Cholestenoic acids regulate motor neuron survival via liver X receptors

PubMed Central

Theofilopoulos, Spyridon; Griffiths, William J.; Crick, Peter J.; Yang, Shanzheng; Meljon, Anna; Ogundare, Michael; Kitambi, Satish Srinivas; Lockhart, Andrew; Tuschl, Karin; Clayton, Peter T.; Morris, Andrew A.; Martinez, Adelaida; Reddy, M. Ashwin; Martinuzzi, Andrea; Bassi, Maria T.; Honda, Akira; Mizuochi, Tatsuki; Kimura, Akihiko; Nittono, Hiroshi; De Michele, Giuseppe; Carbone, Rosa; Criscuolo, Chiara; Yau, Joyce L.; Seckl, Jonathan R.; Schüle, Rebecca; Schöls, Ludger; Sailer, Andreas W.; Kuhle, Jens; Fraidakis, Matthew J.; Gustafsson, Jan-Åke; Steffensen, Knut R.; Björkhem, Ingemar; Ernfors, Patrik; Sjövall, Jan; Arenas, Ernest; Wang, Yuqin

2014-01-01

Cholestenoic acids are formed as intermediates in metabolism of cholesterol to bile acids, and the biosynthetic enzymes that generate cholestenoic acids are expressed in the mammalian CNS. Here, we evaluated the cholestenoic acid profile of mammalian cerebrospinal fluid (CSF) and determined that specific cholestenoic acids activate the liver X receptors (LXRs), enhance islet-1 expression in zebrafish, and increase the number of oculomotor neurons in the developing mouse in vitro and in vivo. While 3β,7α-dihydroxycholest-5-en-26-oic acid (3β,7α-diHCA) promoted motor neuron survival in an LXR-dependent manner, 3β-hydroxy-7-oxocholest-5-en-26-oic acid (3βH,7O-CA) promoted maturation of precursors into islet-1+ cells. Unlike 3β,7α-diHCA and 3βH,7O-CA, 3β-hydroxycholest-5-en-26-oic acid (3β-HCA) caused motor neuron cell loss in mice. Mutations in CYP7B1 or CYP27A1, which encode enzymes involved in cholestenoic acid metabolism, result in different neurological diseases, hereditary spastic paresis type 5 (SPG5) and cerebrotendinous xanthomatosis (CTX), respectively. SPG5 is characterized by spastic paresis, and similar symptoms may occur in CTX. Analysis of CSF and plasma from patients with SPG5 revealed an excess of the toxic LXR ligand, 3β-HCA, while patients with CTX and SPG5 exhibited low levels of the survival-promoting LXR ligand 3β,7α-diHCA. Moreover, 3β,7α-diHCA prevented the loss of motor neurons induced by 3β-HCA in the developing mouse midbrain in vivo.Our results indicate that specific cholestenoic acids selectively work on motor neurons, via LXR, to regulate the balance between survival and death. PMID:25271621

Free fatty acid (FFA) and hydroxy carboxylic acid (HCA) receptors.

PubMed

Offermanns, Stefan

2014-01-01

Saturated and unsaturated free fatty acids (FFAs), as well as hydroxy carboxylic acids (HCAs) such as lactate and ketone bodies, are carriers of metabolic energy, precursors of biological mediators, and components of biological structures. However, they are also able to exert cellular effects through G protein-coupled receptors named FFA1-FFA4 and HCA1-HCA3. Work during the past decade has shown that these receptors are widely expressed in the human body and regulate the metabolic, endocrine, immune and other systems to maintain homeostasis under changing dietary conditions. The development of genetic mouse models and the generation of synthetic ligands of individual FFA and HCA receptors have been instrumental in identifying cellular and biological functions of these receptors. These studies have produced strong evidence that several FFA and HCA receptors can be targets for the prevention and treatment of various diseases, including type 2 diabetes mellitus, obesity, and inflammation.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review.

PubMed

Guo, Yongfei; Li, Wenjuan; Cai, Wenli; Zhang, Yi; Fang, Yijie; Hong, Guobin

2017-01-01

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously.

Diagnostic Value of Gadoxetic Acid-Enhanced MR Imaging to Distinguish HCA and Its Subtype from FNH: A Systematic Review

PubMed Central

Guo, Yongfei; Li, Wenjuan; Cai, Wenli; Zhang, Yi; Fang, Yijie; Hong, Guobin

2017-01-01

Objective: The purpose of this study was to systematically review the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) for differentiation of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH), as well as HCA classification by using the low signal intensity (SI) in the hepatobiliary phase (HBP). Methods: A systematic process was used to review all published data in MEDLINE database about Gd-EOB-DTPA-MRI applied to differentiation of HCA and FNH, and classification of HCA by using low SI in the HBP. The pooled sensitivity and specificity were calculated to assess the diagnostic value of low SI in the HBP. Results: A review of 45 articles identified 10 eligible studies with a total of 288 HCA lesions. The pooled proportion of low SI in the HBP of HCA were 91% (95% CI: 0.81-0.97). In specific, the subtypes of HCA were 75% (95% CI: 0.64-0.85) for I-HCA, 100% (95% CI: 0.95-1.00) for H-HCA, 92% (95% CI: 0.70-1.00) for U-HCA, and 59% (95% CI: 0.00-1.00) for b-HCA, respectively. The pooled specificity and sensitivity of low SI in the HBP for distinguishing FNH from HCA were 95% (95% CI: 0.92-0.98) and 92% (95% CI: 0.87-0.96), respectively. Conclusion: Low SI in the HBP of Gd-EOB-DTPA-MRI is associated with higher accuracy for distinguishing HCA from FNH. However, the diagnostic accuracy may be overvalued, especially for the diagnosis of subtypes of b-HCA and I-HCA. Therefore, the risk factors and conventional imaging findings should be take into account simultaneously. PMID:28824299

Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

PubMed

Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

2017-04-01

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation.

PubMed

Offermanns, Stefan; Schwaninger, Markus

2015-04-01

Neuroinflammation is a pathology common to many neurological diseases, including multiple sclerosis (MS) and stroke. However, therapeutic attempts to modulate neuroinflammation have proved difficult. Neuroinflammatory cells express HCA2, a receptor for the endogenous neuroprotective ketone body β-hydroxybutyrate (BHB) as well as for the drugs dimethyl fumarate (DMF) and nicotinic acid, which have established efficacy in the treatment of MS and experimental stroke, respectively. This review summarizes the evidence that HCA2 is involved in the therapeutic effects of DMF, nicotinic acid, and ketone bodies in reducing neuroinflammation. Furthermore, we discuss the mechanisms underlying the beneficial effects of HCA2 activation in neuroinflammatory diseases and the therapeutic potential of recently developed synthetic ligands of HCA2. Copyright © 2015 Elsevier Ltd. All rights reserved.

The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases.

PubMed

Yamaguchi, Masayoshi

2016-10-01

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder.

Isolation and identification of an allelopathic substance from Hibiscus sabdariffa.

PubMed

Suwitchayanon, Prapaipit; Pukclai, Piyatida; Ohno, Osamu; Suenaga, Kiyotake; Kato-Noguchi, Hisashi

2015-05-01

In this study, an allelopathic substance was isolated from an aqueous methanol extract of Hibiscus sabdariffa L. by column chromatography and reverse phase HPLC. The chemical structure of the substance was determined by 1H NMR spectroscopy and mass spectrometry as trimethyl allo-hydroxycitrate. Trimethyl allo-hydroxycitrate inhibited the growth of cress hypocotyls and roots at concentrations greater than 10 mM. The concentrations required for 50% growth inhibition of the hypocotyls and roots of cress were 20.3 and 14.4 mM, respectively. The inhibitory activity of trimethyl allo-hydroxycitrate suggests that the substance may act as an allelopathic substance of H. sabdariffa.

Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

PubMed

Schwartz, Laurent; Guais, Adeline; Israël, Maurice; Junod, Bernard; Steyaert, Jean-Marc; Crespi, Elisabetta; Baronzio, Gianfranco; Abolhassani, Mohammad

2013-04-01

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

Hydroxycinnamic acid degradation, a broadly conserved trait, protects Ralstonia solanacearum from chemical plant defenses and contributes to root colonization and virulence

PubMed Central

Lowe, Tiffany M.; Ailloud, Florent; Allen, Caitilyn

2014-01-01

Plants produce hydroxycinnamic acid defense compounds (HCAs) to combat pathogens, such as the bacterium Ralstonia solanacearum. We showed that an HCA degradation pathway is genetically and functionally conserved across diverse R. solanacearum strains. Further, a Δfcs (feruloyl-CoA synthetase) mutant that cannot degrade HCAs was less virulent on tomato plants. To understand the role of HCA degradation in bacterial wilt disease, we tested the following hypotheses: HCA degradation helps the pathogen (1) grow, as a carbon source; (2) spread, by reducing physical barriers HCA-derived; and (3) survive plant antimicrobial compounds. Although HCA degradation enabled R. solanacearum growth on HCAs in vitro, HCA degradation was dispensable for growth in xylem sap and root exudate, suggesting that HCAs are not significant carbon sources in planta. Acetyl-bromide quantification of lignin demonstrated that R. solanacearum infections did not affect the gross quantity or distribution of stem lignin. However, the Δfcs mutant was significantly more susceptible to inhibition by two HCAs: caffeate and p-coumarate. Finally, plant colonization assays suggested that HCA degradation facilitates early stages of infection and root colonization. Together, these results indicated that ability to degrade HCAs contributes to bacterial wilt virulence by facilitating root entry and by protecting the pathogen from HCA toxicity. PMID:25423265

Photo-enhanced performance and photo-tunable degradation in LC ecopolymers

NASA Astrophysics Data System (ADS)

Kaneko, Tatsuo

2007-05-01

Photosensitive, liquid crystalline (LC) polymers were prepared by in-bulk polymerization of phytomonomers such as cinnamic acid derivatives. The p-coumaric acid (4HCA) homopolymer showed a thermotropic LC phase where a photoreaction of [2+2] cycloaddition occurred by ultraviolet irradiation. LC phase was exhibited only in a low molecular weight state but the polymer was too brittle to materialize. Then we copolymerized 4HCA with multifunctional cinnamate, 3,4 dihydroxycinnamic acid (caffeic acid; DHCA), to prepare the hyperbranching architecture. Many branches increased the apparent size of the polymer chain but kept the low number-average molecular weight. P(4HCA-co-DHCA)s showed high performances which may be attained through the entanglement by in-bulk formation of hyperbranching, rigid structures. P(4HCA-co-DHCA)s showed a smooth hydrolysis, an in-soil degradation and a photoreaction cross-linking from conjugated cinnamate esters to aliphatic esters. The change in photoconversion degree tuned the polymer performance and chain hydrolysis.

The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

PubMed

Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

2016-08-23

Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boone, Christopher D.; Tu, Chingkuang; McKenna, Robert, E-mail: rmckenna@ufl.edu

The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes tomore » mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.« less

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators.

PubMed

Akocak, Suleyman; Lolak, Nabih; Vullo, Daniela; Durgun, Mustafa; Supuran, Claudiu T

2017-12-01

A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure-activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms.

Cinnamic Acid, an Autoinducer of Its Own Biosynthesis, Is Processed via Hca Enzymes in Photorhabdus luminescens▿

PubMed Central

Chalabaev, Sabina; Turlin, Evelyne; Bay, Sylvie; Ganneau, Christelle; Brito-Fravallo, Emma; Charles, Jean-François; Danchin, Antoine; Biville, Francis

2008-01-01

Photorhabdus luminescens, an entomopathogenic bacterium and nematode symbiont, has homologues of the Hca and Mhp enzymes. In Escherichia coli, these enzymes catalyze the degradation of the aromatic compounds 3-phenylpropionate (3PP) and cinnamic acid (CA) and allow the use of 3PP as sole carbon source. P. luminescens is not able to use 3PP and CA as sole carbon sources but can degrade them. Hca dioxygenase is involved in this degradation pathway. P. luminescens synthesizes CA from phenylalanine via a phenylalanine ammonia-lyase (PAL) and degrades it via the not-yet-characterized biosynthetic pathway of 3,5-dihydroxy-4-isopropylstilbene (ST) antibiotic. CA induces its own synthesis by enhancing the expression of the stlA gene that codes for PAL. P. luminescens bacteria release endogenous CA into the medium at the end of exponential growth and then consume it. Hca dioxygenase is involved in the consumption of endogenous CA but is not required for ST production. This suggests that CA is consumed via at least two separate pathways in P. luminescens: the biosynthesis of ST and a pathway involving the Hca and Mhp enzymes. PMID:18245247

Mussel-mimetic, bioadhesive polymers from plant-derived materials.

PubMed

Hiraishi, Noriko; Kaneko, Daisaku; Taira, Shu; Wang, Siqian; Otsuki, Masayuki; Tagami, Junji

2015-02-01

Mussel-mimetic, bioadhesive polymers are synthesized from plant-derived sources. The strong adhesive action is caused by interactions between the catechol groups at the end of the polymer terminal chains and the substrate surface. Here, we present a preliminary study of the adhesion properties and a discussion of the adhesion mechanism. Two bioadhesive polymers were synthesized from natural plant-derived monomers by the transesterification of: (a) caffeic acid (3,4-dihydroxycinnamic acid; DHCA) and p-coumaric acid (4-hydroxycinnamic acid; 4HCA) to produce poly(DHCA-co-4HCA); and (b) 4-dihydroxyhydrocinnamic acid (DHHCA) and 3-(3-hydroxyphenyl) propionic acid (3HPPA) to produce poly(DHHCA-co-3HPPA). Thermoplastic poly(DHCA-co-4HCA) or poly(DHHCA-co-3HPPA) was placed between glass, carbon, steel, or bovine dentin substrates, and a lap shear adhesion test was conducted to compare them using conventional cyanoacrylate glue and epoxy resin. The greatest adhesion for all tested substrates was exhibited by poly(DHHCA-co-3HPPA), followed by epoxy resin adhesive, poly(DHCA-co-4HCA), and cyanoacrylate adhesive. The adhesive strength of poly(DHHCA-co-3HPPA) was greater than 25.6 MPa for glass, 29.6 MPa for carbon, 15.7 MPa for steel, and 16.3 MPA for bovine dentin. The adhesion of poly(DHHCA-co-3HPPA) might be the strongest reported for a mussel-mimic adhesive system, and could be a feasible alternative to petroleum adhesives. © 2013 Wiley Publishing Asia Pty Ltd.

Aurintricarboxylic acid is a potent inhibitor of phosphofructokinase.

PubMed Central

McCune, S A; Foe, L G; Kemp, R G; Jurin, R R

1989-01-01

Aurintricarboxylic acid (ATA) was found to be a very potent inhibitor of purified rabbit liver phosphofructokinase (PFK), giving 50% inhibition at 0.2 microM. The inhibition was in a manner consistent with interaction at the citrate-inhibitory site of the enzyme. The data suggest that inhibition of PFK by ATA was not due to denaturation of the enzyme or the irreversible binding of inhibitor, since the inhibition could be reversed by addition of allosteric activators of PFK, i.e. fructose 2,6-bisphosphate or AMP. Two other tricarboxylic acids, agaric acid and (-)-hydroxycitrate, were found to inhibit PFK. ATA at much higher concentrations (500 microM) was shown to inhibit fatty acid synthesis from endogenous glycogen in rat hepatocytes; however, protein synthesis was not altered. PMID:2525029

Bioaccessibility of hydroxycinnamic acids and antioxidant capacity from sorghum bran thermally processed during simulated in vitro gastrointestinal digestion.

PubMed

Salazar-López, Norma Julieta; González-Aguilar, Gustavo A; Rouzaud-Sández, Ofelia; Robles-Sánchez, Maribel

2018-06-01

Sorghum is a source of hydroxycinnamic acids (HCA), which have shown antioxidant, anti-inflammatory and anti-proliferative capacities. However, a high proportion of them have low bioaccessibility due the complex structural disposition of the plant's cell wall. The effects of boiling and extrusion processes on sorghum bran and their effects on the antioxidant capacity and bioaccessibility of HCA during simulated in vitro gastrointestinal digestion were investigated. The bioaccessibility of phenolic compounds was significantly higher in extruded sorghum bran (38.4%) than that obtained by boiling (29.5%). This is consistent with the increase of the antioxidant capacity after in vitro digestion. In contrast, a low bioaccessibility of pure monomeric HCA was observed when they were exposed to in vitro gastrointestinal digestion. There were significant bioaccessibility reductions of 36.8, 19.5, 13.5, 62.1% for caffeic, ρ-coumaric, ferulic and sinapic acids, respectively, when unproccessed sorghum bran was added. Although the bioaccessibility of monomeric HCA was low, the total phenolic compounds and antioxidant capacity increased during the digestion simulation due to the thermal processes of extrusion and boiling. Extrusion and boiling could be utilized to produce food based on sorghum bran with biological potential.

Molecular modifiers reveal a mechanism of pathological crystal growth inhibition

NASA Astrophysics Data System (ADS)

Chung, Jihae; Granja, Ignacio; Taylor, Michael G.; Mpourmpakis, Giannis; Asplin, John R.; Rimer, Jeffrey D.

2016-08-01

Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization—citrate and hydroxycitrate—exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.

Hydrophobic cluster analysis of G protein-coupled receptors: a powerful tool to derive structural and functional information from 2D-representation of protein sequences.

PubMed

Lentes, K U; Mathieu, E; Bischoff, R; Rasmussen, U B; Pavirani, A

1993-01-01

Current methods for comparative analyses of protein sequences are 1D-alignments of amino acid sequences based on the maximization of amino acid identity (homology) and the prediction of secondary structure elements. This method has a major drawback once the amino acid identity drops below 20-25%, since maximization of a homology score does not take into account any structural information. A new technique called Hydrophobic Cluster Analysis (HCA) has been developed by Lemesle-Varloot et al. (Biochimie 72, 555-574), 1990). This consists of comparing several sequences simultaneously and combining homology detection with secondary structure analysis. HCA is primarily based on the detection and comparison of structural segments constituting the hydrophobic core of globular protein domains, with or without transmembrane domains. We have applied HCA to the analysis of different families of G-protein coupled receptors, such as catecholamine receptors as well as peptide hormone receptors. Utilizing HCA the thrombin receptor, a new and as yet unique member of the family of G-protein coupled receptors, can be clearly classified as being closely related to the family of neuropeptide receptors rather than to the catecholamine receptors for which the shape of the hydrophobic clusters and the length of their third cytoplasmic loop are very different. Furthermore, the potential of HCA to predict relationships between new putative and already characterized members of this family of receptors will be presented.

Synthesis of layered perovskite oxides, ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs), and characterization of new solid acids, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (O < x [le] 2), exhibiting variable Bronsted acidity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gopalakrishnan, J.; Uma, S.; Bhat, V.

1993-01-01

Layered perovskite oxides of the formula ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs and 0 , x [le] 2) have been prepared. The members adopt the structures of the parent ACa[sub 2]Nb[sub 3]O[sub 10]. Interlayer alkali cations in the niobium-titanium oxide series can be ion-exchanged with Li[sup +], Na[sup +], NG[sub 4][sup +], of H[sup +] to give new derivatives. Intercalation of the protonated derivatives with organic bases reveals that the Bronsted acidity of the solid solution series, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10], depends on the titanium content. While the x = 1 member (HCaLaNb[submore » 2]TiO[sub 10]) is nearly as acidic as the parent HCa[sub 2]Nb[sub 3]O[sub 10], the x = 2 member (HLA[sub 2]NbTi[sub 2]O[sub 10]) is a weak acid hardly intercalating organic bases with pK[sub a] [approximately] 11.3. The variation of acidity is probably due to an ordering of Nb/Ti atoms in the triple octahedral perovskite slabs, [Ca[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10

Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

PubMed

Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

2017-11-09

γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

Effect of different types of sugars in a marinating formulation on the formation of heterocyclic amines in grilled chicken.

PubMed

Hasnol, N D S; Jinap, S; Sanny, M

2014-02-15

The aim of the study was to determine the effect of different types of sugar on the formation of heterocyclic amines (HCA) in marinated grilled chicken. Chicken breast samples were marinated with table sugar, brown sugar, and honey for 24h at 4 °C. The internal temperature, weight loss, free amino acids, sugars, and HCA were determined. The concentrations of all types of HCA (except IQx) in samples that were marinated with table sugar were significantly higher (p<0.006) than brown sugar; whereas those were marinated with honey had the lowest HCA concentrations. A substantial reduction in the concentration of MeIQ, PhIP, DiMeIQx, IQ, IQx, and norharman was achieved in chicken marinated with honey. A correlation study indicated that adding honey into the recipe retarded the formation of most HCA (MeIQ, DiMeIQx, IQ, IQx, norharman, and harman), whereas table sugars enhanced the formation of all HCA except norharman, harman, and AαC. Copyright © 2013 Elsevier Ltd. All rights reserved.

The lathyrus toxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, L.A.; Peterson, N.L.; Koerner, J.F.

2007-02-15

A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the endogenous compound, L-cystine. This phenomenon has been termed QUIS sensitization. A mechanism similar to that previously described for QUIS neurotoxicity has been proposed to describe QUIS sensitization. Specifically, QUIS has been shown to be sequestered into GABAergic interneurons by the System x{sub c} {sup -} and subsequently released by heteroexchange with cystine or L-AP6, resulting in activation of non-NMDA receptors. We now report two additional neurotoxins, the Lathyrusmore » excitotoxin, {beta}-N-oxalyl-L-{alpha},{beta}-diaminopropionic acid (ODAP), and the endogenous compound, L-homocysteic acid (HCA), sensitize CA1 hippocampal neurons > 50-fold to L-AP6 and > 10-fold to cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP- or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA agonist that induces phosphonate or cystine sensitization. Like QUIS sensitization, the sensitization evoked by either ODAP or HCA can be reversed by a subsequent exposure to 2 mM {alpha}-aminoadipic acid. Finally, we have demonstrated that there is a correlation between the potency of inducers for triggering phosphonate or cystine sensitivity and their affinities for System x{sub c} {sup -} and either the non-NMDA or NMDA receptor. Thus, the results of this study support our previous model of QUIS sensitization and have important implications for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.« less

Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors.

PubMed

Vats, Lalit; Sharma, Vikas; Angeli, Andrea; Kumar, Rajiv; Supuran, Claudiu T; Sharma, Pawan K

2018-04-25

The design, synthesis and biological evaluation of a library of 1,2,3-triazole carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the novel compounds were investigated for their inhibition potential against carbonic anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well established drug targets. The cytosolic isoform hCA I was inhibited with K i 's ranging between 53.2 nM and 7.616 μM whereas the glaucoma associated cytosolic isoform hCA II was inhibited with K i 's in the range 21.8 nM-0.807 μM. The membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa among others, was effectively inhibited by some of these compounds with K i  < 60 nM, better than the reference drug acetazolamide (AAZ). The tumor associated isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was also effectively inhibited by some of the new sulfonamides, which possess thus the potential to be used as tools for exploring in more details the selective inhibition of hCAs involved in various pathologies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Rational Design of Antifouling Polymeric Nanocomposite for Sustainable Fluoride Removal from NOM-Rich Water.

PubMed

Zhang, Xiaolin; Zhang, Lu; Li, Zhixian; Jiang, Zhao; Zheng, Qi; Lin, Bin; Pan, Bingcai

2017-11-21

The presence of natural organic matter (NOM) exerts adverse effects on adsorptive removal of various pollutants including fluoride from water. Herein, we designed a novel nanocomposite adsorbent for preferable and sustainable defluoridation from NOM-rich water. The nanocomposite (HZO@HCA) is obtained by encapsulating hydrous zirconium oxide nanoparticles (HZO NPs) inside hyper-cross-linked polystyrene anion exchanger (HCA) binding tertiary amine groups. Another commercially available nanocomposite HZO@D201, with the host of a cross-linked polystyrene anion exchanger (D201) binding ammonium groups, was involved for comparison. HZO@HCA features with abundant micropores instead of meso-/macropores of HZO@D201, resulting in the inaccessible sites for NOM due to the size exclusion. Also, the tertiary amine groups of HCA favor an efficient desorption of the slightly loaded NOM from HZO@HCA. As expected, Sigma-Aldrich humic acid even at 20 mg of DOC/L did not exert any observable effect on fluoride sequestration by HZO@HCA, whereas a significant inhibition was observed for HZO@D201. Cyclic adsorption runs further verified the superior reusability of HZO@HCA for defluoridation from NOM-rich water. In addition, the HZO@HCA column could generate ∼80 bed volume (BV) effluent from a synthetic fluoride-containing groundwater to meet the drinking water standard (<1.5 mg F/L), whereas HCA and HZO@D201 columns could only generate <5 and ∼40 BV effluents, respectively. This study is believed to shed new light on how to rationally design antifouling nanocomposites for water remediation.

Carbonic anhydrase inhibitors. Inhibition of human cytosolic isoforms I and II with (reduced) Schiff's bases incorporating sulfonamide, carboxylate and carboxymethyl moieties.

PubMed

Nasr, Gihane; Cristian, Alina; Barboiu, Mihail; Vullo, Daniella; Winum, Jean-Yves; Supuran, Claudiu T

2014-05-15

A library of Schiff bases was synthesized by condensation of aromatic amines incorporating sulfonamide, carboxylic acid or carboxymethyl functionalities as Zn(2+)-binding groups, with aromatic aldehydes incorporating tert-butyl, hydroxy and/or methoxy groups. The corresponding amines were thereafter obtained by reduction of the imines. These compounds were assayed for the inhibition of two cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes, hCA I and II. The Ki values of the Schiff bases were in the range of 7.0-21,400nM against hCA II and of 52-8600nM against hCA I, respectively. The corresponding amines showed Ki values in the range of 8.6nM-5.3μM against hCA II, and of 18.7-251nM against hCA I, respectively. Unlike the imines, the reduced Schiff bases are stable to hydrolysis and several low-nanomolar inhibitors were detected, most of them incorporating sulfonamide groups. Some carboxylates also showed interesting CA inhibitory properties. Such hydrosoluble derivatives may show pharmacologic applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

4-Functionalized 1,3-diarylpyrazoles bearing 6-aminosulfonylbenzothiazole moiety as potent inhibitors of carbonic anhydrase isoforms hCA I, II, IX and XII.

PubMed

SitaRam; Ceruso, Mariangela; Khloya, Poonam; Supuran, Claudiu T; Sharma, Pawan K

2014-12-15

A series of 24 novel heterocyclic compounds-functionalized at position 4 with aldehyde (5a-5f), carboxylic acid (6a-6f), nitrile (7a-7f) and oxime (8a-8f) functional groups-bearing 6-aminosulfonybenzothiazole moiety at position 1 of pyrazole has been synthesized and investigated for the inhibition of four isoforms of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozyme hCA I, compounds 6a-6f showed medium-weak inhibitory potential with Ki values in the range of 157-690nM with 6a showing better potential than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed excellent to moderate inhibition with Ki values of compounds 5a, 5d, 5f, 6a-6f, 8d and 8f lower than 12nM (Ki of AZA). Against hCA IX, all the compounds showed moderate inhibition with the exception of 6e which showed nearly 9 fold a better profile compared to AZA, whereas against hCA XII, four compounds 6e, 7a, 7b and 7d showed Ki in the same order as that of AZA. Carboxylic acid 6e was found to be an excellent inhibitor of both hCA IX and XII, with Ki values of 2.8nM and 5.5nM, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coordinated Regulation of Species-Specific Hydroxycinnamic Acid Degradation and Siderophore Biosynthesis Pathways in Agrobacterium fabrum

PubMed Central

Baude, Jessica; Vial, Ludovic; Villard, Camille; Campillo, Tony; Lavire, Céline; Nesme, Xavier

2016-01-01

ABSTRACT The rhizosphere-inhabiting species Agrobacterium fabrum (genomospecies G8 of the Agrobacterium tumefaciens species complex) is known to degrade hydroxycinnamic acids (HCAs), especially ferulic acid and p-coumaric acid, via the novel A. fabrum HCA degradation pathway. Gene expression profiles of A. fabrum strain C58 were investigated in the presence of HCAs, using a C58 whole-genome oligoarray. Both ferulic acid and p-coumaric acid caused variations in the expression of more than 10% of the C58 genes. Genes of the A. fabrum HCA degradation pathway, together with the genes involved in iron acquisition, were among the most highly induced in the presence of HCAs. Two operons coding for the biosynthesis of a particular siderophore, as well as genes of the A. fabrum HCA degradation pathway, have been described as being specific to the species. We demonstrate here their coordinated expression, emphasizing the interdependence between the iron concentration in the growth medium and the rate at which ferulic acid is degraded by cells. The coordinated expression of these functions may be advantageous in HCA-rich but iron-starved environments in which microorganisms have to compete for both iron and carbon sources, such as in plant roots. The present results confirm that there is cooperation between the A. fabrum-specific genes, defining a particular ecological niche. IMPORTANCE We previously identified seven genomic regions in Agrobacterium fabrum that were specifically present in all of the members of this species only. Here we demonstrated that two of these regions, encoding the hydroxycinnamic acid degradation pathway and the iron acquisition pathway, were regulated in a coordinated manner. The coexpression of these functions may be advantageous in hydroxycinnamic acid-rich but iron-starved environments in which microorganisms have to compete for both iron and carbon sources, such as in plant roots. These data support the view that bacterial genomic species emerged from a bacterial population by acquiring specific functions that allowed them to outcompete their closest relatives. In conclusion, bacterial species could be defined not only as genomic species but also as ecological species. PMID:27060117

Study on the main components interaction from Flos Lonicerae and Fructus Forsythiae and their dissolution in vitro and intestinal absorption in rats.

PubMed

Zhou, Wei; Tan, Xiaobin; Shan, Jinjun; Wang, Shouchuan; Yin, Ailing; Cai, Baochang; Di, Liuqing

2014-01-01

The Flos Lonicerae-Fructus Forsythiae herb couple is the basic components of Chinese herbal preparations (Shuang-Huang-Lian tablet, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), and its pharmacological effects were significantly higher than that in Flos Lonicerae or Fructus Forsythiae, but the reasons remained unknown. In the present study, pattern recognition analysis (hierarchical cluster analysis (HCA) and principal component analysis (PCA)) combined with UHPLC-ESI/LTQ-Orbitrap MS system were performed to study the chemical constitution difference between co-decoction and mixed decoction in the term of chemistry. Besides, the pharmacokinetics in vivo and intestinal absorption in vitro combined with pattern recognition analysis were used to reveal the discrepancy between herb couple and single herbs in the view of biology. The observation from the chemical view in vitro showed that there was significant difference in quantity between co-decoction and mixed decoction by HCA, and the exposure level of isoforsythoside and 3, 5-dicaffeoylquinic acid in co-decoction, higher than that in mixed decoction, directly resulted in the discrepancy between co-decoction and mixed decoction using both PCA and HCA. The observation from the pharmacokinetics displayed that the exposure level in vivo of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A, higher than that in single herbs, was the main factor contributing to the difference by both PCA and HCA, interestingly consistent with the results obtained from Caco-2 cells in vitro, which indicated that it was because of intestinal absorption improvement of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A that resulted in a better efficacy of herb couple than that of single herbs from the perspective of biology. The results above illustrated that caffeic acid derivatives in Flos Lonicerae-Fructus Forsythiae herb couple could be considered as chemical markers for quality control of its preparations.

Study on the Main Components Interaction from Flos Lonicerae and Fructus Forsythiae and Their Dissolution In Vitro and Intestinal Absorption in Rats

PubMed Central

Zhou, Wei; Tan, Xiaobin; Shan, Jinjun; Wang, Shouchuan; Yin, Ailing; Cai, Baochang; Di, Liuqing

2014-01-01

The Flos Lonicerae-Fructus Forsythiae herb couple is the basic components of Chinese herbal preparations (Shuang-Huang-Lian tablet, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), and its pharmacological effects were significantly higher than that in Flos Lonicerae or Fructus Forsythiae, but the reasons remained unknown. In the present study, pattern recognition analysis (hierarchical cluster analysis (HCA) and principal component analysis (PCA)) combined with UHPLC-ESI/LTQ-Orbitrap MS system were performed to study the chemical constitution difference between co-decoction and mixed decoction in the term of chemistry. Besides, the pharmacokinetics in vivo and intestinal absorption in vitro combined with pattern recognition analysis were used to reveal the discrepancy between herb couple and single herbs in the view of biology. The observation from the chemical view in vitro showed that there was significant difference in quantity between co-decoction and mixed decoction by HCA, and the exposure level of isoforsythoside and 3, 5-dicaffeoylquinic acid in co-decoction, higher than that in mixed decoction, directly resulted in the discrepancy between co-decoction and mixed decoction using both PCA and HCA. The observation from the pharmacokinetics displayed that the exposure level in vivo of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A, higher than that in single herbs, was the main factor contributing to the difference by both PCA and HCA, interestingly consistent with the results obtained from Caco-2 cells in vitro, which indicated that it was because of intestinal absorption improvement of neochlorogenic acid, 3, 4-dicaffeoylquinic acid, isoforsythoside and forsythoside A that resulted in a better efficacy of herb couple than that of single herbs from the perspective of biology. The results above illustrated that caffeic acid derivatives in Flos Lonicerae-Fructus Forsythiae herb couple could be considered as chemical markers for quality control of its preparations. PMID:25275510

Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study

PubMed Central

2013-01-01

Introduction Hypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC). Methods In anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae. Results HCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic solution decreased the contraction force, whereas APD was not influenced. Conclusions MAC preferentially affects the pulmonary circulation, whereas HCA affects the pulmonary, systemic, and regional circulations. The cardiac contractile function was reduced, but the cardiac output was maintained (MAC), or even increased (HCA). The increased ventricular stroke work per minute revealed an increased work demand placed by acidosis on the heart. PMID:24377654

Hibiscus sabdariffa L. - a phytochemical and pharmacological review.

PubMed

Da-Costa-Rocha, Inês; Bonnlaender, Bernd; Sievers, Hartwig; Pischel, Ivo; Heinrich, Michael

2014-12-15

Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects. More well designed controlled clinical trials are needed which use phytochemically characterised preparations. Hs has an excellent safety and tolerability record. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

New 5-O-caffeoylquinic acid derivatives in fruit of the wild eggplant relative Solanum viarum

USDA-ARS?s Scientific Manuscript database

Fruit of cultivated eggplant (Solanum melongena) and several wild relatives (S. aethiopicum, S. macrocarpon, S. anguivi, and S. incanum) have a high content of hydroxycinnamic acid (HCA) conjugates. Typically, caffeoylquinic acid esters predominate, and in particular chlorogenic acid [5-O-(E)-caffeo...

Intercalation of the layered solid acid HCa/sub 2/Nb/sub 3/O/sub 10/ by organic amines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobson, A.J.; Johnson, J.W.; Lewandowski, J.T.

1987-01-01

Layered compounds of formula C/sub n/H/sub 2n+1/NH/sub 3/Ca/sub 2/Nb/sub 3/O/sub 10/ are formed by reaction of n-alkylamines with the solid acid HCa/sub 2/Nb/sub 3/O/sub 10/. Other organic bases such as pyridine can also be intercalated. The lattice constants of the new compounds have been determined by powder X-ray diffraction. The unit cells are tetragonal with a axes that are unchanged with variation of the intercalated amine. The c axes lengths (layer spacings) vary systematically with the hydrocarbon chain length of the alkylamine.

Memantine Protects Rats Treated with Intrathecal Methotrexate from Developing Spatial Memory Deficits

PubMed Central

Cole, Peter D.; Vijayanathan, Veena; Ali, Nafeeza F.; Wagshul, Mark E.; Tanenbaum, Eric J.; Price, Jeremy; Dalal, Vidhi; Gulinello, Maria E.

2014-01-01

Purpose To test whether memantine can prevent methotrexate-induced cognitive deficits in a preclinical model. Experimental Design After noting that methotrexate exposure induces prolonged elevations of the glutamate analog homocysteic acid (HCA) within cerebrospinal fluid, we tested whether intrathecal injection of HCA would produce memory deficits similar to those observed after intrathecal methotrexate. We then tested whether memantine, an antagonist of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors, could protect animals treated with clinically relevant doses of intrathecal methotrexate against developing memory deficits. Finally, we asked whether memantine affected this pathway beyond inhibiting the NMDA receptor by altering expression of the NMDA receptor or affecting concentrations of HCA or glutamate within the central nervous system. Results Four intrathecal doses of methotrexate induced deficits in spatial memory, persisting at least one month following the final injection. Intrathecal HCA was sufficient to reproduce this deficit. Concurrent administration of memantine during the period of methotrexate exposure was protective, decreasing the incidence of methotrexate-induced spatial memory deficits from 56% to 20% (P < 0.05). Memantine neither altered expression of NMDA receptors within the hippocampus nor blunted the methotrexate-induced increases in glutamate or HCA. Conclusions Excitotoxic glutamate analogs including HCA contribute to cognitive deficits observed after intrathecal methotrexate. Memantine, an NMDA receptor antagonist, reduces the incidence of cognitive deficits in rats treated with intrathecal methotrexate, and may therefore benefit patients with cancer receiving similar treatment. PMID:23833301

Imaging of lipids in atherosclerotic lesion in aorta from ApoE/LDLR-/- mice by FT-IR spectroscopy and Hierarchical Cluster Analysis.

PubMed

P Wrobel, Tomasz; Mateuszuk, Lukasz; Chlopicki, Stefan; Malek, Kamilla; Baranska, Malgorzata

2011-12-21

Spectroscopy-based approaches can provide an insight into the biochemical composition of a tissue sample. In the present work Fourier transform infrared (FT-IR) spectroscopy was used to develop a reliable methodology to study the content of free fatty acids, triglycerides, cholesteryl esters as well as cholesterol in aorta from mice with atherosclerosis (ApoE/LDLR(-/-) mice). In particular, distribution and concentration of palmitic, oleic and linoleic acid derivatives were analyzed. Spectral analysis of pure compounds allowed for clear discrimination between free fatty acids and other similar moieties based on the carbonyl band position (1699-1710 cm(-1) range). In order to distinguish cholesteryl esters from triglycerides a ratio of carbonyl band to signal at 1010 cm(-1) was used. Imaging of lipids in atherosclerotic aortic lesions in ApoE/LDLR(-/-) mice was followed by Hierarchical Cluster Analysis (HCA). The aorta from C57Bl/6J control mice (fed with chow diet) was used for comparison. The measurements were completed with an FT-IR spectrometer equipped with a 128 × 128 FPA detector. In cross-section of aorta from ApoE/LDLR(-/-) mice a region of atherosclerotic plaque was clearly identified by HCA, which was later divided into 2 sub-regions, one characterized by the higher content of cholesterol, while the other by higher contents of cholesteryl esters. HCA of tissues deposited on normal microscopic glass, hence limited to the 2200-3800 cm(-1) spectral range, also identified a region of atherosclerotic plaque. Importantly, this region correlates with the area stained by standard histological staining for atherosclerotic plaque (Oil Red O). In conclusion, the use of FT-IR and HCA may provide a novel tool for qualitative and quantitative analysis of contents and distribution of lipids in atherosclerotic plaque.

Predictors of dietary heterocyclic amine intake in three prospective cohorts.

PubMed

Byrne, C; Sinha, R; Platz, E A; Giovannucci, E; Colditz, G A; Hunter, D J; Speizer, F E; Willett, W C

1998-06-01

Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids and creatinine. Although recognized as mutagenic, the etiological role of HCA in human cancer is unclear, due to the lack of information on the effect of typical food cooking methods on HCA concentrations and on variation in HCA exposure in populations. We estimated overall daily dietary HCA intake and variation in intake between individuals, using recent data on HCA concentrations in various meats prepared by cooking methods, temperatures, and times common in United States in the 1990s. Random samples of 250 participants from each of three large prospective cohorts were mailed a questionnaire to assess frequency of consumption, cooking method, and typical outside appearance of pan-fried, broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried, microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in composite samples by solid-phase extraction and high-performance liquid chromatography, were assigned to each food, cooking method, and doneness level. The dietary reports showed approximately 30-fold relative variation in 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6-phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA intake were compared (90th/10th percentile value). These reported variations in HCA exposure among participants in these three large cohorts indicates that estimation of HCA intake and determination of association with disease risk are feasible, if additional information on meat cooking methods is obtained.

Crystal structures of the diastereomeric salt pair of the prostaglandin intermediate 1 R, 2 S(+)- cis-2-hydroxycyclopent-4-enylacetic acid with S- and R- 1-phenylethylamine

NASA Astrophysics Data System (ADS)

Czugler, Mátyás; Csöregh, Ingeborg; Kálmán, Alajos; Faigl, Ferenc; Ács, Mária

1989-05-01

Crystal structures of an enantiomeric salt pair formed between 1 R,2 S- cis-2-hydroxycyclopent-4-enylacetic acid ( S-HCA) and R(+)-1-phenylethylamine ( R-PEA) and the corresponding S-PEA salt have been determined by X-ray crystallography. The S-HCA: R-PEA 1:1 salt ( R-HCA-PEA hereafter) is orthorhombic, P2 12 12 1, with the unit-cell parameters a = 5.806(1), b = 9.261(1), c = 27.624(2) Å and R = 0.056 for 1162 reflections at ambient temperature. The S-HCA: S-PEA 1:1 salt ( S-HCAPEA) is also orthorhombic, P2 12 12 1, with the unit-cell data a = 6.034(2), b = 11.840(7), c = 20.198(11) Å at 170 K, R = 0.082 for 1196 data measured at low temperatures (170 K). The R-HCAPEA salt has its two components assembled into an elongated rod-like shape via two-dimensional hydrogen bonding between cations and anions thus forming a well-ordered crystal. In contrast, the cation and anion in the S-HCAPEA salt forms a more globular aggregate and displays orientation disorder in the five-membered ring part of the anion and maintains an essentially one-dimensional hydrogen-bond network, while the total number of hydrogen bonds between cationic and anionic species remains three in both crystals.

Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds.

PubMed

Özgeriş, Bünyamin; Göksu, Süleyman; Polat Köse, Leyla; Gülçin, İlhami; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Tümer, Ferhan; Supuran, Claudiu T

2016-05-15

In the present study a series of urea and sulfamide compounds incorporating the tetralin scaffolds were synthesized and evaluated for their acetylcholinesterase (AChE), human carbonic anhydrase (CA, EC 4.2.1.1) isoenzyme I, and II (hCA I and hCA II) inhibitory properties. The urea and their sulfamide analogs were synthesized from the reactions of 2-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride, followed by conversion to the corresponding phenols via O-demethylation with BBr3. The novel urea and sulfamide derivatives were tested for inhibition of hCA I, II and AChE enzymes. These derivatives exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values of 2.61-3.69nM against hCA I, 1.64-2.80nM against hCA II, and in the range of 0.45-1.74nM against AChE. In silico techniques such as, atomistic molecular dynamics (MD) and molecular docking simulations, were used to understand the scenario of the inhibition mechanism upon approaching of the ligands into the active site of the target enzymes. In light of the experimental and computational results, crucial amino acids playing a role in the stabilization of the enzyme-inhibitor adducts were identified. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interactions of coffee and bread crust melanoidins with hydroxycinnamic and hydroxybenzoic acids in aqueous radical environment.

PubMed

Çelik, Ecem Evrim; Rubio, Jose Manuel Amigo; Andersen, Mogens Larsen; Gökmen, Vural

2018-06-01

The interactions of coffee and bread crust melanoidins with hydroxycinnamic and hydroxybenzoic acids (HCA/HBA) containing different numbers of -OH and -OCH₃ groups localized at different positions on the aromatic ring were investigated. By doing so, mechanism of the interactions was intended to be explained with a structural approach. Experimental studies were carried out in DPPH radical medium. Chemometric methods were used for experimental design and multivariate data analysis. Area under the curve (AUC) values calculated from the plots of time versus inhibition (%) for coffee and bread crust melanoidins and HCA/HBA derivatives were ranged between 6532 ± 97-19,106 ± 85, 3997 ± 102-7565 ± 159 and - 1678 ± 81-22,486 ± 119, respectively. Synergistic interactions were revealed for both coffee and bread crust melanoidins and HCA/HBA derivatives. The significance of the concentrations of coffee and bread crust melanoidins on radical scavenging activity was clearly centered from the scores plots obtained via Principal component analysis (PCA). Phases of radical scavenging reactions were also revealed from the loadings plots. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dietary fat intake, supplements, and weight loss

NASA Technical Reports Server (NTRS)

Dyck, D. J.

2000-01-01

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

Dietary fat intake, supplements, and weight loss.

PubMed

Dyck, D J

2000-12-01

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design.

PubMed

Temperini, Claudia; Scozzafava, Andrea; Vullo, Daniela; Supuran, Claudiu T

2006-05-18

Activation of six human brain carbonic anhydrases (hCAs, EC 4.2.1.1), hCA I, II, IV, VA, VII, and XIV, with l-/d-phenylalanine was investigated kinetically and by X-ray crystallography. l-Phe was a potent activator of isozymes I, II, and XIV (K(A)s of 13-240 nM), a weaker activator of hCA VA and VII (K(A)s of 9.8-10.9 microM), and a quite inefficient hCA IV activator (K(A) of 52 microM). d-Phe showed good hCA II activatory properties (K(A) of 35 nM), being a moderate hCA VA, VII, and XIV (K(A)s of 4.6-9.7 microM) and a weak hCA I and IV activator (K(A)s of 63-86 microM). X-ray crystallography of the hCA II-l-Phe/d-Phe adducts showed the activators to be anchored at the entrance of the active site, participating in numerous bonds and hydrophobic interactions with amino acid residues His64, Thr200, Trp5, and Pro201. This is the first study showing different binding modes of stereoisomeric activators within the hCA II active site, with consequences for overall proton transfer processes (rate-determining for the catalytic cycle). It also points out differences of activation efficiency between various isozymes with structurally related activators, exploitable for designing alternative proton transfer pathways. CA activators may lead to the design of pharmacologically useful derivatives for the enhancement of synaptic efficacy, which may represent a conceptually new approach for the treatment of Alzheimer's disease, aging, and other conditions in which spatial learning and memory therapy must be enhanced. As the blood and brain concentrations of l-Phe are quite variable (30-73 microM), activity of some brain CAs may strongly be influenced by the level of activator(s) present in such tissues.

Exogenous fatty acids and niacin on acute prostaglandin D2 production in human myeloid cells.

PubMed

Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Lopez, Sergio; Naranjo, Maria C; Romero, Yolanda; Bando-Hidalgo, Maria J; Abia, Rocio; Muriana, Francisco J G

2017-01-01

Niacin activates HCA 2 receptor that results in the release of PGD 2 . However, little is known on PGD 2 -producing cells and the role of fatty acids. Notably M-CSF macrophages exhibited a timely dependent PGD 2 production upon niacin challenge. Short pretreatment of M-CSF macrophages with autologous postprandial TRLs induced the down-regulation of HCA 2 gene and up-regulation of genes encoding COX1 and COX2 enzymes in a fatty acid-dependent manner. These effects were paralleled by a higher PGD 2 production with postprandial TRL-SFAs. The niacin-mediated transcriptional activity of all genes involved in PGD 2 biosynthesis was desensitized in a time-dependent manner by postprandial TRLs, leading to a decreased PGD 2 release. In vivo, the net excursions of PGD 2 in plasma followed similar fatty acid-dependent patterns as those found for PGD 2 release in vitro. The predominant fatty acid class in the diet acutely modulates PGD 2 biosynthetic pathway both in vitro and in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL-triglyceride levels in mice.

PubMed

Li, Zhaosha; Blad, Clara C; van der Sluis, Ronald J; de Vries, Henk; Van Berkel, Theo J C; Ijzerman, Adriaan P; Hoekstra, Menno

2012-10-01

Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect. In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo. Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Quantification of a bacterial secondary metabolite by SERS combined with SLM extraction for bioprocess monitoring.

PubMed

Morelli, Lidia; Andreasen, Sune Zoëga; Jendresen, Christian Bille; Nielsen, Alex Toftgaard; Emnéus, Jenny; Zór, Kinga; Boisen, Anja

2017-11-20

During the last few decades, great advances have been reached in high-throughput design and building of genetically engineered microbial strains, leading to a need for fast and reliable screening methods. We developed and optimized a microfluidic supported liquid membrane (SLM) extraction device and combined it with surface enhanced Raman scattering (SERS) sensing for the screening of a biological process, namely for the quantification of a bacterial secondary metabolite, p-coumaric acid (pHCA), produced by Escherichia coli. The microfluidic device proved to be robust and reusable, enabling efficient removal of interfering compounds from the real samples, reaching more than 13-fold up-concentration of the donor at 10 μL min -1 flow rate. With this method, we quantified pHCA directly from the bacterial supernatant, distinguishing between various culture conditions based on the pHCA production yield. The obtained data showed good correlation with HPLC analysis.

Alkyl sulfonic acide hydrazides: Synthesis, characterization, computational studies and anticancer, antibacterial, anticarbonic anhydrase II (hCA II) activities

NASA Astrophysics Data System (ADS)

O. Ozdemir, Ummuhan; İlbiz, Firdevs; Balaban Gunduzalp, Ayla; Ozbek, Neslihan; Karagoz Genç, Zuhal; Hamurcu, Fatma; Tekin, Suat

2015-11-01

Methane sulfonic acide hydrazide, CH3SO2NHNH2 (1), ethane sulfonic acide hydrazide, CH3CH2SO2NHNH2 (2), propane sulfonic acide hydrazide, CH3CH2CH2SO2NHNH2 (3) and butane sulfonic acide hydrazide, CH3CH2CH2CH2SO2NHNH2 (4) have been synthesized as homologous series and characterized by using elemental analysis, spectrophotometric methods (1H-13C NMR, FT-IR, LC-MS). In order to gain insight into the structure of the compounds, we have performed computational studies by using 6-311G(d, p) functional in which B3LYP functional were implemented. The geometry of the sulfonic acide hydrazides were optimized at the DFT method with Gaussian 09 program package. A conformational analysis of compounds were performed by using NMR theoretical calculations with DFT/B3LYP/6-311++G(2d, 2p) level of theory by applying the (GIAO) approach. The anticancer activities of these compounds on MCF-7 human breast cancer cell line investigated by comparing IC50 values. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Bacillus cereus NRRL-B-3711, Enterococcus faecalis ATCC 29212 and Gram negative bacteria; Escherichia coli ATCC 11230, Pseudomonas aeruginosa ATCC 15442, Klebsiella pneumonia ATCC 70063 by using the disc diffusion method. The inhibition activities of these compounds on carbonic anhydrase II enzyme (hCA II) have been investigated by comparing IC50 and Ki values. The biological activity screening shows that butane sulfonic acide hydrazide (4) has more activity than the others against tested breast cancer cell lines MCF-7, Gram negative/Gram positive bacteria and carbonic anhydrase II (hCA II) isoenzyme.

Synthesis and Biological Evaluation of 4-Sulfamoylphenyl/Sulfocoumarin Carboxamides as Selective Inhibitors of Carbonic Anhydrase Isoforms hCA II, IX, and XII.

PubMed

Angapelly, Srinivas; Angeli, Andrea; Khan, Arbaj Jabbar; Sri Ramya, P V; Supuran, Claudiu T; Arifuddin, Mohammed

2018-04-19

With the aim to develop potent and selective human carbonic anhydrase inhibitors (hCAIs), we synthesized 4-sulfamoylphenyl/sulfocoumarin benzamides (series 5 a-r and series 7 a-q) and evaluated their inhibition profiles against five isoforms of the zinc-containing human carbonic anhydrase (hCA, EC 4.2.1.1): cytosolic hCA I and II, and the transmembrane isozymes hCA IV, IX, and XII. Compounds 5 a-r were found to selectively inhibit hCA II in the nanomolar range, while being less effective against the other hCA isoforms. As noted from the literature, sulfocoumarin (1,2-benzoxathiine 2,2-dioxide) acts as a "prodrug" inhibitor and is hydrolyzed by the esterase activity of hCA to form 2-hydroxyphenylvinylsulfonic acid, which thereafter binds to the enzyme in a manner similar to that of coumarins and sulfoxocoumarins. All these sulfocoumarins (compounds 7 a-q) were found to be very weak or ineffective as inhibitors of the housekeeping off-target hCA isoforms I and II, and effectively inhibited the transmembrane tumor-associated isoforms IX and XII in the high nanomolar to micromolar ranges. Further structural modifications of these molecules could be useful for the development of effective hCA inhibitors used for the treatment of glaucoma, epilepsy, and cancer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

PubMed Central

Alexander, Stephen P. H.; Sharman, Joanna L.; Pawson, Adam J.; Benson, Helen E.; Monaghan, Amy E.; Liew, Wen Chiy; Mpamhanga, Chidochangu P.; Bonner, Tom I.; Neubig, Richard R.; Pin, Jean Philippe; Spedding, Michael; Harmar, Anthony J.

2013-01-01

In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA1 (GPR81) with lactate, HCA2 (GPR109A) with 3-hydroxybutyric acid, HCA3 (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA4 (GPR23), LPA5 (GPR92), LPA6 (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org). PMID:23686350

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

PubMed

Lunsford, Keri E; Bodzin, Adam S; Reino, Diego C; Wang, Hanlin L; Busuttil, Ronald W

2016-12-07

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

A Review of Testing of Hollow Cathodes for the International Space Station Plasma Contactor

NASA Technical Reports Server (NTRS)

Kovaleski, S. D.; Patterson, M. J.; Soulas, G. C.; Sarver-Verhey, T. R.

2001-01-01

Since October 2000, two plasma contactors have been providing charge control on the International Space Station (ISS). At the heart of each of the two plasma contactors is a hollow cathode assembly (HCA) that produces the contacting xenon plasma. The HCA is the result of 9 years of design and testing at the NASA Glenn Research Center. This paper summarizes HCA testing that has been performed to date. As of this time, one cathode has demonstrated approximately 28,000 hr of lifetime during constant, high current use. Another cathode, HCA.014. has demonstrated 42,000 ignitions before cathode heater failure. In addition to these cathodes, four cathodes. HCA.006, HCA.003, HCA.010, and HCA.013 have undergone cyclic testing to simulate the variable current demand expected on the ISS. HCA.006 accumulated 8,000 hr of life test operation prior to being voluntarily stopped for analysis before the flight units were fabricated. HCA.010 has accumulated 15,876 hr of life testing, and 4,424 ignitions during ignition testing. HCA.003 and HCA.0 13 have accumulated 12,415 and 18,823 hr of life testing respectively.

