agonistic interactions with numerous and/or unfamiliar individuals. Additionally, our study suggests that carotenoid bill coloration is independent of the intensity of past sexual selection, as it is not related to either sexual dichromatism or sexual size dimorphism. These results pose a significant challenge to the conventional view that carotenoid-based avian coloration has evolved as a developmentally costly, condition-dependent sexual signal. We also suggest that bare part ornamentation may often signal different information than plumage ornaments., (© 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.)

Compiling, deploying and utilising large-scale databases that integrate environmental and economic data have traditionally been labour- and cost-intensive processes, hindered by the large amount of disparate and misaligned data that must be collected and harmonised. The Australian Industrial Ecology Virtual Laboratory (IELab) is a novel, collaborative approach to compiling large-scale environmentally extended multi-region input-output (MRIO) models. The utility of the IELab product is greatly enhanced by avoiding the need to lock in an MRIO structure at the time the MRIO system is developed. The IELab advances the idea of the "mother-daughter" construction principle, whereby a regionally and sectorally very detailed "mother" table is set up, from which "daughter" tables are derived to suit specific research questions. By introducing a third tier - the "root classification" - IELab users are able to define their own mother-MRIO configuration, at no additional cost in terms of data handling. Customised mother-MRIOs can then be built, which maximise disaggregation in aspects that are useful to a family of research questions. The second innovation in the IELab system is to provide a highly automated collaborative research platform in a cloud-computing environment, greatly expediting workflows and making these computational benefits accessible to all users. Combining these two aspects realises many benefits. The collaborative nature of the IELab development project allows significant savings in resources. Timely deployment is possible by coupling automation procedures with the comprehensive input from multiple teams. User-defined MRIO tables, coupled with high performance computing, mean that MRIO analysis will be useful and accessible for a great many more research applications than would otherwise be possible. By ensuring that a common set of analytical tools such as for hybrid life-cycle assessment is adopted, the IELab will facilitate the harmonisation of fragmented, dispersed and misaligned raw data for the benefit of all interested parties., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Metal-organic frameworks (MOFs) are a class of hybrid network supramolecular solid materials comprised of organized organic linkers and metal cations. They can display enormously high surface areas with tunable pore size and functionality, and can be used as hosts for a range of guest molecules. Since their discovery, MOFs have experienced widespread exploration for their applications in gas storage, drug delivery and sensing. This article covers general and modern synthetic strategies to prepare MOFs, and discusses their structural diversity and properties with respect to application perspectives.

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

Many industrial processes are found to be integrating in nature, for which widely used Ziegler-Nichols tuned PID controllers usually fail to provide satisfactory performance due to excessive overshoot with large settling time. Although, IMC (Internal Model Control) based PID controllers are capable to reduce the overshoot, but little improvement is found in the load disturbance response. Here, we propose an auto-tuning proportional-derivative controller (APD) where a nonlinear gain updating factor α continuously adjusts the proportional and derivative gains to achieve an overall improved performance during set point change as well as load disturbance. The value of α is obtained by a simple relation based on the instantaneous values of normalized error (eN) and change of error (ΔeN) of the controlled variable. Performance of the proposed nonlinear PD controller (APD) is tested and compared with other PD and PID tuning rules for pure integrating plus delay (IPD) and first-order integrating plus delay (FOIPD) processes. Effectiveness of the proposed scheme is verified on a laboratory scale servo position control system., (© 2013 ISA Published by ISA All rights reserved.)

A CuCl2 mediated direct intramolecular oxidative coupling of Csp(2)-H and Csp(3)-H centers gives access to 3,3-disubstituted oxindoles containing aromatic, heteroaromatic and alkyl substituents as well as a heteroatom at the quaternary center in good to excellent yields. The reaction is carried out in the presence of NaOtBu and CuCl2 in DMF at 110 °C. The key step of this reaction is the formation of an amidyl radical by one electron oxidation of amide enolate followed by an intramolecular radical cyclization reaction (homolytic aromatic substitution reaction). A detailed DFT study shows that the cyclization of the amidyl radical is the rate-limiting step in the oxindole synthesis, whereas the second single electron transfer (SET) becomes the rate-determining step in the aza-oxindole formation. Computational data are in agreement with the experimentally observed relative reactivity and regioselectivity.