Preparation, spectroscopic and structural studies on charge-transfer complexes of 2,9-dimethyl-1,10-phenanthroline with some electron acceptors

NASA Astrophysics Data System (ADS)

Gaballa, Akmal S.; Wagner, Christoph; Teleb, Said M.; Nour, El-Metwally; Elmosallamy, M. A. F.; Kaluđerović, Goran N.; Schmidt, Harry; Steinborn, Dirk

2008-03-01

Charge-transfer (CT) complexes formed in the reactions of 2,9-dimethyl-1,10-phenanthroline (Me 2phen) with some acceptors such as chloranil (Chl), picric acid (HPA) and chloranilic acid (H 2CA) have been studied in the defined solvent at room temperature. Based on elemental analysis and infrared spectra of the solid CT-complexes along with the photometric titration curves for the reactions, obtained data indicate the formation of 1:1 charge-transfer complexes [(Me 2phen)(Chl)] ( 1), [(Me 2phenH)(PA)] ( 2) and [(Me 2phenH)(HCA)] ( 3), respectively, was proposed. In the three complexes, infrared and 1H NMR spectroscopic data indicate a charge-transfer interaction and as far as complexes 2 and 3 are concerned this interaction is associated with a hydrogen bonding. The formation constants for the complexes ( KC) were shown to be dependent upon the nature of the electron acceptors used. The X-ray structure of complex 3 indicate the formation of dimeric units [Me 2phenH] 2[(HCA) 2] in which the two anions (HCA) - are connected by two O-H⋯O hydrogen bonds whereas the cations and anions are joined together by strong three-center (bifurcated) N-H⋯O hydrogen bonds. Furthermore, the cations are arranged in a π-π stacking.

Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model.

PubMed

Midulla, P S; Gandsas, A; Sadeghi, A M; Mezrow, C K; Yerlioglu, M E; Wang, W; Wolfe, D; Ergin, M A; Griepp, R B

1994-09-01

Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA.

ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun.

PubMed

Liu, Shuqing; Guo, Chunmei; Wang, Jiasheng; Wang, Bo; Qi, Houbao; Sun, Ming-Zhong

2016-03-29

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma.

ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun

PubMed Central

Wang, Bo; Qi, Houbao; Sun, Ming-Zhong

2016-01-01

Annexin A11 (Anxa11) is associated with various cancers. Using a pair of syngeneic murine hepatocarcinoma cells, Hca-P with ~25% and Hca-F with ~75% lymph node metastatic (LNM) potentials, we demonstrated Anxa11 involvement in hepatocarcinoma lymphatic metastasis. Here, ANXA11 acted as a suppressor for the tumorigenicity, LNM and 5-FU resistance of Hca-P via c-Jun. We constructed monoclonal Hca-P cell line with stable ANXA11 knockdown. Although Bax and Bcl-2 levels increased in shRNA-Anxa11-transfected Hca-P, ANXA11 downregulation showed no clear effect on Hca-P apoptosis. ANXA11 downregulation promoted in vitro migration and invasion capacities of Hca-P. In situ adhesion potential of Hca-P cells toward LN was significantly enhanced following ANXA11 downregulation. Consistently, ANXA11 downregulation promoted the in vivo tumor growth and LNM capacities of Hca-P cells. ANXA11 knockdown enhanced the chemoresistance of Hca-P cells specifically toward 5-FU instead of cisplatin. Its downregulation increased c-Jun (pSer73) and decreased c-Jun (pSer243) levels in Hca-P. c-Jun (pSer243) downregulation seemed to be only correlated with ANXA11 knockdown without the connection to 5-FU treatment. Interestingly, compared with scramble-Hca-P cells, the levels of c-Jun and c-Jun (pSer73) in shRNA-Anxa11-Hca-P cells were upregulated in the presences of 0.1 and 1.0 mg/L 5-FU. The levels changes from c-Jun and c-Jun (pSer73) in Hca-P cells showed a more obvious tendency with the combination of ANXA11 knockdown and 5-FU treatment. ANXA11 level regulates LNM and 5-FU resistance of Hca-P via c-Jun pathway. It might play an important role in hepatocarcinoma cell malignancy and be a therapeutic target for hepatocarcinoma. PMID:26908448

Constitutive expression of HCA(2) in human retina and primary human retinal pigment epithelial cells.

PubMed

Yu, Alice L; Birke, Kerstin; Lorenz, Reinhard L; Welge-Lussen, Ulrich

2014-05-01

HCA2, a receptor of β-hydroxybutyrate and niacin, has recently been described in mouse retina and immortalized human retinal pigment epithelial (RPE) cell lines. As HCA2 might be a pharmacologic target, e.g. in diabetic retinopathy, we studied its expression in human retina and primary human RPE cells. Paraffin sections of human retina and primary human RPE cells were obtained from human donor eyes. Expression of HCA2 in human retina was investigated by immunohistochemistry of paraffin sections and by RT-PCR. HCA2 expression in primary human RPE cells was examined by immunocytochemistry and by Western-blot analysis. Positive immunohistochemical staining for HCA2 was found in paraffin sections of human retina, and positive immunocytochemical staining for HCA2 in primary human RPE cells. RT-PCR analysis detected mRNA expression of HCA2 in human retina. The expression of HCA2 protein was found in primary human RPE cells. Based on these results, HCA2 appears to be constitutively expressed in human retina and in primary human RPE cells. Although its functional role is still unknown, HCA2 may be potentially involved in the pathogenesis of various retinopathies and may offer a new therapeutic target.

Classification of type 2 diabetes rats based on urine amino acids metabolic profiling by liquid chromatography coupled with tandem mass spectrometry.

PubMed

Wang, Chunyan; Zhu, Hongbin; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

2013-09-15

An analytical method for quantifying underivatized amino acids (AAs) in urine samples of rats was developed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Classification of type 2 diabetes rats was based on urine amino acids metabolic profiling. LC-MS/MS analysis was applied through chromatographic separation and multiple reactions monitoring (MRM) transitions of MS/MS. Multivariate profile-wide predictive models were constructed using partial least squares discriminant analysis (PLS-DA) by SIMAC-P 11.5 version software package and hierarchical cluster analysis (HCA) by SPSS 18.0 version software. Some amino acids in urine of rats have significant change. The results of the present study prove that this method could perform the quantification of free AAs in urine of rats by using LC-MS/MS. In summary, the PLS-DA and HCA statistical analysis in our research were preferable to differentiate healthy rats and type 2 diabetes rats by the quantification of AAs in their urine samples. In addition, comparing with health group the seven increased amino acids in urine of type 2 rats were returned to normal under the treatment of acarbose. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors.

PubMed

Akocak, Suleyman; Lolak, Nabih; Nocentini, Alessio; Karakoc, Gulcin; Tufan, Anzel; Supuran, Claudiu T

2017-06-15

A series of sixteen novel aromatic and heterocyclic bis-sulfonamide Schiff bases were prepared by conjugation of well known aromatic and heterocyclic aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores with aromatic and heterocyclic bis-aldehydes. The obtained bis-sulfonamide Schiff bases were investigated as inhibitors of four selected human (h) CA isoforms, hCA I, hCA II, hCA VII and hCA IX. Most of the newly synthesized compounds showed a good inhibitory profile against isoforms hCA II and hCA IX, also showing moderate selectivity against hCA I and VII. Several efficient lead compounds were identified among this bis-sulfonamide Schiff bases with low nanomolar to sub-nanomolar activity against hCA II (K i s ranging between 0.4 and 861.1nM) and IX (K i s between 0.5 and 933.6nM). Since hCA II and hCA IX are important drug targets (antiglaucoma and anti-tumor agents), these isoform-selective inhibitors may be considered of interest for various biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

SiRNA-Mediated Down-Regulation of CLIC4 Gene Inhibits Cell Proliferation and Accelerates Cell Apoptosis of Mouse Liver Cancer Hca-F and Hca-P Cells.

PubMed

Yu, Qiu-Yun; Zhou, Xin-Feng; Xia, Qing; Shen, Jia; Yan, Jia; Zhu, Jiu-Ting; Li, Xiang; Shu, Ming

2018-01-01

This study explored the effects involved in silencing CLIC4 on apoptosis and proliferation of mouse liver cancer Hca-F and Hca-P cells. A CLIC4-target small interfering RNA (siRNA) was designed to compound into two individual complementary oligonucleotide chains. A process of annealing and connection to a pSilencer vector was followed by transfection with Hca-F and Hca-P cells. Quantitative real-time polymerase chain reaction and Western blotting techniques were used to determine CLIC4 mRNA and protein expressions. CCK8 assay and flow cytometry were employed for analysis of the survival and apoptosis rate as well as the cell cycle in an octreotide-induced apoptosis model. Expressions of caspase 3, caspase 9, and cleaved PARP were measured using Western blotting. The CLIC4 mRNA and protein expressions in Hca-F and Hca-P cells transfected by pSilencer-CLIC4 siRNA plasmid in the blank group displayed remarkably decreased levels of expression, when compared with both the control and negative control (NC) groups. Decreased survival rates and cleaved PARP expression, increased cell apoptosis rate,expressions of caspase 3 and caspase 9 in Hca-F and Hca-P cells were detected in groups that had been cultured in a medium containing octreotide. The pSilencer-CLIC4 siRNA-2 group when compared with the control and NC groups exhibited decreased survival rates, cleaved PARP expression, increased cell apoptosis rates, and increased expressions of caspase 3 and caspase 9 of Hca-F and Hca-P cells. The results demonstrated that siRNA-induced down-regulation of CLIC4 could proliferation, while in turn promoting apoptosis of mouse liver cancer Hca-F and Hca-P cells. J. Cell. Biochem. 119: 659-668, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Degradation of hydroxycinnamic acid mixtures in aqueous sucrose solutions by the Fenton process.

PubMed

Nguyen, Danny M T; Zhang, Zhanying; Doherty, William O S

2015-02-11

The degradation efficiencies and behaviors of caffeic acid (CaA), p-coumaric acid (pCoA), and ferulic acid (FeA) in aqueous sucrose solutions containing the mixture of these hydroxycinnamic acids (HCAs) were studied by the Fenton oxidation process. Central composite design and multiresponse surface methodology were used to evaluate and optimize the interactive effects of process parameters. Four quadratic polynomial models were developed for the degradation of each individual acid in the mixture and the total HCAs degraded. Sucrose was the most influential parameter that significantly affected the total amount of HCA degraded. Under the conditions studied there was a <0.01% loss of sucrose in all reactions. The optimal values of the process parameters for a 200 mg/L HCA mixture in water (pH 4.73, 25.15 °C) and sucrose solution (13 mass %, pH 5.39, 35.98 °C) were 77% and 57%, respectively. Regression analysis showed goodness of fit between the experimental results and the predicted values. The degradation behavior of CaA differed from those of pCoA and FeA, where further CaA degradation is observed at increasing sucrose and decreasing solution pH. The differences (established using UV/vis and ATR-FTIR spectroscopy) were because, unlike the other acids, CaA formed a complex with Fe(III) or with Fe(III) hydrogen-bonded to sucrose and coprecipitated with lepidocrocite, an iron oxyhydroxide.

How aromatic compounds block DNA binding of HcaR catabolite regulator

DOE PAGES

Kim, Youngchang; Joachimiak, Grazyna; Bigelow, Lance; ...

2016-04-25

Bacterial catabolism of aromatic compounds from various sources including phenylpropanoids and flavonoids that are abundant in soil plays an important role in the recycling of carbon in the ecosystem. We have determined the crystal structures of apo-HcaR from Acinetobacter sp. ADP1, a MarR/SlyA transcription factor, in complexes with hydroxycinnamates and a specific DNA operator. The protein regulates the expression of the hca catabolic operon in Acinetobacter and related bacterial strains, allowing utilization of hydroxycinnamates as sole sources of carbon. HcaR binds multiple ligands, and as a result the transcription of genes encoding several catabolic enzymes is increased. The 1.9-2.4 Åmore » resolution structures presented here explain how HcaR recognizes four ligands (ferulate, 3,4-dihydroxybenzoate, p-coumarate, and vanillin) using the same binding site. The ligand promiscuity appears to be an adaptation to match a broad specificity of hydroxycinnamate catabolic enzymes while responding to toxic thioester intermediates. Structures of apo-HcaR and in complex with a specific DNA hca operator when combined with binding studies of hydroxycinnamates show how aromatic ligands render HcaR unproductive in recognizing a specific DNA target. Furthermore, the current study contributes to a better understanding of the hca catabolic operon regulation mechanism by the transcription factor HcaR.« less

The effects of some tumor markers on human erythrocyte (HCA-I and HCA-II), bovine erythrocyte (BCA) and bovine lung (CA-IV) carbonic anhydrase enzyme activities in vitro.

PubMed

Demir, N; Nadaroglu, H; Gungor, A A; Demir, Y

2015-01-01

The influence of prostatic acid phosphatase (PAP) and human chorionic gonadotropin (HCG), tumor markers have been investigated on human erythrocyte carbonic anhydrase (HCA-I and HCA-II) and bovine erythrocyte (BCA) and bovine lung carbonic anhydrase (CA-IV) in vitro. Tumor markers are substances that can often be detected in higher-than-normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. Tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. In addition to their role in cancer diagnosis, some tumor marker levels are measured before treatment to help doctors plan appropriate therapy. All of the tumor markers were determined to have inhibition effect, on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes. The effect of each tumor marker on CA was investigated by Wilbur-Andersen method modified by Rickly et al Inhibition effects of two different tumor markers on human CA-I, CA-II, bovine erythrocyte CA (BCA) and bovine lung CA-IV isoenzymes were determined by using the CO2-Hydratase method by plotting activity % vs (tumor markers). I50 values of tumor markers exhibiting inhibition effects were found by means of these graphs (Tab.1, Fig. 2, Ref. 20).

Transcriptional Profile of Brain Injury in Hypothermic Circulatory Arrest and Cardiopulmonary Bypass

PubMed Central

Allen, Jeremiah G.; Weiss, Eric S.; Wilson, Mary Ann; Arnaoutakis, George J.; Blue, Mary E.; Talbot, C. Conover; Jie, Chunfa; Lange, Mary S.; Troncoso, Juan C.; Johnston, Michael V.; Baumgartner, William A.

2011-01-01

Background Little is known about the molecular mechanisms of neurologic complications after hypothermic circulatory arrest (HCA) with cardiopulmonary bypass (CPB). Canine genome sequencing allows profiling of genomic changes after HCA and CPB alone. We hypothesize that gene regulation will increase with increased severity of injury. Methods Dogs underwent 2-hour HCA at 18°C (n = 10), 1-hour HCA (n = 8), or 2-hour CPB at 32°C alone (n = 8). In each group, half were sacrificed at 8 hours and half at 24 hours after treatment. After neurologic scoring, brains were harvested for genomic analysis. Hippocampal RNA isolates were analyzed using canine oligonucleotide expression arrays containing 42,028 probes. Results Consistent with prior work, dogs that underwent 2-hour HCA experienced severe neurologic injury. One hour of HCA caused intermediate clinical damage. Cardiopulmonary bypass alone yielded normal clinical scores. Cardiopulmonary bypass, 1-hour HCA, and 2-hour HCA groups historically demonstrated increasing degrees of histopathologic damage (previously published). Exploratory analysis revealed differences in significantly regulated genes (false discovery rate < 10%, absolute fold change ≥ 1.2), with increases in differential gene expression with injury severity. At 8 hours and 24 hours after insult, 2-hour HCA dogs had 502 and 1,057 genes regulated, respectively; 1-hour HCA dogs had 179 and 56 genes regulated; and CPB alone dogs had 5 and 0 genes regulated. Conclusions Our genomic profile of canine brains after HCA and CPB revealed 1-hour and 2-hour HCA induced markedly increased gene regulation, in contrast to the minimal effect of CPB alone. This adds to the body of neurologic literature supporting the safety of CPB alone and the minimal effect of CPB on a normal brain, while illuminating genomic results of both. PMID:20494057

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting.

PubMed

Bond, S E; Boutlis, C S; Yeo, W W; Pratt, W A B; Orr, M E; Miyakis, S

2017-04-01

Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU$19,222 vs $7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Acinetobacter bacteraemia in Thailand: evidence for infections outside the hospital setting

PubMed Central

PORTER, K. A.; RHODES, J.; DEJSIRILERT, S.; HENCHAICHON, S.; SILUDJAI, D.; THAMTHITIWAT, S.; PRAPASIRI, P.; JORAKATE, P.; KAEWPAN, A.; PERUSKI, L. F.; KERDSIN, A.; PRASERT, K.; YUENPRAKONE, S.; MALONEY, S. A.; BAGGETT, H. C.

2015-01-01

SUMMARY Acinetobacter is a well-recognized nosocomial pathogen. Previous reports of community-associated Acinetobacter infections have lacked clear case definitions and assessment of healthcare-associated (HCA) risk factors. We identified Acinetobacter bacteraemia cases from blood cultures obtained <3 days after hospitalization in rural Thailand and performed medical record reviews to assess HCA risk factors in the previous year and compare clinical and microbiological characteristics between cases with and without HCA risk factors. Of 72 Acinetobacter cases, 32 (44%) had no HCA risk factors. Compared to HCA infections, non-HCA infections were more often caused by Acinetobacter species other than calcoaceticus–baumannii complex species and by antibiotic-susceptible organisms. Despite similar symptoms, the case-fatality proportion was lower in non-HCA than HCA cases (9% vs. 45%, P < 0·01). Clinicians should be aware of Acinetobacter as a potential cause of community-associated infections in Thailand; prospective studies are needed to improve understanding of associated risk factors and disease burden. PMID:24001479

Microwave assisted synthesis of novel acridine-acetazolamide conjugates and investigation of their inhibition effects on human carbonic anhydrase isoforms hCA I, II, IV and VII.

PubMed

Ulus, Ramazan; Aday, Burak; Tanç, Muhammet; Supuran, Claudiu T; Kaya, Muharrem

2016-08-15

4-Amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide was condensed with cyclic-1,3-diketones (dimedone and cyclohexane-1,3-dione) and aromatic aldehydes under microwave irradiation, leading to a series of acridine-acetazolamide conjugates. The new compounds were investigated as inhibitors of carbonic anhydrases (CA, EC 4.2.1.1), and more precisely cytosolic isoforms hCA I, II, VII and membrane-bound one hCA IV. All investigated isoforms were inhibited in low micromolar and nanomolar range by the new compounds. hCA IV and VII were inhibited with KIs in the range of 29.7-708.8nM (hCA IV), and of 1.3-90.7nM (hCA VII). For hCA I and II the KIs were in the range of 6.7-335.2nM (hCA I) and of 0.5-55.4nM (hCA II). The structure-activity relationships (SAR) for the inhibition of these isoforms with the acridine-acetazolamide conjugates reported here were delineated. Copyright © 2016 Elsevier Ltd. All rights reserved.

The human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibition effects of trimethoxyindane derivatives.

PubMed

Taslimi, Parham; Gulcin, Ilhami; Ozgeris, Bunyamin; Goksu, Suleyman; Tumer, Ferhan; Alwasel, Saleh H; Supuran, Claudiu T

2016-01-01

Carbonic anhydrases (CAs, EC 4.2.1.1) had six genetically distinct families described to date in various organisms. There are 16 known CA isoforms in humans. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. Acetylcholine esterase (AChE. EC 3.1.1.7) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine relaying the signal from the nerve. In this study, some trimethoxyindane derivatives were investigated as inhibitors against the cytosolic hCA I and II isoenzymes, and AChE enzyme. Both hCA isozymes were inhibited by trimethoxyindane derivatives in the low nanomolar range. These compounds were good hCA I inhibitors (Kis in the range of 1.66-4.14 nM) and hCA II inhibitors (Kis of 1.37-3.12 nM) and perfect AChE inhibitors (Kis in the range of 1.87-7.53 nM) compared to acetazolamide as CA inhibitor (Ki: 6.76 nM for hCA I and Ki: 5.85 nM for hCA II) and Tacrine as AChE inhibitor (Ki: 7.64 nM).

Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids.

PubMed

Ekinci, Derya; Karagoz, Lutfi; Ekinci, Deniz; Senturk, Murat; Supuran, Claudiu T

2013-04-01

A series of flavonoids, such as quercetin, catechin, apigenin, luteolin, morin, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA). The compounds were tested against four α-CA isozymes purified from human and bovine (hCA I, hCA II, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds. The flavonoids inhibited hCA I with K(I)-s in the range of 2.2-12.8 μM, hCA II with K(I)-s in the range of 0.74-6.2 μM, bCA III with K(I)-s in the range of 2.2-21.3 μM, and hCA IV with inhibition constants in the range of 4.4-15.7, with an esterase assay using 4-nitrophenyl acetate as substrate. Some simple phenols/sulfonamides were also investigated as standard inhibitors. The flavonoids incorporate phenol moieties which inhibit these CAs through a diverse, not yet determined inhibition mechanism, compared to classic inhibitors such as the sulfonamide/sulfamate ones.

Entry of Botulinum Neurotoxin Subtypes A1 and A2 into Neurons

PubMed Central

Kroken, Abby R.; Blum, Faith C.; Zuverink, Madison

2016-01-01

ABSTRACT Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans but also are common therapies for neurological diseases. BoNTs are dichain toxins, comprising an N-terminal catalytic domain (LC) disulfide bond linked to a C-terminal heavy chain (HC) which includes a translocation domain (HN) and a receptor binding domain (HC). Recently, the BoNT serotype A (BoNT/A) subtypes A1 and A2 were reported to possess similar potencies but different rates of cellular intoxication and pathology in a mouse model of botulism. The current study measured HCA1 and HCA2 entry into rat primary neurons and cultured Neuro2A cells. We found that there were two sequential steps during the association of BoNT/A with neurons. The initial step was ganglioside dependent, while the subsequent step involved association with synaptic vesicles. HCA1 and HCA2 entered the same population of synaptic vesicles and entered cells at similar rates. The primary difference was that HCA2 had a higher degree of receptor occupancy for cells and neurons than HcA1. Thus, HCA2 and HCA1 share receptors and entry pathway but differ in their affinity for receptor. The initial interaction of HCA1 and HCA2 with neurons may contribute to the unique pathologies of BoNT/A1 and BoNT/A2 in mouse models. PMID:27795365

Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme.

PubMed

Akdemir, Atilla; De Monte, Celeste; Carradori, Simone; Supuran, Claudiu T

2015-02-01

In previous work, 14 salen and tetrahydrosalen compounds have been synthesized and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX and XII). These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA XII to form a direct interaction with the Zn(2+) ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn(2+) ion.

Systematic review: benefits and harms of transarterial embolisation for treating hepatocellular adenoma.

PubMed

Zhao, C; Pei, S-L; Cucchetti, A; Tong, T-J; Ma, Y-L; Zhong, J-H; Li, L-Q

2017-03-20

Transarterial embolisation (TAE) is a standard treatment for bleeding hepatocellular adenoma (HCA) and, occasionally, symptomatic HCA involving large tumours. Whether TAE is similarly safe and effective as an elective treatment for bleeding and nonbleeding HCA remains unclear. To investigate the benefits and harms of TAE for bleeding and nonbleeding HCA. PubMed, Scopus, Embase and Cochrane Library databases were systematically searched for studies that examined post-TAE tumour reduction in patients with bleeding or nonbleeding HCA and that were published between January 2000 and January 2017. Systematic review of 21 case series involving 1468 patients with HCA in the systematic review identified 140 (9.5%) patients with 189 lesions who received TAE. Of these 140 patients, 66.4% had bleeding HCA and 33.6% had nonbleeding HCA. Intended elective TAE was performed in 27.1% of patients (38.6% of HCA lesions). Adenomatosis was observed in 6.1% of patients, and the rate of β-catenin expression was 4.5%. No malignant transformation was observed among the 189 tumours during a median follow-up time of 40 months. The complete response rate among 70 patients was 10.6%, and the partial response rate was 71.7%. No mortality or severe adverse side effects were reported during the hospitalisation period. The available evidence suggests that TAE can be considered safe for elective managment of HCA as well as for management of bleeding HCA. Elective TAE can be regarded as a reasonable alternative to surgery. High-quality prospective studies with long-term follow-up are needed to corroborate and strengthen available evidence. © 2017 John Wiley & Sons Ltd.

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

48 CFR 819.202-70 - HCA responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false HCA responsibilities. 819.202-70 Section 819.202-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 819.202-70 HCA responsibilities. An HCA must perform the following functions in support of the...

Direct characterization of aqueous extract of Hibiscus sabdariffa using HPLC with diode array detection coupled to ESI and ion trap MS.

PubMed

Rodríguez-Medina, Inmaculada C; Beltrán-Debón, Raúl; Molina, Vicente Micol; Alonso-Villaverde, Carlos; Joven, Jorge; Menéndez, Javier A; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2009-10-01

The phenolic fraction and other polar compounds of the Hibiscus sabdariffa were separated and identified by HPLC with diode array detection coupled to electrospray TOF and IT tandem MS (DAD-HPLC-ESI-TOF-MS and IT-MS). The H. sabdariffa aqueous extract was filtered and directly injected into the LC system. The analysis of the compounds was carried out by RP HPLC coupled to DAD and TOF-MS in order to obtain molecular formula and exact mass. Posterior analyses with IT-MS were performed and the fragmentation pattern and confirmation of the structures were achieved. The H. sabdariffa samples were successfully analyzed in positive and negative ionization modes with two optimized linear gradients. In positive mode, the two most representative anthocyanins and other compounds were identified whereas the phenolic fraction, hydroxycitric acid and its lactone were identified using the negative ionization mode.

Comparison of high-functioning atypical autism and childhood autism by Childhood Autism Rating Scale-Tokyo version.

PubMed

Kanai, Chieko; Koyama, Tomonori; Kato, Seika; Miyamoto, Yuki; Osada, Hirokazu; Kurita, Hiroshi

2004-04-01

To assess autistic symptom differences between high-functioning atypical autism (atypical symptomatology) (HAA; IQ >/= 70) and childhood autism (HCA), 53 HAA children (mean: 6.0 +/- 0.5 years) were compared with 21 HCA children (mean: 8.2 +/- 1.1 years) on the Childhood Autism Rating Scale-Tokyo version (CARS-TV). Because IQ on the Japanese version of the Stanford-Binet and CARS-TV total scores differed significantly between HAA and HCA, analysis of covariance was conducted with IQ and CARS-TV total scores controlled for. In two items of CARS-TV (relationship with people and general impressions) the HAA children were significantly less abnormal than the HCA children. Affect tended to be significantly milder in HAA than HCA. Anxiety reaction was significantly more abnormal in HAA than HCA. These findings may be useful to distinguish between HAA and HCA.

High expression of osteoglycin decreases gelatinase activity of murine hepatocarcinoma Hca-F cells

PubMed Central

Cui, Xiao-Nan; Tang, Jian-Wu; Song, Bo; Wang, Bo; Chen, Shan-Yan; Hou, Li

2009-01-01

AIM: To investigate the possible correlation between osteoglycin expression and gelatinase activity of mouse hepatocarcinoma Hca-F cells. METHODS: A eukaryotic expression plasmid pIRESpuro3 osteoglycin(+) was constructed and transfected into Hca-F cells to investigate the possible correlation between osteoglycin expression and gelatinase activity of Hca-F cells cultured with extract of lymph node, liver, spleen or in DMEM medium. The activity of gelatinases was examined through zymographic analysis. RESULTS: High expression of osteoglycin attenuated the gelatinase activity of Hca-F cells cultured with extract of lymph node, and at the same time, decreased the metastatic potential of Hca-F cells to peripheral lymph nodes in vivo. CONCLUSION: High expression of osteoglycin decreases the gelatinase activity of Hca-F cells cultured with extract of lymph node; regulation of gelatinase activity might be one of mechanisms that osteoglycin contributes to lymphatic metastasis suppression. PMID:20027687

77 FR 59985 - Healthcare Corporation of America (HCA), HCA Mountain Division Including Workers Whose Wages Were...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,558] Healthcare Corporation of America (HCA), HCA Mountain Division Including Workers Whose Wages Were Reported Through Mountainstar Health, Inc. Including Workers Whose Wages Were Reported Through Health Trust Utah Management Services, Inc. Cottonwood Heights, UT; Amended...

Case of telangiectatic/inflammatory hepatocellular adenoma arising in a patient with primary sclerosing cholangitis.

PubMed

Maylee, Hsu; Harada, Kenichi; Igarashi, Saya; Tohda, Gen; Yamamoto, Makoto; Ren, Xiang Shan; Osawa, Takeshi; Hasegawa, Yasuhiro; Takahashi, Norio; Nakanuma, Yasuni

2012-06-01

Hepatocellular adenomas (HCA) have been recently identified as a heterogeneous group, differing based on genotypic as well as morphological characteristics. HCA are most frequently found in women on oral contraception. A type of HCA, inflammatory HCA, is also known as telangiectatic HCA and was previously referred to as telangiectatic focal nodular hyperplasia. We present the first case of HCA arising from the liver with primary sclerosing cholangitis (PSC). This case is a 30-year-old man with a past medical history of PSC, ulcerative colitis and diabetes mellitus. A routine ultrasonography for PSC detected the gradually enlarged intrahepatic mass. Liver biopsy could reveal the diagnosis of telangiectatic/ inflammatory HCA by morphological and immunohistochemical analyses. Partial hepatectomy was performed and the resected liver was pathologically diagnosed as the telangiectatic/inflammatory HCA arising in PSC. This is the first case report of such an association and here we review the current developments and published work of this rare tumor and the association with an activated inflammatory related tumorogenic pathway and PSC. © 2012 The Japan Society of Hepatology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Youngchang; Joachimiak, Grazyna; Bigelow, Lance

Bacterial catabolism of aromatic compounds from various sources including phenylpropanoids and flavonoids that are abundant in soil plays an important role in the recycling of carbon in the ecosystem. We have determined the crystal structures of apo-HcaR from Acinetobacter sp. ADP1, a MarR/SlyA transcription factor, in complexes with hydroxycinnamates and a specific DNA operator. The protein regulates the expression of the hca catabolic operon in Acinetobacter and related bacterial strains, allowing utilization of hydroxycinnamates as sole sources of carbon. HcaR binds multiple ligands, and as a result the transcription of genes encoding several catabolic enzymes is increased. The 1.9-2.4 Åmore » resolution structures presented here explain how HcaR recognizes four ligands (ferulate, 3,4-dihydroxybenzoate, p-coumarate, and vanillin) using the same binding site. The ligand promiscuity appears to be an adaptation to match a broad specificity of hydroxycinnamate catabolic enzymes while responding to toxic thioester intermediates. Structures of apo-HcaR and in complex with a specific DNA hca operator when combined with binding studies of hydroxycinnamates show how aromatic ligands render HcaR unproductive in recognizing a specific DNA target. Furthermore, the current study contributes to a better understanding of the hca catabolic operon regulation mechanism by the transcription factor HcaR.« less

Synthesis, characterization, and fluorescent properties of two Pb(II) complexes: {l_brace}[Pb(hca){sub 2}.DMF].DMF{r_brace} {sub {infinity}} and [Pb(hca){sub 2}(phen).DMF]{sub 2}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Qingfeng; Zhou Qiuxuan; Lu Jianmei

2007-01-15

Two novel Pb(II) complexes, {l_brace}[Pb(hca){sub 2}.DMF].DMF{r_brace} {sub {infinity}} and [Pb(hca){sub 2}(phen).DMF]{sub 2} (hca=trans-4-hydroxycinnamic group), were obtained by solid-phase reactions of PbAc{sub 2} and Hhca and PbAc{sub 2}, Hhca, and phen, respectively, and characterized by spectroscopy. X-ray crystallography analysis reveals that complex 1, {l_brace}[Pb(hca){sub 2}.DMF].DMF{r_brace} {sub {infinity}} , adopts a 2-dimensional structure through the weak interactions of Pb and O atoms and that complex 2, [Pb(hca){sub 2}(phen).DMF]{sub 2}, shows a discrete dimeric structure, in which hydrogen bonds link the dimers into a 2D network. Both complexes 1 and 2 show visible fluorescence and the intensity is stronger than that of themore » ligand. More interestingly, the intensity of emission was increased at least fivefolds when the pH of the solution was adjusted to alkalinity. This can be attributed to that the deprotonization of phenolic group enhancing the conjugation of the ligand hca. These results indicate that this method may be an effective way to increase the emission intensity of similar complexes. - Graphical abstract: Two novel Pb(II) complexes: {l_brace}[Pb(hca){sub 2}.DMF].DMF{r_brace}{sub {infinity}} and [Pb(hca){sub 2}(phen).DMF]{sub 2}, (hca = trans-4-hydroxycinnamic anion) were obtained and characterized. Their structures are also determined by X-ray crystal analysis. Both of complexes in DMF solution show visible fluorescence and the intensity is stronger than that of ligand. Their emission intensities are increased greatly in an alkaline solution of pH 8, which is due to the enhancement of the planar conjugation of ligand hca with the deprotonate of the phenolic group.« less

[Improvement of local lymph node assay for cosmetics safety evaluation].

PubMed

Liu, Zhen; Liu, Junping; Wang, Fei; Xu, Guifeng; Hou, Juan; Wan, Xuying; Zhang, Tianbao

2009-09-01

To improve the local lymph node assay (LLNA) as an alternative method to detect chemicals for both sensitization and irritation. The following chemicals: one negative control: 4-Aminobenzoic Acid, three sensitizers: 2,4-dinitrochlorobenzene (DNCB), Hexyl cinnamic aldehyde (HCA), 2-Aminophenol (2-APC) and two irritations: potassium hydroxide (KOH), sodium lauryl sulphate (SLS) were selected. According to the normal LLNA, groups of female Balb/c mice were treated with test solutions. The thickness of each ear was measured and each auricle was weighed. On the sixth day, the bilateral draining auricular lymph nodes were excised and weighed. The single cell suspensions were prepared, the lymphocyte were counted and the proliferations of lymph cells were detected by cell counting kit-8 (CCK-8). Significant increase in ear thickness and weight were found in groups of KOH, SLS and DNCB (above 0.5%) (P < 0.05), which could be considered as irritants, whereas irritation were not found in 2-APC and HCA. In the allergic test, three sensitizers showed positive, but different sensitivity were found among each index. HCA, DNCB and 2-APC could all obviously augment the weight of lymph node and the lymphocyte count in different groups (P < 0.05). Conspicuous proliferation of lymphocyte were found in DNCB (all group), HCA (above the middle dose) and 2-APC (high dose) by CCK-8. The reformed LLNA using auricle thickness and weighing as observed markers for irritation, and using lymph nodes weighing and proliferation of lymphocyte as observed markers for sensitization, could evaluate both sensitization and irritation at the same time.

Infection Control Link Nurse Program: An interdisciplinary approach n targeting health care-acquired infection

PubMed Central

Sopirala, Madhuri M.; Yahle-Dunbar, Lisa; Smyer, Justin; Wellington, Linda; Dickman, Jeanne; Zikri, Nancy; Martin, Jennifer; Kulich, Pat; Taylor, David; Mekhjian, Hagop; Nash, Mary; Mansfield, Jerry; Pancholi, Preeti; Howard, Mary; Chase, Linda; Brown, Susan; Kipp, Kristopher; Lefeld, Kristen; Myers, Amber; Pan, Xueliang; Mangino, Julie E.

2014-01-01

Background We describe a successful interdisciplinary liaison program that effectively reduced health care-acquired (HCA), methicillin-resistant Staphylococcus aureus (MRSA) in a university hospital setting. Methods Baseline was from January 2006 to March 2008, and intervention period was April 2008 to September 2009. Staff nurses were trained to be liaisons (link nurses) to infection prevention (IP) personnel with clearly defined goals assigned and with ongoing monthly education. HCA-MRSA incidence per 1,000 patient-days (PD) was compared between baseline and intervention period along with total and non-HCA-MRSA, HCA and non-HCA-MRSA bacteremia, and hand soap/sanitizer usage. Hand hygiene compliance was assessed. Results A reduction in MRSA rates was as follows in intervention period compared with baseline: HCA-MRSA decreased by 28% from 0.92 to 0.67 cases per 1,000 PD (incidence rate ratio, 0.72; 95% confidence interval: 0.62–0.83, P < .001), and HCA-MRSA bacteremia rate was reduced by 41% from 0.18 to 0.10 per 1,000 PD (incidence rate ratio, 0.59; 95% confidence interval: 0.42–0.84, P = .003). Total MRSA rate and MRSA bacteremia rate also showed significant reduction with nonsignificant reductions in overall non-HCA-MRSA and non-HCA-MRSA bacteremia. Hand soap/sanitizer usage and compliance with hand hygiene also increased significantly during IP. Conclusion Link nurse program effectively reduced HCA-MRSA. Goal-defined metrics with ongoing reeducation for the nurses by IP personnel helped drive these results. PMID:24548456

Adsorption of aliphatic polyhydroxy carboxylic acids on gibbsite: pH dependency and importance of adsorbate structure.

PubMed

Schneckenburger, Tatjana; Riefstahl, Jens; Fischer, Klaus

2018-01-01

Aliphatic (poly)hydroxy carboxylic acids [(P)HCA] occur in natural, e.g. soils, and in technical (waste disposal sites, nuclear waste repositories) compartments . Their distribution, mobility and chemical reactivity, e.g. complex formation with metal ions and radionuclides, depend, among others, on their adsorption onto mineral surfaces. Aluminium hydroxides, e.g. gibbsite [α-Al(OH) 3 ], are common constituents of related solid materials and mimic the molecular surface properties of clay minerals. Thus, the study was pursued to characterize the adsorption of glycolic, threonic, tartaric, gluconic, and glucaric acids onto gibbsite over a wide pH and (P)HCA concentration range. To consider specific conditions occurring in radioactive wastes, adsorption applying an artificial cement pore water (pH 13.3) as solution phase was investigated additionally. The sorption of gluconic acid at pH 4, 7, 9, and 12 was best described by the "two-site" Langmuir isotherm, combining "high affinity" sorption sites (adsorption affinity constants [Formula: see text] > 1 L mmol -1 , adsorption capacities < 6.5 mmol kg -1 ) with "low affinity" sites ([Formula: see text] < 0.1 L mmol -1 , adsorption capacities ≥ 19 mmol kg -1 ). The total adsorption capacities at pH 9 and 12 were roughly tenfold of that at pH 4 and 7. The S-shaped pH sorption edge of gluconic acid was modelled applying a constant capacitance model, considering electrostatic interactions, hydrogen bonding, surface complex formation, and formation of solved polynuclear complexes between Al 3+ ions and gluconic acid. A Pearson and Spearman rank correlation between (P)HCA molecular properties and adsorption parameters revealed the high importance of the size and the charge of the adsorbates. The adsorption behaviour of (P)HCAs is best described by a combination of adsorption properties of carboxylic acids at acidic pH and of polyols at alkaline pH. Depending on the molecular properties of the adsorbates and on pH, electrostatic interactions, hydrogen bonding, and ternary surface complexation contribute in varying degrees to the adsorption process. Linear distribution coefficients K d between 8.7 and 60.5 L kg -1 (1 mmol L -1 initial PHCA concentration) indicate a considerable mineral surface affinity at very high pH, thus lowering the PHCA fraction available for the complexation of metal ions including radionuclides in solution and their subsequent mobilization.

Qualitative and Quantitative Gadoxetic Acid-enhanced MR Imaging Helps Subtype Hepatocellular Adenomas.

PubMed

Tse, Justin R; Naini, Bita V; Lu, David S K; Raman, Steven S

2016-04-01

To determine which clinical variables and gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging features are associated with histologically proved hepatocellular adenoma (HCA) genotypic subtypes. In this institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study, clinical information and MR images of 49 histologically proved HCAs from January 2002 to December 2013 (21 patients; mean age, 39 years; age range, 15-59 years) were retrospectively reviewed by two radiologists. Qualitative and quantitative imaging features, including the signal intensity ratio relative to liver in each phase, were studied. HCA tissues were stained with subtype-specific markers and subclassified by a pathologist. Clinical and imaging data were correlated with pathologic findings and compared by using Fisher exact or t test, with a Bonferroni correction for multiple comparisons. Forty-nine HCAs were subclassified into 14 inflammatory, 20 hepatocyte nuclear factor (HNF)-1α-mutated, one β-catenin-activated, and 14 unclassified lesions. Intralesional steatosis was exclusively seen in HNF-1α-mutated lesions. Marked hyperintensity on T2-weighted images was seen in 12 of 14 (86%) inflammatory lesions compared with four of 21 (19%) HNF-1α-mutated, seven of 14 (50%) unclassified, and zero of one (0%) β-catenin-activated lesion. Two large lesions (one β-catenin-activated and one unclassified) transformed into hepatocellular carcinomas and were the only lesions to enhance with marked heterogeneity. In the hepatobiliary phase, all HCA subtypes were hypoenhancing compared with surrounding liver parenchyma, and they reached their nadir signal intensity by 10 minutes after the administration of contrast material before plateauing. HNF-1α-mutated lesions had the lowest lesion signal intensity ratio of 0.47 ± 0.09, compared with 0.73 ± 0.18 for inflammatory lesions (P = .0004), 0.82 for the β-catenin-activated lesion, and 0.73 ± 0.06 for the unclassified lesion (P = .00002). In this study, all HCA subtypes were hypoenhancing at Gd-EOB-DTPA-enhanced MR imaging in the hepatobiliary phase and reached their nadir signal intensity at 10 minutes. HNF-1α-mutated lesions could be distinguished from other subtypes by having the lowest lesion signal intensity ratio.

Simultaneous occurrence of focal nodular hyperplasia and HNF1A-inactivated hepatocellular adenoma: a collision tumor simulating a composite FNH-HCA.

PubMed

Shih, Angela; Lauwers, Gregory Y; Balabaud, Charles; Bioulac-Sage, Paulette; Misdraji, Joseph

2015-09-01

Mixed focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) within a single tumor mass is rarely reported, and most of these cases are examples of tumors with features intermediate between FNH and HCA. Although a few reported cases are probably examples of true mixed tumors, none was evaluated immunohistochemically or confirmed by molecular analysis. We report a mixed FNH and HCA arising in a woman with several HNF1A-inactivated adenomas. Our case is the first case of mixed FNH and HNF1A-inactivated HCA documented by immunohistochemistry.

In Utero Exposure to Histological Chorioamnionitis Primes the Exometabolomic Profiles of Preterm CD4+ T Lymphocytes.

PubMed

Matta, Poojitha; Sherrod, Stacy D; Marasco, Christina C; Moore, Daniel J; McLean, John A; Weitkamp, Joern-Hendrik

2017-11-01

Histological chorioamnionitis (HCA) is an intrauterine inflammatory condition that increases the risk for preterm birth, death, and disability because of persistent systemic and localized inflammation. The immunological mechanisms sustaining this response in the preterm newborn remain unclear. We sought to determine the consequences of HCA exposure on the fetal CD4 + T lymphocyte exometabolome. We cultured naive CD4 + T lymphocytes from HCA-positive and -negative preterm infants matched for gestational age, sex, race, prenatal steroid exposure, and delivery mode. We collected conditioned media samples before and after a 6-h in vitro activation of naive CD4 + T lymphocytes with soluble staphylococcal enterotoxin B and anti-CD28. We analyzed samples by ultraperformance liquid chromatography ion mobility-mass spectrometry. We determined the impact of HCA on the CD4 + T lymphocyte exometabolome and identified potential biomarker metabolites by multivariate statistical analyses. We discovered that: 1) CD4 + T lymphocytes exposed to HCA exhibit divergent exometabolomic profiles in both naive and activated states; 2) ∼30% of detected metabolites differentially expressed in response to activation were unique to HCA-positive CD4 + T lymphocytes; 3) metabolic pathways associated with glutathione detoxification and tryptophan degradation were altered in HCA-positive CD4 + T lymphocytes; and 4) flow cytometry and cytokine analyses suggested a bias toward a T H 1-biased immune response in HCA-positive samples. HCA exposure primes the neonatal adaptive immune processes by inducing changes to the exometabolomic profile of fetal CD4 + T lymphocytes. These exometabolomic changes may link HCA exposure to T H 1 polarization of the neonatal adaptive immune response. Copyright © 2017 by The American Association of Immunologists, Inc.

Metabolomic analysis of primary metabolites in citrus leaf during defense responses.

PubMed

Asai, Tomonori; Matsukawa, Tetsuya; Kajiyama, Shin'ichiro

2017-03-01

Mechanical damage is one of the unavoidable environmental stresses to plant growth and development. Plants induce a variety of reactions which defend against natural enemies and/or heal the wounded sites. Jasmonic acid (JA) and salicylic acid (SA), defense-related plant hormones, are well known to be involved in induction of defense reactions and play important roles as signal molecules. However, defense related metabolites are so numerous and diverse that roles of individual compounds are still to be elucidated. In this report, we carried out a comprehensive analysis of metabolic changes during wound response in citrus plants which are one of the most commercially important fruit tree families. Changes in amino acid, sugar, and organic acid profiles in leaves were surveyed after wounding, JA and SA treatments using gas chromatography-mass spectrometry (GC/MS) in seven citrus species, Citrus sinensis, Citrus limon, Citrus paradisi, Citrus unshiu, Citrus kinokuni, Citrus grandis, and Citrus hassaku. GC/MS data were applied to multivariate analyses including hierarchical cluster analysis (HCA), primary component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) to extract stress-related compounds. HCA showed the amino acid cluster including phenylalanine and tryptophan, suggesting that amino acids in this cluster are concertedly regulated during responses against treatments. OPLS-DA exhibited that tryptophan was accumulated after wounding and JA treatments in all species tested, while serine was down regulated. Our results suggest that tryptophan and serine are common biomarker candidates in citrus plants for wound stress. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII.

PubMed

Kumar, Satish; Ceruso, Mariangela; Tuccinardi, Tiziano; Supuran, Claudiu T; Sharma, Pawan K

2016-07-01

Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

The inhibitory effects of phenolic Mannich bases on carbonic anhydrase I and II isoenzymes.

PubMed

Yamali, Cem; Tugrak, Mehtap; Gul, Halise Inci; Tanc, Muhammet; Supuran, Claudiu T

2016-12-01

Phenolic mono Mannich bases [2-[4-hydroxy-3-(aminomethyl)benzylidene]-2,3-dihydro-1H-inden-1-one (8-15)] and bis Mannich bases [2-[4-hydroxy-3,5-bis(aminomethyl)benzylidene]-2, 3-dihydro-1H-inden-1-one (2-7)] were synthesized starting from 2-(4-hydroxybenzylidene)-2, 3-dihydro-inden-1-one (1). This study was designed in order to investigate the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties of a library of compounds incorporating the phenol functional group. All prepared compounds showed a low inhibition percentages on both human (h) isoforms hCA I and hCA II compared to the reference sulfonamide acetazolamide. Mannich bases 2-15 had lower inhibition percentages than the compound 1 on hCA I and hCA II, except compound 14, which is a Mannich base derivative of dipropylamine, which had a similar inhibitory power as compound 1 on hCA II. All compounds synthesized 1-15 were 1.3-1.9 times more effective on hCA II comparing with the effectivenes of the compounds on hCA I.

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

PubMed

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Inhibition of heterocyclic amine formation in beef patties by ethanolic extracts of rosemary.

PubMed

Puangsombat, Kanithaporn; Smith, J Scott

2010-03-01

Heterocyclic amines (HCAs) are mutagenic compounds formed during cooking muscle foods at high temperature. Inhibition of HCAs by rosemary extracts were evaluated with beef patties cooked at 191 degrees C (375 degrees F) for 6 min each side and 204 degrees C (400 degrees F) for 5 min each side. Five rosemary extracts extracted with different solvents were used in this study: extract 100W (100% water), 10E (10% ethanol), 20E (20% ethanol), 30E (30% ethanol), and 40E (40% ethanol). The 5 extracts were directly added to beef patties at 3 levels (0.05%, 0.2%, and 0.5%) before cooking and HCA contents were extracted and quantified. All of the patties contained 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP). There was no statistical difference in the inhibition of HCAs in the 0.05%, 0.2%, and 0.5% rosemary extracts. All rosemary extracts significantly decreased the levels of MeIQx and PhIP at both cooking conditions. When cooking at 204 degrees C (400 degrees F) for 5 min each side, rosemary extracts 10E and 20E were superior to rosemary extracts 100W, 30E, and 40E in inhibiting HCA formation. Rosemary extract 20E showed the greatest inhibition of MeIQx (up to 91.7%) and PhIP (up to 85.3%). The inhibiting effect of rosemary extracts on HCA formation corresponded to their antioxidant activity based on a DPPH scavenging assay. Rosemary extract 10E and 20E contain a mixture of rosmarinic acid, carnosol, and carnosic acid. It is possible that these compounds might act synergistically in inhibiting the formation of HCAs.

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

PubMed Central

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Identification of hidden relationships from the coupling of hydrophobic cluster analysis and domain architecture information.

PubMed

Faure, Guilhem; Callebaut, Isabelle

2013-07-15

Describing domain architecture is a critical step in the functional characterization of proteins. However, some orphan domains do not match any profile stored in dedicated domain databases and are thereby difficult to analyze. We present here an original novel approach, called TREMOLO-HCA, for the analysis of orphan domain sequences and inspired from our experience in the use of Hydrophobic Cluster Analysis (HCA). Hidden relationships between protein sequences can be more easily identified from the PSI-BLAST results, using information on domain architecture, HCA plots and the conservation degree of amino acids that may participate in the protein core. This can lead to reveal remote relationships with known families of domains, as illustrated here with the identification of a hidden Tudor tandem in the human BAHCC1 protein and a hidden ET domain in the Saccharomyces cerevisiae Taf14p and human AF9 proteins. The results obtained in such a way are consistent with those provided by HHPRED, based on pairwise comparisons of HHMs. Our approach can, however, be applied even in absence of domain profiles or known 3D structures for the identification of novel families of domains. It can also be used in a reverse way for refining domain profiles, by starting from known protein domain families and identifying highly divergent members, hitherto considered as orphan. We provide a possible integration of this approach in an open TREMOLO-HCA package, which is fully implemented in python v2.7 and is available on request. Instructions are available at http://www.impmc.upmc.fr/∼callebau/tremolohca.html. isabelle.callebaut@impmc.upmc.fr Supplementary Data are available at Bioinformatics online.

The application of polymerized porcine hemoglobin (pPolyHb) in the rat small bowel preservation.

PubMed

Huang, He; Ma, Jun; Zhu, Wenjin; Sun, Jinghui; Yan, Kunping; Song, Bo; Xue, Yuejin; Xin, Jianguo; Pan, Wencan; Zhu, Hongli; Chen, Chao

2014-10-01

Small bowel transplantation (SBTx) has become a standard clinical treatment for short bowel syndrome or irreversible intestinal function failure. Optimum preservation of the organ is essential for the success of transplantation. In this study, pPolyHb was used as an additive to hypertonic citrate adenine solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution (UW) for 12, 24, and 36 h, respectively. The results suggested that the preservation effect of HCA with pPolyHb was comparable with the UW solution, and more effective than the HCA solution.

New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors.

PubMed

Gul, Halise Inci; Yamali, Cem; Sakagami, Hiroshi; Angeli, Andrea; Leitans, Janis; Kazaks, Andris; Tars, Kaspars; Ozgun, Dilan Ozmen; Supuran, Claudiu T

2018-04-01

In this study, new 4-[3-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (4-[5-(3,4,5-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA I/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA I/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. Copyright © 2018 Elsevier Inc. All rights reserved.

The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior.

PubMed

Buonanno, Martina; Di Fiore, Anna; Langella, Emma; D'Ambrosio, Katia; Supuran, Claudiu T; Monti, Simona Maria; De Simone, Giuseppina

2018-05-24

Although important progress has been achieved in understanding the catalytic mechanism of Carbonic Anhydrases, a detailed picture of all factors influencing the catalytic efficiency of the various human isoforms is still missing. In this paper we report a detailed structural study and theoretical pKa calculations on a hCA VII variant. The obtained data were compared with those already known for another thoroughly investigated cytosolic isoform, hCA II. Our structural studies show that in hCA VII the network of ordered water molecules, which connects the zinc bound solvent molecule to the proton shuttle His64, is altered compared to hCA II, causing a reduction of the catalytic efficiency. Theoretical calculations suggest that changes in solvent network are related to the difference in pKa of the proton shuttle in the two enzymes. The residue that plays a major role in determining the diverse pKa values of the proton shuttle is the one in position four, namely His for hCA II and Gly for hCA VII. This residue is located on the protein surface, outside of the active site cavity. These findings are in agreement with our previous studies that highlighted the importance of histidines on the protein surface of hCA II (among which His4) as crucial residues for the high catalytic efficiency of this isoform.

Coupled Abiotic-Biotic Degradation of Bisphenol A

NASA Astrophysics Data System (ADS)

Im, J.; Prevatte, C.; Campagna, S. R.; Loeffler, F.

2014-12-01

Bisphenol A (BPA) is a ubiquitous environmental contaminant with weak estrogenic activity. BPA is readily biodegradable with oxygen available, but is recalcitrant to microbial degradation under anoxic conditions. However, BPA is susceptible to abiotic transformation under anoxic conditions. To better understand the fate of BPA in anoxic environments, the kinetics of BPA transformation by manganese oxide (d-MnO2) were investigated. BPA was rapidly transformed by MnO2 with a pseudo-first-order rate constant of 0.413 min-1. NMR and LC-MS analyses identified 4-hydroxycumyl alcohol (HCA) as a major intermediate. Up to 64% of the initial amount of BPA was recovered as HCA within 5 min, but the conversion efficiency decreased with time, suggesting that HCA was further degraded by MnO2. Further experiments confirmed that HCA was also susceptible to transformation by MnO2, albeit at 5-fold lower rates than BPA transformation. Mass balance approaches suggested that HCA was the major BPA transformation intermediate, but other compounds may also be formed. The abiotic transformation of BPA by MnO2 was affected by pH, and 10-fold higher transformation rates were observed at pH 4.5 than at pH 10. Compared to BPA, HCA has a lower octanol-water partitioning coefficient (Log Kow) of 0.76 vs 2.76 for BPA and a higher aqueous solubility of 2.65 g L-1 vs 0.31 g L-1 for BPA, suggesting higher mobility of HCA in the environment. Microcosms established with freshwater sediment materials collected from four geographically distinct locations and amended with HCA demonstrated rapid HCA biodegradation under oxic, but not under anoxic conditions. These findings suggest that BPA is not inert under anoxic conditions and abiotic reactions with MnO2 generate HCA, which has increased mobility and is susceptible to aerobic degradation. Therefore, coupled abiotic-biotic processes can affect the fate and longevity of BPA in terrestrial environments.

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.

PubMed

Sun, Xujuan; Wei, Bin; Liu, Shuqing; Guo, Chunmei; Wu, Na; Liu, Qinlong; Sun, Ming-Zhong

2016-12-01

Annexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism. RNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways. We obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways. Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Amino acid distribution in meteorites: diagenesis, extraction methods, and standard metrics in the search for extraterrestrial biosignatures.

PubMed

McDonald, Gene D; Storrie-Lombardi, Michael C

2006-02-01

The relative abundance of the protein amino acids has been previously investigated as a potential marker for biogenicity in meteoritic samples. However, these investigations were executed without a quantitative metric to evaluate distribution variations, and they did not account for the possibility of interdisciplinary systematic error arising from inter-laboratory differences in extraction and detection techniques. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and stochastic probabilistic artificial neural networks (ANNs) were used to compare the distributions for nine protein amino acids previously reported for the Murchison carbonaceous chondrite, Mars meteorites (ALH84001, Nakhla, and EETA79001), prebiotic synthesis experiments, and terrestrial biota and sediments. These techniques allowed us (1) to identify a shift in terrestrial amino acid distributions secondary to diagenesis; (2) to detect differences in terrestrial distributions that may be systematic differences between extraction and analysis techniques in biological and geological laboratories; and (3) to determine that distributions in meteoritic samples appear more similar to prebiotic chemistry samples than they do to the terrestrial unaltered or diagenetic samples. Both diagenesis and putative interdisciplinary differences in analysis complicate interpretation of meteoritic amino acid distributions. We propose that the analysis of future samples from such diverse sources as meteoritic influx, sample return missions, and in situ exploration of Mars would be less ambiguous with adoption of standardized assay techniques, systematic inclusion of assay standards, and the use of a quantitative, probabilistic metric. We present here one such metric determined by sequential feature extraction and normalization (PCA), information-driven automated exploration of classification possibilities (HCA), and prediction of classification accuracy (ANNs).

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

Discrimination of honeys using colorimetric sensor arrays, sensory analysis and gas chromatography techniques.

PubMed

Tahir, Haroon Elrasheid; Xiaobo, Zou; Xiaowei, Huang; Jiyong, Shi; Mariod, Abdalbasit Adam

2016-09-01

Aroma profiles of six honey varieties of different botanical origins were investigated using colorimetric sensor array, gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis. Fifty-eight aroma compounds were identified, including 2 norisoprenoids, 5 hydrocarbons, 4 terpenes, 6 phenols, 7 ketones, 9 acids, 12 aldehydes and 13 alcohols. Twenty abundant or active compounds were chosen as key compounds to characterize honey aroma. Discrimination of the honeys was subsequently implemented using multivariate analysis, including hierarchical clustering analysis (HCA) and principal component analysis (PCA). Honeys of the same botanical origin were grouped together in the PCA score plot and HCA dendrogram. SPME-GC/MS and colorimetric sensor array were able to discriminate the honeys effectively with the advantages of being rapid, simple and low-cost. Moreover, partial least squares regression (PLSR) was applied to indicate the relationship between sensory descriptors and aroma compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetics of Forming Aldehydes in Frying Oils and Their Distribution in French Fries Revealed by LC-MS-Based Chemometrics.

PubMed

Wang, Lei; Csallany, A Saari; Kerr, Brian J; Shurson, Gerald C; Chen, Chi

2016-05-18

In this study, the kinetics of aldehyde formation in heated frying oils was characterized by 2-hydrazinoquinoline derivatization, liquid chromatography-mass spectrometry (LC-MS) analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The aldehydes contributing to time-dependent separation of heated soybean oil (HSO) in a PCA model were grouped by the HCA into three clusters (A1, A2, and B) on the basis of their kinetics and fatty acid precursors. The increases of 4-hydroxynonenal (4-HNE) and the A2-to-B ratio in HSO were well-correlated with the duration of thermal stress. Chemometric and quantitative analysis of three frying oils (soybean, corn, and canola oils) and French fry extracts further supported the associations between aldehyde profiles and fatty acid precursors and also revealed that the concentrations of pentanal, hexanal, acrolein, and the A2-to-B ratio in French fry extracts were more comparable to their values in the frying oils than other unsaturated aldehydes. All of these results suggest the roles of specific aldehydes or aldehyde clusters as novel markers of the lipid oxidation status for frying oils or fried foods.

Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action.

PubMed

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Akdemir, Atilla; Isik, Semra; Lanzi, Cecilia; Scozzafava, Andrea; Masini, Emanuela; Supuran, Claudiu T

2015-05-15

A new series of dithiocarbamates (DTCs) was prepared from primary/secondary amines incorporating amino/hydroxyl-alkyl, mono- and bicyclic aliphatic ring systems based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, and carbon disulfide. The compounds were investigated for the inhibition of four mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, that is, the human (h) hCA I, II, IX and XII, drug targets for antiglaucoma (hCA II and XII) or antitumor (hCA IX/XII) agents. The compounds were moderate or inefficient hCA I inhibitors (off-target isoform for both applications), efficiently inhibited hCA II, whereas some of them were low nanomolar/subnanomolar hCA IX/XII inhibitors. One DTC showed excellent intraocular pressure (IOP) lowering properties in an animal model of glaucoma, with a two times better efficiency compared to the clinically used sulfonamide dorzolamide. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes.

PubMed

Gul, Halise Inci; Yamali, Cem; Bulbuller, Merve; Kirmizibayrak, Petek Ballar; Gul, Mustafa; Angeli, Andrea; Bua, Silvia; Supuran, Claudiu T

2018-08-01

In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1 H NMR, 13 C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively. Copyright © 2018 Elsevier Inc. All rights reserved.

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

48 CFR 301.604-71 - HCA authorities and responsibilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false HCA authorities and responsibilities. 301.604-71 Section 301.604-71 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 301.604-71 HCA authorities and...

Can a decision-making model be justified in the management of hepatocellular adenoma?

PubMed

van Aalten, Susanna M; Witjes, Caroline D M; de Man, Robert A; Ijzermans, Jan N M; Terkivatan, Türkan

2012-01-01

During recent years, there was a great development in the area of hepatocellular adenomas (HCA), especially regarding the pathological subtype classification, radiological imaging and management during pregnancy. This review discusses the current knowledge about diagnosis and treatment modalities of HCA and proposes a decision-making model for HCA. A Medline search of studies relevant to epidemiology, histopathology, complications, imaging and management of HCA lesions was undertaken. References from identified articles were hand-searched for further relevant articles. © 2011 John Wiley & Sons A/S.

Heterocyclic periphery in the design of carbonic anhydrase inhibitors: 1,2,4-Oxadiazol-5-yl benzenesulfonamides as potent and selective inhibitors of cytosolic hCA II and membrane-bound hCA IX isoforms.

PubMed

Krasavin, Mikhail; Shetnev, Anton; Sharonova, Tatyana; Baykov, Sergey; Tuccinardi, Tiziano; Kalinin, Stanislav; Angeli, Andrea; Supuran, Claudiu T

2018-02-01

A series of novel aromatic primary sulfonamides decorated with diversely substituted 1,2,4-oxadiazole periphery groups has been prepared using a parallel chemistry approach. The compounds displayed a potent inhibition of cytosolic hCA II and membrane-bound hCA IX isoforms. Due to a different cellular localization of the two target enzymes, the compounds can be viewed as selective inhibition tools for either isoform, depending on the cellular permeability profile. The SAR findings revealed in this study has been well rationalized by docking simulation of the key compounds against the crystal structures of the relevant hCA isoforms. Copyright © 2017. Published by Elsevier Inc.

2'-Hydroxycinnamaldehyde induces apoptosis through HSF1-mediated BAG3 expression.

PubMed

Nguyen, Hai-Anh; Kim, Soo-A

2017-01-01

BAG3, a member of BAG co-chaperone family, is induced by stressful stimuli such as heat shock and heavy metals. Through interaction with various binding partners, BAG3 is thought to play a role in cellular adaptive responses against stressful conditions in normal and neoplastic cells. 2'-Hydroxycinnamaldehyde (HCA) is a natural derivative of cinnamaldehyde and has antitumor activity in various cancer cells. In the present study, for the first time, we identified that HCA induced BAG3 expression and BAG3-mediated apoptosis in cancer cells. The apoptotic cell death induced by HCA was demonstrated by caspase-7, -9 and PARP activation, and confirmed by Annexin V staining in both SW480 and SW620 colon cancer cells. Notably, both the mRNA and protein levels of BAG3 were largely induced by HCA in a dose- and time-dependent manner. By showing transcription factor HSF1 activation, we demonstrated that HCA induces the expression of BAG3 through HSF1 activation. More importantly, knockdown of BAG3 expression using siRNA largely inhibited HCA-induced apoptosis, suggesting that BAG3 is actively involved in HCA-induced cancer cell death. Considering the importance of the stress response mechanism in cancer progression, our results strongly suggest that BAG3 could be a potential target for anticancer therapy.

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.

PubMed

Shi, Ji; Meng, Longlong; Sun, Ming-Zhong; Guo, Chunmei; Sun, Xujuan; Lin, Qiuyue; Liu, Shuqing

2015-04-01

Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca-P cell, the in vitro proliferation, migration and invasion potentials were significantly enhanced following CRKL stable deregulation. CRKL knock-down significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca-P-transplanted mice. Consistent with our previous work, it can be concluded CRKL plays an important role in hepatocarcinoma cell proliferation, invasion and migration as well hepatocarcinoma malignancy and metastasis. It functions as a potential tumor suppressor in hepatocarcinoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin.

PubMed

Mahmoud, Salma Abdi; Ibrahim, Mohammed Mohammed; Musa, Ahmed Hago; Huang, Yuhong; Zhang, Jun; Wang, Jingwen; Wei, Yuanyi; Wang, Li; Zhou, Shunting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2017-12-23

Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it's effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%). Western blotting and qRT-PCR assay indicated that both in vitro and in vivo Sulf-1 was down-regulated by 75% and 68% and led to up regulation of Msln by 55% in shRNA-transfected-Sulf-1-Hca-P cells compared with Hca-P and nonspecific sequence control plasmid transfected Hca-P cell (shRNA-Nc-Hca-P). The in vitro proliferation, migration and invasion potentials were significantly enhanced following Sulf-1 stable down-regulation. In addition, Sulf-1 knock-down significantly promoted tumor growth and increased LNM rates of shRNA-Sulf-1-Hca-P-transplanted mice by 78.6% (11 out of 14 lymph nodes were positive of cancer). Consistent with our previous work, we confirmed that Sulf-1 plays an important role in hepatocarcinoma cell proliferation, migration, invasion and metastasis. The interaction between Sulf-1 and Msln is a potential therapeutic target in the development of liver cancer therapy.

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

PubMed

Yamazaki, H; Sasagawa, T; Basha, W; Segawa, T; Inoue, M

2001-10-15

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions. Copyright 2001 Wiley-Liss, Inc.

A Chaotic Ordered Hierarchies Consistency Analysis Performance Evaluation Model

NASA Astrophysics Data System (ADS)

Yeh, Wei-Chang

2013-02-01

The Hierarchies Consistency Analysis (HCA) is proposed by Guh in-cooperated along with some case study on a Resort to reinforce the weakness of Analytical Hierarchy Process (AHP). Although the results obtained enabled aid for the Decision Maker to make more reasonable and rational verdicts, the HCA itself is flawed. In this paper, our objective is to indicate the problems of HCA, and then propose a revised method called chaotic ordered HCA (COH in short) which can avoid problems. Since the COH is based upon Guh's method, the Decision Maker establishes decisions in a way similar to that of the original method.

The impact of HCA's 2006 leveraged buyout on hospital performance.

PubMed

McCue, Michael J; Thompson, Jon M

2012-01-01

Leveraged buyout (LBO) arrangements are a reorganization strategy whereby a firm assumes a substantial amount of debt to buy back its publicly held stock to become privately held. LBOs offer a firm several advantages and have the potential to increase efficiency. In the past 20 years, several healthcare firms have engaged in LBOs, but the literature on performance changes in healthcare organizations as a result of an LBO is limited. In this article, we report on a study that examined the performance of Hospital Corporation of America (HCA) hospitals before and after the LBO that was initiated in 2006. We used data from the Medicare Hospital Cost Report Information System and analyzed data from 130 HCA hospitals and 490 comparison hospitals. Findings show that HCA hospitals reduced expenses and their number of full-time equivalents (FTEs) relative to local competitor hospitals. HCA hospitals' cash-flow-margin ratio was substantially higher when adjusted for its local competing hospitals at the beginning of the LBO as well as at end of the LBO. When compared to local hospitals, HCA hospitals had a significant decrease in their capital investment in fixed assets from 2006 to 2009. These findings underscore the effectiveness of HCA's management strategies to repay debt and increase the value of the company, and they are informative for healthcare firms and their managers who are considering LBOs.

Bridge over troubled proline: assignment of intrinsically disordered proteins using (HCA)CON(CAN)H and (HCA)N(CA)CO(N)H experiments concomitantly with HNCO and i(HCA)CO(CA)NH.

PubMed

Hellman, Maarit; Piirainen, Henni; Jaakola, Veli-Pekka; Permi, Perttu

2014-01-01

NMR spectroscopy is by far the most versatile and information rich technique to study intrinsically disordered proteins (IDPs). While NMR is able to offer residue level information on structure and dynamics, assignment of chemical shift resonances in IDPs is not a straightforward process. Consequently, numerous pulse sequences and assignment protocols have been developed during past several years, targeted especially for the assignment of IDPs, including experiments that employ H(N), H(α) or (13)C detection combined with two to six indirectly detected dimensions. Here we propose two new HN-detection based pulse sequences, (HCA)CON(CAN)H and (HCA)N(CA)CO(N)H, that provide correlations with (1)H(N)(i - 1), (13)C'(i - 1) and (15)N(i), and (1)H(N)(i + 1), (13)C'(i) and (15)N(i) frequencies, respectively. Most importantly, they offer sequential links across the proline bridges and enable filling the single proline gaps during the assignment. We show that the novel experiments can efficiently complement the information available from existing HNCO and intraresidual i(HCA)CO(CA)NH pulse sequences and their concomitant usage enabled >95 % assignment of backbone resonances in cytoplasmic tail of adenosine receptor A2A in comparison to 73 % complete assignment using the HNCO/i(HCA)CO(CA)NH data alone.

Annexin A11 knockdown inhibits in vitro proliferation and enhances survival of Hca-F cell via Akt2/FoxO1 pathway and MMP-9 expression.

PubMed

Liu, Shuqing; Wang, Jiasheng; Guo, Chunmei; Qi, Houbao; Sun, Ming-Zhong

2015-03-01

Annexin A11 (Anxa11), a Ca(2+)-regulated phospholipid-binding protein, is involved in cell apoptosis, differentiation, vesicle trafficking, cancer progression and autoimmune diseases. Previous study from our group indicated that Anxa11 was associated with lymphatic metastatic potential of murine hepatocarcinoma cells. Herein, we investigated the effects and action mechanism of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a murine hepatocarcinoma cell with∼75% lymph node metastatic potential. Real-time PCR and western blotting assays indicated that Anxa11 was significantly downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11 knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and active MMP-9 protein levels were significantly elevated in Hca-F cells. In conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11 might play an important role in hepatocarcinoma cell invasion and metastasis and hepatocarcinoma malignancy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Organic Acids: The Pools of Fixed Carbon Involved in Redox Regulation and Energy Balance in Higher Plants

PubMed Central

Igamberdiev, Abir U.; Eprintsev, Alexander T.

2016-01-01

Organic acids are synthesized in plants as a result of the incomplete oxidation of photosynthetic products and represent the stored pools of fixed carbon accumulated due to different transient times of conversion of carbon compounds in metabolic pathways. When redox level in the cell increases, e.g., in conditions of active photosynthesis, the tricarboxylic acid (TCA) cycle in mitochondria is transformed to a partial cycle supplying citrate for the synthesis of 2-oxoglutarate and glutamate (citrate valve), while malate is accumulated and participates in the redox balance in different cell compartments (via malate valve). This results in malate and citrate frequently being the most accumulated acids in plants. However, the intensity of reactions linked to the conversion of these compounds can cause preferential accumulation of other organic acids, e.g., fumarate or isocitrate, in higher concentrations than malate and citrate. The secondary reactions, associated with the central metabolic pathways, in particularly with the TCA cycle, result in accumulation of other organic acids that are derived from the intermediates of the cycle. They form the additional pools of fixed carbon and stabilize the TCA cycle. Trans-aconitate is formed from citrate or cis-aconitate, accumulation of hydroxycitrate can be linked to metabolism of 2-oxoglutarate, while 4-hydroxy-2-oxoglutarate can be formed from pyruvate and glyoxylate. Glyoxylate, a product of either glycolate oxidase or isocitrate lyase, can be converted to oxalate. Malonate is accumulated at high concentrations in legume plants. Organic acids play a role in plants in providing redox equilibrium, supporting ionic gradients on membranes, and acidification of the extracellular medium. PMID:27471516

The effect of sodium pertechnetate human carbonic anhydrase I and II

NASA Astrophysics Data System (ADS)

Sahin, Ali; Senturk, Murat

2017-04-01

The inhibitory effects of Na99mTcO4 (Sodium pertechnetate) on human erythrocyte carbonic anhydrase I and II activity were investigated. For this purpose, hCA I was initially purified 114,29-fold at a yield of 69,19 % and hCA II was initially purified 710,82-fold at a yield of 71,72 % using sepharose 4B-tyrosine-sulfanilamide affinity gel chromatography. The in vitro effect of this compound on hCA I and II isoenzyme were studied. It was detected in in vitro studies that the hCA I and II enzymes are inhibited due to Na99mTcO4.

Brain Injury in Canine Models of Cardiac Surgery

PubMed Central

Blue, Mary E.; Wilson, Mary Ann; Beaty, Claude A.; George, Timothy J.; Arnaoutakis, George J.; Haggerty, Kara A.; Jones, Melissa; Brawn, Jeffrey; Manmohan, Shaliza; Lange, Mary S.; Johnston, Michael V.; Baumgartner, William A.; Troncoso, Juan C.

2014-01-01

Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2 hours, 8 hours, 24 hours or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in CA hippocampus. Neuronal injury was minimal up to 24 hours post-1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that with longer survival time the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB. PMID:25383634

CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells.

PubMed

Lin, Qiuyue; Sun, Ming-Zhong; Guo, Chunmei; Shi, Ji; Chen, Xin; Liu, Shuqing

2015-02-01

The signal adaptor CRK family protein play important roles in cancer cell progression, proliferation, migration and invasion. Previously, we showed that CRK was involved in lymphatic metastatic potential of murine hepatocarcinoma cells. In current work, as a member of CRK family, chicken tumour virus number 10 regulator of kinase-like protein (CRKL) was revealed to be associated with malignant behaviors of Hca-P, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. CRKL overexpression in Hca-P by a constructed eukaryotic expression vector of pcDNA3.1/V5-HisB-CRKL significantly ameliorated its malignant biological properties. CCK-8 and soft agar colony formation assays indicated CRKL overexpression significantly inhibits the cell proliferation and colony formation abilities of Hca-P. Additionally, transwell assays indicated that the Hca-P cell migration and invasion capacities were apparently reduced following CRKL overexpression. As Hca-P is an ideal hepatocarcinoma cell model with low (initial) LNM potential, CRKL is shown to act as a potential suppressor and to provide new insight for both the malignant behaviors of hepatocarcinoma cells and lymphatic metastasis mechanism of hepatocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Effect of Ech1 overexpression on biological behavior of mouse hepatocarcinoma Hca-P cells in vitro].

PubMed

Wang, Mei; Song, Bo; Wang, Bo; Zhang, Jun; Tang, Jian-wu

2013-05-01

To investigate the effect of enoyl coenzyme A hydratase-1 (Ech1) on the proliferation and invasion ability of mouse hepatocarcinoma Hca-P cells in vitro. Recombinant pcDNA3.1(+)-Ech1 gene and pcDNA3.1(+) were transfected into Hca-P cells by cationic liposomes introduction. Clone of PEch1 cells that stably expressing Ech1 and clone of control Pvector cells were screened by G418. The Ech1 expression was identified subsequently by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The malignant behaviors of the cell lines were compared by proliferation, invasion and migration test. The cell line Hca-P cells stably expressing Ech1 gene was constructed. The relative expression of Ech1 mRNA in the PEch1 group was 3.21 ± 0.43 and in the Pvector group was 1.44 ± 0.03, with a significant difference between the two groups (P = 0.029). The results of ELISA revealed that the expression of Ech1 protein was 0.140 ± 0.005 in the PEch1 group, 0.088 ± 0.003 in the Pvector group, and 0.078 ± 0.006 in the Hca-P group, showing a significant difference between the PEch1 group and the Pvector and Hca-P groups (P < 0.05). Transwell migration test showed that the number of penetrated cells in the PEch1 group was 143.00 ± 7.25 cells, significantly higher than that of the Pvector group (95.73 ± 3.88 cells) and un-treated Hca-1 group (106.67 ± 3.54 cells, both P < 0.05). The Transwell invasion assay showed that the number of penetrated cells was 77.20 ± 5.46 cells in the PEch1 group, significantly higher than 46.34 ± 4.35 cells in the Pvector group and 49.80 ± 5.21 cells in the un-treated Hca-1 group (both P < 0.05). The results showed that overexpressed Ech1 in Hca-P cells may significantly increase the cell proliferation in a time-dependent manner. The up-regulation of Ech1 may increase to some extent the migration and invasion capacity of Hca-P cells. The efforts aiming at up-regulation of Ech1 expression may become a therapeutic target in the treatment of hepatocarcinoma.

Molecular Dynamics Simulations of Protein-Ligand Complexes in Near Physiological Conditions

NASA Astrophysics Data System (ADS)

Wambo, Thierry Oscar

Proteins are important molecules for their key functions. However, under certain circumstances, the function of these proteins needs to be regulated to keep us healthy. Ligands are small molecules often used to modulate the function of proteins. The binding affinity is a quantitative measure of how strong the ligand will modulate the function of the protein: a strong binding affinity will highly impact the performance of the protein. It becomes clear that it is critical to have appropriate techniques to accurately compute the binding affinity. The most difficult task in computer simulations is how to efficiently sample the space spanned by the ligand during the binding process. In this work, we have developed some schemes to compute the binding affinity of a ligand to a protein, and of a metal ion to a protein. Application of these techniques to some complexes yield results in agreement with experimental values. These methods are a brute force approach and make no assumption other than that the complexes are governed by the force field used. Specifically, we computed the free energy of binding between (1) human carbonic anhydrase II and the drug acetazolamide (hcaII-AZM), (2) human carbonic anhydrase II and the zinc ion (hcaII-Zinc), and (3) beta-lactoglobulin and five fatty acids complexes (BLG-FAs). We found the following free energies of binding in unit of kcal/mol: -12.96 +/-2.44 (-15.74) for hcaII-Zinc complex, -5.76+/-0.76 (-5.57) for BLG-OCA , -4.44+/-1.08 (-5.22) for BLG-DKA,-6.89+/-1.25 (-7.24) for BLG-DAO, -8.57+/-0.82 (-8.14) for BLG-MYR, -8.99+/-0.87 (-8.72) for BLG-PLM, and -11.87+/-1.8 (-10.8) for hcaII-AZM. The values inside the parentheses are experimental results. The simulations and quantitative analysis of each system provide interesting insights into the interactions between each entity and helps us to better understand the dynamics of these systems.

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

PubMed Central

Son, Jun Seong; Ko, Kwan Soo; Yeom, Joon Sup; Ki, Hyun Kyun; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kim, Yeon-Sook; Jung, Sook-In; Shin, Sang Yop; Oh, Hee Bok; Lee, Yeong Seon; Chung, Doo Ryeon; Lee, Nam Yong; Peck, Kyong Ran

2010-01-01

Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment. PMID:20592888

Simultaneous qualitative and quantitative evaluation of Ilex kudingcha C. J. tseng by using UPLC and UHPLC-qTOF-MS/MS.

PubMed

Zhou, Jie; Yi, Huan; Zhao, Zhong-Xiang; Shang, Xue-Ying; Zhu, Ming-Juan; Kuang, Guo-Jun; Zhu, Chen-Chen; Zhang, Lei

2018-06-05

In this study, a systematic method was established for the holistic quality control of Ilex kudingcha C. J. Tseng, a popular functional drink for adjuvant treatment of diabetes, hypertension, obesity and hyperlipidemia. Both qualitative and quantitative analyses were conducted. For qualitative analysis, an ultra high performance liquid chromatography (UHPLC) coupled with an electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-qTOF-MS) method was established for rapid separation and structural identification of the constituents in Ilex kudingcha. Samples were separated on an ACQUITY UPLC HSS T3C 18 column (2.1 mm × 100 mm, 1.8 μm) by gradient elution using 0.1% (v/v) formic acid (solvent A) and acetonitrile (solvent B) as mobile phases at a flow rate of 0.25 mL min -1 . The chromatographic profiling of Ilex kudingcha by UHPLC-qTOF-MS/MS resulted in the characterization of 53 compounds, comprising 18 compounds that were unambiguously identified by comparison with reference standards. For quantitative analysis, 18 major compounds from 15 batches of Ilex kudingcha samples were simultaneously detected by UPLC-DAD at wavelengths of 210 nm, 260 nm, and 326 nm. The method was validated with respect to precision, linearity, repeatability, stability, accuracy, and so on. The contents of the 18 target compounds were applied for hierarchical clustering analysis (HCA) and principal component analysis (PCA) to differentiate between the samples. The results of HCA and PCA were consistent with each other. Sample No. 1 differed significantly based on HCA and PCA, and the differentiating components were confirmed to originate from different batches of samples. Phenolic acids and triterpenes were found to be the main ingredients in Ilex kudingcha. This strategy was effective and straightforward, and provided a potential approach for holistic quality control of Ilex kudingcha. Copyright © 2018. Published by Elsevier B.V.

Seizures induced in immature rats by homocysteic acid and the associated brain damage are prevented by group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate.

PubMed

Folbergrová, Jaroslava; Druga, Rastislav; Otáhal, Jakub; Haugvicová, Renata; Mares, Pavel; Kubová, Hana

2005-04-01

The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

USAF Strategic Master Plan

DTIC Science & Technology

2015-05-01

objectives, and four annexes: the Human Capital Annex ( HCA ), Strategic Posture Annex (SPA), Capabilities Annex (CA), and the Science and Technology...translate the SMP’s comprehensive goals and objectives into tangible actions and priorities. The four annexes are as follows:  Human Capital Annex ( HCA ...Figure 1: Internal Structure of the SMP Through the HCA , SPA, CA, and STA, the SMP consolidates and transmits strategic direction to staffs

Separation of time scales in the HCA model for sand

NASA Astrophysics Data System (ADS)

Niemunis, Andrzej; Wichtmann, Torsten

2014-10-01

Separation of time scales is used in a high cycle accumulation (HCA) model for sand. An important difficulty of the model is the limited applicability of the Miner's rule to multiaxial cyclic loadings applied simultaneously or in a combination with monotonic loading. Another problem is the lack of simplified objective HCA formulas for geotechnical settlement problems. Possible solutions of these problems are discussed.

Truth in Negotiations Act: Getting the Incentives Right

DTIC Science & Technology

2014-12-01

Audit Agency DCMA Defense Contract Management Agency DOD Department of Defense HCA Head Contract Agency FFP firm fixed price FOUO for...Acquisition Regulation allows for certain TINA waivers under HCA approval. a. Increasing the use of TINA waivers may be a plausible solution if...reasonable expectations exist that fair and reasonable pricing is already established. For example, per FAR 15.403–1(c)(4) the HCA may waive the requirement

New superacid synthesized (fluorinated) tertiary benzenesulfonamides acting as selective hCA IX inhibitors: toward a new mode of carbonic anhydrase inhibition by sulfonamides.

PubMed

Métayer, Benoît; Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

2013-07-11

Tertiary substituted (fluorinated) benzenesulfonamides were synthesized in superacid HF/SbF5 and tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). Strong selectivity toward tumor-associated hCA IX, without inhibiting the offtarget hCA II, was observed, pointing out to a new mechanism of action compared to classical sulfonamides.

Hepatocellular Adenoma: Evaluation with Contrast-Enhanced Ultrasound and MRI and Correlation with Pathologic and Phenotypic Classification in 26 Lesions

PubMed Central

Manichon, Anne-Frédérique; Bancel, Brigitte; Durieux-Millon, Marion; Ducerf, Christian; Mabrut, Jean-Yves; Lepogam, Marie-Annick; Rode, Agnès

2012-01-01

Purpose. To review the contrast-enhanced ultrasonographic (CEUS) and magnetic resonance (MR) imaging findings in 25 patients with 26 hepatocellular adenomas (HCAs) and to compare imaging features with histopathologic results from resected specimen considering the new immunophenotypical classification. Material and Methods. Two abdominal radiologists reviewed retrospectively CEUS cineloops and MR images in 26 HCA. All pathological specimens were reviewed and classified into four subgroups (steatotic or HNF 1α mutated, inflammatory, atypical or β-catenin mutated, and unspecified). Inflammatory infiltrates were scored, steatosis, and telangiectasia semiquantitatively evaluated. Results. CEUS and MRI features are well correlated: among the 16 inflammatory HCA, 7/16 presented typical imaging features: hypersignal T2, strong arterial enhancement with a centripetal filling, persistent on delayed phase. 6 HCA were classified as steatotic with typical imaging features: a drop out signal, slight arterial enhancement, vanishing on late phase. Four HCA were classified as atypical with an HCC developed in one. Five lesions displayed important steatosis (>50%) without belonging to the HNF1α group. Conclusion. In half cases, inflammatory HCA have specific imaging features well correlated with the amount of telangiectasia and inflammatory infiltrates. An HCA with important amount of steatosis noticed on chemical shift images does not always belong to the HNF1α group. PMID:22811588

Increased pressure during retrograde cerebral perfusion provides better preservation of the Na+, K+-ATPase activity.

PubMed

Yang, Luojia; Li, Zhijun; Yang, Yanmin; Zhu, Raymound; Summers, Randy; Deslauriers, Roxanne; Ye, Jian

2006-11-01

This study was carried out to determine if increased perfusion pressure during retrograde cerebral perfusion (RCP) provides better preservation of the brain Na+, K+-ATPase activity. Twenty pigs were subjected to anesthesia alone (control group, n=5), hypothermic circulatory arrest (HCA) (HCA group, n = 5), HCA+RCP at perfusion pressures of 24-29 mmHg (Low-pressure group, n=5), or HCA+RCP at perfusion pressures of 34-40 mmHg (High-pressure group, n = 5). The brain was harvested for the measurement of tissue Na+, K+-ATPase activity. Relative to the control pigs (67.2 +/- 2.1%), significant impairment of Na+, K+-ATPase activity was observed in all three experimental groups (29.8 +/- 7.4% in HCA group, 33.5 +/- 2.9% in the Low-pressure group, and 52.0 +/- 1.8% in the High-pressure group, p < 0.01). The best preservation of the enzyme, particularly in the cortex and cerebellum regions, was observed in the High-pressure group (p < 0.01). In conclusion, HCA causes severe impairment of Na+, K+-ATPase activity, and increasing perfusion pressures from 24-29 to 34-40 mmHg during RCP significantly improves preservation of Na+, K+-ATPase activity, and the improvement of the protection varies in different regions of the brain.

Chorioamnionitis in pregnancy: a comparative study of HIV-positive and HIV-negative parturients.

PubMed

Ocheke, Amaka N; Agaba, Patricia A; Imade, Godwin E; Silas, Olugbenga A; Ajetunmobi, Olanrewaju I; Echejoh, Godwins; Ekere, Clement; Sendht, Ayuba; Bitrus, James; Agaba, Emmanuel I; Sagay, Atiene S

2016-03-01

Chorioamnionitis is an important risk factor for vertical transmission of HIV/AIDS. We compared the prevalence and correlates of histologic chorioamnionitis (HCA) in HIV-positive and HIV-negative pregnant women. HIV-positive and -negative parturients were interviewed, examined and had their placentas examined histologically for chorioamnionitis. Data regarding HIV were also retrieved from their hospital records. A total of 298 parturients (150 HIV positive and 148 HIV negative) were enrolled. The two groups were similar in socio-demographic and obstetric parameters except for age. The prevalence of HCA was 57.1% in HIV-positive women and 61.6% in HIV-negative women (p = 0.43). HCA staging was associated with the number of intrapartum vaginal examinations in HIV-positive subjects and nulliparity in HIV-negative subjects. The number of intrapartum vaginal examinations and coitus in the week prior to delivery significantly affected the grade of HCA in HIV-negative subjects. The prevalence of HCA in both HIV-positive and HIV-negative is high. Most variables did not affect the occurrence of HCA in both groups studied except number of intrapartum examinations, coitus in the preceding one week and nulliparity, which were related to severity of the disease. © The Author(s) 2016.

Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism-related genes on the association of HCA intake with the risk of colorectal adenomas.

PubMed

Barbir, Aline; Linseisen, Jakob; Hermann, Silke; Kaaks, Rudolf; Teucher, Birgit; Eichholzer, Monika; Rohrmann, Sabine

2012-09-01

Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC. A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis. CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance. HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.

A β-cyclodextrin, polyethyleneimine and silk fibroin hydrogel containing Centella asiatica extract and hydrocortisone acetate: releasing properties and in vivo efficacy for healing of pressure sores.

PubMed

Lee, M S; Seo, S R; Kim, J-C

2012-10-01

  Pressure sores are lesions caused by impaired blood flow. Conventional dressings can absorb exudates, but do not promote wound healing. A hydrogel composed of β-cyclodextrin (β-CD), polyethyleneimine (PEI) and silk fibroin (SF) was assessed for use in healing of pressure sores. The hydrogel was prepared by crosslinking β-CD-grafted PEI and SF using epichlorohydrin. The gel was then immersed in an aqueous solution of Centella asiatica extract (CAE) 0.7 mg/mL and/or hydrocortisone acetate (HCA) 0.5 mg/mL. The in vivo pressure sore-healing efficacy of the dry gel (with or without the drugs) was investigated in terms of the hyperplasia of epidermis and the number of neutrophils in the skin tissue. The specific loading of CAE was 0.0091 g/g of dry gel. The percentage of CAE released at 24 h at pH 3.0, 5.0 and 7.4 was approximately 63.9%, 55.0% and 44.4%, respectively. This pH-dependent release is possibly due to the degree of gel swelling, which decreased with increasing pH. The specific loading of HCA was 0.0050 g/g dry gel, and the percentage release of HCA at 24 h was around 20% at all three pH points. It is likely that HCA release is independent of pH. HCA is a hydrophobic compound, and therefore the release of HCA is affected by the partitioning of HCA between the β-CD cavity and the bulk water phase, but not by the degree of swelling of the hydrogel. The pressure sores treated with the hydrogel healed in 6 days, compared with 10 days for controls. In this study, a β-CD/PEI/SF hydrogel containing CAE and HCA reduced the healing time for pressure sores. © The Author(s). CED © 2012 British Association of Dermatologists.

Recurrent otitis media with effusion in preterm infants with histologic chorioamnionitis--a 3 years follow-up study.

PubMed

De Felice, Claudio; De Capua, Bruno; Costantini, Daniele; Martufi, Carla; Toti, Paolo; Tonni, Gabriele; Laurini, Ricardo; Giannuzzi, Annalisa; Latini, Giuseppe

2008-10-01

Recurrent otitis media with effusion (OME) is a leading cause of acquired hearing loss in childhood. Histological chorioamnionitis (HCA) is an important cause of preterm delivery and neonatal morbidity and mortality. Here, we tested the hypothesis of an association between recurrent OME during the first 3 years of life and HCA in very low birth weight (VLBW) infants. A total of 110 randomly selected VLBW preterm newborns with HCA and 135 gestational age and gender-matched, HCA-negative VLBW infants were evaluated prospectively during the first 3 years of life for the presence of OME, as diagnosed on the basis of otoscopy, type B or C tympanogram, ipsilateral absence of transient evoked otoacoustic emissions responses, and ipsilaterally increased threshold at diagnostic auditory brain responses evaluation. Potential risk factors for OME were also examined in the two groups. The HCA-positive infants showed a approximately six times higher frequency of recurrent OME (P<0.0001), increased frequency (>5/yr) of clinical otitis media episodes (P=0.000020), approximately five times higher frequency of adenoid hypertrophy (P<0.00001), a significant seasonal pattern of birth with autumn predominance (P<0.00001), and the first OME occurred earlier (P<0.0001), as compared to the HCA-negative counterparts. Recurrent OME was significantly associated with HCA (O.R.=17.76, 95% CI: 8.98-35.13, P<0.00001), adenoid hypertrophy (O.R.=9.96, 95% CI: 5.17-19.18, P<0.00001), frequency of acute otitis episodes >5/yr (O.R.=8.91, 95% CI: 1.96-40.41, P=0.0005), and birth in autumn (O.R.=5.58, 95% CI: 2.79-11.12, P<0.00001). These findings indicate that HCA is a previously unrecognized risk factor for the development of recurrent bilateral OME in VLBW preterm infants during the first 3 years of life.

Delineation of Stenotrophomonas maltophilia isolates from cystic fibrosis patients by fatty acid methyl ester profiles and matrix-assisted laser desorption/ionization time-of-flight mass spectra using hierarchical cluster analysis and principal component analysis.

PubMed

Vidigal, Pedrina Gonçalves; Mosel, Frank; Koehling, Hedda Luise; Mueller, Karl Dieter; Buer, Jan; Rath, Peter Michael; Steinmann, Joerg

2014-12-01

Stenotrophomonas maltophilia is an opportunist multidrug-resistant pathogen that causes a wide range of nosocomial infections. Various cystic fibrosis (CF) centres have reported an increasing prevalence of S. maltophilia colonization/infection among patients with this disease. The purpose of this study was to assess specific fingerprints of S. maltophilia isolates from CF patients (n = 71) by investigating fatty acid methyl esters (FAMEs) through gas chromatography (GC) and highly abundant proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to compare them with isolates obtained from intensive care unit (ICU) patients (n = 20) and the environment (n = 11). Principal component analysis (PCA) of GC-FAME patterns did not reveal a clustering corresponding to distinct CF, ICU or environmental types. Based on the peak area index, it was observed that S. maltophilia isolates from CF patients produced significantly higher amounts of fatty acids in comparison with ICU patients and the environmental isolates. Hierarchical cluster analysis (HCA) based on the MALDI-TOF MS peak profiles of S. maltophilia revealed the presence of five large clusters, suggesting a high phenotypic diversity. Although HCA of MALDI-TOF mass spectra did not result in distinct clusters predominantly composed of CF isolates, PCA revealed the presence of a distinct cluster composed of S. maltophilia isolates from CF patients. Our data suggest that S. maltophilia colonizing CF patients tend to modify not only their fatty acid patterns but also their protein patterns as a response to adaptation in the unfavourable environment of the CF lung. © 2014 The Authors.

A premerger profile of Columbia and HCA hospitals.

PubMed

McCue, M J

1996-01-01

This article profiles the premerger marketing, management, and mission characteristics of the combined Columbia and Hospital Corporation of America (HCA) entity relative to local market hospitals. The findings show that the Columbia/HCA hospitals had fewer Medicaid patients, lower proportion of outpatient revenues, higher operating cash flow per bed, lower occupancy rates, lower salary expense per discharge, higher debt to total assets, fewer beds, and a higher case-mix index relative to local competitors.

Identification of ATP Citrate Lyase as a Positive Regulator of Glycolytic Function in Glioblastomas

PubMed Central

Beckner, Marie E.; Fellows-Mayle, Wendy; Zhang, Zhe; Agostino, Naomi R.; Kant, Jeffrey A.; Day, Billy W.; Pollack, Ian F.

2009-01-01

Glioblastomas, the most malignant type of glioma, are more glycolytic than normal brain tissue. Robust migration of glioblastoma cells has been previously demonstrated under glycolytic conditions and their pseudopodia contain increased glycolytic and decreased mitochondrial enzymes. Glycolysis is suppressed by metabolic acids, including citric acid which is excluded from mitochondria during hypoxia. We postulated that glioma cells maintain glycolysis by regulating metabolic acids, especially in their pseudopodia. The enzyme that breaks down cytosolic citric acid is ATP citrate lyase (ACLY). Our identification of increased ACLY in pseudopodia of U87 glioblastoma cells on 1D gels and immunoblots prompted investigation of ACLY gene expression in gliomas for survival data and correlation with expression of ENO1, that encodes enolase 1. Queries of the NIH’s REMBRANDT brain tumor database based on Affymetrix data indicated that decreased survival correlated with increased gene expression of ACLY in gliomas. Queries of gliomas and glioblastomas found an association of upregulated ACLY and ENO1 expression by chi square for all probe sets (reporters) combined and correlation for numbers of probe sets indicating shared upregulation of these genes. Real-time quantitative PCR confirmed correlation between ACLY and ENO1 in 21 glioblastomas (p < 0.001). Inhibition of ACLY with hydroxycitrate suppressed (p < 0.05) in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhanced the suppressive effects of a Met inhibitor on cell migration. In summary, gene expression data, proteomics and functional assays support ACLY as a positive regulator of glycolysis in glioblastomas. PMID:19795461

End of an era. Justice Department ends nine-year criminal probe of Columbia/HCA executives, but company recovery began earlier.

PubMed

Galloro, Vince

2002-07-29

The longest, costlest criminal healthcare fraud probe in U.S. history is finally over, but its ripple effects are likely to continue. The Columbia/HCA Healthcare Corp. case raised questions about healthcare accounting practices long before the current wave of corporate scandals. But the consensus is that the most crucial step in retooling HCA's image was restoring Thomas First Jr. (left) as chairman and CEO.

Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms.

PubMed

D'Ascenzio, Melissa; Guglielmi, Paolo; Carradori, Simone; Secci, Daniela; Florio, Rosalba; Mollica, Adriano; Ceruso, Mariangela; Akdemir, Atilla; Sobolev, Anatoly P; Supuran, Claudiu T

2017-12-01

A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (K i s > 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with K i s ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (K i s ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.

High-Content Microscopy Analysis of Subcellular Structures: Assay Development and Application to Focal Adhesion Quantification.

PubMed

Kroll, Torsten; Schmidt, David; Schwanitz, Georg; Ahmad, Mubashir; Hamann, Jana; Schlosser, Corinne; Lin, Yu-Chieh; Böhm, Konrad J; Tuckermann, Jan; Ploubidou, Aspasia

2016-07-01

High-content analysis (HCA) converts raw light microscopy images to quantitative data through the automated extraction, multiparametric analysis, and classification of the relevant information content. Combined with automated high-throughput image acquisition, HCA applied to the screening of chemicals or RNAi-reagents is termed high-content screening (HCS). Its power in quantifying cell phenotypes makes HCA applicable also to routine microscopy. However, developing effective HCA and bioinformatic analysis pipelines for acquisition of biologically meaningful data in HCS is challenging. Here, the step-by-step development of an HCA assay protocol and an HCS bioinformatics analysis pipeline are described. The protocol's power is demonstrated by application to focal adhesion (FA) detection, quantitative analysis of multiple FA features, and functional annotation of signaling pathways regulating FA size, using primary data of a published RNAi screen. The assay and the underlying strategy are aimed at researchers performing microscopy-based quantitative analysis of subcellular features, on a small scale or in large HCS experiments. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

The response of soil solution chemistry in European forests to decreasing acid deposition.

PubMed

Johnson, James; Graf Pannatier, Elisabeth; Carnicelli, Stefano; Cecchini, Guia; Clarke, Nicholas; Cools, Nathalie; Hansen, Karin; Meesenburg, Henning; Nieminen, Tiina M; Pihl-Karlsson, Gunilla; Titeux, Hugues; Vanguelova, Elena; Verstraeten, Arne; Vesterdal, Lars; Waldner, Peter; Jonard, Mathieu

2018-03-31

Acid deposition arising from sulphur (S) and nitrogen (N) emissions from fossil fuel combustion and agriculture has contributed to the acidification of terrestrial ecosystems in many regions globally. However, in Europe and North America, S deposition has greatly decreased in recent decades due to emissions controls. In this study, we assessed the response of soil solution chemistry in mineral horizons of European forests to these changes. Trends in pH, acid neutralizing capacity (ANC), major ions, total aluminium (Al tot ) and dissolved organic carbon were determined for the period 1995-2012. Plots with at least 10 years of observations from the ICP Forests monitoring network were used. Trends were assessed for the upper mineral soil (10-20 cm, 104 plots) and subsoil (40-80 cm, 162 plots). There was a large decrease in the concentration of sulphate (SO42-) in soil solution; over a 10-year period (2000-2010), SO42- decreased by 52% at 10-20 cm and 40% at 40-80 cm. Nitrate was unchanged at 10-20 cm but decreased at 40-80 cm. The decrease in acid anions was accompanied by a large and significant decrease in the concentration of the nutrient base cations: calcium, magnesium and potassium (Bc = Ca 2+  + Mg 2+  + K + ) and Al tot over the entire dataset. The response of soil solution acidity was nonuniform. At 10-20 cm, ANC increased in acid-sensitive soils (base saturation ≤10%) indicating a recovery, but ANC decreased in soils with base saturation >10%. At 40-80 cm, ANC remained unchanged in acid-sensitive soils (base saturation ≤20%, pHCaCl2 ≤ 4.5) and decreased in better-buffered soils (base saturation >20%, pHCaCl2 > 4.5). In addition, the molar ratio of Bc to Al tot either did not change or decreased. The results suggest a long-time lag between emission abatement and changes in soil solution acidity and underline the importance of long-term monitoring in evaluating ecosystem response to decreases in deposition. © 2018 John Wiley & Sons Ltd.

Applications of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS) to study interactions of genetically engineered proteins with noble metal films

NASA Astrophysics Data System (ADS)

Suzuki, Noriaki

Genetically engineered proteins for inorganics (GEPIs) belong to a new class of polypeptides that are designed to have specific affinities to inorganic materials. A "gold binding protein (GBP)" was chosen as a model protein for GEPIs to study the molecular origins of binding specificity to gold using Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS). TOF-SIMS, a surface-sensitive analytical instrument with extremely high mass resolutions, provides information on specific amino acid-surface interactions. We used "principal component analysis (PCA)" to analyze the data. We also introduced a new multivariate technique, "hierarchical cluster analysis (HCA)" to organize the data into meaningful structures by measuring a degree of "similarity" and "dissimilarity" of the data. This report discusses a combined use of PCA and HCA to elucidate the binding specificity of GBP to Au. Based on the knowledge gained from TOF-SIMS measurements, we further investigated the nature of the interaction between selected amino acids and noble metal surfaces by using X-ray photoelectron spectroscopy (XPS). We developed a unique capability to introduce water vapor during the adsorption of a single amino acid and applied this method to study the intrinsic nature of sidechain/Au interactions. To further apply this unique research protocol, we characterized another type of GEPI, "quartz binding protein (QBP)," to identify the possible binding sites. This thesis research aims to provide experimental protocols for analyzing short peptide-substrate interface from complex spectroscopic data by using multivariate analysis techniques.

HCA Richmond Hospitals' new marketing strategy a winning plan.

PubMed

Rees, Tom

2003-01-01

HCA Richmond Hospitals, a five-hospital system in Richmond, Va., is positioning itself as a winner in a highly competitive, healthcare-saturated market since overhauling is marketing strategy a little over a year ago. The marketing strategy enables individual hospital to target their own unique constituencies. "Understanding the intricate marketing dynamics of hospital systems is today of critical importance and equal complexity," said Tony Bejamin, principal of Oxygen Advertising Inc., New York, the agency that remodeled HCA Richmond Hospitals' marketing strategy.

New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

NASA Astrophysics Data System (ADS)

Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

2017-06-01

Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

Characteristics of the divested HCA and AMI hospitals.

PubMed

McCue, M J; Clement, J P

1992-04-01

The primary aim of this study was to compare and contrast the predivestiture managerial and market characteristics of the following: Divested and nondivested hospitals of Hospital Corporation of America (HCA) and American Medical International (AMI). The findings indicated that HCA hospitals with 1) lower occupancy rates, 2) less growth in revenues, 3) higher debt to total asset position, 4) fewer beds, 5) less growth in their elderly populations, and 6) less growth in their markets' per capita incomes had a higher probability of being divested into HealthTrust. The results for the AMI model were similar to those for the HCA model. AMI hospitals with 1) fewer beds, 2) less growth in their markets' per capita incomes, 3) lower salary expenses per discharge, 4) lower occupancy rates, and 5) increased growth in populations had a higher probability of being divested into EPIC.

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II.

PubMed

Kılıcaslan, Soner; Arslan, Mustafa; Ruya, Zeynep; Bilen, Çigdem; Ergün, Adem; Gençer, Nahit; Arslan, Oktay

2016-12-01

Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a-l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC50 = 0.35 μM; Ki: 0.33 μM) for hCA I and hCA II.

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature.

PubMed

Ogielska, Maja; Lanotte, Philippe; Le Brun, Cécile; Valentin, Anne Sophie; Garot, Denis; Tellier, Anne-Charlotte; Halimi, Jean Michel; Colombat, Philippe; Guilleminault, Laurent; Lioger, Bertrand; Vegas, Hélène; De Toffol, Bertrand; Constans, Thierry; Bernard, Louis

2015-08-01

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18-97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.

PubMed

SitaRam; Celik, Gulsah; Khloya, Poonam; Vullo, Daniela; Supuran, Claudiu T; Sharma, Pawan K

2014-03-15

Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII. Copyright © 2014 Elsevier Ltd. All rights reserved.

A generalized analysis of hydrophobic and loop clusters within globular protein sequences

PubMed Central

Eudes, Richard; Le Tuan, Khanh; Delettré, Jean; Mornon, Jean-Paul; Callebaut, Isabelle

2007-01-01

Background Hydrophobic Cluster Analysis (HCA) is an efficient way to compare highly divergent sequences through the implicit secondary structure information directly derived from hydrophobic clusters. However, its efficiency and application are currently limited by the need of user expertise. In order to help the analysis of HCA plots, we report here the structural preferences of hydrophobic cluster species, which are frequently encountered in globular domains of proteins. These species are characterized only by their hydrophobic/non-hydrophobic dichotomy. This analysis has been extended to loop-forming clusters, using an appropriate loop alphabet. Results The structural behavior of hydrophobic cluster species, which are typical of protein globular domains, was investigated within banks of experimental structures, considered at different levels of sequence redundancy. The 294 more frequent hydrophobic cluster species were analyzed with regard to their association with the different secondary structures (frequencies of association with secondary structures and secondary structure propensities). Hydrophobic cluster species are predominantly associated with regular secondary structures, and a large part (60 %) reveals preferences for α-helices or β-strands. Moreover, the analysis of the hydrophobic cluster amino acid composition generally allows for finer prediction of the regular secondary structure associated with the considered cluster within a cluster species. We also investigated the behavior of loop forming clusters, using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic clusters and are highly associated with coils. Finally, the structural information contained in the hydrophobic structural words, as deduced from experimental structures, was compared to the PSI-PRED predictions, revealing that β-strands and especially α-helices are generally over-predicted within the limits of typical β and α hydrophobic clusters. Conclusion The dictionary of hydrophobic clusters described here can help the HCA user to interpret and compare the HCA plots of globular protein sequences, as well as provides an original fundamental insight into the structural bricks of protein folds. Moreover, the novel loop cluster analysis brings additional information for secondary structure prediction on the whole sequence through a generalized cluster analysis (GCA), and not only on regular secondary structures. Such information lays the foundations for developing a new and original tool for secondary structure prediction. PMID:17210072

Developing the role of the healthcare assistant.

PubMed

Hancock, H; Campbell, S

Two studies are described in this article. The first evaluated the preparedness of healthcare assistants (HCAs) to develop a new role and attend an HCA development programme. The second examined the impact of one NHS trust's HCA development programme on the role of the HCA, on other members of the multidisciplinary team and on patients. The research methodology was qualitative and inductive, using a naturalistic approach in both studies, and a 360 degree model of assessment and feedback in study two. For both studies, the data were analysed following the principles of thematic analysis. Findings Eight out of 12 HCAs in study one were prepared to attend the programme and to develop their role. Study two indicated a positive but restricted impact of the HCA development programme on the HCAs' role, that of other healthcare professionals and on patient care. The findings have implications for role development in the NHS and for the development of programmes that aim to address these changes. The HCA development programme has been reviewed and extended, and strategies to promote and support role development in the clinical setting have been introduced in the trust where the research was conducted.

High-Level Heteroatom Doped Two-Dimensional Carbon Architectures for Highly Efficient Lithium-Ion Storage.

PubMed

Wang, Zhijie; Wang, Yanyan; Wang, Wenhui; Yu, Xiaoliang; Lv, Wei; Xiang, Bin; He, Yan-Bing

2018-01-01

In this work, high-level heteroatom doped two-dimensional hierarchical carbon architectures (H-2D-HCA) are developed for highly efficient Li-ion storage applications. The achieved H-2D-HCA possesses a hierarchical 2D morphology consisting of tiny carbon nanosheets vertically grown on carbon nanoplates and containing a hierarchical porosity with multiscale pore size. More importantly, the H-2D-HCA shows abundant heteroatom functionality, with sulfur (S) doping of 0.9% and nitrogen (N) doping of as high as 15.5%, in which the electrochemically active N accounts for 84% of total N heteroatoms. In addition, the H-2D-HCA also has an expanded interlayer distance of 0.368 nm. When used as lithium-ion battery anodes, it shows excellent Li-ion storage performance. Even at a high current density of 5 A g -1 , it still delivers a high discharge capacity of 329 mA h g -1 after 1,000 cycles. First principle calculations verifies that such unique microstructure characteristics and high-level heteroatom doping nature can enhance Li adsorption stability, electronic conductivity and Li diffusion mobility of carbon nanomaterials. Therefore, the H-2D-HCA could be promising candidates for next-generation LIB anodes.

High-Level Heteroatom Doped Two-Dimensional Carbon Architectures for Highly Efficient Lithium-Ion Storage

NASA Astrophysics Data System (ADS)

Wang, Zhijie; Wang, Yanyan; Wang, Wenhui; Yu, Xiaoliang; Lv, Wei; Xiang, Bin; He, Yan-Bing

2018-04-01

In this work, high-level heteroatom doped two-dimensional hierarchical carbon architectures (H-2D-HCA) are developed for highly efficient Li-ion storage applications. The achieved H-2D-HCA possesses a hierarchical 2D morphology consisting of tiny carbon nanosheets vertically grown on carbon nanoplates and containing a hierarchical porosity with multiscale pore size. More importantly, the H-2D-HCA shows abundant heteroatom functionality, with sulfur (S) doping of 0.9 % and nitrogen (N) doping of as high as 15.5 %, in which the electrochemically active N accounts for 84 % of total N heteroatoms. In addition, the H-2D-HCA also has an expanded interlayer distance of 0.368 nm. When used as lithium-ion battery anodes, it shows excellent Li-ion storage performance. Even at a high current density of 5 A g-1, it still delivered a high discharge capacity of 329 mA h g-1 after 1000 cycles. First principle calculations verified that such unique microstructure characteristics and high-level heteroatom doping nature can enhance Li adsorption stability, electronic conductivity and Li diffusion mobility of carbon nanomaterials. Therefore, the H-2D-HCA could be promising candidates for next-generation LIB anodes.

Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer

PubMed Central

Michalczyk, Ryszard; Unkefer, Clifford J.; Bacik, John-Paul; Schrader, Tobias E.; Ostermann, Andreas; Kovalevsky, Andrey Y.; McKenna, Robert; Fisher, Suzanne Zoë

2015-01-01

Human carbonic anhydrase II (HCA II) uses a Zn-bound OH−/H2O mechanism to catalyze the reversible hydration of CO2. This catalysis also involves a separate proton transfer step, mediated by an ordered solvent network coordinated by hydrophilic residues. One of these residues, Tyr7, was previously shown to be deprotonated in the neutron crystal structure at pH 10. This observation indicated that Tyr7 has a perturbed pKa compared with free tyrosine. To further probe the pKa of this residue, NMR spectroscopic measurements of [13C]Tyr-labeled holo HCA II (with active-site Zn present) were preformed to titrate all Tyr residues between pH 5.4–11.0. In addition, neutron studies of apo HCA II (with Zn removed from the active site) at pH 7.5 and holo HCA II at pH 6 were conducted. This detailed interrogation of tyrosines in HCA II by NMR and neutron crystallography revealed a significantly lowered pKa of Tyr7 and how pH and Tyr proximity to Zn affect hydrogen-bonding interactions. PMID:25902526

Proton Environments in Biomimetic Calcium Phosphates Formed from Mesoporous Bioactive CaO-SiO2-P2O5 Glasses in Vitro: Insights from Solid-State NMR.

PubMed

Mathew, Renny; Turdean-Ionescu, Claudia; Yu, Yang; Stevensson, Baltzar; Izquierdo-Barba, Isabel; García, Ana; Arcos, Daniel; Vallet-Regí, María; Edén, Mattias

2017-06-22

When exposed to body fluids, mesoporous bioactive glasses (MBGs) of the CaO-SiO 2 -P 2 O 5 system develop a bone-bonding surface layer that initially consists of amorphous calcium phosphate (ACP), which transforms into hydroxy-carbonate apatite (HCA) with a very similar composition as bone/dentin mineral. Information from various 1 H-based solid-state nuclear magnetic resonance (NMR) experiments was combined to elucidate the evolution of the proton speciations both at the MBG surface and within each ACP/HCA constituent of the biomimetic phosphate layer formed when each of three MBGs with distinct Ca, Si, and P contents was immersed in a simulated body fluid (SBF) for variable periods between 15 min and 30 days. Directly excited magic-angle-spinning (MAS) 1 H NMR spectra mainly reflect the MBG component, whose surface is rich in water and silanol (SiOH) moieties. Double-quantum-single-quantum correlation 1 H NMR experimentation at fast MAS revealed their interatomic proximities. The comparatively minor H species of each ACP and HCA component were probed selectively by heteronuclear 1 H- 31 P NMR experimentation. The initially prevailing ACP phase comprises H 2 O and "nonapatitic" HPO 4 2- /PO 4 3- groups, whereas for prolonged MBG soaking over days, a well-progressed ACP → HCA transformation was evidenced by a dominating O 1 H resonance from HCA. We show that 1 H-detected 1 H → 31 P cross-polarization NMR is markedly more sensitive than utilizing powder X-ray diffraction or 31 P NMR for detecting the onset of HCA formation, notably so for P-bearing (M)BGs. In relation to the long-standing controversy as to whether bone mineral comprises ACP and/or forms via an ACP precursor, we discuss a recently accepted structural core-shell picture of both synthetic and biological HCA, highlighting the close relationship between the disordered surface layer and ACP.

48 CFR 801.695-1 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... experience necessary to make the decisions required of an HCA. (c) Except as provided in the FAR, an HCA may... delegation may include authority to appoint a contracting officer at the Micro-purchase Level or the Level I...

HCA regulation.

PubMed

Dory Rogers, Clare

2016-10-26

I'm proud to be a healthcare assistant (HCA) and aim to do my best by patients and provide evidence-based care. I think it's time for regulation of HCAs. We need the protection, as do the nurses who delegate to us.

Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

PubMed

Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

2012-05-01

This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

Productivity Losses Associated with Head and Neck Cancer Using the Human Capital and Friction Cost Approaches.

PubMed

Pearce, Alison M; Hanly, Paul; Timmons, Aileen; Walsh, Paul M; O'Neill, Ciaran; O'Sullivan, Eleanor; Gooberman-Hill, Rachael; Thomas, Audrey Alforque; Gallagher, Pamela; Sharp, Linda

2015-08-01

Previous studies suggest that productivity losses associated with head and neck cancer (HNC) are higher than in other cancers. These studies have only assessed a single aspect of productivity loss, such as temporary absenteeism or premature mortality, and have only used the Human Capital Approach (HCA). The Friction Cost Approach (FCA) is increasingly recommended, although has not previously been used to assess lost production from HNC. The aim of this study was to estimate the lost productivity associated with HNC due to different types of absenteeism and premature mortality, using both the HCA and FCA. Survey data on employment status were collected from 251 HNC survivors in Ireland and combined with population-level survival estimates and national wage data. The cost of temporary and permanent time off work, reduced working hours and premature mortality using both the HCA and FCA were calculated. Estimated total productivity losses per employed person of working age were EUR253,800 using HCA and EUR6800 using FCA. The main driver of HCA costs was premature mortality (38% of total) while for FCA it was temporary time off (73% of total). The productivity losses associated with head and neck cancer are substantial, and return to work assistance could form an important part of rehabilitation. Use of both the HCA and FCA approaches allowed different drivers of productivity losses to be identified, due to the different assumptions of the two methods. For future estimates of productivity losses, the use of both approaches may be pragmatic.

Heterocyclic amines content of meat and fish cooked by Brazilian methods.

PubMed

Iwasaki, Motoki; Kataoka, Hiroyuki; Ishihara, Junko; Takachi, Ribeka; Hamada, Gerson Shigeaki; Sharma, Sangita; Le Marchand, Loïc; Tsugane, Shoichiro

2010-02-01

Heterocyclic amine (HCA) concentrations were measured in meat and fish samples cooked by pan-frying, grilling and churrasco (Brazilian barbecue) to various levels of doneness in accordance with the cooking methods most commonly used in Brazil. HCAs were extracted by the Blue-rayon absorption method and measured by liquid chromatography-mass spectrometry. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were sharply increased in very well-done meats and fish. HCA levels varied somewhat across cooking methods: levels of PhIP (ng/g) in very well-done, non-marinated samples were particularly high for churrasco (31.8 in the exterior of the sample), compared to lower levels for grilled (16.3), and pan-fried beef (0.58). On comparison across foods, chicken contained higher HCA levels than other non-marinated samples. For example, PhIP levels (ng/g) in very well-done pan-fried foods were 34.6 for chicken with the skin, 0.58 for beef, 7.25 for pork, 2.28 for sardines, and 7.37 for salmon cooked with the skin. HCA levels were lower in marinated meats and fish than in non-marinated samples, except for pan-fried salmon. This study provides valuable information which will allow the estimation of dietary HCA exposure using an epidemiologic questionnaire and the investigation of the association of HCA intake with cancer risk in Brazil.

Heterocyclic amines content of meat and fish cooked by Brazilian methods

PubMed Central

Iwasaki, Motoki; Kataoka, Hiroyuki; Ishihara, Junko; Takachi, Ribeka; Hamada, Gerson Shigeaki; Sharma, Sangita; Le Marchand, Loïc; Tsugane, Shoichiro

2009-01-01

Heterocyclic amine (HCA) concentrations were measured in meat and fish samples cooked by pan-frying, grilling and churrasco (Brazilian barbecue) to various levels of doneness in accordance with the cooking methods most commonly used in Brazil. HCAs were extracted by the Blue-rayon absorption method and measured by liquid chromatography–mass spectrometry. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were sharply increased in very well-done meats and fish. HCA levels varied somewhat across cooking methods: levels of PhIP (ng/g) in very well-done, non-marinated samples were particularly high for churrasco (31.8 in the exterior of the sample), compared to lower levels for grilled (16.3), and pan-fried beef (0.58). On comparison across foods, chicken contained higher HCA levels than other non-marinated samples. For example, PhIP levels (ng/g) in very well-done pan-fried foods were 34.6 for chicken with the skin, 0.58 for beef, 7.25 for pork, 2.28 for sardines, and 7.37 for salmon cooked with the skin. HCA levels were lower in marinated meats and fish than in non-marinated samples, except for pan-fried salmon. This study provides valuable information which will allow the estimation of dietary HCA exposure using an epidemiologic questionnaire and the investigation of the association of HCA intake with cancer risk in Brazil. PMID:20383312

Comparison of total phenolic content, scavenging activity and HPLC-ESI-MS/MS profiles of both young and mature leaves and stems of Andrographis paniculata.

PubMed

Chua, Lee Suan; Yap, Ken Choy; Jaganath, Indu Bala

2013-12-01

The total phenolic content and radical scavenging activity of Andrographis paniculata has been investigated to estimate the amount of phenolic compounds and diterpene lactones, respectively in the plant extracts. The stem extracts exhibited higher total phenolic content and scavenging activity than those of the leaf extracts from both young and mature plants. A range of 19.6-47.8 mg extract of A. paniculata from different parts of the plant is equivalent to the scavenging activity exhibited by one mg of standard Trolox. HPLC-ESI-MS/MS was also used to identify simultaneously the phytochemicals from the leaves and stems of both young and mature plant samples. Of the identified compounds, seven of the sixteen diterpene lactones, three of the six flavonoids, five of the six phenolic acids and two cyclic acids are reported here for the first time for this species. Multivariate statistical approaches such as Hierarchiral Component Analysis (HCA) and Principle Component Analysis (PCA) have clustered the plant extracts into the leaf and stem groups, regardless of plant age. Further classification based on the phytochemical profiles revealed that mostly phenolic acids and flavonoids were from the young leaf extracts, and diterpenoids and their glycosides from the mature leaf extracts. However, the phytochemical profiles for the stems of both young and mature plants were not significantly different as presented in the dendrogram of HCA and the score plot of PCA. The marker for mature plants might be the m/z 557 ion (dihydroxyl dimethyl 19-[(beta-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide), whereas the m/z 521 ion (propyl neoandrographolide) could be the marker for leaf extracts.

High-Level Heteroatom Doped Two-Dimensional Carbon Architectures for Highly Efficient Lithium-Ion Storage

PubMed Central

Wang, Zhijie; Wang, Yanyan; Wang, Wenhui; Yu, Xiaoliang; Lv, Wei; Xiang, Bin; He, Yan-Bing

2018-01-01

In this work, high-level heteroatom doped two-dimensional hierarchical carbon architectures (H-2D-HCA) are developed for highly efficient Li-ion storage applications. The achieved H-2D-HCA possesses a hierarchical 2D morphology consisting of tiny carbon nanosheets vertically grown on carbon nanoplates and containing a hierarchical porosity with multiscale pore size. More importantly, the H-2D-HCA shows abundant heteroatom functionality, with sulfur (S) doping of 0.9% and nitrogen (N) doping of as high as 15.5%, in which the electrochemically active N accounts for 84% of total N heteroatoms. In addition, the H-2D-HCA also has an expanded interlayer distance of 0.368 nm. When used as lithium-ion battery anodes, it shows excellent Li-ion storage performance. Even at a high current density of 5 A g−1, it still delivers a high discharge capacity of 329 mA h g−1 after 1,000 cycles. First principle calculations verifies that such unique microstructure characteristics and high-level heteroatom doping nature can enhance Li adsorption stability, electronic conductivity and Li diffusion mobility of carbon nanomaterials. Therefore, the H-2D-HCA could be promising candidates for next-generation LIB anodes. PMID:29686985

Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

PubMed

Sangchan, Apichat; Chaiyakunapruk, Nathorn; Supakankunti, Siripen; Pugkhem, Ake; Mairiang, Pisaln

2014-01-01

Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

Challenges in Small Screening Laboratories: SaaS to the rescue

PubMed Central

Lemmon, Vance P.; Jia, Yuanyuan; Shi, Yan; Holbrook, S. Douglas; Bixby, John L; Buchser, William

2012-01-01

The Miami Project to Cure Paralysis, part of the University of Miami Miller School of Medicine, includes a laboratory devoted to High Content Analysis (HCA) of neurons. The goal of the laboratory is to uncover signalling pathways, genes, compounds, or drugs that can be used to promote nerve growth. HCA permits the quantification of neuronal morphology, including the lengths and numbers of axons. HCA screening of various libraries on primary neurons requires a team-based approach, a variety of process steps and complex manipulations of cells and libraries to obtain meaningful results. HCA itself produces vast amounts of information including images, well-based data and cell-based phenotypic measures. Managing experimental workflow and library data, along with the extensive amount of experimental results is challenging. For academic laboratories generating large data sets from experiments using thousands of perturbagens, a laboratory information management system (LIMS) is the data tracking solution of choice. With both productivity and efficiency as driving rationales, the Miami Project has equipped its HCA laboratory with a Software As A Service (SAAS) LIMS to ensure the quality of its experiments and workflows. The article discusses this application in detail, and how the system was selected and integrated into the laboratory. The advantages of SaaS are described. PMID:21631415

Inhibitory activity of Asian spices on heterocyclic amines formation in cooked beef patties.

PubMed

Puangsombat, Kanithaporn; Jirapakkul, Wannee; Smith, J Scott

2011-10-01

Heterocyclic amines (HCAs) are mutagenic compounds formed when foods are cooked at high temperatures. Numerous reports have shown that natural antioxidants from spices, fruits, chocolate, and tea can inhibit formation. In this study, we evaluated HCA formation in the presence of 5 of Asian spices: galangal (Alpinia galangal), fingerroot (Boesenbergia pandurata), turmeric (Curcuma longa), cumin (Cuminum cyminum), and coriander seeds (Coriandrum sativum). HCA levels were compared to patties containing rosemary (Rosmarinus officinalis), of which the inhibitory effect is well documented. Inhibition of HCA formation by the spices was evaluated in beef patties cooked at 204 °C (400 °F) for 10 min. All spices were mixed into patties at 0.2% before cooking, and HCAs levels were measured in the final product. All patties, including the control, contained 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl -6-phenylimidazo [4,5-b]pyridine (PhIP). The average HCA content of the control patties was 7 ng/g MeIQx and 6.53 ng/g PhIP. Turmeric (39.2% inhibition), fingerroot (33.5% inhibition), and galangal (18.4% inhibition) significantly decreased HCAs compared with the control. But, only turmeric and fingerroot were as effective as rosemary in preventing HCA formation. The HCA inhibition in patties containing spices was significantly correlated to the total phenolic content (R(2) = 0.80) and the scavenging activity (R(2) = 0.84) of the spices as measured by the 2,2-diphenyl-β-picrylhydrazyl assay. Results of this study suggest that addition of Asian spices can be an important factor in decreasing the levels of HCAs in fried beef patties. © 2011 Institute of Food Technologists®

Breast and prostate cancer productivity costs: a comparison of the human capital approach and the friction cost approach.

PubMed

Hanly, Paul; Timmons, Aileen; Walsh, Paul M; Sharp, Linda

2012-05-01

Productivity costs constitute a substantial proportion of the total societal costs associated with cancer. We compared the results of applying two different analytical methods--the traditional human capital approach (HCA) and the emerging friction cost approach (FCA)--to estimate breast and prostate cancer productivity costs in Ireland in 2008. Data from a survey of breast and prostate cancer patients were combined with population-level survival estimates and a national wage data set to calculate costs of temporary disability (cancer-related work absence), permanent disability (workforce departure, reduced working hours), and premature mortality. For breast cancer, productivity costs per person using the HCA were € 193,425 and those per person using the FCA were € 8,103; for prostate cancer, the comparable estimates were € 109,154 and € 8,205, respectively. The HCA generated higher costs for younger patients (breast cancer) because of greater lifetime earning potential. In contrast, the FCA resulted in higher productivity costs for older male patients (prostate cancer) commensurate with higher earning capacity over a shorter time period. Reduced working hours postcancer was a key driver of total HCA productivity costs. HCA costs were sensitive to assumptions about discount and growth rates. FCA costs were sensitive to assumptions about the friction period. The magnitude of the estimates obtained in this study illustrates the importance of including productivity costs when considering the economic impact of illness. Vastly different results emerge from the application of the HCA and the FCA, and this finding emphasizes the importance of choosing the study perspective carefully and being explicit about assumptions that underpin the methods. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Neutron structure of human carbonic anhydrase II in complex with methazolamide: Mapping the solvent and hydrogen-bonding patterns of an effective clinical drug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aggarwal, Mayank; Kovalevsky, Andrey Y.; Velazquez, Hector

Carbonic anhydrases (CAs; EC 4.2.1.1) catalyze the interconversion of CO 2 and HCO 3 –, and their inhibitors have long been used as diuretics and as a therapeutic treatment for many disorders such as glaucoma and epilepsy. Acetazolamide (AZM) and methazolamide (MZM, a methyl derivative of AZM) are two of the classical CA inhibitory drugs that have been used clinically for decades. The jointly refined X-ray/neutron structure of MZM in complex with human CA isoform II (hCA II) has been determined to a resolution of 2.2 Å with an R cryst of ~16.0%. Presented in this article, along with onlymore » the second neutron structure of a clinical drug-bound hCA, is an in-depth structural comparison and analyses of differences in hydrogen-bonding network, water-molecule orientation and solvent displacement that take place upon the binding of AZM and MZM in the active site of hCA II. Even though MZM is slightly more hydrophobic and displaces more waters than AZM, the overall binding affinity ( K i) for both of the drugs against hCA II is similar (~10 n M). The plausible reasons behind this finding have also been discussed using molecular dynamics and X-ray crystal structures of hCA II–MZM determined at cryotemperature and room temperature. Furthermore, this study not only allows a direct comparison of the hydrogen bonding, protonation states and solvent orientation/displacement of AZM and MZM, but also shows the significant effect that the methyl derivative has on the solvent organization in the hCA II active site.« less

Liver biopsy for diagnosis of presumed benign hepatocellular lesions lacking magnetic resonance imaging diagnostic features of focal nodular hyperplasia.

PubMed

Sannier, Aurélie; Cazejust, Julien; Lequoy, Marie; Cervera, Pascale; Scatton, Olivier; Rosmorduc, Olivier; Wendum, Dominique

2016-11-01

The contribution of liver biopsy for the diagnosis of presumed benign hepatocellular lesions lacking the diagnostic features of focal nodular hyperplasia (FNH) on magnetic resonance imaging (MRI) is unknown. We evaluated liver biopsy and MRI performances in this setting. Magnetic resonance imaging and slides of liver biopsies performed for a presumed benign hepatocellular lesion (2006-2013) without the typical features of FNH on MRI were blindly reviewed (n = 45). Eighteen lesions were surgically removed and also analyzed. The final diagnosis was the diagnosis established after surgery or on the biopsy in the absence of surgery. The final diagnosis was FNH (n = 19), hepatocellular adenoma (HCA, n = 15), hepatocellular carcinoma (n = 3) and indefinite (n = 4). Four lesions corresponded to non hepatocellular lesions. FNH, HNF1A mutated and inflammatory HCA were diagnosed accurately on the biopsy in 95%, 67% and 100% of the cases respectively. Diagnostic performance of liver biopsy for HNF1A mutated HCA was lower because of the lack of non-tumoral tissue. Diagnosis based on morphological analysis was certain and correct in 27 cases. Immunostaining allowed a definite diagnosis in 12 additionnal cases. Radiological diagnosis was in agreement with the histological diagnosis in 75.6% of the cases, with a very high sensitivity (97%) and specificity (100%) for the diagnosis of HNF1A mutated HCA. Liver biopsy has a good diagnostic performance particularly for FNH and inflammatory HCA, and sampling of non-lesional tissue is highly recommended. A biopsy does not seem necessary if H-HCA is diagnosed on MRI. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study.

PubMed

Retamar, Pilar; López-Prieto, María Dolores; Nátera, Clara; de Cueto, Marina; Nuño, Enrique; Herrero, Marta; Fernández-Sánchez, Fernando; Muñoz, Angel; Téllez, Francisco; Becerril, Berta; García-Tapia, Ana; Carazo, Inmaculada; Moya, Raquel; Corzo, Juan E; León, Laura; Muñoz, Leopoldo; Rodríguez-Baño, Jesús; Rodríguez-López, Fernando; García, María V; Fernández-Galán, Verónica; del Arco, Alfonso; Pérez-Santos, María J; Sánchez Porto, Antonio; Torres-Tortosa, Manuel; Martín-Aspas, Andrés; Arroyo, Ascensión; García-Figueras, Carolina; Acosta, Federico; Florez, Carmen; Navas, Petra; Escobar-Lara, Trinidad

2013-07-24

Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006-2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI.

Neutron structure of human carbonic anhydrase II in complex with methazolamide: Mapping the solvent and hydrogen-bonding patterns of an effective clinical drug

DOE PAGES

Aggarwal, Mayank; Kovalevsky, Andrey Y.; Velazquez, Hector; ...

2016-07-22

Carbonic anhydrases (CAs; EC 4.2.1.1) catalyze the interconversion of CO 2 and HCO 3 –, and their inhibitors have long been used as diuretics and as a therapeutic treatment for many disorders such as glaucoma and epilepsy. Acetazolamide (AZM) and methazolamide (MZM, a methyl derivative of AZM) are two of the classical CA inhibitory drugs that have been used clinically for decades. The jointly refined X-ray/neutron structure of MZM in complex with human CA isoform II (hCA II) has been determined to a resolution of 2.2 Å with an R cryst of ~16.0%. Presented in this article, along with onlymore » the second neutron structure of a clinical drug-bound hCA, is an in-depth structural comparison and analyses of differences in hydrogen-bonding network, water-molecule orientation and solvent displacement that take place upon the binding of AZM and MZM in the active site of hCA II. Even though MZM is slightly more hydrophobic and displaces more waters than AZM, the overall binding affinity ( K i) for both of the drugs against hCA II is similar (~10 n M). The plausible reasons behind this finding have also been discussed using molecular dynamics and X-ray crystal structures of hCA II–MZM determined at cryotemperature and room temperature. Furthermore, this study not only allows a direct comparison of the hydrogen bonding, protonation states and solvent orientation/displacement of AZM and MZM, but also shows the significant effect that the methyl derivative has on the solvent organization in the hCA II active site.« less

Dominant behaviours in the expression of human carbonic anhydrase hCA I activity.

PubMed

Abdelrahim, M Yahia M; Tanc, Muhammet; Winum, Jean-Yves; Supuran, Claudiu T; Barboiu, Mihail

2014-07-28

Here we describe the screening via Dynamic Deconvolution of DCLs of inhibitors (CAIs) and activators (CAAs) of hCA I. The inhibitory effects dominate over the activating ones, while the CAAs may be identified in the absence of CAIs.

Communication Apprehension in the Basic Course in Performance of Literature.

ERIC Educational Resources Information Center

Pelias, Mary Hinchcliff; Pelias, Ronald J.

1988-01-01

Examines the narrative accounts of the aesthetic performance experience as related by high communication apprehensives (HCA's) and low communication apprehensives (LCA's). Indicates that while both HCA's and LCA's commonly label themselves as apprehensive about performance, their characterizations of the performance experience differ significantly…

Antioxidant Activity, Acetylcholinesterase, and Carbonic Anhydrase Inhibitory Properties of Novel Ureas Derived from Phenethylamines.

PubMed

Aksu, Kadir; Özgeriş, Bünyamin; Taslimi, Parham; Naderi, Ali; Gülçin, İlhami; Göksu, Süleyman

2016-12-01

A series of ureas derived from phenethylamines were synthesized and evaluated for human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzyme inhibitory activities and antioxidant properties. The ureas were synthesized from the reactions of substituted phenethylamines with N,N-dimethylcarbamoyl chloride; then, the synthesized compounds were converted to their corresponding phenolic derivatives via O-demethylation. hCA I and II were effectively inhibited by the newly synthesized compounds, with K i values in the range of 0.307-0.432 nM for hCA I and 0.149-0.278 nM for hCA II. On the other hand, the K i parameters of these compounds for AChE and BChE were determined in the range of 0.129-0.434 and 0.095-0.207 nM, respectively. Phenolic ureas also showed good antioxidant activities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly Cited Occupational Therapy Articles in the Science Citation Index Expanded and Social Sciences Citation Index: A Bibliometric Analysis.

PubMed

Brown, Ted; Gutman, Sharon A; Ho, Yuh-Shan; Fong, Kenneth N K

A bibliometric analysis was completed of highly cited occupational therapy literature and authors published from 1991 to 2014 and accessible in the Science Citation Index Expanded (SCI-Expanded) and Social Sciences Citation Index (SSCI) databases. Data were obtained from the SCI-Expanded and SSCI. Articles referenced >100 times were categorized as highly cited articles (HCA). Of 6,486 articles found, 31 were categorized as HCA. The American Journal of Occupational Therapy published the largest number of HCA (n = 8; 26%). The 31 HCA were distributed across seven countries: United States (20 articles), Canada (3), United Kingdom (3), Australia (2), the Netherlands (1), New Zealand (1), and Sweden (1). The three authors with the highest Y-index were S. J. Page, F. Clark, and W. Dunn. A latency period of 4 to 5 yr post-publication appears to be needed for a journal article to gain citations. Copyright © 2017 by the American Occupational Therapy Association, Inc.

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations.

PubMed

De Simone, Giuseppina; Langella, Emma; Esposito, Davide; Supuran, Claudiu T; Monti, Simona Maria; Winum, Jean-Yves; Alterio, Vincenzo

2017-12-01

Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.

Proton Environments in Biomimetic Calcium Phosphates Formed from Mesoporous Bioactive CaO–SiO2–P2O5 Glasses in Vitro: Insights from Solid-State NMR

PubMed Central

2017-01-01

When exposed to body fluids, mesoporous bioactive glasses (MBGs) of the CaO–SiO2–P2O5 system develop a bone-bonding surface layer that initially consists of amorphous calcium phosphate (ACP), which transforms into hydroxy-carbonate apatite (HCA) with a very similar composition as bone/dentin mineral. Information from various 1H-based solid-state nuclear magnetic resonance (NMR) experiments was combined to elucidate the evolution of the proton speciations both at the MBG surface and within each ACP/HCA constituent of the biomimetic phosphate layer formed when each of three MBGs with distinct Ca, Si, and P contents was immersed in a simulated body fluid (SBF) for variable periods between 15 min and 30 days. Directly excited magic-angle-spinning (MAS) 1H NMR spectra mainly reflect the MBG component, whose surface is rich in water and silanol (SiOH) moieties. Double-quantum–single-quantum correlation 1H NMR experimentation at fast MAS revealed their interatomic proximities. The comparatively minor H species of each ACP and HCA component were probed selectively by heteronuclear 1H–31P NMR experimentation. The initially prevailing ACP phase comprises H2O and “nonapatitic” HPO42–/PO43– groups, whereas for prolonged MBG soaking over days, a well-progressed ACP → HCA transformation was evidenced by a dominating O1H resonance from HCA. We show that 1H-detected 1H → 31P cross-polarization NMR is markedly more sensitive than utilizing powder X-ray diffraction or 31P NMR for detecting the onset of HCA formation, notably so for P-bearing (M)BGs. In relation to the long-standing controversy as to whether bone mineral comprises ACP and/or forms via an ACP precursor, we discuss a recently accepted structural core–shell picture of both synthetic and biological HCA, highlighting the close relationship between the disordered surface layer and ACP. PMID:28663772

Inhibitory effects of benzimidazole containing new phenolic Mannich bases on human carbonic anhydrase isoforms hCA I and II.

PubMed

Gul, Halise Inci; Yazici, Zehra; Tanc, Muhammet; Supuran, Claudiu T

2016-12-01

New phenolic mono and bis Mannich bases incorporating benzimidazole, such as 2-(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol and 2,6-bis(aminomethyl)-4-(1H-benzimidazol-2-yl)phenol were synthesized starting from 4-(1H-benzimidazol-2-yl)phenol. Amines used for the synthesis included dimethylamine, pyrrolidine, piperidine, N-methylpiperazine and morpholine. The CA inhibitory properties of these compounds were tested on the human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and hCA II. These new compounds, as many phenols show moderate CA inhibitory properties.

Use of transgenic and mutant animal models in the study of heterocyclic amine-induced mutagenesis and carcinogenesis.

PubMed

Dashwood, Roderick H

2003-01-31

Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptDelta. transgenics, XPA-/-, XPC-/-, Msh2+/-, Msh2-/- and p53+/- knock-outs, Apc mutant mice (ApcDelta716, Apc1638N, Apcmin), and A33DeltaNbeta-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac.

Characterization of dissolved organic matter in Dongjianghu Lake by UV-visible absorption spectroscopy with multivariate analysis.

PubMed

Zhu, Yanzhong; Song, Yonghui; Yu, Huibin; Liu, Ruixia; Liu, Lusan; Lv, Chunjian

2017-08-08

UV-visible absorption spectroscopy coupled with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to characterize spectroscopic components, detect latent factors, and investigate spatial variations of dissolved organic matter (DOM) in a large-scale lake. Twelve surface water samples were collected from Dongjianghu Lake in China. DOM contained lignin and quinine moieties, carboxylic acid, microbial products, and aromatic and alkyl groups, which in the northern part of the lake was largely different from the southern part. Fifteen spectroscopic indices were deduced from the absorption spectra to indicate molecular weight or humification degree of DOM. The northern part of the lake presented the smaller molecular weight or the lower humification degree of DOM than the southern part. E 2/4 , E 3/4 , E 2/3 , and S 2 were latent factors of characterizing the molecular weight of DOM, while E 2/5 , E 3/5 , E 2/6 , E 4/5 , E 3/6 , and A 2/1 were latent factors of evaluating the humification degree of DOM. The UV-visible absorption spectroscopy combined with PCA and HCA may not only characterize DOM fractions of lakes, but may be transferred to other types of waterscape.

48 CFR 419.201-71 - Small business coordinators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Small business... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 419.201-71 Small business coordinators. The head of the contracting activity (HCA) or a representative of the HCA shall designate in writing a small business...

Intra-laboratory study to determine the reproducibility of LLNA:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

PubMed

Chen, Wei; Xing, Caihong; Hou, Fenxia

The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for identification the skin sensitization potential of new chemicals. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. An intra-laboratory reproducibility study for the LLNA:BrdU-ELISA was conducted to demonstrate its adequate performance in our laboratory. Ten independent LLNA:BrdU-ELISAs with the preferred positive controls (PCs), i.e., 25% hexyl cinnamic aldehyde (HCA) and 25% eugenol, were conducted within a period of less than one year. In addition, different concentrations of 2,4-dinitrochlorobenzene (DNCB, an extreme sensitizer) (0.01, 0.1 and 0.3%), HCA (10, 25 and 50%) and eugenol (10, 25 and 50%), were tested to determine the EC1.6 values. Special Pathogen Free female CBA/J mice of 8-10weeks old were randomly allocated to the groups, each group having 4 mice. 25μl of AOO (vehicle, acetone: olive oil=4:1, v/v) or HCA, eugenol, DNCB at the needed concentration was applied to the dorsum of each ear of the mice, daily for 3 consecutive days. A single intraperitoneal injection of 0.5ml of BrdU solution (10mg/ml) was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, and BrdU ELISA analysis was conducted. The result for each group is expressed as the mean Stimulation Index (SI). The mean of the 10 mean SIs for 25% HCA (2.58±0.95) and 25% eugenol (3.51±1.25) was not significantly different to that from the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) (i.e., the data on the formal validation study for the LLNA:BrdU-ELISA by the ICCVAM) (3.03±2.00 for 25% HCA, 6.13±6.06 for 25% eugenol) (P>0.05), with even smaller Coefficient of Variations (CV) (36.8% for 25% HCA, 35.6% for 25% eugenol) than that from the ICCVAM (66.0% for 25% HCA, 98.8% for 25% eugenol). In addition, the EC1.6 values for HCA, eugenol and DNCB (15.2, 12.5 and 0.25%, respectively) were consistent with that from the ICCVAM (12.92, 8.85 and 0.34%, respectively). The results indicate that the reliability for our laboratory to conduct the LLNA:BrdU-ELISA is successfully determined. Copyright © 2016 Elsevier Inc. All rights reserved.

Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

Statistics-based optimization of the polarimetric radar hydrometeor classification algorithm and its application for a squall line in South China

NASA Astrophysics Data System (ADS)

Wu, Chong; Liu, Liping; Wei, Ming; Xi, Baozhu; Yu, Minghui

2018-03-01

A modified hydrometeor classification algorithm (HCA) is developed in this study for Chinese polarimetric radars. This algorithm is based on the U.S. operational HCA. Meanwhile, the methodology of statistics-based optimization is proposed including calibration checking, datasets selection, membership functions modification, computation thresholds modification, and effect verification. Zhuhai radar, the first operational polarimetric radar in South China, applies these procedures. The systematic bias of calibration is corrected, the reliability of radar measurements deteriorates when the signal-to-noise ratio is low, and correlation coefficient within the melting layer is usually lower than that of the U.S. WSR-88D radar. Through modification based on statistical analysis of polarimetric variables, the localized HCA especially for Zhuhai is obtained, and it performs well over a one-month test through comparison with sounding and surface observations. The algorithm is then utilized for analysis of a squall line process on 11 May 2014 and is found to provide reasonable details with respect to horizontal and vertical structures, and the HCA results—especially in the mixed rain-hail region—can reflect the life cycle of the squall line. In addition, the kinematic and microphysical processes of cloud evolution and the differences between radar-detected hail and surface observations are also analyzed. The results of this study provide evidence for the improvement of this HCA developed specifically for China.

Impact of commercial farming on household reproductive strategies in Calakmul, Campeche, Mexico.

PubMed

Gurri, Francisco D; Ortega-Muñoz, Allan

2015-01-01

The purpose of this study was to determine if commercial agriculture can lead to changes in peasant reproductive strategies in migrant agriculturalists from Calakmul, Campeche, Mexico. The reproductive histories of 746 women from Calakmul, Campeche, Mexico were collected. The sample was first divided into women who had reproduced within or outside of Calakmul (RC and RO, respectively) and these were further subdivided into those who lived in households practicing subsistence agriculture and those who turned agriculture into a business (Household Subsistence Agricultural Strategy (HSA) and Household Commercial Agricultural Strategy (HCA), respectively). Age-specific fertility rate (ASFR) differences were compared between strategies and place of reproduction. Comparisons between interbirth interval and age at which desired fertility was reached were done with a Kaplan-Meier life table-based statistic. In both strategies, RC women increased ASFRs by reducing age at first birth, and HSA-RC women also reduced interbirth intervals. HCA women had lower ASFRs than HSA women. The latter had a natural fertility pattern while the former expressed a desire to stop reproducing at a younger age. HCA-RC women showed important fertility reductions after age 25 and HCA-RO women after age 30. Fertility reductions in households that practice commercial versus those that practice subsistence agriculture were significant. Also, a "frontier" effect was observed that increased fertility over all, but HCA households were not as influenced by it. © 2015 Wiley Periodicals, Inc.

Challenges in small screening laboratories: implementing an on-demand laboratory information management system.

PubMed

Lemmon, Vance P; Jia, Yuanyuan; Shi, Yan; Holbrook, S Douglas; Bixby, John L; Buchser, William

2011-11-01

The Miami Project to Cure Paralysis, part of the University of Miami Miller School of Medicine, includes a laboratory devoted to High Content Analysis (HCA) of neurons. The goal of the laboratory is to uncover signaling pathways, genes, compounds, or drugs that can be used to promote nerve growth. HCA permits the quantification of neuronal morphology, including the lengths and numbers of axons. HCA of various libraries on primary neurons requires a team-based approach, a variety of process steps and complex manipulations of cells and libraries to obtain meaningful results. HCA itself produces vast amounts of information including images, well-based data and cell-based phenotypic measures. Documenting and integrating the experimental workflows, library data and extensive experimental results is challenging. For academic laboratories generating large data sets from experiments involving thousands of perturbagens, a Laboratory Information Management System (LIMS) is the data tracking solution of choice. With both productivity and efficiency as driving rationales, the Miami Project has equipped its HCA laboratory with an On Demand or Software As A Service (SaaS) LIMS to ensure the quality of its experiments and workflows. The article discusses how the system was selected and integrated into the laboratory. The advantages of a SaaS based LIMS over a client-server based system are described. © 2011 Bentham Science Publishers

Reduced calcification decreases photoprotective capability in the coccolithophorid Emiliania huxleyi.

PubMed

Xu, Kai; Gao, Kunshan

2012-07-01

Intracellular calcification of coccolithophores generates CO₂ and consumes additional energy for acquisition of calcium and bicarbonate ions; therefore, it may correlate with photoprotective processes by influencing the energetics. To address this hypothesis, a calcifying Emiliania huxleyi strain (CS-369) was grown semi-continuously at reduced (0.1 mM, LCa) and ambient Ca²⁺ concentrations (10 mM, HCa) for 150 d (>200 generations). The HCa-grown cells had higher photosynthetic and calcification rates and higher contents of Chl a and carotenoids compared with the naked (bearing no coccoliths) LCa-grown cells. When exposed to stressfull levels of photosynthetically active radiation (PAR), LCa-grown cells displayed lower photochemical yield and less efficient non-photochemical quenching (NPQ). When the LCa- or HCa-grown cells were inversely shifted to their counterpart medium, LCa to HCa transfer increased photosynthetic carbon fixation (P), calcification rate (C), the C/P ratio, NPQ and pigment contents, whereas those shifted from HCa to LCa exhibited the opposite effects. Increased NPQ, carotenoids and quantum yield were clearly linked with increased or sustained calcification in E. huxleyi. The calcification must have played a role in dissipating excessive energy or as an additional drainage of electrons absorbed by the photosynthetic antennae. This phenomenon was further supported by testing two non-calcifying strains, which showed insignificant changes in photosynthetic carbon fixation and NPQ when transferred to LCa conditions.

HCA leading the way to change.

PubMed

2014-06-03

A hospital ward run by healthcare assistants? Some might be sceptical, but not patients at Headley Court Defence Medical Rehabilitation Centre in Surrey who are about to be discharged from the military into civvy street. For them, the HCA-led ward is a welcome change from the traditional medically intense nurse-led units.

Assessment of 16 chemicals on proliferation and apoptosis in human neuroprogenitor cells using high-content image analysis (HCA).

EPA Science Inventory

The need for efficient methods of screening chemicals for the potential to cause developmental neurotoxicity is paramount. We previously described optimization of an HCA assay for proliferation and apoptosis in ReNcell CX cells (ReN), identifying appropriate controls. Utility of ...

Structural and Organisational Features of Sensorimotor Intelligence among Retarded Infants and Toddlers.

ERIC Educational Resources Information Center

Dunst, C. J.; And Others

1981-01-01

The structural features of sensorimotor intelligence were assessed among three groups of retarded infants and toddlers. Hierarchical cluster analysis (HCA) was performed on two measures of relationship (stage congruence and intercorrelations). The potential utility of HCA for studying Piaget's "structure d'ensemble" stage criteria is…

28,000 Hour Xenon Hollow Cathode LifeTest Results

NASA Technical Reports Server (NTRS)

Sarver-Verhey, Timothy R.

1997-01-01

The International Space Station Plasma Contactor System requires a hollow cathode assembly (HCA) with a lifetime of at least 18,000 hours. Critical components of the HCA include the hollow cathode and electron emitter. A series of hollow cathode wear tests was performed which included a life test operated at the maximum current of the HCA. This test sought to verify the hollow cathode design and contamination control protocols. The life test accumulated 27,800 hours of operation before failing to ignite. The hollow cathode exhibited relatively small changes in operating parameters over the course of the test. This life test is the longest duration test of a high current xenon hollow cathode reported to date.

Non-targeted metabolite profiling of citrus juices as a tool for variety discrimination and metabolite flow analysis.

PubMed

Arbona, Vicent; Iglesias, Domingo J; Gómez-Cadenas, Aurelio

2015-02-05

Genetic diversity of citrus includes intrageneric hybrids, cultivars arising from cross-pollination and/or somatic mutations with particular biochemical compounds such as sugar, acids and secondary metabolite composition. Secondary metabolite profiles of juices from 12 commercial varieties grouped into blonde and navel types, mandarins, lemons and grapefruits were analyzed by LC/ESI-QTOF-MS. HCA on metabolite profiling data revealed the existence of natural groups demarcating fruit types and varieties associated to specific composition patterns. The unbiased classification provided by HCA was used for PLS-DA to find the potential variables (mass chromatographic features) responsible for the classification. Abscisic acid and derivatives, several flavonoids and limonoids were identified by analysis of mass spectra. To facilitate interpretation, metabolites were represented as flow charts depicting biosynthetic pathways. Mandarins 'Fortune' and 'Hernandina' along with oranges showed higher ABA contents and ABA degradation products were present as glycosylated forms in oranges and certain mandarins. All orange and grapefruit varieties showed high limonin contents and its glycosylated form, that was only absent in lemons. The rest of identified limonoids were highly abundant in oranges. Particularly, Sucrenya cultivar showed a specific accumulation of obacunone and limonoate A-ring lactone. Polymethoxylated flavanones (tangeritin and isomers) were absolutely absent from lemons and grapefruits whereas kaempferol deoxyhexose hexose isomer #2, naringin and neohesperidin were only present in these cultivars. Analysis of relative metabolite build-up in closely-related genotypes allowed the efficient demarcation of cultivars and suggested the existence of genotype-specific regulatory mechanisms underlying the differential metabolite accumulation.

48 CFR 933.103 - Protests to the agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Executive (for protests at the Headquarters level or those specific HCA protests cited in paragraph (i) of this section) or an HCA (for protests at the contracting activity level) will render a decision on a... Headquarters level shall state whether the protester is willing to utilize ADR techniques such as mediation or...

48 CFR 933.103 - Protests to the agency.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Executive (for protests at the Headquarters level or those specific HCA protests cited in paragraph (i) of this section) or an HCA (for protests at the contracting activity level) will render a decision on a... Headquarters level shall state whether the protester is willing to utilize ADR techniques such as mediation or...

48 CFR 2803.905 - Procedures for investigating complaints.

Code of Federal Regulations, 2010 CFR

2010-10-01

... conduct an investigation and provide a written report of findings to the HCA. (b) The HCA will ensure that the Inspector General provides the report of finding as specified in FAR 3.905(c). (c) The complainant and contractor shall be afforded the opportunity to submit a written response to the report of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

48 CFR 801.695-3 - Authority of the HCA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Authority of the HCA. 801.695-3 Section 801.695-3 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL DEPARTMENT OF VETERANS AFFAIRS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 801.695-3 Authority of...

Selective Transcatheter Arterial Embolization for Treatment of Bleeding Complications or Reduction of Tumor Mass of Hepatocellular Adenomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erdogan, Deha; Delden, Otto M. van; Busch, Olivier R. C.

2007-11-15

Hepatocellular adenomas (HCAs) are benign liver lesions which may be complicated by spontaneous intratumoral bleeding, with or without rupture into the abdominal cavity, or malignant degeneration. Recent advances in radiological interventional techniques now offer selective transcatheter arterial embolization (TAE) as an alternative approach to surgery as the initial treatment to stop the bleeding or as an elective treatment to reduce the tumor mass of the HCA. Herein, we report our initial experience using TAE in the management of HCA. Five female patients and one male patient presented with spontaneous hemorrhage of HCA. Four patients were initially treated with selective TAEmore » to stop the bleeding. In two patients in whom the bleeding stopped spontaneously, TAE was electively undertaken 1 year after presentation to reduce the tumor mass of HCAs >5 cm. Selective TAE as initial treatment in patients with spontaneous bleeding of HCA with or without rupture is effective and will change the need for urgent laparotomy to control bleeding. Selective TAE may also be used as an elective treatment to reduce the tumor mass of larger HCAs.« less

Chorioamnionitis in the Development of Cerebral Palsy: A Meta-analysis and Systematic Review

PubMed Central

Ma, Lin; Luo, Kehuan; Bajaj, Monika; Chawla, Sanjay; Natarajan, Girija; Hagberg, Henrik; Tan, Sidhartha

2017-01-01

CONTEXT: Chorioamnionitis (CA) has often been linked etiologically to cerebral palsy (CP). OBJECTIVES: To differentiate association from risk of CA in the development of CP. DATA SOURCES: PubMed, Cochrane Library, Embase, and bibliographies of original studies were searched by using the keywords (chorioamnionitis) AND ((cerebral palsy) OR brain). STUDY SELECTION: Included studies had to have: (1) controls, (2) criteria for diagnoses, and (3) neurologic follow-up. Studies were categorized based on: (1) finding incidence of CP in a CA population, or risk of CP; and (2) incidence of CA in CP or association with CP. DATA EXTRACTION: Two reviewers independently verified study inclusion and extracted data. RESULTS: Seventeen studies (125 256 CA patients and 5 994 722 controls) reported CP in CA. There was significantly increased CP inpreterm histologic chorioamnionitis (HCA; risk ratio [RR] = 1.34, P < .01), but not in clinical CA (CCA). Twenty-two studies (2513 CP patients and 8135 controls) reported CA in CP. There was increased CCA (RR = 1.43, P < .01), but no increase in HCA in preterm CP. Increased HCA was found (RR = 4.26, P < .05), as well as CCA in term/near-term CP (RR = 3.06, P < .01). CONCLUSIONS: The evidence for a causal or associative role of CA in CP is weak. Preterm HCA may be a risk factor for CP, whereas CCA is not. An association with term and preterm CP was found for CCA, but only with term CP for HCA. PMID:28814548

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression.

PubMed

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli; Modjtahedi, Helmout; Opara, Elizabeth I

2017-09-21

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells' cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7's cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential.

Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases.

PubMed

De Luca, Laura; Mancuso, Francesca; Ferro, Stefania; Buemi, Maria Rosa; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T; Gitto, Rosaria

2018-01-01

Coumarin derivatives are a peculiar class of inhibitors of the family of metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display higher affinity and selectivity toward most relevant and druggable CA isoforms. By decorating the natural compound umbelliferone (1) we have identified a new series of coumarin-based compounds demonstrating high CA inhibitory effects with nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target amenable to develop antitumor agents. The most active tested compounds proved to be potent inhibitors with K i values equal to that of the well-known inhibitor acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As suggested by docking studies the coumarins, that are lacking of the canonical metal binding groups, do not interact with Zinc ion within the catalytic site as found for classical sulfonamide type inhibitors of CAs. Thus, the studied inhibitors might possess a non-classical inhibitory mode of action preventing the carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate ion. Specifically, the most active inhibitor of hCA XII compound 18i (K i value of 5.5 nM) and its supposed hydrolytic products could establish a web of H-bond interactions within the enzymatic cavity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.

PubMed

Jiang, Yan; Su, Jing-Tan; Zhang, Jun; Wei, Xiang; Yan, Yong-Bin; Zhou, Hai-Meng

2008-01-01

Human carbonic anhydrase (HCA) II participates in a variety of important biological processes, and it has long been known that genetic mutations of HCA II are closely correlated to human disease. In this research, we investigated the effects of a genetic single point mutation P237, which is located on the surface of the molecule and does not participate in the HCA II catalysis, on HCA II activity, stability and folding. Spectroscopic studies revealed that the mutation caused more buried Trp residues to become accessible by solvent and caused the NMR signals to become less dispersed, but did not affect the secondary structure or the hydrophobic exposure of the protein. The mutant was less stable than the wild type enzyme against heat- and GdnHCl-induced inactivation, but its pH adaptation was similar to the wild type. The mutation slightly decreased the stability of the molten globular intermediate, but gradually affected the stability of the native state by a 10-fold reduction of the Gibbs free energy for the transition from the native state to the intermediate. This might have led to an accumulation of the aggregation-prone molten globular intermediate, which further trapped the proteins into the off-pathway aggregates during refolding and reduced the levels of active enzyme in vivo. The results herein suggested that the correct positioning of the long loop around P237 might be crucial to the folding of HCA II, particularly the formation of the active site.

Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression

PubMed Central

Jaksevicius, Andrius; Carew, Mark; Mistry, Calli

2017-01-01

It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells’ cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7’s cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential. PMID:28934138

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

PubMed

Laurent, Alexis; Dokmak, Safi; Nault, Jean-Charles; Pruvot, François-René; Fabre, Jean-Michel; Letoublon, Christian; Bachellier, Philippe; Capussotti, Lorenzo; Farges, Olivier; Mabrut, Jean-Yves; Le Treut, Yves-Patrice; Ayav, Ahmet; Suc, Bertrand; Soubrane, Olivier; Mentha, Gilles; Popescu, Irinel; Montorsi, Marco; Demartines, Nicolas; Belghiti, Jacques; Torzilli, Guido; Cherqui, Daniel; Hardwigsen, Jean

2016-09-01

Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. A retrospective cross-sectional study, from 27 European high-volume HPB units. 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Healthcare-associated, community-acquired and hospital-acquired bacteraemic urinary tract infections in hospitalized patients: a prospective multicentre cohort study in the era of antimicrobial resistance.

PubMed

Horcajada, J P; Shaw, E; Padilla, B; Pintado, V; Calbo, E; Benito, N; Gamallo, R; Gozalo, M; Rodríguez-Baño, J

2013-10-01

The clinical and microbiological characteristics of community-onset healthcare-associated (HCA) bacteraemia of urinary source are not well defined. We conducted a prospective cohort study at eight tertiary-care hospitals in Spain, from October 2010 to June 2011. All consecutive adult patients hospitalized with bacteraemic urinary tract infection (BUTI) were included. HCA-BUTI episodes were compared with community-acquired (CA) and hospital-acquired (HA) BUTI. A logistic regression analysis was performed to identify 30-day mortality risk factors. We included 667 episodes of BUTI (246 HCA, 279 CA and 142 HA). Differences between HCA-BUTI and CA-BUTI were female gender (40% vs 69%, p <0.001), McCabe score II-III (48% vs 14%, p <0.001), Pitt score ≥2 (40% vs 31%, p 0.03), isolation of extended spectrum β-lactamase-producing Enterobacteriaciae (13% vs 5%, p <0.001), median hospital stay (9 vs 7 days, p 0.03), inappropriate empirical antimicrobial therapy (21% vs 13%, p 0.02) and mortality (11.4% vs 3.9%, p 0.001). Pseudomonas aeruginosa was more frequently isolated in HA-BUTI (16%) than in HCA-BUTI (4%, p <0.001). Independent factors for mortality were age (OR 1.04; 95% CI 1.01-1.07), McCabe score II-III (OR 3.2; 95% CI 1.8-5.5), Pitt score ≥2 (OR 3.2 (1.8-5.5) and HA-BUTI OR 3.4 (1.2-9.0)). Patients with HCA-BUTI are a specific group with significant clinical and microbiological differences from patients with CA-BUTI, and some similarities with patients with HA-BUTI. Mortality was associated with patient condition, the severity of infection and hospital acquisition. © 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study

PubMed Central

2013-01-01

Background Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. Methods A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006–2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. Results 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. Conclusion HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI. PMID:23883281

The Long-Term Survival of a Patient With Stage IV Renal Cell Carcinoma Following an Integrative Treatment Approach Including the Intravenous α-Lipoic Acid/Low-Dose Naltrexone Protocol.

PubMed

Berkson, Burton M; Calvo Riera, Francisco

2017-12-01

In this case report, we describe the treatment of a 64-year-old male patient diagnosed with metastatic renal cell carcinoma (RCC) in June of 2008. In spite of a left nephrectomy and the standard oncological protocols, the patient developed a solitary left lung metastasis that continued to grow. He was informed that given his diagnosis and poor response to conventional therapy, any further treatment would, at best, be palliative. The patient arrived at the Integrative Medical Center of New Mexico in August of 2010. He was in very poor health, weak, and cachectic. An integrative program-developed by one of the authors using intravenous (IV) α-lipoic acid, IV vitamin C, low-dose naltrexone, and hydroxycitrate, and a healthy life style program-was initiated. From August 2010 to August 2015, the patient's RCC with left lung metastasis was followed closely using computed tomography and positron emission tomography/computed tomography imaging. His most recent positron emission tomography scan demonstrated no residual increased glucose uptake in his left lung. After only a few treatments of IV α-lipoic acid and IV vitamin C, his symptoms began to improve, and the patient regained his baseline weight. His energy and outlook improved, and he returned to work. The patient had stable disease with disappearance of the signs and symptoms of stage IV RCC, a full 9 years following diagnosis, with a gentle integrative program, which is essentially free of side effects. As of November 2017 the patient feels well and is working at his full-time job.

A simple and specific high performance liquid chromatography method for the assay of a series of novel dermal penetration enhancers.

PubMed

Michniak, B B; Seyda, K L

1993-02-01

Synopsis A series of clofibric acid amides has been synthesized and previously reported by the authors as possessing enhancer activity in vitro in athymic nude mouse skin against model drugs, hydrocortisone-21-acetate and beta-methasone-17-valerate. An assay was required for each of these enhancers however, which would be specific for each compound and would also separate model drugs and their metabolite peaks. This study reports reverse phase high performance liquid chromatography assays for clofibric acid amide and seven derivatives (Ia-Ig). All enhancers showed maximum absorption at 232 nm, betamethasone (BM) and its valerate (BMV) at 238 nm, and hydrocortisone (HC) and its acetate (HCA) at 242 nm. Practical units of detection for the amides were 0.46-2.8 mug ml(-1) and peaks were sharp and well-separated from steroid peaks in three vehicles - methanol alone. Franz diffusion cell receptor phase samples (isotonic phosphate buffer), and full-thickness athymic nude mouse skin extracts in methanol. Mobile phases consisted of various proportions of acetonitrile and water, some with 2-propanol. The octyl amide for example, with mobile phase CH(3)CN: H(2)O (85:15) at 1 ml min(-1) had a retention time (t(R)) of 7.9 mins. Under the same conditions, retention times for the steroids were HC, t(R)= 3.3 mins; HCA, t(R)= 4.3 mins; BM, t(R)= 3.4 mins; BMV, t(R)= 4.6 mins. Résumé Les auteurs avaient démontré dans un article précédent le pouvoir accélérateur de pénétration dermique in vitro d'une gamme d'amides d'acide clofibrique sur la peau de souris sans poils, et sans thymus avec des médicaments types tels que l'acetate 21 d'hydrocortisone et le valerate 17 de beta-metasone. Il a cependant été requis, pour chacun de ces accélérateurs, un test spécifique pour chaque composition, permettant de séparer chaque médicament et les pics des métabolites. Cette étude décrit des tests par chromatographie liquide à haute performance en phase inverse pour l'acide chlofibrique et 7 dérivés (Ia-Ig). Tous les accélérateurs ont montré une absorption maximale à 232 nm, la beta-metasone (BM) et son valerate (BMV) à 238 nm, l'hydrocortisone (HC) et son acetate (HCA) à 242 nm. Les unités de détection s'élevaient à 0.46-2.8 mug ml(-1) pour les amides et les pics étaient aigus et distincts des pics stéroïdes et se composaient de 3 véhicules - le méthanol seul, des échantillons du récepteur de cellule de diffusion Franz (tampon du phosphate isotonique) et des extraits de peau de souris sans thymus dans du méthanol. Les phases mobiles étaient constituées de différentes proportions d'acetonitrile et d'eau, certaines avec du propanol-2. L'amide octyl par exemple, avec une phase mobile CH(3)CN: H(2)O (85:15) à 1 ml min(-1) avait un temps de rétention (t(R)) de 7.9 min. Dans des conditions identiques, les temps de rétention pour les stéroïdes étaient les suivants: pour HC, t(R)= 3.3 mins; pour HCA, t(R)= 4.3 mins; pour BM: t(R)= 3.4 mins; pour BMV: t(R)= 4.6 mins.