Background: Injury to the underlying structures of the hand carries the potential for serious handicap. To reduce this risk, even the smallest hand injuries require proper medical care., Aims: To assess wound healing, mobility, and the ability to perform normal essential function post-operatively in open hand injuries associated with fracture., Materials and Methods: Thirty patients with 45 metacarpal and phalangeal fractures of the hand were divided into three groups: Group 1 (n = 13) cases with single fractures of hand, excluding thumb; Group 2 (n = 9) cases with multiple fracture of hand, excluding thumb; Group 3 (n = 8) cases with fractures involving thumb and first metacarpal. Tendon injuries were repaired. For fractures, Kirschner wire fixation was done. In two cases with multiple fractures, Joshi's external support system (JESS) fixator was applied. Patients were followed up for 12 weeks., Results: One patient with proximal phalangeal fracture developed extension lag. No stiffness was observed in any of the cases treated by intramedullary Kirschner wire fixation. No non-union or delayed union was observed following cross-wire fixation with two Kirschner wires. Two case of open fracture developed superficial infection. Two patients with multiple fractures developed angulation at fracture site after the Kirschner wires were removed 4 weeks postoperatively, and two cases of multiple fractures developed hypertrophic non-union., Conclusions: Delicate handling of tissues, preservation of gliding planes for tendons, prevention of infection, accurate reduction and fixation, and early and appropriate physiotherapy affect prognosis in case of hand injuries.

A rare hybrid Metal-Oxide incorporated Zeolitic Imidazolate Framework, MOZIF-1, containing tetrahedral Zn(II) and Mo(VI) centres has been synthesized. MOZIF-1 can degrade methyl orange and orange II dyes under visible light. Na3[PMo12O40] is the source of Mo(VI) in MOZIF-1.

Six organic-inorganic hybrid materials were synthesized by the in situ oxidation of neocuproine by using MoO3 /Na2 MoO4 as the catalyst in the presence of Cu(NO3)2. The crystal structures of Mo8-Cu4-PHEN and Mo8-Cu2-5(2PIC) are composed of [Mo8 O26 ](4-) polyoxometalate (POM) units, whereas the crystal structure of Mo6-Cu-COPHEN is composed of a [Mo6 O19 ](2-) POM unit; both POM units could be considered as the active form of the catalyst. Reaction of the hybrid materials with 1,3,5-benzenetricarboxylic acid (BTC) resulted in the formation of two different coordination polymers (CPs) under different reaction conditions. These CPs, depending on their structural attributes, exhibit distinct differences in the adsorption of H2, CO2, and water. The use of 2-methylpyridine instead of neocuproine does not give any oxidation products under the same reaction conditions due to the incorrect positioning of the methyl group with respect to the Cu(II) center., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel efficient NaOtBu-mediated protocol for the synthesis of 3,3-disubstituted aza-oxindoles proceeds via a Truce-Smiles rearrangement-cyclisation pathway.

Purpose: Laryngotracheobronchial injuries (LTBI) are serious injuries because of their consequences in terms of ventilation, coupled with the severity of other injuries associated with them. We share our experience in managing these patients perioperatively in our level 1 trauma centre., Methods: A retrospective analysis of the records of 30 patients with LTBI who presented at Jai Prakash Narayan Apex Trauma Center (JPNATC) from December 2007 to February 2011 was done. The demographics, mechanism of injury, clinical presentation, diagnostic modalities, anaesthetic management and outcome in these patients were reviewed., Results: Intrathoracic location of the injury and Injury Severity Score (ISS) had a direct correlation with the outcome of the patients. The overall mortality was 6.7 %., Conclusion: Meticulous examination, details about the mechanism of injury, careful diagnostic evaluation, and skilful airway and surgical management are necessary for a better outcome in patients with airway injuries. A high degree of suspicion in occult injuries and liberal use of a fibreoptic bronchoscope aids diagnosis and management. Prompt airway management in the pre-hospital setting before transfer to a higher level trauma centre ensures better outcomes.

Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD., (© 2011 Blackwell Publishing Ltd.)

A Cu(II) mediated oxidative C(sp(2))-H and C(sp(3))-H coupling protocol gives access to aza-oxindoles in good to excellent yield in the presence of NaOtBu as base and toluene as solvent.

A Cu(II)-phenanthroline connected Strandberg-type polyoxometalate based proton conducting MOF, Cu(3)Mo(5)P(2), that contains one dimensional parallel water channels has been reported. Cu(3)Mo(5)P(2) shows proton conduction at room temperature as well as elevated temperature., (This journal is © The Royal Society of Chemistry 2012)

A Cu-based double chain MOF was synthesized in hydrothermal conditions using an in situ ligand formation method. This double chain MOF shows temperature dependent ferromagnetic (long range ordering) and antiferromagnetic (intra double chain) coupling. The magnetic behaviour originating from the individual double chain remains almost same even after structural collapse due to the removal of guest water molecules.

Fish compensate for acid-base disturbances primarily by modulating the branchial excretion of acid-base equivalents, with a supporting role played by adjustment of urinary acid excretion. The present study used metabolic acid-base disturbances in rainbow trout, Oncorhynchus mykiss, to evaluate the role played by cortisol in stimulating compensatory responses. Trout infused with acid (an iso-osmotic solution of 70 mmol L(-1) HCl), base (140 mmol L(-1) NaHCO(3)) or saline (140 mmol L(-1) NaCl) for 24 h exhibited significant elevation of circulating cortisol concentrations. Acid infusion significantly increased both branchial (by 328 μmol kg(-1) h(-1)) and urinary (by 5.9 μmol kg(-1) h(-1)) net acid excretion, compensatory responses that were eliminated by pre-treatment of trout with the cortisol synthesis inhibitor metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone). The significant decrease in net acid excretion (equivalent to enhanced base excretion) of 203 μmol kg(-1) h(-1) detected in base-infused trout was unaffected by metyrapone treatment. Acid- and base-infusions also were associated with significant changes in the relative mRNA expression of branchial and renal cytosolic carbonic anhydrase (tCAc) and renal membrane-linked CA IV (tCA IV). Cortisol treatment caused changes in CA gene expression that tended to parallel those observed with acid but not base infusion. For example, significant increases in renal relative tCA IV mRNA expression were detected in both acid-infused (~2x) and cortisol-treated (~10x) trout, whereas tCA IV mRNA expression was significantly reduced (~5x) in base-infused fish. Despite changes in CA gene expression in acid- or base-infused fish, neither acid nor base infusion affected CAc protein levels in the gill, but both caused significant increases in branchial CA activity. Cortisol treatment similarly increased branchial CA activity in the absence of an effect on branchial CAc protein expression. Taken together, these findings provide support for the hypothesis that in rainbow trout, cortisol is involved in mediating acid-base compensatory responses to a metabolic acidosis, and that cortisol exerts its effects at least in part through modulation of CA.

Responses of high-order systems under Ziegler-Nichols tuned PI controllers (ZNPIs) are characterized by excessive oscillation with a large overshoot. Although, a fixed set-point weighting based PI controller (FSWPI) may decrease the overshoot considerably, it fails to reduce the oscillation in the set-point response. Moreover, both FSWPI and ZNPI exhibit equally poor load regulation. Keeping in mind an overall improved performance, we propose an online dynamic set-point weighting technique for ZNPIs. The dynamic set-point weighting factor (β(d)) is heuristically derived from the instantaneous process trend. Performance of the proposed dynamic set-point weighting based PI controller (DSWPI) for various second- and third-order processes including a pH process shows a significant improvement during both the set-point and load disturbance responses over other methods. Stability and robustness of the proposed DSWPI are addressed. Effectiveness of the DSWPI is demonstrated through the real-time implementation on a practical DC position control system., (Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.)