Kinin effects on ion transport in monolayers of HCA-7 cells, a line from a human colonic adenocarcinoma.

PubMed

Cuthbert, A W; Kirkland, S C; MacVinish, L J

1985-09-01

Using epithelial monolayers of HCA-7 cells, derived from a primary human colonic adenocarcinoma and grown on pervious supports, it is shown that responses to lysylbradykinin can be elicited from either side. It is proposed that kinin receptors are inserted into both apical and basolateral membrane domains.

Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

PubMed

Burmaoglu, Serdar; Yilmaz, Ali O; Taslimi, Parham; Algul, Oztekin; Kilic, Deryanur; Gulcin, Ilhami

2018-02-01

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K i values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM against α-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against hCA II. © 2018 Deutsche Pharmazeutische Gesellschaft.

Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology.

PubMed

Angeli, Andrea; di Cesare Mannelli, Lorenzo; Trallori, Elena; Peat, Thomas S; Ghelardini, Carla; Carta, Fabrizio; Supuran, Claudiu T

2018-05-10

A series of novel selenides bearing benzenesulfonamide moieties was synthesized and investigated for their inhibition on six human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms such as the physiologically relevant hCA I, II, VA, VB, VII, and IX and the X-ray complex in adduct with hCA II for some of them investigated. These enzymes are involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis, metabolic disorders, and cancer. The investigated compounds showed potent inhibitory action against hCA VA, VII, and IX, in the low nanomolar range, thus making them of interest for the development of isoform-selective inhibitors and as candidates for various biomedical applications.

Thermal analysis of radiometer containers for the 122m hoop column antenna concept

NASA Technical Reports Server (NTRS)

Dillon-Townes, L. A.

1986-01-01

A thermal analysis was conducted for the 122 Meter Hoop Column Antenna (HCA) Radiometer electronic package containers. The HCA radiometer containers were modeled using the computer aided graphics program, ANVIL 4000, and thermally simulated using two thermal programs, TRASYS and MITAS. The results of the analysis provided relationships between the absorptance-emittance ratio and the average surface temperature of the orbiting radiometer containers. These relationships can be used to specify the surface properties, absorptance and reflectance, of the radiometer containers. This is an initial effort in determining the passive thermal protection needs for the 122 m HCA radiometer containers. Several recommendations are provided which expand this effort so specific passive and active thermal protection systems can be defined and designed.

An evaluation of independent consumer assistance centers on problem resolution and user satisfaction: the consumer perspective.

PubMed

Nascimento, Lori Miller; Cousineau, Michael R

2005-04-01

Individuals who wish to receive independent assistance to resolve access to care health problems have limited options. The Health Consumer Alliance (HCA) is an independent, coordinated effort of nine legal services organizations that provide free assistance to low-income health consumers in 10 California counties. The need for the HCA stems from the vast number of health consumers with unanswered questions and unresolved problems relating to access to care issues, among both insured and uninsured populations. However, little is known about the effectiveness of independent consumer assistance centers. This paper examines the effectiveness of a network of independent consumer assistance programs in resolving consumer problems and consumers' level of satisfaction with services received. As the project evaluators, we conducted telephone surveys with 1,291 users of the HCA to assess if this independent program resolved consumer problems, and to measure the level of satisfaction among HCA users. Specifically, we asked questions about the HCA's influence on problem resolution, consumer satisfaction, health insurance status and use of preventive care services. From 1997 to 2001, more than 46,000 consumers contacted the seven health consumer centers (HCCs). According to our sample of respondents, results show that the HCCs are an important resource for low-income Californians trying to access health care. After contacting the HCCs, 62 percent of the participants report that their problems were resolved. In addition, 87 percent of the participants said the HCCs were helpful and 95 percent said they would be likely to contact the HCC again if necessary.

Novel eugenol derivatives: Potent acetylcholinesterase and carbonic anhydrase inhibitors.

PubMed

Topal, Fevzi; Gulcin, Ilhami; Dastan, Arif; Guney, Murat

2017-01-01

Eugenol was used as starting material to obtain some phenolic compounds. The synthesis of these phenolic compounds was performed in a two-step procedure. The structures of the formed products (novel eugenol derivatives 1-6) have been determined on the basis of NMR spectroscopy and other spectroscopic methods. The compounds were tested in terms of carbonic anhydrase (CA) inhibition potency. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes, which catalyse the reaction between carbon dioxide (CO 2 ) and water (H 2 O), to generate bicarbonate (HCO 3 - ) and protons (H + ). CO 2 , HCO 3 - and H + are essential molecules and ions for many important physiologic processes occurring in all living organisms. Acetylcholinesterase (AChE, E.C.3.1.1.7) is found in high concentrations in the red blood cells and brain. Novel eugenol derivatives (1-6) were tested for the inhibition of two cytosolic CA isoforms I, and II (hCA I, and II) and AChE. These compounds demonstrated effective inhibitory profiles with Ki values in ranging of 113.48-738.69nM against hCA I, 92.35-530.81nM against hCA II, and 90.10-379.57nM against AChE, respectively. On the other hand, acetazolamide clinically used as CA inhibitor, shoed Ki value of 594.11nM against hCA I, and 120.68nM against hCA II, respectively. Also, AChE was inhibited by tacrine as an AChE inhibitor at the 71.18nM level. Copyright © 2016 Elsevier B.V. All rights reserved.

Dual-Valve and Counter-Flow Surface Plasmon Resonance.

PubMed

Wang, Xiaoying; Zhou, Feimeng

2018-04-17

Two six-port injector valves and one selector valve commonly used in flow injection analysis are combined with a surface plasmon resonance (SPR) instrument wherein solutions introduced from the two inlets counter-flow inside the flow cell. The system is versatile as the same or different solutions can be rapidly and repeatedly introduced to the two fluidic channels in series or in parallel. Unlike most commercial SPR instruments employing a single injector valve, solutions separately injected from the two injector valves can be readily exchanged (<1 s) between the two channels. This new method, referred to as the alternate injection mode, not only saves analysis time but also facilitates efficient and facile surface reactions for ligand immobilization and prevents immobilized species from desorbing. These advantages are demonstrated with the measurements of binding of acetazolamide (222.2 Da) to histidine-tagged human carbonic anhydrase II (his-tagged HCA). Amine-containing residues of his-tagged HCA molecules tethered at Ni-nitrilotriacetic acid (NTA) sensors were rapidly cross-linked to the underlying carboxymethylated dextran. The higher ligand densities and more stable surfaces are essential for SPR detection of small molecule binding. In a different application, microglobulin solutions of increasing concentrations were introduced for continuous binding to the preimmobilized antibody. The kinetic and affinity measurements can be conducted without performing repeated dissociation and surface regeneration reactions.

[Quantitative analysis of nucleosides in four Cordyceps genus by HPLC].

PubMed

Qian, Zheng-Ming; Li, Wen-Qing; Wang, Chuan-Xi; Zhou, Miao-Xia; Sun, Min-Tian; Gao, Hao; Li, Wen-Jia

2016-07-01

To compare the main nucleosides in Cordyceps genus herbs (C. sinensis, C. millitaris, Hirsutella sinensis and C. sobolifera), an HPLC method for simultaneous determination of uridine, inosine, guanosine, adenosine and cordycepine in Cordyceps genus herbs was developed. The sample was extracted with 0.5% phosphoric acid solution to prepare test solution. The separation was performed on a Zorbax SB-Aq (4.6 mm×150 mm, 5 μm) column with gradient elution by 0.04 mol•L⁻¹ potassium dihydrogen phosphate solution and acetonitrile, column temperature 30 ℃,flow rate 0.8 mL•min⁻¹,and detection wavelength 260 nm. The content of nucleosides in four Cordyceps genus herbs was evaluated by fingerprint analysis and hierarchical cluster analysis (HCA). The calibration curves of five nucleosides showed good linear regression (r>0.99) and the average recoveries were between 95.0% and 105.0%. The contents of the five nucleosides in the four Cordyceps genus herbs were different and could be obviously distinguished by HCA. The fingerprint analysis result showed that the similarity between C. sinensis and the others was less than 0.9. The method was accurate and reliable, which can be used for quality control of Cordyceps genus herbs. Copyright© by the Chinese Pharmaceutical Association.

Botulinum Neurotoxin Serotype A Recognizes Its Protein Receptor SV2 by a Different Mechanism than Botulinum Neurotoxin B Synaptotagmin

PubMed Central

Weisemann, Jasmin; Stern, Daniel; Mahrhold, Stefan; Dorner, Brigitte G.; Rummel, Andreas

2016-01-01

Botulinum neurotoxins (BoNTs) exhibit extraordinary potency due to their exquisite neurospecificity, which is achieved by dual binding to complex polysialo-gangliosides and synaptic vesicle proteins. The luminal domain 4 (LD4) of the three synaptic vesicle glycoprotein 2 isoforms, SV2A‐C, identified as protein receptors for the most relevant serotype BoNT/A, binds within the 50 kDa cell binding domain HC of BoNT/A. Here, we deciphered the BoNT/A‐SV2 interactions in more detail. In pull down assays, the binding of HCA to SV2-LD4 isoforms decreases from SV2C >> SV2A > SV2B. A binding constant of 200 nM was determined for BoNT/A to rat SV2C-LD4 in GST pull down assay. A similar binding constant was determined by surface plasmon resonance for HCA to rat SV2C and to human SV2C, the latter being slightly lower due to the substitution L563F in LD4. At pH 5, as measured in acidic synaptic vesicles, the binding constant of HCA to hSV2C is increased more than 10-fold. Circular dichroism spectroscopy reveals that the quadrilateral helix of SV2C-LD4 already exists in solution prior to BoNT/A binding. Hence, the BoNT/A‐SV2C interaction is of different nature compared to BoNT/B‐Syt-II. In particular, the preexistence of the quadrilateral β-sheet helix of SV2 and its pH-dependent binding to BoNT/A via backbone–backbone interactions constitute major differences. Knowledge of the molecular details of BoNT/A‐SV2 interactions drives the development of high affinity peptides to counteract BoNT/A intoxications or to capture functional BoNT/A variants in innovative detection systems for botulism diagnostic. PMID:27196927

Veterans Affairs Contracting: Improved Oversight Needed for Certain Contractual Arrangements

DTIC Science & Technology

2015-07-01

Federally Funded Research and Development Center HCA Head of Contracting Activity IAA interagency agreement IDIQ indefinite-delivery indefinite...contracts reside in six different VA organizations. Each of these organizations has an individual designated as Head of Contracting Activity ( HCA ), who...properly trained, stating that HCAs shall develop and implement guidance ensuring only qualified individuals with appropriate training are assigned to

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

HCA Voices Make Council Debut.

PubMed

Cardwell, David

2012-11-28

I have been an RCN member since 2002 when healthcare assistants (HCAs) had to have an NVQ level 3 to join - so I got one. Soon after, with encouragement from the general secretary and chair of congress, I was the first HCA to vote and speak at RCN congress - in a speech in favour of nursery nurses joining the RCN with an NVQ level 2 qualification.

50 CFR Figure 17 to Part 679 - Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA)

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Northern Bering Sea Research Area and Saint Lawrence Island Habitat Conservation Area (HCA) 17 Figure 17 to part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE...

Volatile organic compounds obtained by in vitro callus cultivation of Plectranthus ornatus Codd. (Lamiaceae).

PubMed

Passinho-Soares, Helna C; Meira, Paloma R; David, Juceni P; Mesquita, Paulo R R; do Vale, Ademir E; de M Rodrigues, Frederico; de P Pereira, Pedro A; de Santana, José Raniere F; de Oliveira, Fabio S; de Andrade, Jailson B; David, Jorge M

2013-08-26

Plectranthus spp (Lamiaceae) are plants of economic importance because they are sources of aromatic essential oils and are also cultivated and several species of this genus are used as folk medicines. This paper describes the effects of different concentrations of the 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthaleneacetic acid (NAA) on the induction of callus from nodal segments of Plectranthus ornatus Codd and in the production of volatile organic compounds (monoterpenes and sesquiterpenes). The 20 and 40 day calli were subjected to solid phase micro extraction (HS-SPME) and submitted to GCMS analysis. Variations in VOCs between the samples were observed and, a direct relationship was observed between of the major constituent detected (α-terpinyl acetate) and the monoterpenes α-thujene, α-pinene, β-pinene, camphene, sabinene and α-limonene that were present in the volatile fractions. Besides α-terpinyl acetate, isobornyl acetate and α-limonene were also major constituents. Variations were observed in VOCs in the analyzed periods. The best cultivation media for the production of VOCs was found to be MS0 (control). Moderate success was achieved by treatment with 2.68 µM and 5:37 µM NAA (Group 2). With 2,4-D (9.0 µM), only the presence of α-terpinyl acetate and isocumene were detected and, with 2.26 µM of 2,4-D was produced mainly α-terpinyl acetate, α-thujene and β-caryophyllene (16.2%). The VOC profiles present in P. ornatus were interpreted using PCA and HCA. The results permitted us to determine the best cultivation media for VOC production and, the PCA and HCA analysis allowed us to recognize four groups among the different treatments from the compounds identified in this set of treatments.

Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study.

PubMed

Lourenço, Ana M; Schmidt, Vanessa; São Braz, Berta; Nóbrega, Diana; Nunes, Telmo; Duarte-Correia, José H; Matias, Daniela; Maruhashi, Emi; Rème, Christophe A; Nuttall, Tim

2016-04-01

Long-term remission between flares of canine atopic dermatitis (CAD) can be difficult to achieve. Therefore, additional strategic forms of treatment are needed in order to target flare prevention. The concept of proactive therapy is recommended in the European guidelines for the treatment of human atopic eczema. To evaluate the efficacy of a proactive treatment regimen with a 0.0584% hydrocortisone aceponate (HCA) spray for CAD. Client-owned dogs with spontaneous atopic dermatitis (AD) (n = 41). This pilot study was conducted as a randomised, placebo-controlled, double-blinded clinical trial with an end-point of treatment failure. Dogs were treated once daily to remission, then randomly assigned to receive either the HCA spray (n = 21) or a placebo (n = 20) spray on two consecutive days each week. All dogs were on appropriate flea control. No topical or systemic anti-inflammatory or antimicrobial agents were permitted. Intention-to-treat analysis was used. At Day 0, all the dogs were in remission or had mild AD based on their Canine Atopic Dermatitis Extent and Severity Index, version 3 (CADESI-03) scores. The time to relapse was significantly higher in the HCA group (median 115 d; range 31-260 d) compared to the placebo group (median 33 d; range 15-61 d) (P < 0.0001). No adverse events were attributable to the HCA spray. Four dogs were lost to follow-up and four were withdrawn after receiving prohibited medication. These results indicate that proactive long-term therapy of CAD with an HCA spray administered on two consecutive days each week is effective and well-tolerated. © 2016 ESVD and ACVD.

Use of a Machine Learning-Based High Content Analysis Approach to Identify Photoreceptor Neurite Promoting Molecules.

PubMed

Fuller, John A; Berlinicke, Cynthia A; Inglese, James; Zack, Donald J

2016-01-01

High content analysis (HCA) has become a leading methodology in phenotypic drug discovery efforts. Typical HCA workflows include imaging cells using an automated microscope and analyzing the data using algorithms designed to quantify one or more specific phenotypes of interest. Due to the richness of high content data, unappreciated phenotypic changes may be discovered in existing image sets using interactive machine-learning based software systems. Primary postnatal day four retinal cells from the photoreceptor (PR) labeled QRX-EGFP reporter mice were isolated, seeded, treated with a set of 234 profiled kinase inhibitors and then cultured for 1 week. The cells were imaged with an Acumen plate-based laser cytometer to determine the number and intensity of GFP-expressing, i.e. PR, cells. Wells displaying intensities and counts above threshold values of interest were re-imaged at a higher resolution with an INCell2000 automated microscope. The images were analyzed with an open source HCA analysis tool, PhenoRipper (Rajaram et al., Nat Methods 9:635-637, 2012), to identify the high GFP-inducing treatments that additionally resulted in diverse phenotypes compared to the vehicle control samples. The pyrimidinopyrimidone kinase inhibitor CHEMBL-1766490, a pan kinase inhibitor whose major known targets are p38α and the Src family member lck, was identified as an inducer of photoreceptor neuritogenesis by using the open-source HCA program PhenoRipper. This finding was corroborated using a cell-based method of image analysis that measures quantitative differences in the mean neurite length in GFP expressing cells. Interacting with data using machine learning algorithms may complement traditional HCA approaches by leading to the discovery of small molecule-induced cellular phenotypes in addition to those upon which the investigator is initially focusing.

ConnectX2 In niBand Management Queues: New support for Network Of oaded

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, Richard L; Poole, Stephen W; Shamis, Pavel

2010-01-01

This paper introduces the newly developed InfiniBand (IB) Management Queue capability, used by the Host Channel Adapter (HCA) to manage network task data flow dependancies, and progress the communications associated with such flows. These tasks include sends, receives, and the newly supported wait task, and are scheduled by the HCA based on a data dependency description provided by the user. This functionality is supported by the ConnectX-2 HCA, and provides the means for delegating collective communication management and progress to the HCA, also known as collective communication offload. This provides a means for overlapping collective communications managed by the HCAmore » and computation on the Central Processing Unit (CPU), thus making it possible to reduce the impact of system noise on parallel applications using collective operations. This paper further describes how this new capability can be used to implement scalable Message Passing Interface (MPI) collective operations, describing the high level details of how this new capability is used to implement the MPI Barrier collective operation, focusing on the latency sensitive performance aspects of this new capability. This paper concludes with small scale benchmark experiments comparing implementations of the barrier collective operation, using the new network offload capabilities, with established point-to-point based implementations of these same algorithms, which manage the data flow using the central processing unit. These early results demonstrate the promise this new capability provides to improve the scalability of high-performance applications using collective communications. The latency of the HCA based implementation of the barrier is similar to that of the best performing point-to-point based implementation managed by the central processing unit, starting to outperform these as the number of processes involved in the collective operation increases.« less

ConnectX-2 InfiniBand Management Queues: First Investigation of the New Support for Network Offloaded Collective Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graham, Richard L; Poole, Stephen W; Shamis, Pavel

2010-01-01

This paper introduces the newly developed Infini-Band (IB) Management Queue capability, used by the Host Channel Adapter (HCA) to manage network task data flow dependancies, and progress the communications associated with such flows. These tasks include sends, receives, and the newly supported wait task, and are scheduled by the HCA based on a data dependency description provided by the user. This functionality is supported by the ConnectX-2 HCA, and provides the means for delegating collective communication management and progress to the HCA, also known as collective communication offload. This provides a means for overlapping collective communications managed by the HCAmore » and computation on the Central Processing Unit (CPU), thus making it possible to reduce the impact of system noise on parallel applications using collective operations. This paper further describes how this new capability can be used to implement scalable Message Passing Interface (MPI) collective operations, describing the high level details of how this new capability is used to implement the MPI Barrier collective operation, focusing on the latency sensitive performance aspects of this new capability. This paper concludes with small scale benchmark experiments comparing implementations of the barrier collective operation, using the new network offload capabilities, with established point-to-point based implementations of these same algorithms, which manage the data flow using the central processing unit. These early results demonstrate the promise this new capability provides to improve the scalability of high performance applications using collective communications. The latency of the HCA based implementation of the barrier is similar to that of the best performing point-to-point based implementation managed by the central processing unit, starting to outperform these as the number of processes involved in the collective operation increases.« less

Impact of chorioamnionitis on short- and long-term outcomes in very low birth weight preterm infants: the Neonatal Research Network Japan.

PubMed

Miyazaki, Ken; Furuhashi, Madoka; Ishikawa, Kaoru; Tamakoshi, Koji; Hayashi, Kazutoshi; Kai, Akihiko; Ishikawa, Hiroshi; Murabayashi, Nao; Ikeda, Tomoaki; Kono, Yumi; Kusuda, Satoshi; Fujimura, Masanori

2016-01-01

To evaluate the short- and long-term outcomes among very low birth weight (VLBW) preterm infants after histologic chorioamnionitis (HCA). We performed a retrospective analysis of 5849 single infants (birth weight <1500 g) born at a gestational age between 22 + 0 and 33 + 6 weeks. Clinical data were obtained from the Neonatal Research Network Japan between 2003 and 2007. Multivariable logistic regression analyses were performed to assess the effect of HCA on short- and long-term outcome. According to logistic regression analysis, HCA was associated with lower incidence of respiratory distress syndrome (odds ratio [OR] = 0.54; p < 0.001), increased chronic lung disease (OR = 1.68; p < 0.001) and sepsis (OR = 1.71; p < 0.001) and as a short-term outcomes. There was no significant association with intraventricular hemorrhage (OR = 1.11; p = 0.33), periventricular leukomalacia (OR = 1.07; p = .070) and death before discharge (OR = 0.97; p = 0.084). HCA was associated with increased home oxygen therapy (OR = 3.09; p < 0.001), but not with cerebral palsy (CP; OR = 0.91; p = 0.63), develop quotient < 70 (OR = 1.27; p = 0.17), visual impairment (OR = 1.08; p = 0.77), severe hearing impairment (OR = 1.28; p = 0.62) and death (OR = 0.98; p = 0.91) before three years of age. In this retrospective population-based study in Japan, HCA was not a risk factor for death, neurodevelopmental impairment and CP in VLBW three-year-old preterm infants.

Healthcare-Associated Infective Endocarditis: a Case Series in a Referral Hospital from 2006 to 2011

PubMed Central

Francischetto, Oslan; da Silva, Luciana Almenara Pereira; Senna, Katia Marie Simões e; Vasques, Marcia Regina; Barbosa, Giovanna Ferraiuoli; Weksler, Clara; Ramos, Rosana Grandelle; Golebiovski, Wilma Felix; Lamas, Cristiane da Cruz

2014-01-01

Background Healthcare-associated infective endocarditis (HCA-IE), a severe complication of medical care, shows a growing incidence in literature. Objective To evaluate epidemiology, etiology, risk factors for acquisition, complications, surgical treatment, and outcome of HCA-IE. Methods Observational prospective case series study (2006-2011) in a public hospital in Rio de Janeiro. Results Fifty-three patients with HCA-IE from a total of 151 cases of infective endocarditis (IE) were included. There were 26 (49%) males (mean age of 47 ± 18.7 years), 27 (51%) females (mean age of 42 ± 20.1 years). IE was acute in 37 (70%) cases and subacute in 16 (30%) cases. The mitral valve was affected in 19 (36%) patients and the aortic valve in 12 (36%); prosthetic valves were affected in 23 (43%) patients and native valves in 30 (57%). Deep intravenous access was used in 43 (81%) cases. Negative blood cultures were observed in 11 (21%) patients, Enterococcus faecalis in 10 (19%), Staphylococcus aureus in 9 (17%), and Candida sp. in 7 (13%). Fever was present in 49 (92%) patients, splenomegaly in 12 (23%), new regurgitation murmur in 31 (58%), and elevated C-reactive protein in 44/53 (83%). Echocardiograms showed major criteria in 46 (87%) patients, and 34 (64%) patients were submitted to cardiac surgery. Overall mortality was 17/53 (32%). Conclusion In Brazil HCA-IE affected young subjects. Patients with prosthetic and native valves were affected in a similar proportion, and non-cardiac surgery was an infrequent predisposing factor, whereas intravenous access was a common one. S. aureus was significantly frequent in native valve HCA-IE, and overall mortality was high. PMID:25352503

CMV viral load measurements in whole blood and plasma--which is best following renal transplantation?

PubMed

Barrett-Muir, W; Breuer, J; Millar, C; Thomas, J; Jeffries, D; Yaqoob, M; Aitken, C

2000-07-15

Quantitative commercial assays for cytomegalovirus (CMV) detection have recently been developed. Their role in the management of patients after transplantation needs to be evaluated. Widespread use of these assays will allow for comparison of results between centers and meaningful interpretation of the significance of viral load measurements. Sequential samples from 52 patients after renal transplantation were tested in the murex hybrid capture assay (HCA) and the Roche Amplicor CMV DNA assay (QPCR) and correlated with the development of CMV disease. A comparison of viral loads in plasma and whole blood was also made. Both assays were sensitive and detected all cases of CMV disease. The specificity and positive predictive value increased from 0.34 and 0.36 to 0.85 and 0.96 for the HCA and 0.37, 0.37 to 0.72 and 0.63 for the QPCR following a receiver operator curve analysis. Higher viral loads were measured using the HCA compared to the QPCR. Response to ganciclovir was associated with a greater than 80% reduction in viral load by HCA or greater than 70% using the QPCR. Both assays were highly sensitive. By using a receiver operator curve analysis a cutoff viral load can be determined which maximizes the clinical utility of these assays.

Hepatocellular adenoma in a woman who was undergoing testosterone treatment for gender identity disorder.

PubMed

Kato, Keizo; Abe, Hiroshi; Hanawa, Noriko; Fukuzawa, Junya; Matsuo, Ryota; Yonezawa, Takeshi; Itoh, Sadahiro; Sato, Yoshiyuki; Ika, Makiko; Shimizu, Shohei; Endo, Shinji; Hano, Hiroshi; Izu, Asami; Sugitani, Masahiko; Tsubota, Akihito

2018-03-27

A 32-year-old Japanese woman was admitted to our hospital for the diagnosis and treatment of multiple liver tumors. She had been receiving 125 mg testosterone enanthate every 2 weeks following female-to-male gender identity disorder (GID) diagnosis at 20 years of age. Ultrasonography, computed tomography, and magnetic resonance imaging showed 11 hepatic nodular tumors with a maximum diameter of 28 mm. Liver tumors with hepatocellular adenoma (HCA) were diagnosed with needle biopsy. Segmentectomy of the left lateral lobe including two lesions, subsegmentectomy of S6 including two lesions, enucleation of each tumor in S5 and S7, and open surgical radiofrequency ablation for each tumor in S4 and S7 were performed. Immunohistochemical specimens showed that the tumor cells were diffusely and strongly positive for glutamine synthetase and that the nuclei were ectopically positive for β-catenin. Thus, the tumors were diagnosed as β-catenin-activated HCA (b-HCA). Transcatheter arterial chemoembolization plus subsequent radiofrequency ablation was performed for the 3 residual lesions in S4 and S8. Although testosterone enanthate was being continued for GID, no recurrence was observed until at least 22 months after the intensive treatments. HCA development in such patients receiving testosterone should be closely monitored using image inspection.

The incidence of histological chorioamnionitis in IVF/GIFT preterm births.

PubMed

Williams, H; Jeffery, H

1994-08-01

A retrospective case control study was designed to investigate the role of subclinical infection as a risk factor for the high rate of preterm deliveries in IVF/GIFT pregnancies. The cases and the controls were identified from the records of consecutive livebirths of < 35 weeks' gestational age (GA), at King George V Hospital from 1987-1993. Fifty one singleton and 58 twin IVF/GIFT preterm births were matched for GA, year of birth, plurality, maternal age, parity, preclampsia and antepartum haemorrhage. As a marker of subclinical infection, the incidence of histological chorioamnionitis (HCA) in the 2 groups (as defined by the standardized, semiquantitative method of Benirschke) was compared. The matched variables did not differ significantly between the IVF/GIFT group and the control group. No significant difference in the incidence of HCA was detected between IVF/GIFT and control groups for singletons or twins. Overall 24% of IVF/GIFT and 30% of controls showed evidence of HCA, odds ratio (95% confidence intervals), 0.72 (0.40-1.31). This study showed no evidence that the incidence of HCA, is significantly increased in IVF/GIFT preterm births compared with other matched, preterm births. Therefore, we conclude that subclinical infection/inflammation cannot explain the 4-fold increase in preterm births in the IVF/GIFT population.

Chemometric analysis of minerals in gluten-free products.

PubMed

Gliszczyńska-Świgło, Anna; Klimczak, Inga; Rybicka, Iga

2018-06-01

Numerous studies indicate mineral deficiencies in people on a gluten-free (GF) diet. These deficiencies may indicate that GF products are a less valuable source of minerals than gluten-containing products. In the study, the nutritional quality of 50 GF products is discussed taking into account the nutritional requirements for minerals expressed as percentage of recommended daily allowance (%RDA) or percentage of adequate intake (%AI) for a model celiac patient. Elements analyzed were calcium, potassium, magnesium, sodium, copper, iron, manganese, and zinc. Analysis of %RDA or %AI was performed using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Using PCA, the differentiation between products based on rice, corn, potato, GF wheat starch and based on buckwheat, chickpea, millet, oats, amaranth, teff, quinoa, chestnut, and acorn was possible. In the HCA, four clusters were created. The main criterion determining the adherence of the sample to the cluster was the content of all minerals included to HCA (K, Mg, Cu, Fe, Mn); however, only the Mn content differentiated four formed groups. GF products made of buckwheat, chickpea, millet, oats, amaranth, teff, quinoa, chestnut, and acorn are better source of minerals than based on other GF raw materials, what was confirmed by PCA and HCA. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Retrograde cerebral perfusion (RCP) in aortic arch surgery: efficacy and possible mechanisms of brain protection.

PubMed

Bavaria, J E; Pochettino, A

1997-07-01

Retrograde cerebral perfusion (RCP) was first introduced to treat air embolism during cardiopulmonary bypass (CPB). Its use was reintroduced to extend the safety of hypothermic circulatory arrest (HCA) during operations involving an open aortic arch. RCP seems to prevent cerebral rewarming during HCA. Both clinical and animal data suggest that RCP provides between 10% and 30% of baseline cerebral blood flow when administered through the superior vena cava (SVC) at jugular pressures of 20 to 25 mm Hg. RCP flows producing jugular venous pressures higher than 30 mm Hg may cause cerebral edema. Cerebral blood flow generated by RCP is able to sustain some cerebral metabolic activity, yet is not able to fully meet cerebral energy demands even at temperatures of 12 degrees to 18 degrees C. RCP may further prevent embolic events during aortic arch surgery when administered at moderate jugular vein pressures (< 40 mm Hg). Clinical results suggest that RCP, when applied during aortic arch reconstruction, may extend the safe HCA period and improve morbidity and mortality, especially when HCA times are more than 60 minutes. RCP applied in patients and severe carotid and brachiocephalic occlusive disease may be ineffective, and caution is in order when RCP times are greater than 90 minutes.

Optimism, community attachment and serostatus disclosure among HIV-positive men who have sex with men.

PubMed

Murphy, Patrick J; Hevey, David; O'Dea, Siobhán; Ní Rathaille, Neans; Mulcahy, Fiona

2015-01-01

This study investigated the relationship between HIV health optimism (HHO) (the belief that health will remain good after HIV infection due to treatment efficacy), HIV-positive community attachment (HCA), gay community attachment (GCA) and serostatus disclosure to casual sex partners by HIV-positive men who have sex with men (MSM). Cross-sectional questionnaire data were gathered from 97 HIV-positive MSM attending an HIV treatment clinic in Dublin, Ireland. Based on self-reported disclosure to casual partners, participants were classified according to their pattern of disclosure (consistent, inconsistent or non-disclosers). Multinomial logistic regression was used to assess HHO, HCA and GCA as predictors of participants' pattern of disclosure. Classification as a non-discloser (compared to a consistent discloser) was associated with higher HHO, less HCA and greater GCA. Classification as an inconsistent discloser (compared to a consistent discloser) was associated with higher GCA. The study provided novel quantitative evidence for associations between the constructs of interest. The results suggest that (1) HHO is associated with reduced disclosure, suggesting optimism may preclude individuals reaping the benefits of serostatus disclosure and (2) HCA and GCA represent competing attachments with conflicting effects on disclosure behaviour. Limitations and areas for future research are discussed.

Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects.

PubMed

Gul, Halise Inci; Kucukoglu, Kaan; Yamali, Cem; Bilginer, Sinan; Yuca, Hafize; Ozturk, Iknur; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T

2016-08-01

In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by (1)H NMR, (13)CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1-S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1-S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with Kis in the range of 1.79 ± 0.22-2.73 ± 0.08 nM against hCA I and in the range of 1.72 ± 0.58-11.64 ± 5.21 nM against hCA II, respectively.

Prostaglandin E₂ regulates cellular migration via induction of vascular endothelial growth factor receptor-1 in HCA-7 human colon cancer cells.

PubMed

Fujino, Hiromichi; Toyomura, Kaori; Chen, Xiao-bo; Regan, John W; Murayama, Toshihiko

2011-02-01

An important event in the development of tumors is angiogenesis, or the formation of new blood vessels. Angiogenesis is also known to be involved in tumor cell metastasis and is dependent upon the activity of the vascular endothelial growth factor (VEGF) signaling pathway. Studies of mice in which the EP3 prostanoid receptors have been genetically deleted have shown a role for these receptors in cancer growth and angiogenesis. In the present study, human colon cancer HCA-7 cells were used as a model system to understand the potential role of EP3 receptors in tumor cell migration. We now show that stimulation of HCA-7 cells with PGE₂ enhanced the up-regulation of VEGF receptor-1 (VEGFR-1) expression by a mechanism involving EP3 receptor-mediated activation of phosphatidylinositol 3-kinase and the extracellular signal-regulated kinases. Moreover, the PGE₂ stimulated increase in VEGFR-1 expression was accompanied by an increase in the cellular migration of HCA-7 cells. Given the known involvement of VEGFR-1 in cellular migration, our results suggest that EP3 receptors may contribute to tumor cell metastasis by increasing cellular migration through the up-regulation of VEGFR-1 signaling. Copyright © 2010 Elsevier Inc. All rights reserved.

Pseudomonas putida F1 uses energy taxis to sense hydroxycinnamic acids

PubMed Central

Hughes, Jonathan G.; Zhang, Xiangsheng; Parales, Juanito V.; Ditty, Jayna L.; Parales, Rebecca E.

2017-01-01

Soil bacteria such as pseudomonads are widely studied due to their diverse metabolic capabilities, particularly the ability to degrade both naturally occurring and xenobiotic aromatic compounds. Chemotaxis, the directed movement of cells in response to chemical gradients, is common in motile soil bacteria and the wide range of chemicals detected often mirrors the metabolic diversity observed. Pseudomonas putida F1 is a soil isolate capable of chemotaxis toward, and degradation of, numerous aromatic compounds. We showed that P. putida F1 is capable of degrading members of a class of naturally occurring aromatic compounds known as hydroxycinnamic acids, which are components of lignin and are ubiquitous in the soil environment. We also demonstrated the ability of P. putida F1 to sense three hydroxycinnamic acids: p-coumaric, caffeic and ferulic acids. The chemotaxis response to hydroxycinnamic acids was induced during growth in the presence of hydroxycinnamic acids and was negatively regulated by HcaR, the repressor of the hydroxycinnamic acid catabolic genes. Chemotaxis to the three hydroxycinnamic acids was dependent on catabolism, as a mutant lacking the gene encoding feruloyl-CoA synthetase (Fcs), which catalyzes the first step in hydroxycinnamic acid degradation, was unable to respond chemotactically toward p-coumaric, caffeic, or ferulic acids. We tested whether an energy taxis mutant could detect hydroxycinnamic acids and determined that hydroxycinnamic acid sensing is mediated by the energy taxis receptor Aer2. PMID:28954643

Two-material optimization of plate armour for blast mitigation using hybrid cellular automata

NASA Astrophysics Data System (ADS)

Goetz, J.; Tan, H.; Renaud, J.; Tovar, A.

2012-08-01

With the increased use of improvised explosive devices in regions at war, the threat to military and civilian life has risen. Cabin penetration and gross acceleration are the primary threats in an explosive event. Cabin penetration crushes occupants, damaging the lower body. Acceleration causes death at high magnitudes. This investigation develops a process of designing armour that simultaneously mitigates cabin penetration and acceleration. The hybrid cellular automaton (HCA) method of topology optimization has proven efficient and robust in problems involving large, plastic deformations such as crash impact. Here HCA is extended to the design of armour under blast loading. The ability to distribute two metallic phases, as opposed to one material and void, is also added. The blast wave energy transforms on impact into internal energy (IE) inside the solid medium. Maximum attenuation occurs with maximized IE. The resulting structures show HCA's potential for designing blast mitigating armour structures.

Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

PubMed

Métayer, Benoît; Martin-Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

2013-11-21

A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

"Experience Keeps a Dear School": the Effects of Ethnicity and Caregiving Experience on Hiring a Healthcare Advocate.

PubMed

Van Liew, Charles; Santoro, Maya; Kothari, Dhwani; Wooldridge, Jennalee; Cronan, Terry A

2016-12-01

In the present study, ethnic differences in evaluating the severity and associated needs of medical complications experienced by an elderly man and the likelihood of seeking professional assistance (i.e., hire a healthcare advocate [HCA]) to care for him, and for one's own family or parent should they become ill, as a function of previous caregiving experience, were investigated. The 974 participants were White, Black, Hispanic, or Asian/Pacific Islander. They read a hypothetical vignette about a 75-year-old man, Daryl, who was experiencing health problems. Participants were instructed to imagine that they were James, Daryl's son, and asked to indicate how severe his condition(s) were, how much medical assistance he would require, and how likely they would be to hire an HCA to assist him. They were also asked to report whether they previously had assisted a parent with activities of daily living (Assistance) and whether they would be likely to hire an HCA in the future if 1) a family member or 2) a parent, specifically, became ill. Two, 2 (Assistance) × 4 (Ethnicity) multivariate analyses of covariance (MANCOVA) were performed to assess differential responses among individuals of different ethnicities as a function of previous caregiver experience. A priori interaction contrasts were examined to determine whether Black, Hispanic, or Asian/Pacific Islander participants differed on the outcomes from White participants as a function of previous caregiver experience. There were no significant differences between Black or Asian/Pacific Islander and White participants, but Hispanic participants assigned significantly higher severity and need for medical assistance ratings and were significantly more likely to indicate that they would seek assistance from an HCA with respect to the vignette and for their own parents in the future if they had provided caregiving to a parent in the past, whereas White participants were less likely to seek assistance from an HCA if they had provided caregiving in the past to a parent. Although ethnic differences in evaluations of Daryl's condition and in the reported likelihoods of hiring an HCA in various contexts as a function of previous caregiving experience were limited, there are important inter-cultural differences to recognize. It may be important in future research to assess ethnic differences in the expectations and experiences of caregiving.

Trends in Breast Cancer Stage and Mortality in Michigan (1992–2009) by Race, Socioeconomic Status, and Area Healthcare Resources

PubMed Central

Akinyemiju, Tomi F.; Soliman, Amr S.; Copeland, Glenn; Banerjee, Mousumi; Schwartz, Kendra; Merajver, Sofia D.

2013-01-01

The long-term effect of socioeconomic status (SES) and healthcare resources availability (HCA) on breast cancer stage of presentation and mortality rates among patients in Michigan is unclear. Using data from the Michigan Department of Community Health (MDCH) between 1992 and 2009, we calculated annual proportions of late-stage diagnosis and age-adjusted breast cancer mortality rates by race and zip code in Michigan. SES and HCA were defined at the zip-code level. Joinpoint regression was used to compare the Average Annual Percent Change (AAPC) in the median zip-code level percent late stage diagnosis and mortality rate for blacks and whites and for each level of SES and HCA. Between 1992 and 2009, the proportion of late stage diagnosis increased among white women [AAPC = 1.0 (0.4, 1.6)], but was statistically unchanged among black women [AAPC = −0.5 (−1.9, 0.8)]. The breast cancer mortality rate declined among whites [AAPC = −1.3% (−1.8,−0.8)], but remained statistically unchanged among blacks [AAPC = −0.3% (−0.3, 1.0)]. In all SES and HCA area types, disparities in percent late stage between blacks and whites appeared to narrow over time, while the differences in breast cancer mortality rates between blacks and whites appeared to increase over time. PMID:23637921

Different approaches to valuing the lost productivity of patients with migraine.

PubMed

Lofland, J H; Locklear, J C; Frick, K D

2001-01-01

To calculate and compare the human capital approach (HCA) and friction cost approach (FCA) methods for estimating the cost of lost productivity of migraineurs after the initiation of sumatriptan from a US societal perspective. Secondary, retrospective analysis to a prospective observational study. A mixed-model managed care organisation in western Pennsylvania, USA. Patients with migraine using sumatriptan therapy. Patient-reported questionnaires collected at baseline, 3 and 6 months after initiation of sumatriptan therapy. The cost of lost productivity estimated with the HCA and FCA methods. Of the 178 patients who completed the study, 51% were full-time employees, 13% were part-time, 18% were not working and 17% changed work status. Twenty-four percent reported a clerical or administrative position. From the HCA, the estimated total cost of lost productivity for 6 months following the initiation of sumatriptan was $US117905 (1996 values). From the FCA, the six-month estimated total cost of lost productivity ranged from $US28329 to $US117905 (1996 values). This was the first study to retrospectively estimate lost productivity of patients with migraine using the FCA methodology. Our results demonstrate that depending on the assumptions and illustrations employed, the FCA can yield lost productivity estimates that vary greatly as a percentage of the HCA estimate. Prospective investigations are needed to better determine the components and the nature of the lost productivity for chronic episodic diseases such as migraine headache.

Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example.

PubMed

Takeyoshi, Masahiro; Sawaki, Masakuni; Yamasaki, Kanji; Kimber, Ian

2003-09-30

The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.

Aortic arch repair under moderate hypothermic circulatory arrest with or without antegrade cerebral perfusion based on the extent of repair

PubMed Central

Park, Sung Jun; Jeon, Bo Bae; Kim, Hee Jung

2018-01-01

Background For aortic-arch repair, moderate hypothermic circulatory arrest (HCA) have shown favorable outcomes over conventional deep HCA when coupled with antegrade cerebral perfusion (ACP); however, recent studies have shown that ACP may not be essential when circulatory arrest time is less than 30 minutes. This study aims to evaluate the stratified arch repair strategy of moderate HCA with or without ACP based on the extent of procedure. Methods Consecutive 138 patients (63 female; mean age, 60.2±15.7 years) undergoing open arch repair due to acute aortic syndrome (n=69) or chronic aneurysm (n=69) from January 2012 through April 2017 were enrolled in this study. Stratified neuroprotective strategy was employed according to the extent of repair: hemi-arch repair (n=93) was performed under moderated HCA alone and total-arch repair (n=45) under moderate HCA combined with unilateral ACP. Results Median total circulatory arrest and total procedural times were 8.0 minutes [interquartile range (IQR), 6.0–10.0] and 233.0 minutes (IQR, 196.0–290.0 minutes), respectively in the hemi-arch group, and 25.0 minutes (IQR, 12.0–33.0 minutes) and 349.0 minutes (IQR, 276.0–406.0 minutes), respectively in the total-arch group. Early mortality occurred in 2 patients (1.4%) who underwent hemi-arch repair for acute aortic dissection. There was no permanent neurological injury, but 2 cases (1.4%) of temporary neurologic deficit in the hemi-arch group. Other complications included re-exploration for bleeding in 6 (4.3%), postoperative extracorporeal life support in 5 (3.6%) and new-dialysis in 6 (4.3%). Conclusions Stratified cerebral perfusion strategy using moderate hypothermia for aortic-arch surgery based on the extent of arch repair showed satisfactory safety and reasonable efficiency. PMID:29707342

'Doing it for real now' - The transition from healthcare assistant to newly qualified nurse: A qualitative study.

PubMed

Draper, Jan

2018-07-01

There has been increasing international research and policy interest concerning the transition from student to newly qualified nurse (NQN). However, the influence of previous employment as a healthcare assistant (HCA) on students' experiences of this transition is comparatively under-researched. To explore the experiences of NQNs also employed as HCAs during their pre-registration education programme and how this prior and ongoing HCA experience influenced their transition experiences. Qualitative research design using a descriptive method. Former students (n = 14) of a unique four year, part-time, employer-sponsored pre-registration nursing programme, specifically designed for HCAs and delivered by supported open learning, located in different regions and nations of the United Kingdom who had qualified within the last two years. Telephone interviews, digitally recorded, transcribed verbatim and analysed using NVivo8. Four themes described participants' experiences of transition: In at the deep end, Changing identities, Coming together and Scaffolding. Findings confirm existing literature that all NQNs appear to experience a similar overarching experience of transition, including those with prior HCA experience. However, familiarity with people, place and routines afforded by this previous experience appeared to ease transition, particularly if the NQNs stayed in their previous HCA work location. However, managing the dual roles of being both HCA and student and adapting to their changing identities were frequently cited as particular challenges. Van Gennep's Rites de Passage and Bridge's work on organisational change were combined to theoretically analyse participants' accounts of transition. This illustrated that transition is not always linear with clearly defined and bounded stages but can also be seen as a more undulating or organic process with curving, slanting and overlapping phases. NQNs can therefore simultaneously occupy more than once phase in their journey of transition. Implications for students, higher education and practice are highlighted. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

[In vitro evaluation of cutaneous allergic reaction induced by chemicals using dendritic cells].

PubMed

Zhang, Yu-bin; Lin, Hui-fen; Lv, Luo; Hua, Wei-guang; Tian, Fang; Shen, Guang-zu; Xia, Zhao-lin; Jin, Xi-peng

2008-03-01

To investigate the use of dendritic cells derived from mice bone marrow to evaluate the cutaneous allergic reaction induced by chemical sensitizers. Dendritic cells derived from mice bone marrow were cultured and administrated with 2, 4-dinitrochlorobenzene (DNCB), nickel sulfate (NiSO4), sodium dodecyl sulfate (SDS) and hexyl cinnamic aldehyde (HCA), respectively. Cell membrane molecule CD86 and extracellular IL-1 beta, IL-6 and IL-12 were detected after 0, 1, 6, 12, 24, 36, 48 hour's administration, respectively. CD86 expression reached the highest level after exposure to DNCB for 48 h, and increased by about 279% compared with the control (P < 0.05), while it was lower than that of control after administrated with NiSO4 and HCA for 1 h and 6 h, and SDS for 36 h, respectively (P < 0.05). Extracellular IL-1 beta increased greatly after exposure to NiSO4 just for 1 h, with the maximum at 48 h (298 pg/ml, P < 0.05), and after exposure to HCA for 6 h, with maximum at 48 h (84 pg/ml, P < 0.05). However, it didn't fluctuate significantly after administrated with DNCB and SDS respectively, compared with the control. Extracellular IL-6 increased significantly after exposure to NiSO4 for 1 h, with the maximum at 24 h (2152 pg/ml, P < 0.05). After exposure to HCA, extracellular IL-6 reached the maximum at 1 h (1403 pg/ml), and then it was decreased quickly, but still higher than the control (P < 0.05), while it didn't change significantly after treatment with DNCB and SDS, compared with the control (P > 0.05). Extracellular IL-12 was not detected out among all the groups. Chemical sensitizer DNCB could induce the high expression of CD86 on DC membrane, and NiSO4 and HCA could induce DC to release IL-1 beta and IL-6. However, the irritant SDS had no such effect.

Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: Selective inhibitors for the tumor-associated hCA IX isoform.

PubMed

Ibrahim, Hany S; Allam, Heba Abdelrasheed; Mahmoud, Walaa R; Bonardi, Alessandro; Nocentini, Alessio; Gratteri, Paola; Ibrahim, Eslam S; Abdel-Aziz, Hatem A; Supuran, Claudiu T

2018-05-25

The synthesis and characterization of two new sets of arylsulfonehydrazone benzenesulfonamides (4a-4i with phenyl tail and 4j-4q with tolyl tail) are reported. The compounds were designed according to a dual-tails approach to modulate the interactions of the ligands portions at the outer rim of both hydrophobic and hydrophilic active site halves of human isoforms of carbonic anhydrase (CA, EC 4.2.1.1). The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IV and IX. With the latter being a validated anticancer drug target and a marker of tumor hypoxia, attractive results arose from the Compounds' inhibitory screening in terms of potency and selectivity. Indeed, whereas the first subset of compounds 4a-4i exhibited great efficacy in inhibiting both the ubiquitous, off-target hCA II (K I s 9.5-172.0 nM) and hCA IX (K I s 7.5-131.5 nM), the second subset of tolyl-bearing derivatives 4j-4q were shown to possess a selective hCA IX inhibitory action over isoforms I, II and IV. The most selective compounds 4l and 4n were further screened for their in vitro cytotoxic activity against MCF-7 and MDA-MB-231 cancer cell lines under hypoxic conditions. The selective IX/II inhibitory trend of 4j-4q compared to those of compounds 4a-4i was unveiled by docking studies. Further exploration of these molecules could be useful for the development of novel antitumor agents with a selective CA inhibitory mechanism. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Navy-NGO Coordination for Health-Related HCA Missions: A Suggested Planning Framework

DTIC Science & Technology

2008-11-01

however, on how to work with NCOs in the HCA setting. As a result, there is currendy no systematic frame - work for military-NGO coordination. The...agencies and NGOs, make up a tertiary audience. The issues are framed in a way that reflects the Navy’s current views and thinking, but NGO perspectives...it is written mainly from a Navy-centric perspective. The framing of the issues, in particular, reflects the Navy’s current views and thinking. NGO

Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

2016-01-01

The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties

NASA Astrophysics Data System (ADS)

Erdemir, Fatoş; Barut Celepci, Duygu; Aktaş, Aydın; Taslimi, Parham; Gök, Yetkin; Karabıyık, Hasan; Gülçin, İlhami

2018-03-01

This study contains novel a serie synthesis of N-heterocyclic carbene (NHC) precursors that 2-hydroxyethyl substituted. The NHC precursors have been prepared from 1-(2- hydroxyethyl)benzimidazole and alkyl halides. The novel NHC precursors have been characterized by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. Molecular and crystal structures of 2a, 2d, 2e, 2f and 2g were obtained with single-crystal X-ray diffraction studies. These novel NHC precursor's derivatives effectively inhibited the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Inhibition constant (Ki) were found in the range of 0.30-9.22 nM for α-glycosidase, 13.90-41.46 nM for hCA I, 12.82-49.95 nM for hCA II, 145.82-882.01 nM for BChE, and 280.92-1370.01 nM for AChE, respectively.

The impact of the Tulane-HCA joint venture on academic and clinical missions.

PubMed

Whitecloud, T S; Smathers, J E; Barrack, R L

2001-10-01

As with any joint venture in any given industry, positive and negative impacts are felt. Tulane University School of Medicine experienced impacts on its academic and clinical missions as a result of the joint venture between Tulane University and HCA, a for-profit public company. The laws of business had entered the halls of medicine. Although patients, personnel, and physicians experienced culture shock and inconveniences, Tulane University School of Medicine has been able to maintain viable training programs, and its faculty physicians have a hospital and corporately run clinics across the street. In addition, multidisciplinary centers of excellence, long spoken of in the academic realm, came to fruition through the corporate world. This may not have been the case, had Tulane University not entered into ajoint venture with HCA. Is it worth the effort? For Tulane University, whether one likes the entire package or not, the answer must be yes. The greatest impact is that the orthopaedic surgeons still are in a position to fulfill their academic and clinical missions.

Serious anaphylactic shock induced by hemocoagulase agkistrodon during anesthesia in a 5-year-old child.

PubMed

Xu, Ying-Yi; Li, Bi-Lian; Jin, Yu-Lin; Wang, Zi-Xin; Song, Xing-Rong; Ni, Jin

2015-01-01

We report a case of serious anaphylactic shock in a 5-year-old child undergoing scheduled surgery blank space of a right femoral intramedullary nail removal. The boy had undergone right femoral elastic intramedullary nail fixation surgery 14 months prior, but had no history of allergies. Within 5 minutes of intravenous bonus injection of hemocoagulase agkistrodon (HCA) 1 unit, a widespread transient diffuse erythema was seen on the front of his chest. After 20 minutes, sudden, profound cardiovascular collapse occurred. The child was treated effectively and sent to a ward 5 hours later. In this period, he received intravenously infused 200 ml hydroxyethyl starch solution and epinephrine at a rate of 0.05-0.01 μg kg(-1) min(-1). Total amount of dexamethasone sodium phosphate 14 mg was used. To the best of our knowledge, few case reports of HCA-induced anaphylactic shock in children exist. Our report will, therefore, increase awareness of the allergic potential of HCA among pediatric anesthesiologists.

High Current Hollow Cathode Plasma Plume Measurements

NASA Technical Reports Server (NTRS)

Thomas, Robert E.; Kamhawi, Hani; Williams, George J., Jr.

2014-01-01

Plasma plume measurements are reported for a hollow cathode assembly (HCA) operated at discharge currents of 50, 70, and 100 A at xenon flow rates between 19 - 46 standard cubic centimeter per minute. The HCA was centrally mounted in the NASA-300MS Hall Thruster and was operated in the "spot" and "plume" modes with additional data taken with an applied magnetic field. Langmuir probes, retarding potential analyzers, and optical emission spectroscopy were employed to measure plasma properties near the orifice of the HCA and to assess the charge state of the near-field plasma. Electron temperatures (2-6 electron volt) and plasma potentials are consistent with probe-measured values in previous investigations. Operation with an applied-field yields higher discharge voltages, increased Xe III production, and increased signals from the 833.5 nm C I line. While operating in plume mode and with an applied field, ion energy distribution measurements yield ions with energies significantly exceeding the applied discharge voltage. These findings are correlated with high-frequency oscillations associated with each mode.

High Current Hollow Cathode Plasma Plume Measurements

NASA Technical Reports Server (NTRS)

Thomas, Robert E.; Kamhawi, Hani; Williams, George J., Jr.

2013-01-01

Plasma plume measurements are reported for a hollow cathode assembly (HCA) oper-ated at discharge currents of 50, 70, and 100 A at xenon ow rates between 19 - 46 sccm.The HCA was centrally mounted in the annulus of the NASA-300MS Hall Thruster andwas operated in the spot and plume modes with additional data taken with an appliedmagnetic eld. Langmuir probes, retarding potential analyzers, and optical emission spec-troscopy were employed to measure plasma properties near the orice of the HCA and toassess the charge state of the near-eld plasma. Electron temperatures (2-6 eV) and plasmapotentials are consistent with probe-measured values in previous investigations. Operationwith an applied-eld yields higher discharge voltages, increased Xe III production, andincreased signals from the 833.5 nm C I line. While operating in plume mode and with anapplied eld, ion energy distribution measurements yield ions with energies signicantlyexceeding the applied discharge voltage. These ndings are correlated with high-frequencyoscillations associated with each mode.

Destructive Evaluation of a Xenon Hollow Cathode after a 28,000 Hour Life Test

NASA Technical Reports Server (NTRS)

Sarver-Verhey, Timothy R.

1998-01-01

International Space Station (ISS) plasma contactor system requires a hollow cathode assembly (HCA) with a lifetime of at least 18,000 hours. In order to demonstrate the lifetime capability of the HCA, a series of hollow cathode wear tests was performed which included a life test operated at the maximum current of the HCA. This test sought to verify hollow cathode lifetime capability and contamination control protocols. This hollow cathode accumulated 27,800 hours of operation before it failed during a restart attempt. The cathode was subsequently destructively analyzed in order to determine the failure mechanism. Microscopic examination of the cathode interior determined that relatively small changes in the cathode physical geometry had occurred and barium tungstates, which are known to limit the emission process, had formed over a majority of the electron emitter surface. Because the final state of the insert was consistent with expected impregnate chemistry, the hollow cathode was believed to have reached the end of its usable life under the test conditions.

Multi-time scale control of demand flexibility in smart distribution networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattarai, Bishnu; Myers, Kurt; Bak-Jensen, Birgitte

This study presents a multi-timescale control strategy to deploy demand flexibilities of electric vehicles (EV) for providing system balancing and local congestion management by simultaneously ensuring economic benefits to participating actors. First, the EV charging problem from consumer, aggregator, and grid operator’s perspective is investigated. A hierarchical control architecture (HCA) comprising scheduling, coordinative, and adaptive layers is then designed to realize their coordinative goal. This is realized by integrating a multi-time scale control, which works from a day-ahead scheduling up to real-time adaptive control. The performance of the developed method is investigated with high EV penetration in a typical distributionmore » network. The simulation results demonstrates that HCA exploit EV flexibility to solve grid unbalancing and congestions with simultaneous maximization of economic benefits by ensuring EV participation to day-ahead, balancing, and regulation markets. For the given network configuration and pricing structure, HCA ensures the EV owners to get paid up to 5 times the cost they were paying without control.« less

Multi-time scale control of demand flexibility in smart distribution networks

DOE PAGES

Bhattarai, Bishnu; Myers, Kurt; Bak-Jensen, Birgitte; ...

2017-01-01

This study presents a multi-timescale control strategy to deploy demand flexibilities of electric vehicles (EV) for providing system balancing and local congestion management by simultaneously ensuring economic benefits to participating actors. First, the EV charging problem from consumer, aggregator, and grid operator’s perspective is investigated. A hierarchical control architecture (HCA) comprising scheduling, coordinative, and adaptive layers is then designed to realize their coordinative goal. This is realized by integrating a multi-time scale control, which works from a day-ahead scheduling up to real-time adaptive control. The performance of the developed method is investigated with high EV penetration in a typical distributionmore » network. The simulation results demonstrates that HCA exploit EV flexibility to solve grid unbalancing and congestions with simultaneous maximization of economic benefits by ensuring EV participation to day-ahead, balancing, and regulation markets. For the given network configuration and pricing structure, HCA ensures the EV owners to get paid up to 5 times the cost they were paying without control.« less

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII).

PubMed

Scozzafava, Andrea; Passaponti, Maurizio; Supuran, Claudiu T; Gülçin, İlhami

2015-01-01

Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated for their inhibition of all the catalytically active mammalian isozymes of the Zn(2+)-containing CA (EC 4.2.1.1). All the phenolic compounds effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and XII), with Kis in the range of 2.20-515.98 μM. The various isozymes showed diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4-methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of the tumour-associated transmembrane isoforms (hCA IX and XII) in the submicromolar range, with high selectivity. The results obtained from this research may lead to the design of more effective carbonic anhydrase isoenzyme inhibitors (CAIs) based on such phenolic compound scaffolds.

Comparison of the induced fields using different coil configurations during deep transcranial magnetic stimulation.

PubMed

Lu, Mai; Ueno, Shoogo

2017-01-01

Stimulation of deeper brain structures by transcranial magnetic stimulation (TMS) plays a role in the study of reward and motivation mechanisms, which may be beneficial in the treatment of several neurological and psychiatric disorders. However, electric field distributions induced in the brain by deep transcranial magnetic stimulation (dTMS) are still unknown. In this paper, the double cone coil, H-coil and Halo-circular assembly (HCA) coil which have been proposed for dTMS have been numerically designed. The distributions of magnetic flux density, induced electric field in an anatomically based realistic head model by applying the dTMS coils were numerically calculated by the impedance method. Results were compared with that of standard figure-of-eight (Fo8) coil. Simulation results show that double cone, H- and HCA coils have significantly deep field penetration compared to the conventional Fo8 coil, at the expense of induced higher and wider spread electrical fields in superficial cortical regions. Double cone and HCA coils have better ability to stimulate deep brain subregions compared to that of the H-coil. In the mean time, both double cone and HCA coils increase risk for optical nerve excitation. Our results suggest although the dTMS coils offer new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions, the selection of the most suitable coil settings for a specific clinical application should be based on a balanced evaluation between stimulation depth and focality.

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells.

PubMed

Liang, Shenxuan; Yin, Lei; Shengyang Yu, Kevin; Hofmann, Marie-Claude; Yu, Xiaozhong

2017-01-01

Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparison of the induced fields using different coil configurations during deep transcranial magnetic stimulation

PubMed Central

Ueno, Shoogo

2017-01-01

Stimulation of deeper brain structures by transcranial magnetic stimulation (TMS) plays a role in the study of reward and motivation mechanisms, which may be beneficial in the treatment of several neurological and psychiatric disorders. However, electric field distributions induced in the brain by deep transcranial magnetic stimulation (dTMS) are still unknown. In this paper, the double cone coil, H-coil and Halo-circular assembly (HCA) coil which have been proposed for dTMS have been numerically designed. The distributions of magnetic flux density, induced electric field in an anatomically based realistic head model by applying the dTMS coils were numerically calculated by the impedance method. Results were compared with that of standard figure-of-eight (Fo8) coil. Simulation results show that double cone, H- and HCA coils have significantly deep field penetration compared to the conventional Fo8 coil, at the expense of induced higher and wider spread electrical fields in superficial cortical regions. Double cone and HCA coils have better ability to stimulate deep brain subregions compared to that of the H-coil. In the mean time, both double cone and HCA coils increase risk for optical nerve excitation. Our results suggest although the dTMS coils offer new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions, the selection of the most suitable coil settings for a specific clinical application should be based on a balanced evaluation between stimulation depth and focality. PMID:28586349

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherukuri, Durga Prasad; Chen, Xiao B.O.; Goulet, Anne-Christine

Accumulating evidence indicates that elevated levels of prostaglandin E{sub 2} (PGE{sub 2}) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE{sub 2} exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE{sub 2} to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE{sub 2}-induced ERK phosphorylation and cell proliferation of HCA-7 cells.more » In order to identify downstream target genes of ERK1/2 signaling, we found that PGE{sub 2} induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE{sub 2} treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE{sub 2} driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE{sub 2} in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer.« less

Linguistic Stereotyping in Older Adults' Perceptions of Health Care Aides.

PubMed

Rubin, Donald; Coles, Valerie Berenice; Barnett, Joshua Trey

2016-07-01

The cultural and linguistic diversity of the U.S. health care provider workforce is expanding. Diversity among health care personnel such as paraprofessional health care assistants (HCAs)-many of whom are immigrants-means that intimate, high-stakes cross-cultural and cross-linguistic contact characterizes many health interactions. In particular, nonmainstream HCAs may face negative patient expectations because of patients' language stereotypes. In other contexts, reverse linguistic stereotyping has been shown to result in negative speaker evaluations and even reduced listening comprehension quite independently of the actual language performance of the speaker. The present study extends the language and attitude paradigm to older adults' perceptions of HCAs. Listeners heard the identical speaker of Standard American English as they watched interactions between an HCA and an older patient. Ethnolinguistic identities-either an Anglo native speaker of English or a Mexican nonnative speaker-were ascribed to HCAs by means of fabricated personnel files. Dependent variables included measures of perceived HCA language proficiency, personal characteristics, and professional competence, as well as listeners' comprehension of a health message delivered by the putative HCA. For most of these outcomes, moderate effect sizes were found such that the HCA with an ascribed Anglo identity-relative to the Mexican guise-was judged more proficient in English, socially superior, interpersonally more attractive, more dynamic, and a more satisfactory home health aide. No difference in listening comprehension emerged, but the Anglo guise tended to engender a more compliant listening mind set. Results of this study can inform both provider-directed and patient-directed efforts to improve health care services for members of all linguistic and cultural groups.

A Systematic Review of Tools Used to Assess Team Leadership in Health Care Action Teams.

PubMed

Rosenman, Elizabeth D; Ilgen, Jonathan S; Shandro, Jamie R; Harper, Amy L; Fernandez, Rosemarie

2015-10-01

To summarize the characteristics of tools used to assess leadership in health care action (HCA) teams. HCA teams are interdisciplinary teams performing complex, critical tasks under high-pressure conditions. The authors conducted a systematic review of the PubMed/MEDLINE, CINAHL, ERIC, EMBASE, PsycINFO, and Web of Science databases, key journals, and review articles published through March 2012 for English-language articles that applied leadership assessment tools to HCA teams in all specialties. Pairs of reviewers assessed identified articles for inclusion and exclusion criteria and abstracted data on study characteristics, tool characteristics, and validity evidence. Of the 9,913 abstracts screened, 83 studies were included. They described 61 team leadership assessment tools. Forty-nine tools (80%) provided behaviors, skills, or characteristics to define leadership. Forty-four tools (72%) assessed leadership as one component of a larger assessment, 13 tools (21%) identified leadership as the primary focus of the assessment, and 4 (7%) assessed leadership style. Fifty-three studies (64%) assessed leadership at the team level; 29 (35%) did so at the individual level. Assessments of simulated (n = 55) and live (n = 30) patient care events were performed. Validity evidence included content validity (n = 75), internal structure (n = 61), relationship to other variables (n = 44), and response process (n = 15). Leadership assessment tools applied to HCA teams are heterogeneous in content and application. Comparisons between tools are limited by study variability. A systematic approach to team leadership tool development, evaluation, and implementation will strengthen understanding of this important competency.

Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

PubMed Central

Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

2011-01-01

In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

Anti-metastasis effect of fucoidan from Undaria pinnatifida sporophylls in mouse hepatocarcinoma Hca-F cells.

PubMed

Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

2014-01-01

Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways.

Omnisphero: a high-content image analysis (HCA) approach for phenotypic developmental neurotoxicity (DNT) screenings of organoid neurosphere cultures in vitro.

PubMed

Schmuck, Martin R; Temme, Thomas; Dach, Katharina; de Boer, Denise; Barenys, Marta; Bendt, Farina; Mosig, Axel; Fritsche, Ellen

2017-04-01

Current developmental neurotoxicity (DNT) testing in animals faces major limitations, such as high cost and time demands as well as uncertainties in their methodology, evaluation and regulation. Therefore, the use of human-based 3D in vitro systems in combination with high-content image analysis (HCA) might contribute to DNT testing with lower costs, increased throughput and enhanced predictivity for human hazard identification. Human neural progenitor cells (hNPCs) grown as 3D neurospheres mimic basic processes of brain development including hNPC migration and differentiation and are therefore useful for DNT hazard identification. HCA of migrated neurospheres creates new challenges for automated evaluations because it encompasses variable cell densities, inconsistent z-layers and heterogeneous cell populations. We tackle those challenges with our Omnisphero software, which assesses multiple endpoints of the 'Neurosphere Assay.' For neuronal identification, Omnisphero reaches a true positive rate (TPR) of 83.8 % and a false discovery rate (FDR) of 11.4 %, thus being comparable to the interindividual difference among two researchers (TPR = 94.3, FDR = 11.0 %) and largely improving the results obtained by an existing HCA approach, whose TPR does not exceed 50 % at a FDR above 50 %. The high FDR of existing methods results in incorrect measurements of neuronal morphological features accompanied by an overestimation of compound effects. Omnisphero additionally includes novel algorithms to assess 'neurosphere-specific' endpoints like radial migration and neuronal density distribution within the migration area. Furthermore, a user-assisted parameter optimization procedure makes Omnisphero accessible to non-expert end users.

Anti-Metastasis Effect of Fucoidan from Undaria pinnatifida Sporophylls in Mouse Hepatocarcinoma Hca-F Cells

PubMed Central

Wang, Peisheng; Liu, Zhichao; Liu, Xianli; Teng, Hongming; Zhang, Cuili; Hou, Lin; Zou, Xiangyang

2014-01-01

Metastasis is one of the major causes of cancer-related death. It is a complex biological process involving multiple genes, steps, and phases. It is also closely connected to many biological activities of cancer cells, such as growth, invasion, adhesion, hematogenous metastasis, and lymphatic metastasis. Fucoidan derived from Undaria pinnatifida sporophylls (Ups-fucoidan) is a sulfated polysaccharide with more biological activities than other fucoidans. However, there is no information on the effects of Ups-fucoidan on tumor invasion and metastasis. We used the mouse hepatocarcinoma Hca-F cell line, which has high invasive and lymphatic metastasis potential in vitro and in vivo, to examine the effect of Ups-fucoidan on cancer cell invasion and metastasis. Ups-fucoidan exerted a concentration- and time-dependent inhibitory effect on tumor metastasis in vivo and inhibited Hca-F cell growth, migration, invasion, and adhesion capabilities in vitro. Ups-fucoidan inhibited growth and metastasis by downregulating vascular endothelial growth factor (VEGF) C/VEGF receptor 3, hepatocyte growth factor/c-MET, cyclin D1, cyclin-dependent kinase 4, phosphorylated (p) phosphoinositide 3-kinase, p-Akt, p-extracellular signal regulated kinase (ERK) 1/2, and nuclear transcription factor-κB (NF-κB), and suppressed adhesion and invasion by downregulating L-Selectin, and upregulating protein levels of tissue inhibitor of metalloproteinases (TIMPs). The results suggest that Ups-fucoidan suppresses Hca-F cell growth, adhesion, invasion, and metastasis capabilities and that these functions are mediated through the mechanism involving inactivation of the NF-κB pathway mediated by PI3K/Akt and ERK signaling pathways. PMID:25162296

Effect of alkali earth oxides on hydroxy-carbonated apatite nano layer formation for SiO2-BaO-CaO-Na2O-P2O5 glass system

NASA Astrophysics Data System (ADS)

Kiran, P.; Ramakrishna, V.; Shashikala, H. D.; Udayashankar, N. K.

2017-11-01

Barium soda lime phosphosilicate [(58SiO2-(32 - x)BaO- xCao-6Na2O-4P2O5 (where x = 15, 20, 25 and 30 mol%)] samples were synthesised using conventional sol-gel method at 700 °C sintering temperature. Thermal, structural properties were studied using thermo gravimetric analysis and differential thermal analysis, X-ray diffraction, scanning electron microscopy, fourier transform infrared and Raman spectroscopy. Using Raman spectra non-bridging oxygen concentrations were estimated. The hydroxy-carbonated apatite (HCA) layer formation on samples was analysed for 7 days using simulated body fluid (SBF) soaked samples. The growth of HCA layers self-assembled on the sample surface was discussed as a function of NBO/BO ratio. Results indicated that the number of Ca2+ ions released into SBF solution in dissolution process and weight loss of SB-treated samples vary with NBO/BO ratio. The changes in NBO/BO ratios were observed to be proportional to HCA forming ability of barium soda lime phosphosilicate glasses.

Chemotaxonomic Study of Citrus, Poncirus and Fortunella Genotypes Based on Peel Oil Volatile Compounds - Deciphering the Genetic Origin of Mangshanyegan (Citrus nobilis Lauriro)

PubMed Central

Liu, Cuihua; Jiang, Dong; Cheng, Yunjiang; Deng, Xiuxin; Chen, Feng; Fang, Liu; Ma, Zhaocheng; Xu, Juan

2013-01-01

Volatile profiles yielded from gas chromatography-mass spectrometry (GC-MS) analysis provide abundant information not only for metabolism-related research, but also for chemotaxonomy. To study the chemotaxonomy of Mangshanyegan, its volatile profiles of fruit and leaf and those of 29 other genotypes of Citrus, Poncirus, and Fortunella were subjected to phylogenetic analyses. Results showed that 145 identified (including 64 tentatively identified) and 15 unidentified volatile compounds were detected from their peel oils. The phylogenetic analysis of peel oils based on hierarchical cluster analysis (HCA) demonstrated a good agreement with the Swingle taxonomy system, in which the three genera of Citrus, Poncirus, and Fortunella were almost completely separated. As to Citrus, HCA indicated that Citrophorum, Cephalocitrus, and Sinocitrus fell into three subgroups, respectively. Also, it revealed that Mangshanyegan contain volatile compounds similar to those from pummelo, though it is genetically believed to be a mandarin. These results were further supported by the principal component analysis of the peel oils and the HCA results of volatile profiles of leaves in the study. PMID:23516475

Process for testing a xenon gas feed system of a hollow cathode assembly

NASA Technical Reports Server (NTRS)

Patterson, Michael J. (Inventor); Verhey, Timothy R. R. (Inventor); Soulas, George C. (Inventor)

2004-01-01

The design and manufacturing processes for Hollow Cathode Assemblies (HCA's) that operate over a broad range of emission currents up to 30 Amperes, at low potentials, with lifetimes in excess of 17,500 hours. The processes include contamination control procedures which cover hollow cathode component cleaning procedures, gas feed system designs and specifications, and hollow cathode activation and operating procedures to thereby produce cathode assemblies that have demonstrated stable and repeatable operating conditions, for both the discharge current and voltage. The HCA of this invention provides lifetimes of greater than 10,000 hours, and expected lifetimes of greater than 17,500 hours, whereas the present state-of-the-art is less than 500 hours at emission currents in excess of 1 Ampere. Stable operation is provided over a large range of operating emission currents, up to a 6:1 ratio, and this HCA can emit electron currents of up to 30 Amperes in magnitude to an external anode that simulates the current drawn to a space plasma, at voltages of less than 20 Volts.

Process for Ignition of Gaseous Electrical Discharge Between Electrodes of a Hollow Cathode Assembly

NASA Technical Reports Server (NTRS)

Patterson, Michael J. (Inventor); Verhey, Timothy R. R. (Inventor); Soulas, George C. (Inventor)

2000-01-01

The design and manufacturing processes for Hollow Cathode Assemblies (HCA's) that operate over a broad range of emission currents up to 30 Amperes, at low potentials, with lifetimes in excess of 17,500 hours. The processes include contamination control procedures which cover hollow cathode component cleaning procedures, gas feed system designs and specifications, and hollow cathode activation and operating procedures to thereby produce cathode assemblies that have demonstrated stable and repeatable operating conditions, for both the discharge current and voltage. The HCA of this invention provides lifetimes of greater than 10,000 hours, and expected lifetimes of greater than 17,500 hours, whereas the present state-of-the-art is less than 500 hours at emission currents in excess of 1 Ampere. Stable operation is provided over a large range of operating emission currents, up to a 6:1 ratio, and this HCA can emit electron currents of up to 30 Amperes in magnitude to an external anode that simulates the current drawn to a space plasma, at voltages of less than 20 Volts.

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases.

PubMed

Yamali, Cem; Gul, Halise Inci; Sakagami, Hiroshi; Supuran, Claudiu T

2016-01-01

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25-43%) and hCA II (6-25%) isoforms at 10 μM concentration of inhibitor, the compounds were more selective (1.5-5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.

Space Station Cathode Design, Performance, and Operating Specifications

NASA Technical Reports Server (NTRS)

Patterson, Michael J.; Verhey, Timothy R.; Soulas, George; Zakany, James

1998-01-01

A plasma contactor system was baselined for the International Space Station (ISS) to eliminate/mitigate damaging interactions with the space environment. The system represents a dual-use technology which is a direct outgrowth of the NASA electric propulsion program and, in particular, the technology development efforts on ion thruster systems. The plasma contactor includes a hollow cathode assembly (HCA), a power electronics unit, and a xenon gas feed system. Under a pre-flight development program, these subsystems were taken to the level of maturity appropriate for transfer to U.S. industry for final development. NASA's Lewis Research Center was subsequently requested by ISS to manufacture and deliver the engineering model, qualification model, and flight HCA units. To date, multiple units have been built. One cathode has demonstrated approximately 28,000 hours lifetime, two development unit HCAs have demonstrated over 10,000 hours lifetime, and one development unit HCA has demonstrated more than 32,000 ignitions. All 8 flight HCAs have been manufactured, acceptance tested, and are ready for delivery to the flight contractor. This paper discusses the requirements, mechanical design, performance, operating specifications, and schedule for the plasma contactor flight HCAs.

The impact of hydroquinone on acetylcholine esterase and certain human carbonic anhydrase isoenzymes (hCA I, II, IX, and XII).

PubMed

Scozzafava, Andrea; Kalın, Pınar; Supuran, Claudiu T; Gülçin, İlhami; Alwasel, Saleh H

2015-12-01

Carbonic anhydrases (CAs) are widespread and the most studied members of a great family of metalloenzymes in higher vertebrates including humans. CAs were investigated for their inhibition of all of the catalytically active mammalian isozymes of the Zn(2+)-containing CA, (CA, EC 4.2.1.1). On the other hand, acetylcholinesterase (AChE. EC 3.1.1.7), a serine protease, is responsible for ACh hydrolysis and plays a fundamental role in impulse transmission by terminating the action of the neurotransmitter ACh at the cholinergic synapses and neuromuscular junction. In the present study, the inhibition effect of the hydroquinone (benzene-1,4-diol) on AChE activity was evaluated and effectively inhibited AChE with Ki of 1.22 nM. Also, hydroquinone strongly inhibited some human cytosolic CA isoenzymes (hCA I and II) and tumour-associated transmembrane isoforms (hCA IX, and XII), with Kis in the range between micromolar (415.81 μM) and nanomolar (706.79 nM). The best inhibition was observed in cytosolic CA II.

Detection of l-Cysteine in wheat flour by Raman microspectroscopy combined chemometrics of HCA and PCA.

PubMed

Cebi, Nur; Dogan, Canan Ekinci; Develioglu, Ayşen; Yayla, Mediha Esra Altuntop; Sagdic, Osman

2017-08-01

l-Cysteine is deliberately added to various flour types since l-Cysteine has enabled favorable baking conditions such as low viscosity, increased elasticity and rise during baking. In Turkey, usage of l-Cysteine as a food additive isn't allowed in wheat flour according to the Turkish Food Codex Regulation on food additives. There is an urgent need for effective methods to detect l-Cysteine in wheat flour. In this study, for the first time, a new, rapid, effective, non-destructive and cost-effective method was developed for detection of l-Cysteine in wheat flour using Raman microscopy. Detection of l-Cysteine in wheat flour was accomplished successfully using Raman microscopy combined chemometrics of PCA (Principal Component Analysis) and HCA (Hierarchical Cluster Analysis). In this work, 500-2000cm -1 spectral range (fingerprint region) was determined to perform PCA and HCA analysis. l-Cysteine and l-Cystine were determined with detection limit of 0.125% (w/w) in different wheat flour samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

HPLC-PDA Combined with Chemometrics for Quantitation of Active Components and Quality Assessment of Raw and Processed Fruits of Xanthium strumarium L.

PubMed

Jiang, Hai; Yang, Liu; Xing, Xudong; Yan, Meiling; Guo, Xinyue; Yang, Bingyou; Wang, Qiuhong; Kuang, Haixue

2018-01-25

As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in 30 batches of raw and processed Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common peaks were detected and eight compounds of caffeoylquinic acids were simultaneously quantified in RXF and PXF. All the analytes were detected with satisfactory linearity (R² > 0.9991) over wide concentration ranges. Simultaneously, the chemically latent information was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that there were significant differences between RXF and PXF from different regions in terms of the content of eight caffeoylquinic acids. Potential chemical markers for XF were found during processing by chemometrics.

Discrimination of three Pegaga (Centella) varieties and determination of growth-lighting effects on metabolites content based on the chemometry of 1H nuclear magnetic resonance spectroscopy.

PubMed

H, Maulidiani; Khatib, Alfi; Shaari, Khozirah; Abas, Faridah; Shitan, Mahendran; Kneer, Ralf; Neto, Victor; Lajis, Nordin H

2012-01-11

The metabolites of three species of Apiaceae, also known as Pegaga, were analyzed utilizing (1)H NMR spectroscopy and multivariate data analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) resolved the species, Centella asiatica, Hydrocotyle bonariensis, and Hydrocotyle sibthorpioides, into three clusters. The saponins, asiaticoside and madecassoside, along with chlorogenic acids were the metabolites that contributed most to the separation. Furthermore, the effects of growth-lighting condition to metabolite contents were also investigated. The extracts of C. asiatica grown in full-day light exposure exhibited a stronger radical scavenging activity and contained more triterpenes (asiaticoside and madecassoside), flavonoids, and chlorogenic acids as compared to plants grown in 50% shade. This study established the potential of using a combination of (1)H NMR spectroscopy and multivariate data analyses in differentiating three closely related species and the effects of growth lighting, based on their metabolite contents and identification of the markers contributing to their differences.

Stream gradient Hotspot and Cluster Analysis (SL-HCA) for improving the longitudinal profiles metrics

NASA Astrophysics Data System (ADS)

Troiani, Francesco; Piacentini, Daniela; Seta Marta, Della

2016-04-01

Many researches successfully focused on stream longitudinal profiles analysis through Stream Length-gradient (SL) index for detecting, at different spatial scales, either tectonic structures or hillslope processes. The analysis and interpretation of spatial variability of SL values, both at a regional and local scale, is often complicated due to the concomitance of different factors generating SL anomalies, including the bedrock composition. The creation of lithologically-filtered SL maps is often problematic in areas where homogeneously surveyed geological maps, with a sufficient resolution are unavailable. Moreover, both the SL map classification and the unbiased anomaly detection are rather difficult. For instance, which is the best threshold to define the anomalous SL values? Further, is there a minimum along-channel extent of anomalous SL values for objectively defining over-steeped segments on long-profiles? This research investigates the relevance and potential of a new approach based on Hotspot and Cluster Analysis of SL values (SL-HCA) for detecting knickzones on long-profiles at a regional scale and for fine-tuning the interpretation of their geological-geomorphological meaning. We developed this procedure within a 2800 km2-wide area located in the mountainous sector of the Northern Apennines of Italy. The Getis-Ord Gi∗ statistic is applied for the SL-HCA approach. The value of SL, calculated starting from a 5x5 m Digital Elevation Model, is used as weighting factor and the Gi∗ index is calculated for each 50 m-long channel segment for the whole fluvial system. The outcomes indicate that high positive Gi∗ values imply the clustering of SL anomalies, thus the occurrence of knickzones on the stream long-profiles. Results show that high and very high Gi* values (i.e. values beyond two standard deviations from the mean) correlate well with the principal knickzones detected with existent lithologically-filtered SL maps. Field checks and remote sensing analysis conducted on 52 clusters of high and very high Gi* values indicate that mass movement of slope material represents the dominant process producing over-steeped long-profiles along connected streams, whereas the litho-structure accounts for the main anomalies along disconnected steams. Tectonic structures generally provide to the largest clusters. Our results demonstrate that SL-HCA maps have the same potential of lithologically-filtered SL maps for detecting knickzones due to hillslope processes and/or tectonic structures. The reduced-complexity model derived from SL-HCA approach highly improve the readability of the morphometric outcomes, thus the interpretation at a regional scale of the geological-geomorphological meaning of over-steeped segments on long-profiles. SL-HCA maps are useful to investigate and better interpret knickzones within regions poorly covered by geological data and where field surveys are difficult to be performed.

The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans.

PubMed

Beltrán-Debón, R; Alonso-Villaverde, C; Aragonès, G; Rodríguez-Medina, I; Rull, A; Micol, V; Segura-Carretero, A; Fernández-Gutiérrez, A; Camps, J; Joven, J

2010-03-01

Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity. Copyright 2009 Elsevier GmbH. All rights reserved.

Availability of weight-loss supplements: Results of an audit of retail outlets in a southeastern city.

PubMed

Sharpe, Patricia A; Granner, Michelle L; Conway, Joan M; Ainsworth, Barbara E; Dobre, Mirela

2006-12-01

The sale of nonprescription weight-loss products accounts for millions of dollars spent by Americans trying to lose weight, yet there is little evidence for effectiveness and there are multiple safety concerns. The purpose of this study was to determine what products, and ingredients within products, were available at retail outlets in a metropolitan area. A purposive sampling strategy identified 73 retail outlets. An audit form was used to collect information from product labels. The audit identified 402 products containing 4,053 separate ingredients. The mean number of ingredients per product was 9.9+/-8.96 (range = 1 to 96). A database search was conducted regarding evidence for effectiveness, safety precautions, and side effects for the 10 ingredients that appeared most often across products. Modest evidence of effectiveness exists for green tea (Camellia sinensis), chromium picolinate, and ma huang (Ephedra major). For the remaining seven (ginger root [Zingiber officinale], guarana [Paullinia cupana], hydroxycitric acid [Garcinia cambogia], white willow [Salix alba], Siberian ginseng [Eleutherococcus senticosus], cayenne [Capsicum annuum], and bitter orange/zhi shi [Citrus aurantium]), inadequate or negative evidence exists. Although precautions and contraindications were found for all 10 ingredients, the strongest concerns in the literature appear for ma huang, bitter orange, and guarana. Our audit revealed numerous weight-loss products available to consumers, yet there is little evidence to support the effectiveness of the top 10 ingredients identified and many potential adverse reactions; therefore, food and nutrition professionals should discuss dietary supplement use with their clients.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Swiss veterinary health care providers: detection of livestock- and healthcare-associated clones.

PubMed

Wettstein Rosenkranz, K; Rothenanger, E; Brodard, I; Collaud, A; Overesch, G; Bigler, B; Marschall, J; Perreten, V

2014-07-01

We screened a total of 340 veterinarians (including general practitioners, small animal practitioners, large animal practitioners, veterinarians working in different veterinary services or industry), and 29 veterinary assistants for nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP) at the 2012 Swiss veterinary annual meeting. MRSA isolates (n = 14) were detected in 3.8 % (95 % CI 2.1 - 6.3 %) of the participants whereas MRSP was not detected. Large animal practitioners were carriers of livestock-associated MRSA (LA-MRSA) ST398-t011-V (n = 2), ST398-t011-IV (n = 4), and ST398-t034-V (n = 1). On the other hand, participants working with small animals harbored human healthcare-associated MRSA (HCA-MRSA) which belonged to epidemic lineages ST225-t003-II (n = 2), ST225-t014-II (n = 1), ST5-t002-II (n = 2), ST5-t283-IV (n = 1), and ST88-t186-IV (n = 1). HCA-MRSA harbored virulence factors such as enterotoxins, β-hemolysin converting phage and leukocidins. None of the MRSA isolates carried Panton-Valentine leukocidin (PVL). In addition to the methicillin resistance gene mecA, LA-MRSA ST398 isolates generally contained additional antibiotic resistance genes conferring resistance to tetracycline [tet(M) and tet(K)], trimethoprim [dfrK, dfrG], and the aminoglycosides gentamicin and kanamycin [aac(6')-Ie - aph(2')-Ia]. On the other hand, HCA-MRSA ST5 and ST225 mainly contained genes conferring resistance to the macrolide, lincosamide and streptogramin B antibiotics [erm(A)], to spectinomycin [ant(9)-Ia], amikacin and tobramycin [ant(4')-Ia], and to fluoroquinolones [amino acid substitutions in GrlA (S84L) and GyrA (S80F and S81P)]. MRSA carriage may represent an occupational risk and veterinarians should be aware of possible MRSA colonization and potential for developing infection or for transmitting these strains. Professional exposure to animals should be reported upon hospitalization and before medical intervention to allow for preventive measures. Infection prevention measures are also indicated in veterinary medicine to avoid MRSA transmission between humans and animals, and to limit the spread of MRSA both in the community, and to animal and human hospitals.

Influence of different calcium concentrations in the diet on bone metabolism in growing dairy goats and sheep.

PubMed

Liesegang, A; Risteli, J

2005-01-01

The purpose of this study was to investigate, if different Ca concentrations in diets have an influence on bone mineral metabolism in growing goats and sheep. Twelve growing goats and sheep were divided into two groups. The two control groups received 6.1 g calcium/day (nG) and 6.7 g calcium/day (nS) for goat and sheep respectively. The other two groups were fed 17.7 g calcium/day (hG) and 18.5 g calcium/day (hS). Blood samples were taken 2, 4, 5 and 6 weeks after the start of the experiment. In serum Ca and vitamin D were determined and bone metabolism was measured using crosslinked carboxyterminal telopeptide of type I collagen (ICTP), crosslaps, bone-specific alkaline phosphatase and osteocalcin (OC). Bone mineral density (BMD) was quantified using quantitative computed tomography. Bone resorption marker (ICTP) concentrations were significantly different between both groups control sheep/control goat and hS/hG, but no significant differences were evident in the different feeding groups within one species. OC concentrations showed a similar course to ICTP. The goats had significantly higher concentrations compared with sheep. The 1,25 dihydroxyvitamin D (VITD) concentrations in both hCa groups were significantly lower than in the control groups. BMD increased in the hCa groups compared with the control groups with the time, but significant differences were only evident in sheep in week 2. The hCa diet did not induce differences between the groups within one species for all bone markers. The control Ca diet seems to improve the active Ca absorption via VITD whereas the hCa diet leads to a higher amount of Ca apparently digested. Higher BMD was only observed in group hS compared with nS.

Hepatic glucose-6-phosphatase-α deficiency leads to metabolic reprogramming in glycogen storage disease type Ia.

PubMed

Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

2018-04-15

Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis. The enhanced hepatic glycolysis is reflected by increased lactate accumulation, increased expression of many glycolytic enzymes, and elevated expression of c-Myc that stimulates glycolysis. The increased HMS is reflected by increased glucose-6-phosphate dehydrogenase activity and elevated production of NADPH and the reduced glutathione. We have previously shown that restoration of hepatic G6Pase-α expression in G6Pase-α-deficient liver corrects metabolic abnormalities, normalizes autophagy, and prevents HCA/HCC development in GSD-Ia. We now show that restoration of hepatic G6Pase-α expression normalizes both glycolysis and HMS in GSD-Ia. Moreover, the HCA/HCC lesions in L-G6pc-/- mice exhibit elevated levels of hexokinase 2 (HK2) and the M2 isoform of pyruvate kinase (PKM2) which play an important role in aerobic glycolysis and cancer cell proliferation. Taken together, hepatic G6Pase-α deficiency causes metabolic reprogramming, leading to enhanced glycolysis and elevated HMS that along with impaired autophagy can contribute to HCA/HCC development in GSD-Ia. Published by Elsevier Inc.

Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia.

PubMed

Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

2018-05-08

Glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unclear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. SIRT1 is a NAD + -dependent deacetylase that can deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial integrity, biogenesis, and function. We hypothesized that downregulation of hepatic SIRT1 signaling in G6Pase-α-deficient livers impairs PGC-1α activity, leading to mitochondrial dysfunction. Here we show that the G6Pase-α-deficient livers display defective PGC-1α signaling, reduced numbers of functional mitochondria, and impaired oxidative phosphorylation. Overexpression of hepatic SIRT1 restores PGC-1α activity, normalizes the expression of electron transport chain components, and increases mitochondrial complex IV activity. We have previously shown that restoration of hepatic G6Pase-α expression normalized SIRT1 signaling. We now show that restoration of hepatic G6Pase-α expression also restores PGC-1α activity and mitochondrial function. Finally, we show that HCA/HCC lesions found in G6Pase-α-deficient livers contain marked mitochondrial and oxidative DNA damage. Taken together, our study shows that downregulation of hepatic SIRT1/PGC-1α signaling underlies mitochondrial dysfunction and that oxidative DNA damage incurred by damaged mitochondria may contribute to HCA/HCC development in GSD-Ia.

External carotid compression: a novel technique to improve cerebral perfusion during selective antegrade cerebral perfusion for aortic arch surgery.

PubMed

Grocott, Hilary P; Ambrose, Emma; Moon, Mike

2016-10-01

Selective antegrade cerebral perfusion (SACP) involving cannulation of either the axillary or innominate artery is a commonly used technique for maintaining cerebral blood flow (CBF) during the use of hypothermic cardiac arrest (HCA) for operations on the aortic arch. Nevertheless, asymmetrical CBF with hypoperfusion of the left cerebral hemisphere is a common occurrence during SACP. The purpose of this report is to describe an adjunctive maneuver to improve left hemispheric CBF during SACP by applying extrinsic compression to the left carotid artery. A 77-yr-old male patient with a history of aortic valve replacement presented for emergent surgical repair of an acute type A aortic dissection of a previously known ascending aortic aneurysm. His intraoperative course included cannulation of the right axillary artery, which was used as the aortic inflow during cardiopulmonary bypass and also allowed for subsequent SACP during HCA. After the onset of HCA, the innominate artery was clamped at its origin to allow for SACP. Shortly thereafter, however, the left-sided cerebral oxygen saturation (SrO2) began to decrease. Augmenting the PaO2, PaCO2 and both SACP pressure and flow failed to increase left hemispheric SrO2. Following the use of ultrasound guidance to confirm the absence of atherosclerotic disease in the carotid artery, external pressure was applied partially compressing the artery. With the carotid compression, the left cerebral saturation abruptly increased, suggesting pressurization of the left cerebral hemispheric circulation and augmentation of CBF. Direct ultrasound visualization and cautious partial compression of the left carotid artery may address asymmetrical CBF that occurs with SACP during HCA for aortic arch surgery. This strategy may lead to improved symmetry of CBF and corresponding cerebral oximetry measurements during aortic arch surgery.

Evaluation of an ex vivo murine local lymph node assay: multiple endpoint comparison.

PubMed

Piccotti, Joseph R; Knight, Stephanie A; Gillhouse, Kimberly; Lagattuta, Mark S; Bleavins, Michael R

2006-01-01

The local lymph node assay (LLNA) is used to assess the skin sensitization potential of chemicals. In the standard assay, mice are treated topically on the dorsum of both ears with test substance for 3 days. Following 2 days of rest, the initiation of the hypersensitivity response is evaluated by injecting (3)H-thymidine into a tail vein, and then measuring the levels of radioisotope incorporated into the DNA of lymph node cells draining the ears. In the current study, BALB/c mice were treated with the contact sensitizers hexylcinnamic aldehyde (HCA) and oxazolone, and the nonsensitizer methyl salicylate. The proliferative response of lymph node cells was evaluated in an ex vivo assay, in which isolated cells were cultured in vitro with (3)H-thymidine. Treatment of mice with HCA at 5-50% resulted in concentration-related increases in (3)H-thymidine incorporation, with stimulation indices ranging from 3 to 14. Low animal-to-animal variability was seen in three replicate assays testing HCA at 25%. As anticipated, the proliferative response induced by the potent sensitizer oxazolone at 0.25% was greater than HCA at all concentrations tested. Stimulation indices of 1.5 and 3 were seen in two independent experiments with methyl salicylate. These equivocal findings were likely due to the irritancy properties of the compound. Importantly, measuring ex vivo (3)H-thymidine incorporation was more sensitive than evaluating lymph node weight and cellularity, and in vitro bromodeoxyuridine incorporation. Furthermore, the results of the ex vivo LLNA were comparable to the standard assay. This study provided evidence that supports the use of an ex vivo LLNA for hazard assessment of contact hypersensitivity. Copyright 2006 John Wiley & Sons, Ltd.

Development and psychometric testing of the Supportive Supervisory Scale.

PubMed

McGilton, Katherine S

2010-06-01

To describe the development and psychometric testing of the Supportive Supervisory Scale (SSS). The development of the items of the scale was based on Winnicott's relationship theory and on focus groups with 26 healthcare aides (HCAs) and 30 supervisors from six long-term care (LTC) facilities in Ontario, Canada. Content validity of the 15-item instrument was established by a panel of experts. Based on a secondary analysis of data collected from 222 HCAs in 10 LTC facilities in Ontario, Canada, the SSS was subjected to principal components analysis with oblique rotation. A two-factor solution was accepted, which is consistent with the theoretical conceptualization of the instrument. Factor I was labeled Respects Uniqueness and Factor II was labeled Being Reliable. Internal consistency of Factor I was .95, and that of Factor II was .91. Discriminant validity was also established. The focus groups revealed that "being available to staff" while "recognizing the HCA as an individual, and taking a moment to get to know them" was essential to feeling supported by their supervisor. The SSS is a reliable and valid measure of supervisory support of supervisors working in LTC facilities. At the core of supportive supervision is the supervisor's ability to develop and maintain positive relationships with each HCA. It is through respecting the uniqueness of each HCA and being reliable that supervisor-HCA relationships can flourish. Supportive leadership in LTC settings is a major contributor to HCAs' job satisfaction and retention and to quality of patient care. Therefore, a tool developed and tested to measure supervisors' supportive capacities in LTC is primal to evaluate the effectiveness of supervisors in these environments.

Changes in paced signals may predict in-hospital cardiac arrest.

PubMed

Attin, Mina; Rosero, Spencer Z; Ding, Jimmy; Nolan, Scot; Tucker, Rebecca

2018-01-01

An increasing number of patients with chronic illnesses have implanted cardiac rhythm devices such as pacemakers and implantable cardioverter-defibrillators (ICDs). This study was conducted to identify potentially useful predictors of in-hospital cardiac arrest (I-HCA) within paced electrocardiogram (ECG) signals from cardiovascular patients with implanted medical devices. In this retrospective study of 17 subjects, full-disclosure ECG traces prior to the time of documented I-HCA were analyzed to determine R-R intervals and QRS durations (QRSd). Ventricular paced QRSd prolongation was observed prior to I-HCA in 10/16 (63%) subjects. QRSd was significantly greater immediately preceding cardiac arrest than during each of the 8 hours prior to cardiac arrest (P < 0.05). Heart rate changes (measured using standard deviation) within 15 minutes of cardiac arrest were significantly greater in subjects with pulseless electrical activity (PEA)/asystolic arrest compared to those with cardiac arrests due to ventricular tachycardia/ventricular fibrillation (VT/VF) (10.13 vs 3.31; P  =  0.024). Significant differences over the 8 hours preceding cardiac arrest in heart rate (74 vs 86 beats/min; P  =  0.002) and QRS duration (172 ms vs 137 ms; P < 0.001) were observed between subjects with initial rhythms of VT/VF and those with initial rhythms of PEA/asystole. Patterns of diagnostic ECG features can be extracted from the telemetry data of patients with implanted medical devices prior to adverse events including I-HCA. The detection of these significant changes might have an immediate prognostic impact on the timely treatment of some patients at risk of adverse events. © 2017 Wiley Periodicals, Inc.

Hippocampal Ghrelin-positive neurons directly project to arcuate hypothalamic and medial amygdaloid nuclei. Could they modulate food-intake?

PubMed

Russo, Cristina; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania

2017-07-13

Feeding is a process controlled by a complex of associations between external and internal stimuli. The processes that involve learning and memory seem to exert a strong control over appetite and food intake, which is modulated by a gastrointestinal hormone, Ghrelin (Ghre). Recent studies claim that Ghre is involved in cognitive and neurobiological mechanisms that underlie the conditioning of eating behaviors. The expression of Ghre increases in anticipation of food intake based on learned behaviors. The hippocampal Ghre-containing neurons neurologically influence the orexigenic hypothalamus and consequently the learned feeding behavior. The CA1 field of Ammon's horn of the hippocampus (H-CA1) constitutes the most important neural substrate to control both appetitive and ingestive behavior. It also innervates amygdala regions that in turn innervate the hypothalamus. A recent study also implies that Ghre effects on cue-potentiated feeding behavior occur, at the least, via indirect action on the amygdala. In the present study, we investigate the neural substrates through which endogenous Ghre communicates conditioned appetite and feeding behavior within the CNS. We show the existence of a neural Ghre dependent pathway whereby peripherally-derived Ghre activates H-CA1 neurons, which in turn activate Ghre-expressing hypothalamic and amygdaloid neurons to stimulate appetite and feeding behavior. To highlight this pathway, we use two fluorescent retrograde tracers (Fluoro Gold and Dil) and immunohistochemical detection of Ghre expression in the hippocampus. Triple fluorescent-labeling has determined the presence of H-CA1 Ghre-containing collateralized neurons that project to the hypothalamus and amygdala monosynaptically. We hypothesize that H-Ghre-containing neurons in H-CA1 modulate food-intake behavior through direct pathways to the arcuate hypothalamic nucleus and medial amygdaloid nucleus. Copyright © 2017 Elsevier B.V. All rights reserved.

What is the link between nonlocalizing sestamibi scans, multigland disease, and persistent hypercalcemia? A study of 401 consecutive patients undergoing parathyroidectomy.

PubMed

Chiu, Bill; Sturgeon, Cord; Angelos, Peter

2006-09-01

We hypothesized that nonlocalizing sestamibi scans would correlate with multigland disease and persistent primary hyperparathyroidism. We reviewed records for 401 consecutive patients who underwent parathyroidectomy from 1999 to 2004. Gender, age, preoperative imaging, surgical findings, gland weight and volume, and 6-month calcium levels (Ca) were examined. We identified 289 women and 112 men, 297 of whom had a preoperative sestamibi scan localized to a single gland (localized group; LG). Ninety-six percent of the LG were found to have single-gland disease, and 4% had multigland disease (MGD). In the nonlocalized group (NLG), 76% had single-gland disease and 24% MGD. Mean gland weight was greater in the LG than in the NLG (1128 mg vs 699 mg; P < .05). Mean gland volume was larger in the LG (1.34 cc vs 0.89 cc; P < .05). A localizing sestamibi scan had a positive predictive value (PPV) of 96% and a likelihood ratio of 2.29 for predicting "curative" intraoperative parathyroid hormone drop after removal of a single abnormal gland. Patients were stratified into normocalcemic (NCa) and hypercalcemic (HCa) groups based on 6-month postoperative serum calcium data (n = 328). HCa incidence at 6 months did not differ significantly between the LG (5%) and NLG (3%). A localizing scan had a PPV of 95% for normocalcemia at 6 months. A nonlocalizing scan had a PPV of 21% for HCa at 6 months. Nonlocalizing sestamibi scans were more common in primary hyperparathyroidism with MGD and were associated with smaller-volume abnormal glands found at operation. Preoperative sestamibi scan-results did not predict HCa at 6 months.

A systematic quantitative approach to rational drug design and discovery of novel human carbonic anhydrase IX inhibitors.

PubMed

Sethi, Kalyan K; Verma, Saurabh M

2014-08-01

Drug design involves the design of small molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of carbonic anhydrase IX inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques with the help of SYBYL 7.1 software. The large set of 36 different aromatic/heterocyclic sulfamates carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, such as hCA IX, was chosen for this study. The conventional ligand-based 3D-QSAR studies were performed based on the low energy conformations employing database alignment rule. The ligand-based model gave q(2) values 0.802 and 0.829 and r(2) values 1.000 and 0.994 for CoMFA and CoMSIA, respectively, and the predictive ability of the model was validated. The predicted r(2) values are 0.999 and 0.502 for CoMFA and CoMSIA, respectively. SEA (steric, electrostatic, hydrogen bond acceptor) of CoMSIA has the significant contribution for the model development. The docking of inhibitors into hCA IX active site using Glide XP (Schrödinger) software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps are well in agreement with the structural characteristics of the binding pocket of hCA IX active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved hCA IX inhibitors as leads for various types of metastatic cancers including those of cervical, renal, breast and head and neck origin.

Theoretical study on the reaction mechanism of CH 4 with CaO

NASA Astrophysics Data System (ADS)

Yang, Hua-Qing; Hu, Chang-Wei; Qin, Song

2006-11-01

The reaction pathways and energetics for the reaction of methane with CaO are discussed on the singlet spin state potential energy surface at the B3LYP/6-311+G(2df,2p) and QCISD/6-311++G(3df,3pd)//B3LYP/6-311+G(2df,2p) levels of theory. The reaction of methane with CaO is proposed to proceed in the following reaction pathways: CaO + CH 4 → CaOCH 4 → [TS] → CaOH + CH 3, CaO + CH 4 → OCaCH 4 → [TS] → HOCaCH 3 → CaOH + CH 3 or [TS] → CaCH 3OH → Ca + CH 3OH, and OCaCH 4 → [TS] → HCaOCH 3 → CaOCH 3 + H or [TS] → CaCH 3OH → Ca + CH 3OH. The gas-phase methane-methanol conversion by CaO is suggested to proceed via two kinds of important reaction intermediates, HOCaCH 3 and HCaOCH 3, and the reaction pathway via the hydroxy intermediate (HOCaCH 3) is energetically more favorable than the other one via the methoxy intermediate (HCaOCH 3). The hydroxy intermediate HOCaCH 3 is predicted to be the energetically most preferred configuration in the reaction of CaO + CH 4. Meanwhile, these three product channels (CaOH + CH 3, CaOCH 3 + H and Ca + CH 3OH) are expected to compete with each other, and the formation of methyl radical is the most preferable pathway energetically. On the other hand, the intermediates HCaOCH 3 and HOCaCH 3 are predicted to be the energetically preferred configuration in the reaction of Ca + CH 3OH, which is precisely the reverse reaction of methane hydroxylation.

Chromophore dynamics in the PYP photocycle from femtosecond stimulated Raman spectroscopy.

PubMed

Creelman, Mark; Kumauchi, Masato; Hoff, Wouter D; Mathies, Richard A

2014-01-23

Femtosecond stimulated Raman spectroscopy (FSRS) is used to examine the structural dynamics of the para-hydroxycinnamic acid (HCA) chromophore during the first 300 ps of the photoactive yellow protein (PYP) photocycle, as the system transitions from its vertically excited state to the early ground state cis intermediate, I0. A downshift in both the C7═C8 and C1═O stretches upon photoexcitation reveals that the chromophore has shifted to an increasingly quinonic form in the excited state, indicating a charge shift from the phenolate moiety toward the C9═O carbonyl, which continues to increase for 170 fs. In addition, there is a downshift in the C9═O carbonyl out-of-plane vibration on an 800 fs time scale as PYP transitions from its excited state to I0, indicating that weakening of the hydrogen bond with Cys69 and out-of-plane rotation of the C9═O carbonyl are key steps leading to photoproduct formation. HOOP intensity increases on a 3 ps time scale during the formation of I0, signifying distortion about the C7═C8 bond. Once on the I0 surface, the C7═C8 and C1═O stretches blue shift, indicating recovery of charge to the phenolate, while persistent intensity in the HOOP and carbonyl out-of-plane modes reveal HCA to be a cissoid structure with significant distortion about the C7═C8 bond and of C9═O out of the molecular plane.

Comparative Chemometric Analysis for Classification of Acids and Bases via a Colorimetric Sensor Array.

PubMed

Kangas, Michael J; Burks, Raychelle M; Atwater, Jordyn; Lukowicz, Rachel M; Garver, Billy; Holmes, Andrea E

2018-02-01

With the increasing availability of digital imaging devices, colorimetric sensor arrays are rapidly becoming a simple, yet effective tool for the identification and quantification of various analytes. Colorimetric arrays utilize colorimetric data from many colorimetric sensors, with the multidimensional nature of the resulting data necessitating the use of chemometric analysis. Herein, an 8 sensor colorimetric array was used to analyze select acid and basic samples (0.5 - 10 M) to determine which chemometric methods are best suited for classification quantification of analytes within clusters. PCA, HCA, and LDA were used to visualize the data set. All three methods showed well-separated clusters for each of the acid or base analytes and moderate separation between analyte concentrations, indicating that the sensor array can be used to identify and quantify samples. Furthermore, PCA could be used to determine which sensors showed the most effective analyte identification. LDA, KNN, and HQI were used for identification of analyte and concentration. HQI and KNN could be used to correctly identify the analytes in all cases, while LDA correctly identified 95 of 96 analytes correctly. Additional studies demonstrated that controlling for solvent and image effects was unnecessary for all chemometric methods utilized in this study.

Ca2+-exchange in layered zirconium orthophosphate, α-ZrP: Chemical study and potential application for zinc corrosion inhibition

NASA Astrophysics Data System (ADS)

Bouali, Imane; Rocca, Emmanuel; Veys-Renaux, Delphine; Rhouta, Benaissa; Khalil, Aziza; Aït Aghzzaf, Ahmed

2017-11-01

The control of the corrosion phenomenon occurring at the metal interface requires the development of new non-toxic anticorrosion additives. For this purpose, zirconium orthophosphate compounds (Zr(HPO4)2,H2O noted α-ZrP) were synthesized by both hydrothermal and refluxing methods The Ca2+-cationic exchange in the layered structure is kinetically favoured by low crystallinity of α-ZrP synthesized by refluxing process, and leads to the formation of CaZr(PO4)2,4H2O, noted Ca2+-ZrP. The H+/Ca2+ exchange mechanism is mainly triggered by acid-base considerations, and especially the pKa of α-ZrP/Ca2+-ZrP acid-base couple (evaluated to 2.5). Both compounds are acidic compounds by internal exchangeable H+ for α-ZrP and surface protons for Ca2+-ZrP, and can be used as potential inhibitors of zinc corrosion. Electrochemical measurements show that Ca2+-ZrP compounds dispersed in the NaCl electrolyte buffer the pH value over a long time and therefore allow controlling the corrosion rate of zinc.

Dithiocarbamates with potent inhibitory activity against the Saccharomyces cerevisiae β-carbonic anhydrase.

PubMed

Bozdag, Murat; Carta, Fabrizio; Vullo, Daniela; Isik, Semra; AlOthman, Zeid; Osman, Sameh M; Scozzafava, Andrea; Supuran, Claudiu T

2016-01-01

Dithiocarbamates (DTCs) prepared from primary or secondary amines, which incorporated amino/hydroxyl-alkyl, mono-/bicyclic aliphatic/heterocyclic rings based on the quinuclidine, piperidine, hydroxy-/carboxy-/amino-substituted piperidine, morpholine and piperazine scaffolds, were investigated for the inhibition of α- and β-carbonic anhydrases (CAs, EC 4.2.1.1) of pharmacologic relevance, such as the human (h) isoform hCA I and II, as well as the Saccharomyces cerevisiae β-CA, scCA. The yeast and its β-CA were shown earlier to be useful models of pathogenic fungal infections. The DTCs investigated here were medium potency hCA I inhibitors (K(I)s of 66.5-910 nM), were more effective as hCA II inhibitors (K(I)s of 8.9-107 nM) and some of them showed excellent, low nanomolar activity against the yeast enzyme, with inhibition constants ranging between 6.4 and 259 nM. The detailed structure activity relationship for inhibition of the yeast and human enzymes is discussed. Several of the investigated DTCs showed excellent selectivity ratios for inhibiting the yeast over the human cytosolic CA isoforms.

Genotoxicity assessment of some cosmetic and food additives.

PubMed

Di Sotto, Antonella; Maffei, Francesca; Hrelia, Patrizia; Di Giacomo, Silvia; Pagano, Ester; Borrelli, Francesca; Mazzanti, Gabriela

2014-02-01

α-Hexylcinnamaldehyde (HCA) and p-tert-butyl-alpha-methylhydrocinnamic aldehyde (BMHCA) are synthetic aldehydes, characterized by a typical floral scent, which makes them suitable to be used as fragrances in personal care (perfumes, creams, shampoos, etc.) and household products, and as flavouring additives in food and pharmaceutical industry. The aldehydic structure suggests the need for a safety assessment for these compounds. Here, HCA and BMHCA were evaluated for their potential genotoxic risk, both at gene level (frameshift or base-substitution mutations) by the bacterial reverse mutation assay (Ames test), and at chromosomal level (clastogenicity and aneuploidy) by the micronucleus test. In order to evaluate a primary and repairable DNA damage, the comet assay has been also included. In spite of their potential hazardous chemical structure, a lack of mutagenicity was observed for both compounds in all bacterial strains tested, also in presence of the exogenous metabolic activator, showing that no genotoxic derivatives were produced by CYP450-mediated biotransformations. Neither genotoxicity at chromosomal level (i.e. clastogenicity or aneuploidy) nor single-strand breaks were observed. These findings will be useful in further assessing the safety of HCA and BMHCA as either flavour or fragrance chemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo.