The paper presents major lipid classes and their fatty acids investigated from Ascaridia galli, a nematode parasite of country fowl. Thin layer chromatography (TLC) reveals that the percent of total lipid, neutral lipid, phospholipids, and glycolipids are 1.94, 54.39, 26.95 and 18.66, respectively. Gas-liquid chromatography (GLC) analysis shows that the saturated fatty acids are the major components in all the lipid fractions followed by monoenes and dienes. Polyunsaturated fatty acids (PUFA) were present in low amount. Stearic acids (C(18)) were the chief components among all the fatty acids in all the lipid fractions.

An improved auto-tuning scheme is proposed for Ziegler-Nichols (ZN) tuned PID controllers (ZNPIDs), which usually provide excessively large overshoots, not tolerable in most of the situations, for high-order and nonlinear processes. To overcome this limitation ZNPIDs are upgraded by some easily interpretable heuristic rules through an online gain modifying factor defined on the instantaneous process states. This study is an extension of our earlier work [Mudi RK., Dey C. Lee TT. An improved auto-tuning scheme for PI controllers. ISA Trans 2008; 47: 45-52] to ZNPIDs, thereby making the scheme suitable for a wide range of processes and more generalized too. The proposed augmented ZNPID (AZNPID) is tested on various high-order linear and nonlinear dead-time processes with improved performance over ZNPID, refined ZNPID (RZNPID), and other schemes reported in the literature. Stability issues are addressed for linear processes. Robust performance of AZNPID is observed while changing its tunable parameters as well as the process dead-time. The proposed scheme is also implemented on a real time servo-based position control system.

Discrimination of tRNA(Gln) is an integral function of several bacterial glutamyl-tRNA synthetases (GluRS). The origin of the discrimination is thought to arise from unfavorable interactions between tRNA(Gln) and the anticodon-binding domain of GluRS. From experiments on an anticodon-binding domain truncated Escherichia coli (E. coli) GluRS (catalytic domain) and a chimeric protein, constructed from the catalytic domain of E. coli GluRS and the anticodon-binding domain of E. coli glutaminyl-tRNA synthetase (GlnRS), we show that both proteins discriminate against E. coli tRNA(Gln). Our results demonstrate that in addition to the anticodon-binding domain, tRNA(Gln) discriminatory elements may be present in the catalytic domain in E. coli GluRS as well.

Ziegler-Nichols tuned PI and PID controllers are usually found to provide poor performances for high-order and nonlinear systems. In this study, an improved auto-tuning scheme is presented for Ziegler-Nichols tuned PI controllers (ZNPICs). With a view to improving the transient response, the proportional and integral gains of the proposed controller are continuously modified based on the current process trend. The proposed controller is tested for a number of high-order linear and nonlinear dead-time processes under both set-point change and load disturbance. It exhibits significantly improved performance compared to ZNPIC, and Refined Ziegler-Nichols tuned PI controller (RZNPIC). Robustness of the proposed scheme is established by varying the controller parameters as well as the dead-time of the process under control.

Background: Relationships between income inequality and various health indicators have been the subject of much study and some controversy. We investigated associations between child mortality and income inequality amongst the wealthier OECD countries as well as changes in their relative child mortality rankings over time., Methods: Data were drawn from the 2003-2006 'State of the World's Children' reports published by UNICEF; Gini coefficients on income inequality were also used. Pearson correlation coefficients were calculated to investigate associations. Longitudinal child mortality data was used to compare rankings., Results: We discovered very strong associations between child mortality and income inequality. In contrast to earlier results, these associations persist when the USA is excluded from the analysis. The countries with the worst child mortality figures were previously singled out in a 1993 UNICEF study on child neglect in rich nations. We also report their worsening child mortality rankings, since 1960, relative to the other OECD countries., Conclusions: The results strengthen the existing evidence linking child mortality with income inequality in wealthy nations, and add to the evidence that sociopolitical factors are important in this regard.

Unconscious patients are frequently referred to radiology departments for computed tomography (CT) of the brain. The objectives of these examinations are to define the underlying cause of impaired consciousness and in some cases to determine the severity of associated brain injury. There is often little history available to guide the clinician or radiologist, particularly in patients referred from the casualty department. In this review, we present the typical CT appearances of adult patients presenting with loss of consciousness for CT examination. We focus on the most common abnormalities that are identified in everyday radiological practice, emphasize important diagnostic signs that may enable a confident diagnosis to be made and discuss when further imaging may be warranted.