PubMed

Mahmoud, Salma; Ibrahim, Mohammed; Hago, Ahmed; Huang, Yuhong; Wei, Yuanyi; Zhang, Jun; Zhang, Qingqing; Xiao, Yu; Wang, Jingwen; Adam, Munkaila; Guo, Yu; Wang, Li; Zhou, Shuting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2016-11-15

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its over expression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy.

Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo

PubMed Central

Mahmoud, Salma; Ibrahim, Mohammed; Hago, Ahmed; Huang, Yuhong; Wei, Yuanyi; Zhang, Jun; Zhang, Qingqing; Xiao, Yu; Wang, Jingwen; Adam, Munkaila; Guo, Yu; Wang, Li; Zhou, Shuting; Xin, Boyi; Xuan, Wei; Tang, Jianwu

2016-01-01

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that upregulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 downregulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its overexpression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy. PMID:27626699

CTX-M-15-H30Rx-ST131 subclone is one of the main causes of healthcare-associated ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain.

PubMed

Merino, Irene; Shaw, Evelyn; Horcajada, Juan Pablo; Cercenado, Emilia; Mirelis, Beatriz; Pallarés, M Angeles; Gómez, Juliá; Xercavins, M; Martínez-Martínez, Luis; De Cueto, Marina; Cantón, Rafael; Ruiz-Garbajosa, Patricia

2016-08-01

The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of urinary origin (BUO) in Spain. An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n = 425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated. ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes [14% (30/215) versus 4.3% (9/210); P = 0.001]. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20). The CTX-M-15-ST131-H30Rx subclone is a relevant MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone with comparatively less diversity of virulence profiles reflects the spread of a successful and MDR ESBL ST131 lineage in Spain. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long-term Variation of Ventilation System in the East Sea (Japan Sea) Revealed by Heat Content Change and Water Mass Analysis

NASA Astrophysics Data System (ADS)

Yoon, S.; Chang, K. I.; Kim, K. R.; Lobanov, V. B.

2016-02-01

The semi-enclosed East Sea (ES) is called a miniature ocean with its own thermohaline circulation characterized by the formation of deep and intermediate water masses in the Japan Basin, southward discharge of those subsurface water masses towards the Ulleung and Yamato basins, and northward heat transport by the Tsushima Warm Current in the upper layer. Reports have been given of rapid changes of physical and biogeochemical properties associated with its ventilation system. We present results on upper ocean heat content variations and changes in water mass structure and properties from the analysis of historical and most recent hydrographic data. The analysis of non-seasonal heat content (HCA) variations in the upper 500 m from 1976 to 2007 highlights the 2-year lagged in-phase decadal-scale HCA variations in the eastern and western ES until 1995 followed by uncorrelated variations between two regions thereafter with pronounced interannual variations. Long-term trend of HCA in the entire ES shows an increasing trend, but with a large increase in the eastern part and relatively weaker but statistically significant decrease in the western part. The thickness variation of water warmer than 10°C mainly contributes to the HCA variation. Analyses of upper circulation in conjunction with climate indices suggest the importance of the wind-stress curl pattern represented by the Western Pacific index in the western ES and the influence of the Siberian High in the eastern ES. The thickness and temperature variation of 1-5°C representing the East Sea Intermediate Water (ESIW) is relatively minor contributor to the HCA variation in the upper 500 m. However, the thickness (temperature) of the ESIW has been increased (decreased) in the entire ES since 1992, which implies that the formation of the ESIW has been activated in recent decades. To investigate water mass changes in deeper than 500 m, we use full-depth CTD data obtained from CREAMS expeditions from 1993 to 2015. Temperature deeper than 1000 m has been increased about 0.03°C during 20 years and the depth of deep salinity minimum depth which is the lower (upper) limit of the East Sea Central Water (Deep Water) has been deepened. Other characteristics of water mass structure and property changes will be presented.

Combination of Garcinia cambogia Extract and Pear Pomace Extract Additively Suppresses Adipogenesis and Enhances Lipolysis in 3T3-L1 Cells.

PubMed

Sharma, Kushal; Kang, Siwon; Gong, Dalseong; Oh, Sung-Hwa; Park, Eun-Young; Oak, Min-Ho; Yi, Eunyoung

2018-01-01

Inhibition of adipogenesis has been a therapeutic target for reducing obesity and obesity-related disorders such as diabetes, hypertension, atherosclerosis, and cancer. For decades, anti-adipogenic potential of many herbal extracts has been investigated. One example is Garcinia cambogia extract (GE) containing (-)-hydroxycitric acid as an active ingredient. GE is currently marketed as a weight loss supplement, used alone or with other ingredients. Pear pomace extract (PE), another natural product, has been also shown to have anti-adipogenic activity in a recent report. It was tested if the mixture of PE and GE (MIX) would produce more effective anti-adipogenic activity than PE or GE alone. Differentiation of 3T3-L1 preadipocyte was induced by adding insulin, dexamethasone, and isobutylmethylxanthine and lipid accumulation was measured by Oil Red O staining. Cellular markers for adipogenesis and lipolysis such as CCAAT/enhancer binding protein (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) was measured using immunocytochemistry. MIX, compared to PE or GE alone, showed greater inhibition of lipid accumulation. Furthermore, MIX reduced the expression of adipogenesis-related factors C/EBP-α, PPAR-γ, and FAS more than PE or GE alone did. In contrast, the expression of HSL the enzyme required for lipolysis was further enhanced in MIX-treated adipocytes compared to the PE or GE alone treated groups. Anti-adipogenic effect of PE and GE appears synergistic, and the MIX may be a useful therapeutic combination for the treatment of obesity and obesity-related diseases. PE and GE efficiently inhibited adipocyte differentiation by suppressing the expression of adipogenic transcription factor CEBP-α and PPAR-γ.PE and GE significantly decreased the expression of adipogenic enzyme FAS.PE and GE increased the expression of lipid degrading enzyme HSL.Mixture of PE and GE exhibited additive or moderately synergistic effect on adipocyte differentiation and lipid accumulation. Abbreviations used: CEBP-a: CCAT/enhancer binding protein alpha, CI: Combination Index, FAS: Fatty acid synthase, GE: Garcinia cambogia extract, HSL: Hormone sensitive lipase, PE: Pear pomace extract, PPAR-γ: Peroxisome proliferator-activated receptor gamma.

Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

PubMed Central

Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

2010-01-01

Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

Operational Status of the International Space Station Plasma Contactor Hollow Cathode Assemblies July 2001 to May 2013

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Yim, John T.; Patterson, Michael J.; Dalton, Penni J.

2013-01-01

The International Space Station has onboard two Aerojet Rocketdyne developed plasma contactor units that perform the function of charge control. The plasma contactor units contain NASA Glenn Research Center developed hollow cathode assemblies. NASA Glenn Research Center monitors the on-orbit operation of the flight hollow cathode assemblies. As of May 31, 2013, HCA.001-F has been ignited and operated 123 times and has accumulated 8072 hours of operation, whereas, HCA.003-F has been ignited and operated 112 times and has accumulated 9664 hours of operation. Monitored hollow cathode ignition times and anode voltage magnitudes indicate that they continue to operate nominally.

Operational Status of the International Space Station Plasma Contactor Hollow Cathode Assemblies from July 2011 to May 2013

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Yim, John T.; Patterson, Michael J.; Dalton, Penni J.

2014-01-01

The International Space Station has onboard two Aerojet Rocketdyne developed plasma contactor units that perform the function of charge control. The plasma contactor units contain NASA Glenn Research Center developed hollow cathode assemblies. NASA Glenn Research Center monitors the onorbit operation of the flight hollow cathode assemblies. As of May 31, 2013, HCA.001-F has been ignited and operated 123 times and has accumulated 8072 hours of operation, whereas, HCA.003-F has been ignited and operated 112 times and has accumulated 9664 hours of operation. Monitored hollow cathode ignition times and anode voltage magnitudes indicate that they continue to operate nominally.

Study on elemental fingerprint of traditional marine Chinese medicine oysters from Jiaozhou Bay, China

NASA Astrophysics Data System (ADS)

Zheng, Yongjun; Zheng, Kang; Li, Yantuan

2012-09-01

In order to investigate the relationship between the trace elements and the characteristics of the oysters, we analyzed the trace elements present in the germplasm of oysters from different producing areas in the Jiaozhou Bay. The element fingerprints were established to reflect the elemental characteristics of the oysters. Concentration patterns of the elements were deciphered by principle component analysis (PCA) and hierarchical cluster analysis (HCA). The six regions were discriminated with accuracy using HCA and PCA based on the concentration of 16 trace elements. The elements were viewed as characteristic elements of the oysters and the fingerprints of these elements could be used to distinguish the quality of the oysters.

Effects of different types of soy sauce on the formation of heterocyclic amines in roasted chicken.

PubMed

Alam Shah, Syifaa; Selamat, Jinap; Haque Akanda, Md Jahurul; Sanny, Maimunah; Khatib, Alfi

2018-05-01

The objective of the study was to determine the effect of different types of soy sauce and marinating time on the formation of heterocyclic amines (HCAs) in roasted chicken. Chicken breast samples were marinated with sweet, salty, light and dark soy sauce at 0, 3, 6 and 12 h (control treatment was the chicken without marinade). The concentrations of free amino acids, sugars and creatinine were determined before roasting while HCA concentrations were determined after roasting. All types of soy sauce significantly increased (p ≤ 0.05) the concentration of HCAs in roasted chicken with increasing marinating time. The highest increment of total concentration of HCAs was found in samples marinated with light soy sauce (887%) followed by dark (375%), salty (193%) and sweet (169%) at 12 h. PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) showed a substantial reduction in samples only momentarily marinated with sweet, salty and dark soy sauce (0 h). Free amino acids were found to be more strongly correlated with the formation of HCAs than reducing sugars or creatinine.

Occurrence of heterocyclic amines in cooked meat products.

PubMed

Puangsombat, Kanithaporn; Gadgil, Priyadarshini; Houser, Terry A; Hunt, Melvin C; Smith, J Scott

2012-03-01

Heterocyclic amines (HCAs), potent mutagens and a risk factor for human cancers, are produced in meats cooked at high temperature. The aim of this study was to determine the HCA content in cooked meat products (beef, chicken, pork, fish) prepared by various cooking methods (pan frying, oven broiling, and oven baking at 170 to 230°C) that are preferred by U.S. meat consumers. The primary HCAs in these samples were PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine) (1.49-10.89ng/g), MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline) (not detected-4.0ng/g), and DiMeIQx (2-amino-3,4,8-trimethyl-imidazo [4,5-f]quinoxaline) (not detected-3.57ng/g). Type and content of HCAs in cooked meat samples were highly dependent on cooking conditions. The total HCA content in well-done meat was 3.5 times higher than that of medium-rare meat. Fried pork (13.91ng/g) had higher levels of total HCAs than fried beef (8.92ng/g) and fried chicken (7.00ng/g). Among the samples, fried bacon contained the highest total HCA content (17.59ng/g). Copyright © 2011 Elsevier Ltd. All rights reserved.

Fingerprint analysis of Hibiscus mutabilis L. leaves based on ultra performance liquid chromatography with photodiode array detector combined with similarity analysis and hierarchical clustering analysis methods

PubMed Central

Liang, Xianrui; Ma, Meiling; Su, Weike

2013-01-01

Background: A method for chemical fingerprint analysis of Hibiscus mutabilis L. leaves was developed based on ultra performance liquid chromatography with photodiode array detector (UPLC-PAD) combined with similarity analysis (SA) and hierarchical clustering analysis (HCA). Materials and Methods: 10 batches of Hibiscus mutabilis L. leaves samples were collected from different regions of China. UPLC-PAD was employed to collect chemical fingerprints of Hibiscus mutabilis L. leaves. Results: The relative standard deviations (RSDs) of the relative retention times (RRT) and relative peak areas (RPA) of 10 characteristic peaks (one of them was identified as rutin) in precision, repeatability and stability test were less than 3%, and the method of fingerprint analysis was validated to be suitable for the Hibiscus mutabilis L. leaves. Conclusions: The chromatographic fingerprints showed abundant diversity of chemical constituents qualitatively in the 10 batches of Hibiscus mutabilis L. leaves samples from different locations by similarity analysis on basis of calculating the correlation coefficients between each two fingerprints. Moreover, the HCA method clustered the samples into four classes, and the HCA dendrogram showed the close or distant relations among the 10 samples, which was consistent to the SA result to some extent. PMID:23930008

Third sector primary health care in New Zealand.

PubMed

Crampton, P; Dowell, A C; Bowers, S

2000-03-24

To describe key organisational characteristics of selected third sector (non-profit and non-government) primary health care organisations. Data were collected, in 1997 and 1998, from 15 third sector primary care organisations that were members of a network of third sector primary care providers, Health Care Aotearoa (HCA). Data were collected by face-to-face interviews of managers and key informants using a semi-structured interview schedule, and from practice computer information systems. Overall the populations served were young: only 4% of patients were aged 65 years or older, and the ethnicity profile was highly atypical, with 21.8% European, 36% Maori, 22.7% Pacific Island, 12% other, and 7.5% not stated. Community services card holding rates were higher than recorded in other studies, and registered patients tended to live in highly deprived areas. HCA organisations had high patient to doctor ratios, in general over 2000:1, and there were significant differences in management structures between HCA practices and more traditional general practice. Third sector organisations provide services for populations that are disadvantaged in many respects. It is likely that New Zealand will continue to develop a diverse range of primary care organisational arrangements. Effort is now required to measure quality and effectiveness of services provided by different primary care organisations serving comparable populations.

Rapid core measure improvement through a "business case for quality".

PubMed

Perlin, Jonathan B; Horner, Stephen J; Englebright, Jane D; Bracken, Richard M

2014-01-01

Incentives to improve performance are emerging as revenue or financial penalties are linked to the measured quality of service provided. The HCA "Getting to Green" program was designed to rapidly increase core measure performance scores. Program components included (1) the "business case for quality"-increased awareness of how quality drives financial performance; (2) continuous communication of clinical and financial performance data; and (3) evidence-based clinical protocols, incentives, and tools for process improvement. Improvement was measured by comparing systemwide rates of adherence to national quality measures for heart failure (HF), acute myocardial infarction (AMI), pneumonia (PN), and surgical care (SCIP) to rates from all facilities reporting to the Centers for Medicare and Medicaid Services (CMS). As of the second quarter of 2011, 70% of HCA total measure set composite scores were at or above the 90th percentile of CMS scores. A test of differences in regression coefficients between the CMS national average and the HCA average revealed significant differences for AMI (p = .001), HF (p = .012), PN (p < .001), and SCIP (p = .015). This program demonstrated that presentation of the financial implications of quality, transparency in performance data, and clearly defined goals could cultivate the desire to use improvement tools and resources to raise performance. © 2012 National Association for Healthcare Quality.

Health care and lost productivity costs of overweight and obesity in New Zealand.

PubMed

Lal, Anita; Moodie, Marj; Ashton, Toni; Siahpush, Mohammad; Swinburn, Boyd

2012-12-01

To estimate the costs of health care and lost productivity attributable to overweight and obesity in New Zealand (NZ) in 2006. A prevalence-based approach to costing was used in which costs were calculated for all cases of disease in the year 2006. Population attributable fractions (PAFs) were calculated based on the relative risks obtained from large cohort studies and the prevalence of overweight and obesity. For each disease, the PAF was multiplied by the total health care cost. The costs of lost productivity associated with premature mortality were estimated using both the Human Capital approach (HCA) and Friction Cost approach (FCA). Health care costs attributable to overweight and obesity were estimated to be NZ$686m or 4.5% of New Zealand's total health care expenditure in 2006. The costs of lost productivity using the FCA were estimated to be NZ$98m and NZ$225m using the HCA. The combined costs of health care and lost productivity using the FCA were $784m and $911m using the HCA. The cost burden of overweight and obesity in NZ is considerable. Policies and interventions are urgently needed to reduce the prevalence of obesity thereby decreasing these substantial costs. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

PubMed Central

Li, Xiaolan; Milan Bonotto, Rafaela; No, Joo Hwan; Kim, Keum Hyun; Baek, Sungmin; Kim, Hee Young; Windisch, Marc Peter; Pamplona Mosimann, Ana Luiza; de Borba, Luana; Liuzzi, Michel; Hansen, Michael Adsetts Edberg; Nunes Duarte dos Santos, Claudia; Freitas-Junior, Lucio Holanda

2013-01-01

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. PMID:23437413

Hydrogeochemistry and quality of surface water and groundwater in the vicinity of Lake Monoun, West Cameroon: approach from multivariate statistical analysis and stable isotopic characterization.

PubMed

Kamtchueng, Brice T; Fantong, Wilson Y; Wirmvem, Mengnjo J; Tiodjio, Rosine E; Takounjou, Alain F; Ndam Ngoupayou, Jules R; Kusakabe, Minoru; Zhang, Jing; Ohba, Takeshi; Tanyileke, Gregory; Hell, Joseph V; Ueda, Akira

2016-09-01

With the use of conventional hydrogeochemical techniques, multivariate statistical analysis, and stable isotope approaches, this paper investigates for the first time surface water and groundwater from the surrounding areas of Lake Monoun (LM), West Cameroon. The results reveal that waters are generally slightly acidic to neutral. The relative abundance of major dissolved species are Ca(2+) > Mg(2+) > Na(+) > K(+) for cations and HCO3 (-) ≫ NO3 (-) > Cl(-) > SO4 (2-) for anions. The main water type is Ca-Mg-HCO3. Observed salinity is related to water-rock interaction, ion exchange process, and anthropogenic activities. Nitrate and chloride have been identified as the most common pollutants. These pollutants are attributed to the chlorination of wells and leaching from pit latrines and refuse dumps. The stable isotopic compositions in the investigated water sources suggest evidence of evaporation before recharge. Four major groups of waters were identified by salinity and NO3 concentrations using the Q-mode hierarchical cluster analysis (HCA). Consistent with the isotopic results, group 1 represents fresh unpolluted water occurring near the recharge zone in the general flow regime; groups 2 and 3 are mixed water whose composition is controlled by both weathering of rock-forming minerals and anthropogenic activities; group 4 represents water under high vulnerability of anthropogenic pollution. Moreover, the isotopic results and the HCA showed that the CO2-rich bottom water of LM belongs to an isolated hydrological system within the Foumbot plain. Except for some springs, groundwater water in the area is inappropriate for drinking and domestic purposes but good to excellent for irrigation.

High affinity binding of a fungal oligopeptide elicitor to parsley plasma membranes triggers multiple defense responses.

PubMed

Nürnberger, T; Nennstiel, D; Jabs, T; Sacks, W R; Hahlbrock, K; Scheel, D

1994-08-12

An oligopeptide of 13 amino acids (Pep-13) identified within a 42 kDa glycoprotein elicitor from P. mega-sperma was shown to be necessary and sufficient to stimulate a complex defense response in parsley cells comprising H+/Ca2+ influxes, K+/Cl- effluxes, an oxidative burst, defense-related gene activation, and phytoalexin formation. Binding of radiolabeled Pep-13 to parsley microsomes and protoplasts was specific, reversible, and saturable. Identical structural features of Pep-13 were found to be responsible for specific binding and initiation of all plant responses analyzed. The high affinity binding site recognizing the peptide ligand (KD = 2.4 nM) may therefore represent a novel class of receptors in plants, and the rapidly induced ion fluxes may constitute elements of the signal transduction cascade triggering pathogen defense in plants.

Impact of perinatal factors on growth deficits of preterm infants.

PubMed

Goulart, Ana Lucia; Morais, Mauro Batista de; Kopelman, Benjamin Israel

2011-01-01

To review perinatal factors associated with a growth deficit in preterm infants at a corrected age of one year. Cohort study of preterm infants with a birth weight < 2,000 g. Percentiles and Z scores of body weight (W/A), length (L/A) and head circumference (HC/A) at one year of corrected age were calculated by using the Centers for Disease Control and Prevention curves. Among 303 preterm infants, the frequencies of measures below the 10th percentile (P10) and Z scores -2 were 43.2% and 24.4% for W/A, 22.1% and 8.6% for L/A and 15.8% and 4.6% for HC/A, respectively. Logistic regression analyses showed factors associated with higher odds for W/A < P10 were resuscitation at birth (1.8 times) and small for gestational age infants (3.0 times). In infants rated as small at full-term postconceptual age, the odds for W/A < P10 were 4.0 times as high in those with a birth weight between 1,000 and 1,499 g and 3.5 times as high in those > 1,500 g. As birth length was reduced, the odds for L/A < P10 increased, but this was not associated with birth weight. The odds for HC/A < P10 were 2.5 times as high in small for gestational age infants. In infants with a body weight < 1,000 g, the odds for HC/A < P10 were 4.4 times higher, compared with those between 1,000 g and 1,499 g and 5.3 times higher if compared with those > 1,500 g. At a corrected age of one year, preterm infants with a birth weight < 2,000 g were found with high growth deficits frequencies, and associated factors were variable, depending on the analyzed deficit, with intrauterine and postnatal growth restriction being outstanding predictors.

An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: A randomized trial.

PubMed

Merli, Manuela; Lucidi, Cristina; Di Gregorio, Vincenza; Lattanzi, Barbara; Giannelli, Valerio; Giusto, Michela; Farcomeni, Alessio; Ceccarelli, Giancarlo; Falcone, Marco; Riggio, Oliviero; Venditti, Mario

2016-05-01

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug-resistant (MDR) infections are on the increase in health care settings. Health-care-associated (HCA) infections are still frequently treated as community-acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in-hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety-six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In-hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post-hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. © 2015 by the American Association for the Study of Liver Diseases.

Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

PubMed

McNeil, J Chase; Kok, Eric Y; Forbes, Andrea R; Lamberth, Linda; Hulten, Kristina G; Vallejo, Jesus G; Mason, Edward O; Kaplan, Sheldon L

2016-03-01

Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine. Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 μg/mL. A vancomycin trough >15 μg/mL was, however, an independent risk factor for AKI. Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

31-P NMR studies of intracellular pH (pH/sub i/) of the in vitro resting rat diaphragm (D) exposed to hypercapnia (HC), plus amiloride (HCA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fitzgerald, R.; Howell, S.; Jacobus, W.

1986-03-05

The authors have previously reported that the pH/sub i/ of the resting rat D in vitro fell when exposed to HC. Since pH/sub i/ influences cellular functions, it is important to understand mechanisms whereby a tissue maintains its pH/sub i/ One mechanism reported to exist in some vertebrate tissues is a sodium-proton pump which is inhibited by amiloride. If the rat D had the Na/sup +/-H/sup +/ pump, the resting rat D pH/sub i/, when exposed to hypercapnia, would decrease more if amiloride was present than if there was no amiloride. The D was placed in a 25 mm NMRmore » sample tube and superfused with buffer gassed with 95%O/sub 2/-5%CO/sub 2/ at 37/sup 0/C. Two 15 minute pulsed Fourier transform spectra were acquired at 72.89 MHz using 2 sec repetition rate during normocapnia. The D was next superfused for 60 minutes with buffer gassed with 80%O/sub 2/-20%CO/sub 2/ and containing 5 x 10/sup -4/M amiloride (n=5; HCA) or not (n=8; HC). Four 15 minute spectra were obtained; pH/sub i/ was determined from the chemical shift of P/sub i/ resonance. The pH/sub i/ (X vector +/- SE) of HC D's fell from 7.14 +/- .04 to 6.85 +/- .05 at 1 hour of exposure. The pH/sub i/ of HCA D's fell from 6.95 +/- .05 to 6.57 +/- .03. The decrease in pH/sub i/ during hypercapnia is significantly greater (P<0.01) for HCA D's. These data suggest that the rat D uses a Na/sup +/-H/sup +/ pump to regulate pH/sub i/ and that this pump operates in the in vitro resting rat D exposed to hypercapnia.« less

Cathodes Delivered for Space Station Plasma Contactor System

NASA Technical Reports Server (NTRS)

Patterson, Michael J.

1999-01-01

The International Space Station's (ISS) power system is designed with high-voltage solar arrays that typically operate at output voltages of 140 to 160 volts (V). The ISS grounding scheme electrically ties the habitat modules, structure, and radiators to the negative tap of the solar arrays. Without some active charge control method, this electrical configuration and the plasma current balance would cause the habitat modules, structure, and radiators to float to voltages as large as -120 V with respect to the ambient space plasma. With such large negative floating potentials, the ISS could have deleterious interactions with the space plasma. These interactions could include arcing through insulating surfaces and sputtering of conductive surfaces as ions are accelerated by the spacecraft plasma sheath. A plasma contactor system was baselined on the ISS to prevent arcing and sputtering. The sole requirement for the system is contained within a single directive (SSP 30000, paragraph 3.1.3.2.1.8): "The Space Station structure floating potential at all points on the Space Station shall be controlled to within 40 V of the ionospheric plasma potential using a plasma contactor." NASA is developing this plasma contactor as part of the ISS electrical power system. For ISS, efficient and rapid emission of high electron currents is required from the plasma contactor system under conditions of variable and uncertain current demand. A hollow cathode plasma source is well suited for this application and was, therefore, selected as the design approach for the station plasma contactor system. In addition to the plasma source, which is referred to as a hollow cathode assembly, or HCA, the plasma contactor system includes two other subsystems. These are the power electronics unit and the xenon gas feed system. The Rocketdyne Division of Boeing North American is responsible for the design, fabrication, assembly, test, and integration of the plasma contactor system. Because of technical and schedule considerations, the NASA Lewis Research Center was asked to manufacture and deliver the engineering model, the qualification model, and the flight HCA units for the plasma contactor system as government furnished equipment. To date, multiple units have been built. One cathode has demonstrated approximately 28 000-hr lifetime, two development HCA units have demonstrated over 15 000-hr lifetime, and one HCA unit has demonstrated more than 38 000 ignitions. All eight flight HCA's have been manufactured, acceptance tested, and are ready for delivery to the flight contractor.

Successful repair of injured hepatic veins and inferior vena cava following blunt traumatic injury, by using cardiopulmonary bypass and hypothermic circulatory arrest.

PubMed

Kaoutzanis, Christodoulos; Evangelakis, Erotokritos; Kokkinos, Chrysostomos; Kaoutzanis, Gavriel

2011-01-01

Traumatic injury to the retrohepatic veins continues to carry high mortality rates. In the last few decades various management strategies have been proposed. However, treatment of such injuries still remains highly variable and technically challenging due to the surgically inaccessible location of these vessels and the consequent difficulty controlling bleeding. We report a successful repair of complete transection of the two main extraparenchymal hepatic veins and laceration of the retrohepatic inferior vena cava using cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) following blunt abdominal trauma. Immediate CPB with or without HCA can be life-saving and should be considered for patients with complex isolated retrohepatic venous injuries.

Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca2+ Current Inhibitors for Hypotensive Agent Discovery.

PubMed

Carreyre, Hélène; Carré, Grégoire; Ouedraogo, Maurice; Vandebrouck, Clarisse; Bescond, Jocelyn; Supuran, Claudiu T; Thibaudeau, Sébastien

2017-05-31

Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius , which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine's vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca 2+ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins.

48 CFR 309.403 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Acquisition Policy and Accountability (DAS/GAPA). Initiating official means the Contracting Officer, the HCA, the Associate DAS for Acquisition, or the Inspector General (IG). Suspending official means the DAS...

SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED β-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.

PubMed

Berber, Nurcan; Arslan, Mustafa; Bilen, Çiğdem; Sackes, Zübeyde; Gençer, Nahit; Arslan, Oktay

2015-01-01

A new series of phthalazine substituted β-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted β-lactam derivatives. The β-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.

Ureaplasma species and Mycoplasma hominis in cervical fluid of pregnancies complicated by preterm prelabor rupture of membranes.

PubMed

Musilova, Ivana; Pliskova, Lenka; Kutova, Radka; Hornychova, Helena; Jacobsson, Bo; Kacerovsky, Marian

2016-01-01

To evaluate Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid and their association with microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). A prospective study of 68 women with singleton pregnancies complicated by PPROM between 24(0/7) and 36(6/7) weeks was conducted. Cervical fluid and amniotic fluid were collected from all women at the time of admission. The Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid were identified using specific real-time PCR. Ureaplasma species and Mycoplasma hominis DNA were identified in 59% (40/69) of the cervical fluid samples. Women with the presence of Ureaplasma species DNA with and without Mycoplasma hominis DNA in the cervical fluid had a higher rate of MIAC alone [35% (14/40) versus 11% (3/28); p = 0.02] and a higher rate of the presence of both MIAC and HCA [30% (12/40) versus 4% (1/28); p = 0.01] than women without Ureaplasma species and Mycoplasma hominis DNA in the cervical fluid. The presence of Ureaplasma species DNA with and without Mycoplasma hominis DNA in the cervical fluid is associated with a higher risk of MIAC or MIAC and HCA together in pregnancies complicated by PPROM.

48 CFR 1405.502 - Authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... obtain written authorization of the HCA before placing an advertisement in a newspaper to advertise a contracting opportunity. (b) Advertisements placed in media other than newspapers do not require advance...

48 CFR 3409.506 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... COMPETITION AND ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational and Consultant Conflicts of... performance to be in the best interest of the Federal government. (b) The HCA is designated as the official to...

48 CFR 301.603-71 - Waivers to warrant standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities... and policies in writing to the Senior Procurement Executive (SPE), through the HCA, for review and...

48 CFR 2905.202 - Exceptions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Secretary for Administration and Management is authorized to make the determination prescribed in FAR 5.202... reasonable must be submitted by the HCA for appropriate action including communication with the officials...

Design and development of a mobile exercise application for home care aides and older adult medicaid home and community-based clients.

PubMed

Danilovich, Margaret K; Diaz, Laura; Saberbein, Gustavo; Healey, William E; Huber, Gail; Corcos, Daniel M

2017-01-01

We describe a community-engaged approach with Medicaid home and community-based services (HCBS), home care aide (HCA), client, and physical therapist stakeholders to develop a mobile application (app) exercise intervention through focus groups and interviews. Participants desired a short exercise program with modification capabilities, goal setting, and mechanisms to track progress. Concerns regarding participation were training needs and feasibility within usual care services. Technological preferences were for simple, easy-to-use, and engaging content. The app was piloted with HCA-client dyads (n = 5) to refine the intervention and evaluate content. Engaging stakeholders in intervention development provides valuable user-feedback on both desired exercise program contents and mobile technology preferences for HCBS recipients.

Production of Cinnamic and p-Hydroxycinnamic Acids in Engineered Microbes.

PubMed

Vargas-Tah, Alejandra; Gosset, Guillermo

2015-01-01

The aromatic compounds cinnamic and p-hydroxycinnamic acids (pHCAs) are phenylpropanoids having applications as precursors for the synthesis of thermoplastics, flavoring, cosmetic, and health products. These two aromatic acids can be obtained by chemical synthesis or extraction from plant tissues. However, both manufacturing processes have shortcomings, such as the generation of toxic subproducts or a low concentration in plant material. Alternative production methods are being developed to enable the biotechnological production of cinnamic and (pHCAs) by genetically engineering various microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, Pseudomonas putida, and Streptomyces lividans. The natural capacity to synthesize these aromatic acids is not existent in these microbial species. Therefore, genetic modification have been performed that include the heterologous expression of genes encoding phenylalanine ammonia-lyase and tyrosine ammonia-lyase activities, which catalyze the conversion of l-phenylalanine (l-Phe) and l-tyrosine (l-Tyr) to cinnamic acid and (pHCA), respectively. Additional host modifications include the metabolic engineering to increase carbon flow from central metabolism to the l-Phe or l-Tyr biosynthetic pathways. These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate. These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass. A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement.

Production of Cinnamic and p-Hydroxycinnamic Acids in Engineered Microbes

PubMed Central

Vargas-Tah, Alejandra; Gosset, Guillermo

2015-01-01

The aromatic compounds cinnamic and p-hydroxycinnamic acids (pHCAs) are phenylpropanoids having applications as precursors for the synthesis of thermoplastics, flavoring, cosmetic, and health products. These two aromatic acids can be obtained by chemical synthesis or extraction from plant tissues. However, both manufacturing processes have shortcomings, such as the generation of toxic subproducts or a low concentration in plant material. Alternative production methods are being developed to enable the biotechnological production of cinnamic and (pHCAs) by genetically engineering various microbial hosts, including Escherichia coli, Saccharomyces cerevisiae, Pseudomonas putida, and Streptomyces lividans. The natural capacity to synthesize these aromatic acids is not existent in these microbial species. Therefore, genetic modification have been performed that include the heterologous expression of genes encoding phenylalanine ammonia-lyase and tyrosine ammonia-lyase activities, which catalyze the conversion of l-phenylalanine (l-Phe) and l-tyrosine (l-Tyr) to cinnamic acid and (pHCA), respectively. Additional host modifications include the metabolic engineering to increase carbon flow from central metabolism to the l-Phe or l-Tyr biosynthetic pathways. These strategies include the expression of feedback insensitive mutant versions of enzymes from the aromatic pathways, as well as genetic modifications to central carbon metabolism to increase biosynthetic availability of precursors phosphoenolpyruvate and erythrose-4-phosphate. These efforts have been complemented with strain optimization for the utilization of raw material, including various simple carbon sources, as well as sugar polymers and sugar mixtures derived from plant biomass. A systems biology approach to production strains characterization has been limited so far and should yield important data for future strain improvement. PMID:26347861

Development of a PEGylated-Based Platform for Efficient Delivery of Dietary Antioxidants Across the Blood-Brain Barrier.

PubMed

Fernandes, Carlos; Pinto, Miguel; Martins, Cláudia; Gomes, Maria João; Sarmento, Bruno; Oliveira, Paulo J; Remião, Fernando; Borges, Fernanda

2018-05-16

The uptake and transport of dietary antioxidants remains the most important setback for their application in therapy. To overcome the limitations, a PEGylated-based platform was developed to improve the delivery properties of two dietary hydroxycinnamic (HCA) antioxidants-caffeic and ferulic acids. The antioxidant properties of the new polymer-antioxidant conjugates (PEGAntiOxs), prepared by linking poly(ethylene glycol) (PEG) to the cinnamic acids by a one-step Knovenagel condensation reaction, were evaluated. PEGAntiOxs present a higher lipophilicity than the parent compounds (caffeic and ferulic acids) and similar, or higher, antioxidant properties. PEGAntiOxs were not cytotoxic at the tested concentrations in SH-SY5Y, Caco-2, and hCMEC/D3 cells. By contrast, cytotoxic effects in hCMEC/D3 and SH-SY5Y cells were observed, at 50 and 100 μM, for caffeic and ferulic acids. PEGAntiOxs operate as antioxidants against several oxidative stress-cellular inducers in a neuronal cell-based model, and were able to inhibit glycoprotein-P in Caco-2 cells. PEGAntiOxs can cross hCMEC/D3 monolayer cells, a model of the blood-brain barrier (BBB) endothelial membrane. In summary, PEGAntiOxs are valid antioxidant prototypes that can uphold the antioxidant properties of HCAs, reduce their cytotoxicity, and improve their BBB permeability. PEGAntiOxs can be used in the near future as drug candidates to prevent or slow oxidative stress associated with neurodegenerative diseases.

Trends in antimicrobial resistance and empiric antibiotic therapy of bloodstream infections at a general hospital in Mid-Norway: a prospective observational study.

PubMed

Mehl, Arne; Åsvold, Bjørn Olav; Kümmel, Angela; Lydersen, Stian; Paulsen, Julie; Haugan, Ingvild; Solligård, Erik; Damås, Jan Kristian; Harthug, Stig; Edna, Tom-Harald

2017-02-02

The occurrence of bloodstream infection (BSI) and antimicrobial resistance have been increasing in many countries. We studied trends in antimicrobial resistance and empiric antibiotic therapy at a medium-sized general hospital in Mid-Norway. Between 2002 and 2013, 1995 prospectively recorded episodes of BSI in 1719 patients aged 16-99 years were included. We analyzed the antimicrobial non-susceptibility according to place of acquisition, site of infection, microbe group, and time period. There were 934 community-acquired (CA), 787 health care-associated (HCA) and 274 hospital-acquired (HA) BSIs. The urinary tract was the most common site of infection. Escherichia coli was the most frequently isolated infective agent in all three places of acquisition. Second in frequency was Streptococcus pneumoniae in CA and Staphylococcus aureus in both HCA and HA. Of the BSI microbes, 3.5% were non-susceptible to the antimicrobial regimen recommended by the National Professional Guidelines for Use of Antibiotics in Hospitals, consisting of penicillin, gentamicin, and metronidazole (PGM). In contrast, 17.8% of the BSI microbes were non-susceptible to cefotaxime and 27.8% were non-susceptible to ceftazidime. Antimicrobial non-susceptibility differed by place of acquisition. For the PGM regimen, the proportions of non-susceptibility were 1.4% in CA, 4.8% in HCA, and 6.9% in HA-BSI (p < 0.001), and increasing proportions of non-susceptibility over time were observed in HA-BSI, 2.2% in 2002-2005, 6.2% in 2006-2009, and 11.7% in 2010-2013 (p = 0.026), mainly caused by inherently resistant microbes. We also observed increasing numbers of bacteria with acquired resistance, particularly E. coli producing ESBL or possessing gentamicin resistance, and these occurred predominantly in CA- and HCA-BSI. Generally, antimicrobial resistance was a far smaller problem in our BSI cohort than is reported from countries outside Scandinavia. In our cohort, appropriate empiric antibiotic therapy could be achieved to a larger extent by replacing second- and third-generation cephalosporins with penicillin-gentamicin or piperacillin-tazobactam.

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

48 CFR 2448.104-3 - Sharing collateral savings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DEVELOPMENT CONTRACT MANAGEMENT VALUE ENGINEERING 2448.104-3 Sharing collateral savings. (a) The authority of the HCA to determine that the cost of calculating and tracking collateral savings will exceed the...

48 CFR 2825.302 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ACQUISITION Balance of Payments Program 2825.302 Policy. The HCA, or designee at a level not lower than the... evaluation of domestic and foreign offers under the Balance of Payments Program. All determinations made...

48 CFR 2825.302 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ACQUISITION Balance of Payments Program 2825.302 Policy. The HCA, or designee at a level not lower than the... evaluation of domestic and foreign offers under the Balance of Payments Program. All determinations made...

Anion inhibition profiles of the γ-carbonic anhydrase from the pathogenic bacterium Burkholderia pseudomallei responsible of melioidosis and highly drug resistant to common antibiotics.

PubMed

Del Prete, Sonia; Vullo, Daniela; Di Fonzo, Pietro; Osman, Sameh M; AlOthman, Zeid; Supuran, Claudiu T; Capasso, Clemente

2017-01-15

Burkholderia pseudomallei is a Gram-negative saprophytic bacterium responsible of melioidosis, an endemic disease of tropical and sub-tropical regions of the world. A recombinant γ-CA (BpsγCA) identified in the genome of this bacterium was cloned and purified. Its catalytic activity and anion inhibition profiles were investigated. The enzyme was an efficient catalyst for the CO 2 hydration showing a k cat of 5.3×10 5 s -1 and k cat /K m of 2.5×10 7 M -1 ×s -1 . The best BpsγCA inhibitors were sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid, which showed K I in the range of 49-83μM (these inhibitors showed millimolar inhibition constant against hCA II), followed by diethyldithiocarbamate, selenate, tellurate, perrhenate, selenocyanate, trithiocarbonate, tetraborato, pyrophosphate, stannate, carbonate, bicarbonate, azide, cyanide, thiocyanate and cyanate with K I s in the range of 0.55-9.1mM. In our laboratories, work is in progress to resolve the X-ray crystal structures of BpsγCA, which may allow the development of small molecule inhibitors with desired properties for targeting and inhibiting specifically the bacterial over the human CAs, considering the fact that B. pseudomallei is involved in a serious bacterial disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

48 CFR 401.301 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contracting activity (HCA) is authorized to issue or authorize the issuance of, at any organizational level... Health Inspection Service. 4M [Reserved] 4N Departmental Administration. 4O-4P [Reserved] 4R Office of...

48 CFR 401.301 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contracting activity (HCA) is authorized to issue or authorize the issuance of, at any organizational level... Health Inspection Service. 4M [Reserved] 4N Departmental Administration. 4O-4P [Reserved] 4R Office of...

48 CFR 2448.102 - Policies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MANAGEMENT VALUE ENGINEERING 2448.102 Policies. (a) The authority of the agency head to exempt contracts from including Value Engineering (VE) procedures and processes under 48 CFR 48.102(a) is delegated to the HCA for...

48 CFR 2448.102 - Policies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... MANAGEMENT VALUE ENGINEERING 2448.102 Policies. (a) The authority of the agency head to exempt contracts from including Value Engineering (VE) procedures and processes under 48 CFR 48.102(a) is delegated to the HCA for...

48 CFR 2822.406-8 - Investigations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the report of violations to the HCA or designee at a level not lower than the BPC. That official shall... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Labor Standards for Contracts Involving Construction 2822...

Health care administration in the year 2000: practitioners' views of future issues and job requirements.

PubMed

Hudak, R P; Brooke, P P; Finstuen, K; Riley, P

1993-01-01

This research identifies the most important domains in health care administration (HCA) from now to the year 2000 and differentiates job skill, knowledge, and ability requirements necessary for successful management. Fellows of the American College of Healthcare Executives from about half of the United States responded to two iterations of a Delphi mail inquiry. Fellows identified 102 issues that were content-analyzed into nine domains by an HCA expert panel. Domains, in order of ranked importance, were cost/finance, leadership, professional staff interactions, health care delivery concepts, accessibility, ethics, quality/risk management, technology, and marketing. In the second Delphi iteration, Fellows reviewed domain results and rated job requirements on required job importance. Results indicated that while a business orientation is needed for organizational survival, an equal emphasis on person-oriented skills, knowledge, and abilities is required.

Inhibitory effects of isatin Mannich bases on carbonic anhydrases, acetylcholinesterase, and butyrylcholinesterase.

PubMed

Ozgun, Dilan Ozmen; Yamali, Cem; Gul, Halise Inci; Taslimi, Parham; Gulcin, Ilhami; Yanik, Telat; Supuran, Claudiu T

2016-12-01

The effects of isatin Mannich bases incorporating (1-[piperidin-1-yl (P1)/morpholin-4-yl (P2)/N-methylpiperazin-1-yl (P3)]methyl)-1H-indole-2,3-dione) moieties against human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes hCA I and hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes were evaluated. P1-P3 demonstrated impressive inhibition profiles against AChE and BChE and also inhibited both CAs at nanomolar level. These inhibitory effects were more powerful in all cases than the reference compounds used for all these enzymes. This study suggests that isatin Mannich bases P1-P3 are good candidate compounds especially for the development of new cholinesterase inhibitors since they were 2.2-5.9 times better inhibitors than clinically used drug Tacrine.

Geographical classification of Epimedium based on HPLC fingerprint analysis combined with multi-ingredients quantitative analysis.

PubMed

Xu, Ning; Zhou, Guofu; Li, Xiaojuan; Lu, Heng; Meng, Fanyun; Zhai, Huaqiang

2017-05-01

A reliable and comprehensive method for identifying the origin and assessing the quality of Epimedium has been developed. The method is based on analysis of HPLC fingerprints, combined with similarity analysis, hierarchical cluster analysis (HCA), principal component analysis (PCA) and multi-ingredient quantitative analysis. Nineteen batches of Epimedium, collected from different areas in the western regions of China, were used to establish the fingerprints and 18 peaks were selected for the analysis. Similarity analysis, HCA and PCA all classified the 19 areas into three groups. Simultaneous quantification of the five major bioactive ingredients in the Epimedium samples was also carried out to confirm the consistency of the quality tests. These methods were successfully used to identify the geographical origin of the Epimedium samples and to evaluate their quality. Copyright © 2016 John Wiley & Sons, Ltd.

Origins and Structural Properties of Novel and De Novo Protein Domains During Insect Evolution.

PubMed

Klasberg, Steffen; Bitard-Feildel, Tristan; Callebaut, Isabelle; Bornberg-Bauer, Erich

2018-05-26

Over long time scales, protein evolution is characterised by modular rearrangements of protein domains. Such rearrangements are mainly caused by gene duplication, fusion and terminal losses. To better understand domain emergence mechanisms we investigated 32 insect genomes covering a speciation gradient ranging from ~ 2 to ~ 390 my. We use established domain models and foldable domains delineated by Hydrophobic-Cluster-Analysis (HCA), which does not require homologous sequences, to also identify domains which have likely arisen de novo, i.e. from previously non-coding DNA. Our results indicate that most novel domains emerge terminally as they originate from ORF extensions while fewer arise in middle arrangements, resulting from exonisation of intronic or intergenic regions. Many novel domains rapidly migrate between terminal or middle positions and single- and multi-domain arrangements. Young domains, such as most HCA defined domains, are under strong selection pressure as they show signals of purifying selection. De novo domains, linked to ancient domains or defined by HCA, have higher degrees of intrinsic disorder and disorder-to-order transition upon binding than ancient domains. However, the corresponding DNA sequences of the novel domains of denovo origins could only rarely be found in sister genomes. We conclude that novel domains are often recruited by other proteins and undergo important structural modifications shortly after their emergence, but evolve too fast to be characterised by cross-species comparisons alone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Extra virgin (EV) and ordinary (ON) olive oils: distinction and detection of adulteration (EV with ON) as determined by direct infusion electrospray ionization mass spectrometry and chemometric approaches.

PubMed

Alves, Júnia de O; Neto, Waldomiro B; Mitsutake, Hery; Alves, Paulo S P; Augusti, Rodinei

2010-07-15

Extra virgin (EV), the finest and most expensive among all the olive oil grades, is often adulterated by the cheapest and lowest quality ordinary (ON) olive oil. A new methodology is described herein that provides a simple, rapid, and accurate way not only to detect such type of adulteration, but also to distinguish between these olive oil grades (EV and ON). This approach is based on the application of direct infusion electrospray ionization mass spectrometry in the positive ion mode, ESI(+)-MS, followed by the treatment of the MS data via exploratory statistical approaches, PCA (principal component analysis) and HCA (hierarchical clustering analysis). Ten distinct brands of each EV and ON olive oil, acquired at local stores, were analyzed by ESI(+)-MS and the results from HCA and PCA clearly indicated the formation of two distinct groups related to these two categories. For the adulteration study, one brand of each olive oil grade (EV and ON) was selected. The counterfeit samples (a total of 20) were then prepared by adding assorted proportions, from 1 to 20% w/w, with increments of 1% w/w, of the ON to the EV olive oil. The PCA and HCA methodologies, applied to the ESI(+)-MS data from the counterfeit (20) and authentic (10) EV samples, were able to readily detect adulteration, even at levels as low as 1% w/w. Copyright 2010 John Wiley & Sons, Ltd.

Effects of strain differences and vehicles on results of local lymph node assays.

PubMed

Anzai, Takayuki; Ullmann, Ludwig G; Hayashi, Daisuke; Satoh, Tetsuo; Kumazawa, Takeshi; Sato, Keizo

2010-01-01

The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

Bioactivity and cytotoxicity of glass and glass-ceramics based on the 3CaO·P₂O₅--SiO₂--MgO system.

PubMed

Daguano, Juliana K M F; Rogero, Sizue O; Crovace, Murilo C; Peitl, Oscar; Strecker, Kurt; Dos Santos, Claudinei

2013-09-01

The mechanical strength of bioactive glasses can be improved by controlled crystallization, turning its use as bulk bone implants viable. However, crystallization may affect the bioactivity of the material. The aim of this study was to develop glass-ceramics of the nominal composition (wt%) 52.75(3CaO·P₂O₅)-30SiO₂-17.25MgO, with different crystallized fractions and to evaluate their in vitro cytotoxicity and bioactivity. Specimens were heat-treated at 700, 775 and 975 °C, for 4 h. The major crystalline phase identified was whitlockite, an Mg-substituted tricalcium phosphate. The evaluation of the cytotoxicity was carried out by the neutral red uptake methodology. Ionic exchanges with the simulated body fluid SBF-K9 acellular solution during the in vitro bioactivity tests highlight the differences in terms of chemical reactivity between the glass and the glass-ceramics. The effect of crystallinity on the rates of hydroxycarbonate apatite (HCA) formation was followed by Fourier transformed infrared spectroscopy. Although all glass-ceramics can be considered bioactive, the glass-ceramic heat-treated at 775 °C (V775-4) presented the most interesting result, because the onset for HCA formation is at about 24 h and after 7 days the HCA layer dominates completely the spectrum. This occurs probably due to the presence of the whitlockite phase (3(Ca,Mg)O·P₂O₅). All samples were considered not cytotoxic.

Development and Validation of A Scheduled Shifts Staffing (ASSiST) Measure of Unit-Level Staffing in Nursing Homes.

PubMed

Cummings, Greta G; Doupe, Malcolm; Ginsburg, Liane; McGregor, Margaret J; Norton, Peter G; Estabrooks, Carole A

2017-06-01

To (a) describe A Scheduled Shifts Staffing measure (ASSiST) to derive care aide worked hours per resident day (HCA WHRD) at facility and unit levels in nursing homes, (b) report reliability through comparisons to administrative staffing data; (c) report validity by examining associations between HCA WHRD, staff outcomes (job satisfaction, emotional exhaustion), and resident quality indicators (QIs) (e.g. falls, delirium, stage 2+ pressure ulcers), and (d) explore intrafacility variation in staffing intensity levels related to unit-level variation in resident and staff outcomes. We used data from 40 care units in 12 Canadian nursing homes between 2007 and 2012. Descriptive statistics and tests of association and difference described relationships of two measures of staffing with resident and staff outcomes. Annualized rates of HCA WHRD from both data sources compared well at the facility level (Pearson Product Correlation; R = 0.847, p < .001), and were correlated similarly to staff work life and many QIs. Using ASSiST data, we show that staffing levels can vary by up to 40% at the unit-level within nursing homes. ASSiST is easy to collect, more timely to retrieve than administrative data, has good criterion and construct validity, and reflects intrafacility variation in health care aide staffing levels. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Leadership training in health care action teams: a systematic review.

PubMed

Rosenman, Elizabeth D; Shandro, Jamie R; Ilgen, Jonathan S; Harper, Amy L; Fernandez, Rosemarie

2014-09-01

To identify and describe the design, implementation, and evidence of effectiveness of leadership training interventions for health care action (HCA) teams, defined as interdisciplinary teams whose members coordinate their actions in time-pressured, unstable situations. The authors conducted a systematic search of the PubMed/MEDLINE, CINAHL, ERIC, EMBASE, PsycINFO, and Web of Science databases, key journals, and review articles published through March 2012. They identified peer-reviewed English-language articles describing leadership training interventions targeting HCA teams, at all levels of training and across all health care professions. Reviewers, working in duplicate, abstracted training characteristics and outcome data. Methodological quality was evaluated using the Medical Education Research Study Quality Instrument (MERSQI). Of the 52 included studies, 5 (10%) focused primarily on leadership training, whereas the remainder included leadership training as part of a larger teamwork curriculum. Few studies reported using a team leadership model (2; 4%) or a theoretical framework (9; 17%) to support their curricular design. Only 15 studies (29%) specified the leadership behaviors targeted by training. Forty-five studies (87%) reported an assessment component; of those, 31 (69%) provided objective outcome measures including assessment of knowledge or skills (21; 47%), behavior change (8; 18%), and patient- or system-level metrics (8; 18%). The mean MERSQI score was 11.4 (SD 2.9). Leadership training targeting HCA teams has become more prevalent. Determining best practices in leadership training is confounded by variability in leadership definitions, absence of supporting frameworks, and a paucity of robust assessments.

Mechanism of thrombin-induced vasodilation in human coronary arterioles.

PubMed

Bosnjak, John J; Terata, Ken; Miura, Hiroto; Sato, Atsushi; Nicolosi, Alfred C; McDonald, Monica; Manthei, Sara A; Saito, Takashi; Hatoum, Ossama A; Gutterman, David D

2003-04-01

Thrombin (Thromb), activated as part of the clotting cascade, dilates conduit arteries through an endothelial pertussis toxin (PTX)-sensitive G-protein receptor and releases nitric oxide (NO). Thromb also acts on downstream microvessels. Therefore, we examined whether Thromb dilates human coronary arterioles (HCA). HCA from right atrial appendages were constricted by 30-50% with endothelin-1. Dilation to Thromb (10(-4)-1 U/ml) was assessed before and after inhibitors with videomicroscopy. There was no tachyphylaxis to Thromb dilation (maximum dilation = 87.0%, ED(50) = 1.49 x 10(-2)). Dilation to Thromb was abolished with either hirudin or denudation but was not affected by PTX. Neither N(omega)-nitro-l-arginine methyl ester (n = 7), indomethacin (n = 9), (1)H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (n = 6), tetraethylammonium chloride (n = 5), nor iberiotoxin (n = 4) reduced dilation to Thromb. However, KCl (maximum dilation = 89 +/- 5 vs. 20 +/- 10%; P < 0.05; n = 7), tetrabutylammonium chloride (maximum dilation = 79 +/- 7 vs. 21 +/- 4%; P < 0.05; n = 5), and charybdotoxin (maximum dilation = 89 +/- 4 vs. 10 +/- 2%; P < 0.05; n = 4) attenuated dilation to Thromb. In contrast to animal models, Thromb-induced dilation in human arterioles is independent of G(i)-protein activation and NO release. However, Thromb dilation is endothelium dependent, is maintained on consecutive applications, and involves activation of K(+) channels. We speculate that an endothelium-derived hyperpolarizing factor contributes to Thromb-induced dilation in HCA.

Healthcare assistant fined for accessing medical records of friends and colleagues.

PubMed

2017-08-23

NHS staff are being reminded of the potentially serious consequences of prying into patients' records without a valid reason after a healthcare assistant (HCA) secretly accessed medical information on 29 people.

Chemoprevention of heterocyclic amine-induced carcinogenesis by phenolic compounds in rats.