Aims/hypothesis: On the basis of our previous studies, we investigated the possible role of focal adhesion kinase (FAK) in the development of insulin resistance in skeletal muscle, a major organ responsible for insulin-stimulated glucose uptake., Materials and Methods: Insulin-resistant C2C12 skeletal muscle cells were transfected with FAK wild-type or FAK mutant plasmids, knocked down using small interfering RNA (siRNA), and their effects on the levels and activities of insulin-signalling molecules and on glucose uptake were determined., Results: A significant decrease in tyrosine phosphorylation of FAK in insulin-resistant C2C12 cells was observed. A similar decrease was observed in skeletal muscle obtained from insulin-resistant Sprague-Dawley rats fed a high-fat diet. Increased levels of FAK in insulin-resistant C2C12 skeletal muscle cells increased insulin sensitivity and glucose uptake. These effects were reversed by an increase in the level of kinase activity mutant FAK or suppression of endogenous FAK by siRNA. FAK was also found to interact downstream with insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase C and glycogen synthase kinase 3beta, leading to translocation of glucose transporter 4 and resulting in the regulation of glucose uptake., Conclusions/interpretation: The present study provides strong evidence that the modulation of FAK level regulates the insulin sensitivity of skeletal muscle cells. The results demonstrate a direct role of FAK in insulin-resistant skeletal muscle cells for the first time.

The present study focuses on the physical and chemical stability of insulin under iontophoretic conditions using HPLC, SDS-PAGE, RIA and biological assay. Influence of pH, concentration of insulin, current strength and duration of current application on the stability of insulin was studied. Anodal iontophoresis at pH 7.4 caused more than 80% degradation of insulin, while the degradation was minimal at pH 3.6. The degradation was not influenced by insulin concentration, but increase in current strength above 0.75 mA/cm2 or application of current for 12 h (at 0.5 mA/cm2) led to 80 and 20% degradation respectively. All the samples showed biological activity comparable to intact insulin.

Aims/hypothesis: Miltefosine, the first oral anti-leishmanial drug, is reported to inhibit phosphatidylinositol 3-kinase (PI3K)/Akt activity in carcinoma cell lines. Inhibition of the PI3K/Akt pathway is known to result in insulin resistance. Therefore, we investigated whether miltefosine has any deleterious effect(s) on insulin sensitivity in L6E9 skeletal muscle cells., Materials and Methods: L6E9 myotubes were treated with miltefosine and its effect was observed on insulin-signalling proteins such as Akt, PI3K, insulin receptor-beta, IRS-1, c-Jun N-terminal kinase, p38 and glycogen synthase kinase beta, as well as on glucose uptake., Results: Miltefosine caused skeletal muscle insulin resistance in vitro by interfering with the insulin-signalling pathway and inhibiting insulin-stimulated glucose uptake., Conclusions/interpretation: Miltefosine may contribute to the risk of type 2 diabetes and needs further clinical exploration.

Traumatic hip dislocation in the paediatric population is a relatively rare occurrence and constitutes an orthopaedic emergency. A trivial force is all that is required and non-accidental injury should not be necessarily suspected. A case report involving a hip dislocation in a 21-month-old child, the youngest in the recent English literature is detailed.

In this study the anti-leishmanial activity and anti-microtubule effects of paclitaxel, trifluralin and a combination of paclitaxel and trifluralin have been tested in a wild type and sodium arsenite-resistant strain of Leishmania donovani. Both paclitaxel and trifluralin have been shown to be effective in limiting parasite growth. Specific alterations in morphology, tubulin polymerization dynamics, post-translational modifications and cellular distribution of the tubulins have been confirmed to be a part of the intracellular anti-microtubule-events that occur in arsenite-resistant L. donovani in response to these agents, ultimately leading to death of the parasite. DNA analyses of the drug-treated wild type and arsenite-resistant strains revealed an apoptosis-like death in response to paclitaxel and the combination but not to trifluralin. Data provide valuable information for further development of chemotherapeutic strategies based on anti-microtubule agents against drug resistant Leishmania parasites.

RNA interference, part of a complicated network of interconnected pathways for cellular defence, RNA surveillance and development, has become a powerful tool for the experimental manipulation of gene expression. It is the process by which double-stranded (dsRNA) silences specific gene expression through homology-dependent degradation of cognate mRNA. The dsRNA is converted into 21nt small interfering RNAs (siRNAs), which directs a complex ribonuclease system to substrate mRNA targets. The degradation of the target mRNA is initiated with the cleavage at a position corresponding to the centre of the siRNA. Dissecting individual cellular pathways to reveal the function of numerous proteins is an approach to drug discovery. Interfering RNA (RNAi) serves as a rapid and convenient tool, which works in various organisms. RNAi technology has the potential to facilitate our understanding of biological processes and potentially lead to exciting new drugs. Here we review various experimental approaches adopted with RNAi and possible therapeutic applications.

Transdermal iontophoresis is a physical enhancement strategy primarily for charged molecules and offers a number of advantages for the delivery of peptides and proteins. The singular advantage of iontophoresis lies in the precise control of dose by manipulating the current protocol. The objective of the present investigation was to understand the role of electronic parameters on iontophoretic transport of large peptides using insulin as a model peptide. Ex vivo permeation experiments were conducted using excised rat skin and the influence of varying current strengths, duration, on/off ratios and switching iontophoresis on insulin permeation were studied. High performance liquid chromatography (HPLC), polyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) were used to assess the electrochemical stability of insulin; while Fourier transform infra-red (FT-IR) spectroscopy and thermogravimetric analysis (TGA) were used to understand the biophysical changes in skin during iontophoresis. The permeation of insulin was found to increase as a function of current strength and duration of current application. Skin barrier integrity and electrochemical stability of insulin was dependent on the charge applied during iontophoresis. FT-IR spectroscopy and TGA studies showed that the skin hydration increased with increase in the charge applied and thus facilitated the transport of insulin. Periodic iontophoresis did not show any significant difference in insulin permeation compared with continuous current application; 1:1 on/off ratio resulted in higher amount of insulin permeation, while flux was highest with mixed duty cycle. Switching iontophoresis was useful in reducing the pH shift and in improving the electrochemical stability of insulin at pH 3.6 and 7.4, respectively. The electroosmotic flow was influenced by the pH of the donor medium, as well as by the electrode polarity during switching and non-switching iontophoresis. Overall, the study demonstrates the issues related to the optimization of electronic parameters for the iontophoretic delivery of a large peptide.

Western immunoblot analyses of whole cell lysates probed with a human specific monoclonal anti-topoisomerase IIalpha antibody identified a 190 kDa protein over expressed in the arsenite resistant Leishmania donovani strain. The crude nuclear extract of the resistant strain showed higher topoisomerase II-like enzyme activity. suggesting a possible regulatory role of putative topoisomerase II in arsenite resistant Leishmania.

Microtubules are cytoskeletal polymers essential for the survival of all eukaryotes. These proteins are the proposed cellular targets of many anticancerous, antifungal and antihelminthic drugs. Sufficient differences exist between the microtubules of kinetoplastid parasites like Leishmania and humans to explore the selective targeting of these proteins for therapeutic purposes. This review describes the basic structure of microtubules and its dynamics in general, with specific insights into leishmanial microtubules, the salient features of microtubule-drug interactions including the specificity of certain drugs for parasitic microtubules. Chemotherapy against leishmanial parasites is failing because of the emergence of drug resistant strains. The possible mechanisms of resistance to antimicrotubule agents along with insights into the role of microtubules in mediating drug resistance in Leishmania are discussed.

Differentiation of Leishmania donovani promastigotes into infectious amastigotes is accompanied by differential tubulin gene expression. Tubulin is one of the proposed targets of clinically useful antileishmanial agents and its expression is known to alter due to drug resistance. In this study, beta- and gamma-tubulin expression under various stages of differentiation was measured in an in vitro generated arsenite-resistant L. donovani strain. Results showed higher constitutive expression of beta-tubulin in the arsenite-resistant promastigotes and amastigotes compared with the wild-type. beta-Tubulin expression in the resistant promastigotes increased on paclitaxel treatment. Significant differences in gamma-tubulin expression were observed only between the amastigotes, but not between promastigotes, of wild-type and resistant strains. Paclitaxel did not produce any significant change in the expression profile of gamma-tubulin in either of the strains, neither before nor after differentiation. Data suggest that the beta- and gamma-tubulin expression and the response to paclitaxel is affected due to arsenite resistance.

Immunomodulatory activity of an Ayurvedic polyherbal formulation, Immu-21 containing extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia was studied on proliferative response of splenic leukocytes to T cell mitogens, concanavalin (Con)-A and phytohemagglutinin (PHA) and B cell mitogen, lipopolysaccharide (LPS) in vitro by [3H]-thymidine uptake assay in mice. The cytotoxic activity of Immu-21 was tested by measuring the splenic leukocyte natural killer (NK) cell activity against K 562 cells. Intraperitoneal (i.p.) treatment with Immu-21 (30 mg/kg) once a day for 14 and 21 days did not cause change in body weight and spleen weight, where as splenocytes/spleen count was increased. Treatment of Immu-21 (30 mg/kg, i.p.) for 14 days and 1 mg/kg for 21 days significantly increased LPS induced leukocyte proliferation. NK cell activity was significantly increased when mice were pretreated with Immu-21 (10 and 30 mg/kg, i.p.) once a day for 7 days. The results indicate that pretreatment with Immu-21 selectively increased the proliferation of splenic leukocyte to B cell mitogen, LPS and cytotoxic activity against K 562 cells in mice.

During the past decade, indicators for the assessment, monitoring, and evaluation of services provided by humanitarian organizations to populations affected by complex emergencies (CEs) were developed to improve the effectiveness and accountability of humanitarian response. The quality of data used to develop individual indicators and their relationship to positive health outcomes varies greatly. This article states the essential characteristics necessary for the development and implementation of effective indicators in CE response and proposes the establishment of an evidence-based grading system. The importance of trend analysis and the modification or addition of various indicators and their thresholds, according to phase and location of CEs, are stressed. Limitations in the development, implementation, and interpretation of these indicators, including those outside of the organizations' control are discussed. More evidence-based research is needed as to the type and thresholds of indicators that lead to improved health outcomes in populations affected by CEs. The use of indicators by non-governmental organizations, and how they affect their program's decision-making in different phases and settings within CEs need further study. Finally, the establishment of a regulating body with the authority to enforce the attainment of standards by use of these indicators is necessary to avoid inappropriate humanitarian assistance causing loss of life in the future.

An arsenite-resistant strain of Leishmania donovani was generated in vitro by the sequential exposure of a wild type strain to increasing concentrations of sodium m-arsenite. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of whole cell lysates of the two strains revealed that a protein band at the 55 kDa position showed slower migration in the resistant samples. This band was identified as tubulin by immunoblotting, with both alpha- and beta-tubulin showing retarded migration in the resistant strain. Investigations into the reason for the observed slower migration revealed that phosphorylation of tubulin on both serine and tyrosine residues was enhanced in the resistant strain when compared to the wild type strain.

Tubulin expression is known to alter due to drug resistance. Differentiation of Leishmania promastigotes into infectious amastigotes has been reported to be accompanied by differential tubulin gene expression. In this study, alpha-tubulin expression under various stages of differentiation was measured in an in vitro generated arsenite-resistant L. donovani strain. While levels of expression of alpha-tubulin were similar in wild type and resistant promastigotes, during conversion into axenic amastigotes the changes in the expression levels of alpha-tubulin varied widely between the two strains. Sensitivity of the two strains to paclitaxel (known to promote tubulin assembly) differed, with the resistant strain being two-fold more sensitive than the wild type strain. Paclitaxel was also seen to cause differential effects on alpha-tubulin levels in the two strains.