PubMed

Hirose, M; Takahashi, S; Ogawa, K; Futakuchi, M; Shirai, T; Shibutani, M; Uneyama, C; Toyoda, K; Iwata, H

1999-09-01

Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), BHA, BHT, tert-butylhydroquinone (TBHQ) and propyl gallate, each at a dose of 0.25%, and troglitazone at doses 0.5 and 0.1%, potently inhibited development of glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone values. Of these antioxidants, HTHQ showed the greatest activity. Green tea catechins tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistin all exerted significant enhancing effects. HTHQ also inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon carcinogenesis in a two stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. Immunohistochemically detected PhIP-DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. Methoxyresorfin O-demethylase activity in rat liver microsomes in vitro was clearly inhibited by the addition of HTHQ, BHA, BHT, TBHQ or propyl gallate, with particularly strong inhibition being observed in HTHQ. However, the CYP1A2 level in rat liver increased after oral treatment with HTHQ for 2 weeks. These results indicate that synthetic antioxidants, HTHQ in particular, is a very strong chemopreventor of HCA-induced carcinogenesis. It is suggested that depression of metabolic activation rather than antioxidant activity is responsible for the observed effect. However, other mechanisms, including the effects on phase II enzymes cannot be ruled out.

Expression of kyphosis in young pigs is induced by a reduction of supplemental vitamin D in maternal diets and vitamin D, Ca, and P concentrations in nursery diets.

PubMed

Rortvedt, L A; Crenshaw, T D

2012-12-01

Kyphosis is an idiopathic disease characterized by abnormal, outward spinal curvature. A spontaneous outbreak and subsidence of kyphosis over a 4-mo period in the University of Wisconsin Swine Research and Teaching Center herd coincided with an accidental omission of vitamin D(3) in 1 of 2 premixes used in sow diets. This controlled experiment was conducted to determine whether vitamin D deletion from premixes used in sow diets would induce kyphosis in their offspring. Crossbred (Landrace × Large White), multiparous sows (n = 8) were fed corn-soybean meal diets supplemented with either 325 IU vitamin D(3)/kg (+D) or 45 IU vitamin D(3)/kg (-D) diet from breeding through lactation. The vitamin D concentrations duplicated formulations of diets fed during the earlier spontaneous outbreak. At weaning (approximately 4 wk), pigs were fed diets devoid of supplemental vitamin D and formulated to supply either 120% of the Ca and P requirements (HCaP) or 80% of the Ca and P requirements (LCaP) until wk 9. At wk 9, all pigs were fed the HCaP diet until wk 13. No evidence of kyphosis was observed in pigs at weaning. Pigs produced by -D sows and fed LCaP diets exhibited a 17% incidence (4/23 pigs) of kyphosis at wk 9. At wk 13, the incidence of kyphosis had increased to 32% (6/19 pigs). Unexpectedly at wk 13, pigs produced by +D sows and fed LCaP diets exhibited a 26% incidence (5/19 pigs) of kyphosis. None of the pigs fed HCaP diets from wk 4 to 13 displayed kyphosis, regardless of maternal diets. Evidence of kyphosis was detected at a younger age if pigs were produced by sows fed -D diets. Whole body and femur bone mineral content determined with dual energy X-ray absorptiometry were reduced (P < 0.05) in pigs fed LCaP vs. HCaP diets, but pigs produced by -D sows were more severely affected. Femur bending moments were reduced (P < 0.05) at wk 9 and 13 in pigs fed LCaP vs. HCaP diets. At wk 13, pigs produced by -D sows and fed LCaP diets had reduced (P < 0.05) bone mineral density and femur yield bending moment compared with pigs from +D sows fed LCaP diets. In conclusion, the 20 to 30% incidence of kyphosis induced by altering vitamin D, Ca, and P concentrations in maternal and nursery diets mimics the incidence observed in spontaneous outbreaks in afflicted herds. A reproducible vitamin D-induced kyphosis in young pigs offers a suitable model to study skeletal tissue characteristics, fetal skeletal tissue development, and potential treatments for pigs and human patients afflicted by this disease.

48 CFR 2811.103 - Market acceptance.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... Pursuant to FAR 11.103, the HCA or designee at a level not lower than the BPC has the authority to require offerors to demonstrate that the items offered meet the criteria set forth in FAR 11.103(a). ...

Home care and technology: a case study.

PubMed

Stroulia, Eleni; Nikolaidisa, Ioanis; Liua, Lili; King, Sharla; Lessard, Lysanne

2012-01-01

Health care aides (HCAs) are the backbone of the home care system and provide a range of services to people who, for various reasons related to chronic conditions and aging, are not able to take care of themselves independently. The demand for HCA services will increase and the current HCA supply will likely not keep up with this increasing demand without fundamental changes in the current environment. Information and communication technology (ICT) can address some of the workflow challenges HCAs face. In this project, we conducted an ethnographic study to document and analyse HCAs' workflows and team interactions. Based on our findings, we designed an ICT tool suite, integrating easily available existing and newly developed (by our team) technologies to address these issues. Finally, we simulated the deployment of our technologies, to assess the potential impact of these technological solutions on the workflow and productivity of HCAs, their healthcare teams and client care.

Deep hypothermic circulatory arrest

PubMed Central

Ziganshin, Bulat A.

2013-01-01

Effective cerebral protection remains the principle concern during aortic arch surgery. Hypothermic circulatory arrest (HCA) is entrenched as the primary neuroprotection mechanism since the 70s, as it slows injury-inducing pathways by limiting cerebral metabolism. However, increases in HCA duration has been associated with poorer neurological outcomes, necessitating the adjunctive use of antegrade (ACP) and retrograde cerebral perfusion (RCP). ACP has superseded RCP as the preferred perfusion strategy as it most closely mimic physiological perfusion, although there exists uncertainty regarding several technical details, such as unilateral versus bilateral perfusion, flow rate and temperature, perfusion site, undue trauma to head vessels, and risks of embolization. Nevertheless, we believe that the convenience, simplicity and effectiveness of straight DHCA justifies its use in the majority of elective and emergency cases. The following perspective offers a historical and clinical comparison of the DHCA with other techniques of cerebral protection. PMID:23977599

Authentication of monofloral Yemeni Sidr honey using ultraviolet spectroscopy and chemometric analysis.

PubMed

Roshan, Abdul-Rahman A; Gad, Haidy A; El-Ahmady, Sherweit H; Khanbash, Mohamed S; Abou-Shoer, Mohamed I; Al-Azizi, Mohamed M

2013-08-14

This work describes a simple model developed for the authentication of monofloral Yemeni Sidr honey using UV spectroscopy together with chemometric techniques of hierarchical cluster analysis (HCA), principal component analysis (PCA), and soft independent modeling of class analogy (SIMCA). The model was constructed using 13 genuine Sidr honey samples and challenged with 25 honey samples of different botanical origins. HCA and PCA were successfully able to present a preliminary clustering pattern to segregate the genuine Sidr samples from the lower priced local polyfloral and non-Sidr samples. The SIMCA model presented a clear demarcation of the samples and was used to identify genuine Sidr honey samples as well as detect admixture with lower priced polyfloral honey by detection limits >10%. The constructed model presents a simple and efficient method of analysis and may serve as a basis for the authentication of other honey types worldwide.

Heavy metal ion inhibition studies of human, sheep and fish α-carbonic anhydrases.

PubMed

Demirdağ, Ramazan; Yerlikaya, Emrah; Şentürk, Murat; Küfrevioğlu, Ö İrfan; Supuran, Claudiu T

2013-04-01

Carbonic anhydrases (CAs, EC 4.2.1.1) were purified from sheep kidney (sCA IV), from the liver of the teleost fish Dicentrarchus labrax (dCA) and from human erythrocytes (hCA I and hCA II). The purification procedure consisted of a single step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The kinetic parameters of these enzymes were determined for their esterase activity with 4-nitrophenyl acetate as substrate. The following metal ions, Pb(2+), Co(2+), Hg(2+), Cd(2+), Zn(2+), Se(2+), Cu(2+), Al(3+) and Mn(3+) showed inhibitory effects on these enzymes. The tested metal ions inhibited these CAs competitively in the low milimolar/submillimolar range. The susceptibility to various cations inhibitors differs significantly between these vertebrate α-CAs and is probably due to their binding to His64 or the histidine cluster.

The respective roles of polar/nonpolar binary patterns and amino acid composition in protein regular secondary structures explored exhaustively using hydrophobic cluster analysis.

PubMed

Rebehmed, Joseph; Quintus, Flavien; Mornon, Jean-Paul; Callebaut, Isabelle

2016-05-01

Several studies have highlighted the leading role of the sequence periodicity of polar and nonpolar amino acids (binary patterns) in the formation of regular secondary structures (RSS). However, these were based on the analysis of only a few simple cases, with no direct mean to correlate binary patterns with the limits of RSS. Here, HCA-derived hydrophobic clusters (HC) which are conditioned binary patterns whose positions fit well those of RSS, were considered. All the HC types, defined by unique binary patterns, which were commonly observed in three-dimensional (3D) structures of globular domains, were analyzed. The 180 HC types with preferences for either α-helices or β-strands distinctly contain basic binary units typical of these RSS. Therefore a general trend supporting the "binary pattern preference" assumption was observed. HC for which observed RSS are in disagreement with their expected behavior (discordant HC) were also examined. They were separated in HC types with moderate preferences for RSS, having "weak" binary patterns and versatile RSS and HC types with high preferences for RSS, having "strong" binary patterns and then displaying nonpolar amino acids at the protein surface. It was shown that in both cases, discordant HC could be distinguished from concordant ones by well-differentiated amino acid compositions. The obtained results could, thus, help to complement the currently available methods for the accurate prediction of secondary structures in proteins from the only information of a single amino acid sequence. This can be especially useful for characterizing orphan sequences and for assisting protein engineering and design. © 2016 Wiley Periodicals, Inc.

Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience.

PubMed

Grieser, Christian; Steffen, Ingo G; Kramme, Incken-Birthe; Bläker, Hendrik; Kilic, Ergin; Perez Fernandez, Carmen Maria; Seehofer, Daniel; Schott, Eckart; Hamm, Bernd; Denecke, Timm

2014-06-01

Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI. Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n=44; HCAs, n=71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n=53 patients (lesions: FNHs, n=37; HCAs, n=53); biopsy, n=15 (lesions: FNHs, n=7; HCAs, n=18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus. For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4)%and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89%and 90 %, respectively; P<0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %). For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination. EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.

Chemically induced disseminated pythiosis in BALB/c mice: A new experimental model for Pythium insidiosum infection.

PubMed

Tondolo, Juliana S M; Loreto, Érico S; Ledur, Pauline C; Jesus, Francielli P K; Silva, Taiara M; Kommers, Glaucia D; Alves, Sydney H; Santurio, Janio M

2017-01-01

Pythiosis is a severe and life-threatening disease that affects humans and various animal species. We report a model of vascular/disseminated pythiosis occurring after subcutaneous inoculation of 2 x 104 Pythium insidiosum zoospores/mL in immunocompromised BALB/c mice. For this model, we carried out two rounds of experiments. First, we evaluated two protocols of immunosuppression before inoculation: cyclophosphamide at 150 mg/kg (CYP group) and cyclophosphamide 200 mg/kg plus hydrocortisone acetate at 250 mg/kg (CYP+HCA group). It was not possible to obtain mortality in the CYP group; however, the combination of CYP+HCA altered disease outcomes, with mortality rates reaching 60%. Second, we used the CYP+HCA immunosuppression protocol to analyze the histological and immunological statuses triggered by disease. When we inoculated immunocompetent mice with P. insidiosum zoospores, self-healing occurred via increased levels of IL-2, IFN-γ and IL-17A, which are characteristic of the Th1/Th17 cytokine response. For infected and immunosuppressed mice, the cytokine profiles showed high levels of IL-10, IL-6 and TNF-α. Increased IL-10 values are related to fungal infection susceptibility and led us to speculate that infection may be established through suppression of the host immune response. In addition, histopathological evaluation of the kidneys and liver demonstrated the presence of hyphae and the cellular findings suggested an acute vascular inflammation that mimics vascular/disseminated pythiosis in humans. This is the first murine model for pythiosis that is useful both for understanding the pathogenesis of this disease and for evaluating new treatment approaches.

Calcium phosphate/chitosan composite coating: Effect of different concentrations of Mg2+ in the m-SBF on its bioactivity

NASA Astrophysics Data System (ADS)

Zhang, Jie; Dai, Changsong; Wei, Jie; Wen, Zhaohui; Zhang, Shujuan; Lin, Lemin

2013-09-01

The purpose of this study was to investigate the effect of different concentration of Mg2+ in a modified simulated body fluid (m-SBF) on the bioactivity of calcium phosphate/chitosan composite coating. Calcium phosphate/chitosan composite coating was prepared on graphite substrate via electrophoretic deposition (EPD) followed by conversion in a phosphate buffer solution (PBS). The obtained samples were soaked in the m-SBF containing different concentration of Mg2+ for different times. And then, the composite coatings were assessed using X-ray diffractometer (XRD), Fourier-transformed infrared spectroscopy (FTIR), Raman spectra, and scanning electron microscope (SEM) with an energy dispersive spectrometer (EDS). The soaking solution was evaluated by inductively coupled plasma optical emission spectrometer (ICP-OES) test. The analytical results showed that hydroxyapatite (HA) and bone-like apatite (HCA) grew on the surface of calcium phosphate/chitosan composite coating after incubation in different m-SBF. With Mg2+ concentration in m-SBF increased from 1× Mg to 10× Mg, HA in the composite coating first presented a dissolving process and then a precipitating one slowly, while HCA presented a growing trend, continuously. The increasing of Mg2+ concentration in the m-SBF inhibited the total growing process of HA and HCA as a whole. The structure of the composite coating changed from spherical into irregular morphology with the concentration of Mg2+ increasing from 1× Mg to 10× Mg. Over all, with the Mg2+ concentration increasing, the bioactivity of calcium phosphate/chitosan composite coating tended to decrease.

Principles of Automation for Patient Safety in Intensive Care: Learning From Aviation.

PubMed

Dominiczak, Jason; Khansa, Lara

2018-06-01

The transition away from written documentation and analog methods has opened up the possibility of leveraging data science and analytic techniques to improve health care. In the implementation of data science techniques and methodologies, high-acuity patients in the ICU can particularly benefit. The Principles of Automation for Patient Safety in Intensive Care (PASPIC) framework draws on Billings's principles of human-centered aviation (HCA) automation and helps in identifying the advantages, pitfalls, and unintended consequences of automation in health care. Billings's HCA principles are based on the premise that human operators must remain "in command," so that they are continuously informed and actively involved in all aspects of system operations. In addition, automated systems need to be predictable, simple to train, to learn, and to operate, and must be able to monitor the human operators, and every intelligent system element must know the intent of other intelligent system elements. In applying Billings's HCA principles to the ICU setting, PAPSIC has three key characteristics: (1) integration and better interoperability, (2) multidimensional analysis, and (3) enhanced situation awareness. PAPSIC suggests that health care professionals reduce overreliance on automation and implement "cooperative automation" and that vendors reduce mode errors and embrace interoperability. Much can be learned from the aviation industry in automating the ICU. Because it combines "smart" technology with the necessary controls to withstand unintended consequences, PAPSIC could help ensure more informed decision making in the ICU and better patient care. Copyright © 2018 The Joint Commission. Published by Elsevier Inc. All rights reserved.

Relationships and redundancies of selected hemodynamic and structural parameters for characterizing virtual treatment of cerebral aneurysms with flow diverter devices.

PubMed

Karmonik, C; Anderson, J R; Beilner, J; Ge, J J; Partovi, S; Klucznik, R P; Diaz, O; Zhang, Y J; Britz, G W; Grossman, R G; Lv, N; Huang, Q

2016-07-26

To quantify the relationship and to demonstrate redundancies between hemodynamic and structural parameters before and after virtual treatment with a flow diverter device (FDD) in cerebral aneurysms. Steady computational fluid dynamics (CFD) simulations were performed for 10 cerebral aneurysms where FDD treatment with the SILK device was simulated by virtually reducing the porosity at the aneurysm ostium. Velocity and pressure values proximal and distal to and at the aneurysm ostium as well as inside the aneurysm were quantified. In addition, dome-to-neck ratios and size ratios were determined. Multiple correlation analysis (MCA) and hierarchical cluster analysis (HCA) were conducted to demonstrate dependencies between both structural and hemodynamic parameters. Velocities in the aneurysm were reduced by 0.14m/s on average and correlated significantly (p<0.05) with velocity values in the parent artery (average correlation coefficient: 0.70). Pressure changes in the aneurysm correlated significantly with pressure values in the parent artery and aneurysm (average correlation coefficient: 0.87). MCA found statistically significant correlations between velocity values and between pressure values, respectively. HCA sorted velocity parameters, pressure parameters and structural parameters into different hierarchical clusters. HCA of aneurysms based on the parameter values yielded similar results by either including all (n=22) or only non-redundant parameters (n=2, 3 and 4). Hemodynamic and structural parameters before and after virtual FDD treatment show strong inter-correlations. Redundancy of parameters was demonstrated with hierarchical cluster analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

PubMed

Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

2014-11-01

A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of the High-Performance Liquid Chromatography Fingerprints and Quantitative Analysis of Multicomponents by Single Marker of Products of Fermented Cordyceps sinensis

PubMed Central

Guan, Yong-mei; Jin, Chen; Zhu, Wei-feng; Yang, Ming

2018-01-01

Fermented Cordyceps sinensis, the succedaneum of Cordyceps sinensis which is extracted and separated from Cordyceps sinensis by artificial fermentation, is commonly used in eastern Asia in clinical treatments due to its health benefit. In this paper, a new strategy for differentiating and comprehensively evaluating the quality of products of fermented Cordyceps sinensis has been established, based on high-performance liquid chromatography (HPLC) fingerprint analysis combined with similar analysis (SA), hierarchical cluster analysis (HCA), and the quantitative analysis of multicomponents by single marker (QAMS). Ten common peaks were collected and analysed using SA, HCA, and QAMS. These methods indicated that 30 fermented Cordyceps sinensis samples could be categorized into two groups by HCA. Five peaks were identified as uracil, uridine, adenine, guanosine, and adenosine, and according to the results from the diode array detector, which can be used to confirm peak purity, the purities of these compounds were greater than 990. Adenosine was chosen as the internal reference substance. The relative correction factors (RCF) between adenosine and the other four nucleosides were calculated and investigated using the QAMS method. Meanwhile, the accuracy of the QAMS method was confirmed by comparing the results of that method with those of an external standard method with cosines of the angles between the groups. No significant difference between the two methods was observed. In conclusion, the method established herein was efficient, successful in identifying the products of fermented Cordyceps sinensis, and scientifically valid to be applicable in the systematic quality control of fermented Cordyceps sinensis products. PMID:29850373

Analysis of the High-Performance Liquid Chromatography Fingerprints and Quantitative Analysis of Multicomponents by Single Marker of Products of Fermented Cordyceps sinensis.

PubMed

Chen, Li-Hua; Wu, Yao; Guan, Yong-Mei; Jin, Chen; Zhu, Wei-Feng; Yang, Ming

2018-01-01

Fermented Cordyceps sinensis , the succedaneum of Cordyceps sinensis which is extracted and separated from Cordyceps sinensis by artificial fermentation, is commonly used in eastern Asia in clinical treatments due to its health benefit. In this paper, a new strategy for differentiating and comprehensively evaluating the quality of products of fermented Cordyceps sinensis has been established, based on high-performance liquid chromatography (HPLC) fingerprint analysis combined with similar analysis (SA), hierarchical cluster analysis (HCA), and the quantitative analysis of multicomponents by single marker (QAMS). Ten common peaks were collected and analysed using SA, HCA, and QAMS. These methods indicated that 30 fermented Cordyceps sinensis samples could be categorized into two groups by HCA. Five peaks were identified as uracil, uridine, adenine, guanosine, and adenosine, and according to the results from the diode array detector, which can be used to confirm peak purity, the purities of these compounds were greater than 990. Adenosine was chosen as the internal reference substance. The relative correction factors (RCF) between adenosine and the other four nucleosides were calculated and investigated using the QAMS method. Meanwhile, the accuracy of the QAMS method was confirmed by comparing the results of that method with those of an external standard method with cosines of the angles between the groups. No significant difference between the two methods was observed. In conclusion, the method established herein was efficient, successful in identifying the products of fermented Cordyceps sinensis , and scientifically valid to be applicable in the systematic quality control of fermented Cordyceps sinensis products.

Li Storage of Calcium Niobates for Lithium Ion Batteries.

PubMed

Yim, Haena; Yu, Seung-Ho; Yoo, So Yeon; Sung, Yung-Eun; Choi, Ji-Won

2015-10-01

New types of niobates negative electrode were studied for using in lithium-ion batteries in order to alternate metallic lithium anodes. The potassium intercalated compound KCa2Nb3O10 and proton intercalated compound HCa2Nb3O10 were studied, and the electrochemical results showed a reversible cyclic voltammetry profile with acceptable discharge capacity. The as-prepared KCa2Nb3O10 negative electrode had a low discharge capacity caused by high overpotential, but the reversible intercalation and deintercalation reaction of lithium ions was activated after exchanging H+ ions for intercalated K+ ions. The initial discharge capacity of HCa2Nb3O10 was 54.2 mAh/g with 92.1% of coulombic efficiency, compared with 10.4 mAh/g with 70.2% of coulombic efficiency for KCa2Nb3O10 at 1 C rate. The improved electrochemical performance of the HCa2Nb3O10 was related to the lower bonding energy between proton cation and perovskite layer, which facilitate Li+ ions intercalating into the cation site, unlike potassium cation and perovskite layer. Also, this negative material can be easily exfoliated to Ca2Nb3O10 layer by using cation exchange process. Then, obtained two-dimensional nanosheets layer, which recently expected to be an advanced electrode material because of its flexibility, chemical stable, and thin film fabricable, can allow Li+ ions to diffuse between the each perovskite layer. Therefore, this new type layered perovskite niobates can be used not only bulk-type lithium ion batteries but also thin film batteries as a negative material.

Digitization of Electrocardiogram From Telemetry Prior to In-hospital Cardiac Arrest: A Pilot Study.

PubMed

Attin, Mina; Wang, Lu; Soroushmehr, S M Reza; Lin, Chii-Dean; Lemus, Hector; Spadafore, Maxwell; Najarian, Kayvan

2016-03-01

Analyzing telemetry electrocardiogram (ECG) data over an extended period is often time-consuming because digital records are not widely available at hospitals. Investigating trends and patterns in the ECG data could lead to establishing predictors that would shorten response time to in-hospital cardiac arrest (I-HCA). This study was conducted to validate a novel method of digitizing paper ECG tracings from telemetry systems in order to facilitate the use of heart rate as a diagnostic feature prior to I-HCA. This multicenter study used telemetry to investigate full-disclosure ECG papers of 44 cardiovascular patients obtained within 1 hr of I-HCA with initial rhythms of pulseless electrical activity and asystole. Digital ECGs were available for seven of these patients. An algorithm to digitize the full-disclosure ECG papers was developed using the shortest path method. The heart rate was measured manually (averaging R-R intervals) for ECG papers and automatically for digitized and digital ECGs. Significant correlations were found between manual and automated measurements of digitized ECGs (p < .001) and between digitized and digital ECGs (p < .001). Bland-Altman methods showed bias = .001 s, SD = .0276 s, lower and upper 95% limits of agreement for digitized and digital ECGs = .055 and -.053 s, and percentage error = 0.22%. Root mean square (rms), percentage rms difference, and signal to noise ratio values were in acceptable ranges. The digitization method was validated. Digitized ECG provides an efficient and accurate way of measuring heart rate over an extended period of time. © The Author(s) 2015.

48 CFR 2936.516 - Quality surveys.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Quality surveys. 2936.516... REQUIREMENTS CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 2936.516 Quality surveys. The HCA... original and final surveys as prescribed in FAR 36.516. ...

48 CFR 2936.516 - Quality surveys.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Quality surveys. 2936.516... REQUIREMENTS CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 2936.516 Quality surveys. The HCA... original and final surveys as prescribed in FAR 36.516. ...

48 CFR 2936.516 - Quality surveys.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Quality surveys. 2936.516... REQUIREMENTS CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 2936.516 Quality surveys. The HCA... original and final surveys as prescribed in FAR 36.516. ...

48 CFR 2936.516 - Quality surveys.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Quality surveys. 2936.516... REQUIREMENTS CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 2936.516 Quality surveys. The HCA... original and final surveys as prescribed in FAR 36.516. ...

48 CFR 2936.516 - Quality surveys.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Quality surveys. 2936.516... REQUIREMENTS CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 2936.516 Quality surveys. The HCA... original and final surveys as prescribed in FAR 36.516. ...

48 CFR 2912.302 - Tailoring of provisions and clauses for the acquisition of commercial items.

Code of Federal Regulations, 2010 CFR

2010-10-01

... tailor terms inconsistent with customary commercial practice must be documented in a written justification by the contracting officer, and may be approved by the HCA on an individual or class basis. ...

48 CFR 303.104-7 - Violations or possible violations of the Procurement Integrity Act.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... That individual shall— (i) Refer the matter immediately to the Associate DAS for Acquisition for review... or concurrence of the Associate DAS for Acquisition before proceeding with an action. (b) The HCA...

48 CFR 1432.407 - Interest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Interest. 1432.407 Section... REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 1432.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 2932.407 - Interest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Interest. 2932.407 Section... CONTRACT FINANCING Advance Payments for Non-Commercial Items 2932.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 1432.407 - Interest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Interest. 1432.407 Section... REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 1432.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 2932.407 - Interest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Interest. 2932.407 Section... CONTRACT FINANCING Advance Payments for Non-Commercial Items 2932.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 1432.407 - Interest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Interest. 1432.407 Section... REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 1432.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 2932.407 - Interest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Interest. 2932.407 Section... CONTRACT FINANCING Advance Payments for Non-Commercial Items 2932.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 1432.407 - Interest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Interest. 1432.407 Section... REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 1432.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 2932.407 - Interest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Interest. 2932.407 Section... CONTRACT FINANCING Advance Payments for Non-Commercial Items 2932.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 1432.407 - Interest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Interest. 1432.407 Section... REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 1432.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

48 CFR 2932.407 - Interest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Interest. 2932.407 Section... CONTRACT FINANCING Advance Payments for Non-Commercial Items 2932.407 Interest. The HCA may authorize advance payments without interest pursuant to FAR 32.407. ...

Using Unsupervised Learning to Unlock the Potential of Hydrologic Similarity

NASA Astrophysics Data System (ADS)

Chaney, N.; Newman, A. J.

2017-12-01

By clustering environmental data into representative hydrologic response units (HRUs), hydrologic similarity aims to harness the covariance between a system's physical environment and its hydrologic response to create reduced-order models. This is the primary approach through which sub-grid hydrologic processes are represented in large-scale models (e.g., Earth System Models). Although the possibilities of hydrologic similarity are extensive, its practical implementations have been limited to 1-d bins of oversimplistic metrics of hydrologic response (e.g., topographic index)—this is a missed opportunity. In this presentation we will show how unsupervised learning is unlocking the potential of hydrologic similarity; clustering methods enable generalized frameworks to effectively and efficiently harness the petabytes of global environmental data to robustly characterize sub-grid heterogeneity in large-scale models. To illustrate the potential that unsupervised learning has towards advancing hydrologic similarity, we introduce a hierarchical clustering algorithm (HCA) that clusters very high resolution (30-100 meters) elevation, soil, climate, and land cover data to assemble a domain's representative HRUs. These HRUs are then used to parameterize the sub-grid heterogeneity in land surface models; for this study we use the GFDL LM4 model—the land component of the GFDL Earth System Model. To explore HCA and its impacts on the hydrologic system we use a ¼ grid cell in southeastern California as a test site. HCA is used to construct an ensemble of 9 different HRU configurations—each configuration has a different number of HRUs; for each ensemble member LM4 is run between 2002 and 2014 with a 26 year spinup. The analysis of the ensemble of model simulations show that: 1) clustering the high-dimensional environmental data space leads to a robust representation of the role of the physical environment in the coupled water, energy, and carbon cycles at a relatively low number of HRUs; 2) the reduced-order model with around 300 HRUs effectively reproduces the fully distributed model simulation (30 meters) with less than 1/1000 of computational expense; 3) assigning each grid cell of the fully distributed grid to an HRU via HCA enables novel visualization methods for large-scale models—this has significant implications for how these models are applied and evaluated. We will conclude by outlining the potential that this work has within operational prediction systems including numerical weather prediction, Earth System models, and Early Warning systems.

Topometry optimization of sheet metal structures for crashworthiness design using hybrid cellular automata

NASA Astrophysics Data System (ADS)

Mozumder, Chandan K.

The objective in crashworthiness design is to generate plastically deformable energy absorbing structures which can satisfy the prescribed force-displacement (FD) response. The FD behavior determines the reaction force, displacement and the internal energy that the structure should withstand. However, attempts to include this requirement in structural optimization problems remain scarce. The existing commercial optimization tools utilize models under static loading conditions because of the complexities associated with dynamic/impact loading. Due to the complexity of a crash event and the consequent time required to numerically analyze the dynamic response of the structure, classical methods (i.e., gradient-based and direct) are not well developed to solve this undertaking. This work presents an approach under the framework of the hybrid cellular automaton (HCA) method to solve the above challenge. The HCA method has been successfully applied to nonlinear transient topology optimization for crashworthiness design. In this work, the HCA algorithm has been utilized to develop an efficient methodology for synthesizing shell-based sheet metal structures with optimal material thickness distribution under a dynamic loading event using topometry optimization. This method utilizes the cellular automata (CA) computing paradigm and nonlinear transient finite element analysis (FEA) via ls-dyna. In this method, a set field variables is driven to their target states by changing a convenient set of design variables (e.g., thickness). These rules operate locally in cells within a lattice that only know local conditions. The field variables associated with the cells are driven to a setpoint to obtain the desired structure. This methodology is used to design for structures with controlled energy absorption with specified buckling zones. The peak reaction force and the maximum displacement are also constrained to meet the desired safety level according to passenger safety regulations. Design for prescribed FD response by minimizing the error between the actual response and desired FD curve is implemented. With the use of HCA rules, manufacturability constraints (e.g., rolling) and structures which can be manufactured by special techniques, such as, tailor-welded blanks (TWB), have also been implemented. This methodology is applied to shock-absorbing structural components for passengers in a crashing vehicle. These results are compared to previous designs showing the benefits of the method introduced in this work.

Soil carbon storage in plantation forests and pastures: land-use change implications

NASA Astrophysics Data System (ADS)

Scott, Neal A.; Tate, Kevin R.; Ford-Robertson, Justin; Giltrap, David J.; Tattersall Smith, C.

1999-04-01

Afforestation may lead to an accumulation of carbon (C) in vegetation, but little is known about changes in soil C storage with establishment of plantation forests. Plantation forest carbon budget models often omit mineral soil C changes from stand-level C budget calculations, while including forest floor C accumulation, or predict continuous soil C increases over several rotations. We used national soil C databases to quantify differences in soil C content between pasture and exotic pine forest plantations dominated by P. radiata (D. Don), and paired site studies to quantify changes in soil C with conversion of pasture to plantation forest in New Zealand. Overall, mineral soil C to 0.10 m was 20 40% lower under pine for all soil types (p<0.01) except soils with high clay activity (HCA), where there was no difference. Similar trends were observed in the 0.1 0.3 m layer. Moreover, mineral soil C to 0.1 m was 17 40% lower under pine than pasture in side-by-side comparisons. The only non-significant difference occurred at a site located on a HCA soil (p=0.08). When averaged across the site studies and the national databases, the difference in soil C between pasture and pine was about 16 t C ha1on non-HCA soils. This is similar to forest floor C averaged across our individual sites (about 20 t C ha1). The decrease in mineral soil C could result in about a 15% reduction in the average C sequestration potential (112 t C ha1) when pasture is converted to exotic plantation forest on non-HCA soils. The relative importance of this change in mineral soil C will likely vary depending on the productivity potential of a site and harvest impacts on the forest floor C pool. Our results emphasize that changes in soil C should be included in any calculations of C sequestration attributed to plantation forestry.

New Paradigms and Improved Results for the Surgical Treatment of Acute Type A Dissection

PubMed Central

Bavaria, Joseph E.; Pochettino, Alberto; Brinster, Derek R.; Gorman, Robert C.; McGarvey, Michael L.; Gorman, Joseph H.; Escherich, Alison; Gardner, Timothy J.

2001-01-01

Objective To examine the effect of an integrated surgical approach to the treatment of acute type A dissections. Summary Background Data Acute type A dissection requires surgery to prevent death from proximal aortic rupture or malperfusion. Most series of the past decade have reported a death rate in the range of 15% to 30%. Methods From January 1994 to March 2001, 104 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) to replace the aortic arch; HCA established after 5 minutes of electroencephalographic (EEG) silence in neuromonitored patients (66%) or after 45 minutes of cooling in patients who were not neuromonitored (34%); reinforcement of the residual arch tissue with a Teflon felt “neo-media”; cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt “neo-media” and aortic valve resuspension (78%) or replacement with a biologic or mechanical valved conduit (22%). Results Mean age was 59 ± 15 (range 22–86) years, with 71% men and 13% redo sternotomy after a previous cardiac procedure. Mean cardiopulmonary bypass time was 196 ± 50 minutes. Mean HCA with RCP time was 42 ± 12 minutes (range 19–84). Mean cardiac ischemic time was 140 ± 45 minutes. Eleven percent of patients presented with a preoperative neurologic deficit, and 5% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9%. Excluding the patients who presented neurologically unresponsive or with ongoing cardiopulmonary resuscitation (n = 5), the death rate was 4%. In six patients adverse cerebral outcomes were potentially avoided when immediate surgical fenestration was prompted by a sudden change in the EEG during cooling. Forty-five percent of neuromonitored patients required greater than 30 minutes to achieve EEG silence. Conclusion The authors have shown that the surgical integration of sinus segment repair or aortic root replacement, the use of EEG monitoring, partial or total arch replacement using RCP, routine antegrade graft perfusion, and the uniform use of transesophageal echocardiography substantially decrease the death and complication rates of acute type A dissection repair. PMID:11524586

The chemotaxonomic classification of Rhodiola plants and its correlation with morphological characteristics and genetic taxonomy.

PubMed

Liu, Zhenli; Liu, Yuanyan; Liu, Chunsheng; Song, Zhiqian; Li, Qing; Zha, Qinglin; Lu, Cheng; Wang, Chun; Ning, Zhangchi; Zhang, Yuxin; Tian, Cheng; Lu, Aiping

2013-07-12

Rhodiola plants are used as a natural remedy in the western world and as a traditional herbal medicine in China, and are valued for their ability to enhance human resistance to stress or fatigue and to promote longevity. Due to the morphological similarities among different species, the identification of the genus remains somewhat controversial, which may affect their safety and effectiveness in clinical use. In this paper, 47 Rhodiola samples of seven species were collected from thirteen local provinces of China. They were identified by their morphological characteristics and genetic and phytochemical taxonomies. Eight bioactive chemotaxonomic markers from four chemical classes (phenylpropanoids, phenylethanol derivatives, flavonoids and phenolic acids) were determined to evaluate and distinguish the chemotaxonomy of Rhodiola samples using an HPLC-DAD/UV method. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to compare the two classification methods between genetic and phytochemical taxonomy. The established chemotaxonomic classification could be effectively used for Rhodiola species identification.

The chemotaxonomic classification of Rhodiola plants and its correlation with morphological characteristics and genetic taxonomy

PubMed Central

2013-01-01

Background Rhodiola plants are used as a natural remedy in the western world and as a traditional herbal medicine in China, and are valued for their ability to enhance human resistance to stress or fatigue and to promote longevity. Due to the morphological similarities among different species, the identification of the genus remains somewhat controversial, which may affect their safety and effectiveness in clinical use. Results In this paper, 47 Rhodiola samples of seven species were collected from thirteen local provinces of China. They were identified by their morphological characteristics and genetic and phytochemical taxonomies. Eight bioactive chemotaxonomic markers from four chemical classes (phenylpropanoids, phenylethanol derivatives, flavonoids and phenolic acids) were determined to evaluate and distinguish the chemotaxonomy of Rhodiola samples using an HPLC-DAD/UV method. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to compare the two classification methods between genetic and phytochemical taxonomy. Conclusions The established chemotaxonomic classification could be effectively used for Rhodiola species identification. PMID:23844866

Application of chemometrics in quality control of Turmeric (Curcuma longa) based on Ultra-violet, Fourier transform-infrared and 1H NMR spectroscopy.

PubMed

Gad, Haidy A; Bouzabata, Amel

2017-12-15

Turmeric (Curcuma longa L.) belongs to the family Zingiberaceae that is widely used as a spice in food preparations in addition to its biological activities. UV, FT-IR, 1 H NMR in addition to HPLC were applied to construct a metabolic fingerprint for Turmeric in an attempt to assess its quality. 30 samples were analyzed, and then principal component analysis (PCA) and hierarchical clustering analysis (HCA) were utilized to assess the differences and similarities between collected samples. PCA score plot based on both HPLC and UV spectroscopy showed the same discriminatory pattern, where the samples were segregated into four main groups depending on their total curcuminoids content. The results revealed that UV could be utilized as a simple and rapid alternative for HPLC. However, FT-IR failed to discriminate between the same species. By applying 1 H NMR, the metabolic variability between samples was more evident in the essential oils/fatty acid region. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emerging approach for analytical characterization and geographical classification of Moroccan and French honeys by means of a voltammetric electronic tongue.

PubMed

El Alami El Hassani, Nadia; Tahri, Khalid; Llobet, Eduard; Bouchikhi, Benachir; Errachid, Abdelhamid; Zine, Nadia; El Bari, Nezha

2018-03-15

Moroccan and French honeys from different geographical areas were classified and characterized by applying a voltammetric electronic tongue (VE-tongue) coupled to analytical methods. The studied parameters include color intensity, free lactonic and total acidity, proteins, phenols, hydroxymethylfurfural content (HMF), sucrose, reducing and total sugars. The geographical classification of different honeys was developed through three-pattern recognition techniques: principal component analysis (PCA), support vector machines (SVMs) and hierarchical cluster analysis (HCA). Honey characterization was achieved by partial least squares modeling (PLS). All the PLS models developed were able to accurately estimate the correct values of the parameters analyzed using as input the voltammetric experimental data (i.e. r>0.9). This confirms the potential ability of the VE-tongue for performing a rapid characterization of honeys via PLS in which an uncomplicated, cost-effective sample preparation process that does not require the use of additional chemicals is implemented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultraviolet spectroscopy combined with ultra-fast liquid chromatography and multivariate statistical analysis for quality assessment of wild Wolfiporia extensa from different geographical origins.

PubMed

Li, Yan; Zhang, Ji; Jin, Hang; Liu, Honggao; Wang, Yuanzhong

2016-08-05

A quality assessment system comprised of a tandem technique of ultraviolet (UV) spectroscopy and ultra-fast liquid chromatography (UFLC) aided by multivariate analysis was presented for the determination of geographic origin of Wolfiporia extensa collected from five regions in Yunnan Province of China. Characteristic UV spectroscopic fingerprints of samples were determined based on its methanol extract. UFLC was applied for the determination of pachymic acid (a biomarker) presented in individual test samples. The spectrum data matrix and the content of pachymic acid were integrated and analyzed by partial least squares discriminant analysis (PLS-DA) and hierarchical cluster analysis (HCA). The results showed that chemical properties of samples were clearly dominated by the epidermis and inner part as well as geographical origins. The relationships among samples obtained from these five regions have been also presented. Moreover, an interesting finding implied that geographical origins had much greater influence on the chemical properties of epidermis compared with that of the inner part. This study demonstrated that a rapid tool for accurate discrimination of W. extensa by UV spectroscopy and UFLC could be available for quality control of complicated medicinal mushrooms. Copyright © 2016 Elsevier B.V. All rights reserved.

48 CFR 1409.506 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... organizational conflict of interest, then the contracting officer shall refer the documentation of the potential conflict and proposed resolution prepared in accordance with 7.105(b)(18) to the HCA for approval... ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Organizational and Consultant Conflicts of Interest 1409.506...

48 CFR 2832.903 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 2832.903 Section 2832.903 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Prompt Payment 2832.903 Policy. The HCA is responsible for promulgating policies and...

48 CFR 2832.903 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. 2832.903 Section 2832.903 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE General Contracting Requirements CONTRACT FINANCING Prompt Payment 2832.903 Policy. The HCA is responsible for promulgating policies and...

48 CFR 2832.903 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 2832.903 Section 2832.903 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Prompt Payment 2832.903 Policy. The HCA is responsible for promulgating policies and...

ABIOTIC REDUCTIVE DECHLORINATION OF CARBON TETRACHLORIDE AND HEXACHLOROETHANE BY ENVIRONMENTAL REDUCTANTS

EPA Science Inventory

The transformation rates of hexachloroethane (HCA) and carbon tetrachloride (CTET) have been measured in model systems representing the ground water environment and in slurries of fractionated Borden aquifer material. his report summarizes research conducted to identify the envir...

48 CFR 825.202 - Exceptions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Exceptions. 825.202 Section 825.202 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC... HCA believes that the non-availability of an article is likely to affect future acquisitions, include...

48 CFR 3432.402 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false General. 3432.402 Section 3432.402 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments 3432.402 General. (a)-(d) [Reserved] (e) The HCA...

48 CFR 3432.407 - Interest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Interest. 3432.407 Section 3432.407 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments 3432.407 Interest. The HCA is designated to...

Quality Assessment of Kumu Injection, a Traditional Chinese Medicine Preparation, Using HPLC Combined with Chemometric Methods and Qualitative and Quantitative Analysis of Multiple Alkaloids by Single Marker.

PubMed

Wang, Ning; Li, Zhi-Yong; Zheng, Xiao-Li; Li, Qiao; Yang, Xin; Xu, Hui

2018-04-09

Kumu injection (KMI) is a common-used traditional Chinese medicine (TCM) preparation made from Picrasma quassioides (D. Don) Benn. rich in alkaloids. An innovative technique for quality assessment of KMI was developed using high performance liquid chromatography (HPLC) combined with chemometric methods and qualitative and quantitative analysis of multi-components by single marker (QAMS). Nigakinone (PQ-6, 5-hydroxy-4-methoxycanthin-6-one), one of the most abundant alkaloids responsible for the major pharmacological activities of Kumu, was used as a reference substance. Six alkaloids in KMI were quantified, including 6-hydroxy- β -carboline-1-carboxylic acid (PQ-1), 4,5-dimethoxycanthin-6-one (PQ-2), β -carboline-1-carboxylic acid (PQ-3), β -carboline-1-propanoic acid (PQ-4), 3-methylcanthin-5,6-dione (PQ-5), and PQ-6. Based on the outcomes of twenty batches of KMI samples, the contents of six alkaloids were used for further chemometric analysis. By hierarchical cluster analysis (HCA), radar plots, and principal component analysis (PCA), all the KMI samples could be categorized into three groups, which were closely related to production date and indicated the crucial influence of herbal raw material on end products of KMI. QAMS combined with chemometric analysis could accurately measure and clearly distinguish the different quality samples of KMI. Hence, QAMS is a feasible and promising method for the quality control of KMI.

Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry

PubMed Central

Shi, Zhilong; Liu, Zhenjie; Liu, Chunsheng; Wu, Mingquan; Su, Haibin; Ma, Xiao; Zang, Yimei; Wang, Jiabo; Zhao, Yanling; Xiao, Xiaohe

2016-01-01

The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4-Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF. PMID:26869929

48 CFR 1437.102 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Policy. 1437.102 Section... CONTRACTING SERVICE CONTRACTING Service Contracts-General 1437.102 Policy. The HCA is responsible for establishing internal review and approval procedures for service contracts in accordance with OFPP Policy...

48 CFR 2814.407-3 - Other mistakes disclosed before award.

Code of Federal Regulations, 2010 CFR

2010-10-01

...), and (d) of FAR 14.407-3 is delegated to the HCA or designee at a level not lower that the BPC. (b) The..., General Accounting Office, Washington, D.C. 20548, and contain the following: (i) The name and address of...

48 CFR 422.804-2 - Construction.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Construction. 422.804-2... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Equal Employment Opportunity 422.804-2 Construction. The HCA shall ensure that each contracting office, awarding nonexempt construction contracts, maintains a...

48 CFR 422.804-2 - Construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Construction. 422.804-2... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Equal Employment Opportunity 422.804-2 Construction. The HCA shall ensure that each contracting office, awarding nonexempt construction contracts, maintains a...

48 CFR 422.804-2 - Construction.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Construction. 422.804-2... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Equal Employment Opportunity 422.804-2 Construction. The HCA shall ensure that each contracting office, awarding nonexempt construction contracts, maintains a...

48 CFR 422.804-2 - Construction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Construction. 422.804-2... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Equal Employment Opportunity 422.804-2 Construction. The HCA shall ensure that each contracting office, awarding nonexempt construction contracts, maintains a...

48 CFR 422.804-2 - Construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Construction. 422.804-2... APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Equal Employment Opportunity 422.804-2 Construction. The HCA shall ensure that each contracting office, awarding nonexempt construction contracts, maintains a...

48 CFR 3015.604 - Agency points of contact.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Agency points of contact. 3015.604 Section 3015.604 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY... clearinghouse for distributing information or assistance regarding unsolicited proposals. Each HCA is...

48 CFR 305.202 - Exceptions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... acquisition channels, including the HCA, to Associate DAS for Acquisition requesting an exception to synopsizing. The Associate DAS for Acquisition shall review the request and decide whether an exception is appropriate and reasonable. If it is, the Associate DAS for Acquisition shall take the necessary coordinating...

48 CFR 2936.604 - Performance evaluation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Performance evaluation... Performance evaluation. (a) The HCA must establish procedures to evaluate architect-engineer contractor performance as required in FAR 36.604. Normally, the performance report must be prepared by the contracting...

48 CFR 2936.604 - Performance evaluation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Performance evaluation... Performance evaluation. (a) The HCA must establish procedures to evaluate architect-engineer contractor performance as required in FAR 36.604. Normally, the performance report must be prepared by the contracting...

48 CFR 2936.604 - Performance evaluation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Performance evaluation... Performance evaluation. (a) The HCA must establish procedures to evaluate architect-engineer contractor performance as required in FAR 36.604. Normally, the performance report must be prepared by the contracting...

48 CFR 2936.604 - Performance evaluation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Performance evaluation... Performance evaluation. (a) The HCA must establish procedures to evaluate architect-engineer contractor performance as required in FAR 36.604. Normally, the performance report must be prepared by the contracting...

48 CFR 2936.604 - Performance evaluation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Performance evaluation... Performance evaluation. (a) The HCA must establish procedures to evaluate architect-engineer contractor performance as required in FAR 36.604. Normally, the performance report must be prepared by the contracting...

Sensory analysis of calcium-biofortified lettuce

USDA-ARS?s Scientific Manuscript database

Vegetables represent an attractive means of providing increased calcium nutrition to the public. In this study, it was demonstrated that lettuce expressing the deregulated Arabidopsis H(+)/Ca(2+) transporter sCAX1 (cation exchanger 1) contained 25-32% more calcium than controls. These biofortified l...

48 CFR 304.7100 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Policy. 304.7100 Section 304.7100 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE MATTERS Review and Approval of Proposed Contract Actions 304.7100 Policy. (a) The HCA (non-delegable...

48 CFR 1401.602-1 - Authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Authority. 1401.602-1... THE INTERIOR ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and Responsibilities 1401.602-1 Authority. Information on the limits of CO's authority shall be maintained by the HCA...

48 CFR 1432.402 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false General. 1432.402 Section 1432.402 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING... shall submit a recommendation for approval or disapproval of the contractor's request to the HCA through...

48 CFR 2932.402 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false General. 2932.402 Section 2932.402 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL CONTRACTING REQUIREMENTS... officer must submit a recommendation for approval or disapproval of the contractor's request to the HCA. ...

48 CFR 301.602-3 - Ratification of unauthorized commitments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and... legal review is necessary, the HCA or CCO shall coordinate the request for ratification with the Office...) The Contracting Officer shall review the submitted material and, if the Contracting Officer determines...

48 CFR 2936.201 - Evaluation of contractor performance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Evaluation of contractor... Construction 2936.201 Evaluation of contractor performance. The HCA must establish procedures to evaluate construction contractor performance and prepare performance reports as required by FAR 36.201. ...

48 CFR 1448.102 - Policies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Policies. 1448.102 Section 1448.102 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT VALUE ENGINEERING Policies and Procedures 1448.102 Policies. The HCA shall establish procedures for processing and...

48 CFR 432.114 - Unusual contract financing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Unusual contract financing... CONTRACTING REQUIREMENTS CONTRACT FINANCING Non-Commercial Item Purchase Financing 432.114 Unusual contract financing. The HCA is authorized to approve unusual contract financing. The signed determination and finding...

Conditional Covariance-Based Nonparametric Multidimensionality Assessment.

ERIC Educational Resources Information Center

Stout, William; And Others

1996-01-01

Three nonparametric procedures that use estimates of covariances of item-pair responses conditioned on examinee trait level for assessing dimensionality of a test are described. The HCA/CCPROX, DIMTEST, and DETECT are applied to a dimensionality study of the Law School Admission Test. (SLD)

University Hospitals for Sale.

ERIC Educational Resources Information Center

Culliton, Barbara J.

1984-01-01

Although faculty opposition stopped the sale of Harvard's McLean Hospital to the Hospital Corporation of America (HCA), a partnership remains a possibility. Issues related to the proposed sale as well as those affecting hospital economics are considered. Proposed terms of the sale are included. (JN)

Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice.

PubMed

Braeuning, Albert; Gavrilov, Alina; Geissler, Miriam; Wenz, Christine; Colnot, Sabine; Templin, Markus F; Metzger, Ute; Römer, Michael; Zell, Andreas; Schwarz, Michael

2016-06-01

Activation of Wnt/β-catenin signaling is important for human and rodent hepatocarcinogenesis. In mice, the tumor promoter phenobarbital (PB) selects for hepatocellular tumors with activating β-catenin mutations via constitutive androstane receptor activation. PB-dependent tumor promotion was studied in mice with genetic inactivation of Apc, a negative regulator of β-catenin, to circumvent the problem of randomly induced mutations by chemical initiators and to allow monitoring of PB- and Wnt/β-catenin-dependent tumorigenesis in the absence of unknown genomic alterations. Moreover, the study was designed to investigate PB-induced proliferation of liver cells with activated β-catenin. PB treatment provided Apc-deficient hepatocytes with only a minor proliferative advantage, and additional connexin 32 deficiency did not affect the proliferative response. PB significantly promoted the outgrowth of Apc-deficient hepatocellular adenoma (HCA), but simultaneously inhibited the formation of Apc-deficient hepatocellular carcinoma (HCC). The probability of tumor promotion by PB was calculated to be much lower for hepatocytes with loss of Apc, as compared to mutational β-catenin activation. Comprehensive transcriptomic and phosphoproteomic characterization of HCA and HCC revealed molecular details of the two tumor types. HCC were characterized by a loss of differentiated hepatocellular gene expression, enhanced proliferative signaling, and massive over-activation of Wnt/β-catenin signaling. In conclusion, PB exerts a dual role in liver tumor formation by promoting the growth of HCA but inhibiting the growth of HCC. Data demonstrate that one and the same compound can produce opposite effects on hepatocarcinogenesis, depending on context, highlighting the necessity to develop a more differentiated view on the tumorigenicity of this model compound.

Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

PubMed

McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

2017-07-01

Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

Reshaping the folding energy landscape by chloride salt: impact on molten-globule formation and aggregation behavior of carbonic anhydrase.

PubMed

Borén, Kristina; Grankvist, Hannah; Hammarström, Per; Carlsson, Uno

2004-05-21

During chemical denaturation different intermediate states are populated or suppressed due to the nature of the denaturant used. Chemical denaturation by guanidine-HCl (GuHCl) of human carbonic anhydrase II (HCA II) leads to a three-state unfolding process (Cm,NI=1.0 and Cm,IU=1.9 M GuHCl) with formation of an equilibrium molten-globule intermediate that is stable at moderate concentrations of the denaturant (1-2 M) with a maximum at 1.5 M GuHCl. On the contrary, urea denaturation gives rise to an apparent two-state unfolding transition (Cm=4.4 M urea). However, 8-anilino-1-naphthalene sulfonate (ANS) binding and decreased refolding capacity revealed the presence of the molten globule in the middle of the unfolding transition zone, although to a lesser extent than in GuHCl. Cross-linking studies showed the formation of moderate oligomer sized (300 kDa) and large soluble aggregates (>1000 kDa). Inclusion of 1.5 M NaCl to the urea denaturant to mimic the ionic character of GuHCl leads to a three-state unfolding behavior (Cm,NI=3.0 and Cm,IU=6.4 M urea) with a significantly stabilized molten-globule intermediate by the chloride salt. Comparisons between NaCl and LiCl of the impact on the stability of the various states of HCA II in urea showed that the effects followed what could be expected from the Hofmeister series, where Li+ is a chaotropic ion leading to decreased stability of the native state. Salt addition to the completely urea unfolded HCA II also led to an aggregation prone unfolded state, that has not been observed before for carbonic anhydrase. Refolding from this state only provided low recoveries of native enzyme.

Optimized retrograde cerebral perfusion reduces ischemic energy depletion.

PubMed

Oda, Teiji; Kimura, Tetsuhiro; Ogata, Yoshitaka; Fujise, Yutaka

2004-01-01

It has been reported that retrograde cerebral perfusion (RCP) provides minimal capillary flow; however, the extent to which RCP can provide aerobic metabolic support is unknown. We evaluated whether perfusate composition optimization for RCP would preserve brain energy metabolism during hypothermic circulatory arrest (HCA) at 20 degrees C in rats. Three types of perfusates were prepared: hemoglobin-free saline, rat red blood cells, and artificial blood substitute (liposome-encapsulated hemoglobin); perfusates were made hypertonic, cooled to 20 degrees C, and oxygenated and CO(2) was administered (pH-stat management). Circulatory arrest was induced in 24 pH-stat-ventilated Wistar rats that had been surface cooled to 20 degrees C; 18 were assigned to the RCP group in which one of the three ( n = 6 each) perfusates was administered via the maxillary vein, and 6 received no perfusion. In two similarly surface-cooled rats (controls), brains were excised when the temperature reached 20 degrees C. After 20 min of RCP or HCA, brains were excised and immediately frozen; brain high-energy phosphates, adenosine, and water content were measured. The liposome-encapsulated hemoglobin perfusate preserved levels of brain tissue adenosine triphosphates and energy charge, but not significantly better than rat red blood cells. Both maintained significantly higher levels than perfusion with oxygenated saline or hypothermic circulatory arrest alone ( P = 0.0419-0.0001), under which regimes high-energy phosphates and energy charge declined to similar low values. RCP with hypertonic solution prevented brain edema. RCP with optimized composition perfusate (pH-stat, hypertonic rat red blood cells or liposome-encapsulated hemoglobin) reduced ischemic energy depletion during 20 min of HCA at 20 degrees C in rats.

The Africa Yoga Project: A Participant-Driven Concept Map of Kenyan Teachers' Reported Experiences.

PubMed

Klein, Jessalyn E; Cook-Cottone, Catherine; Giambrone, Carla

2015-01-01

The Africa Yoga Project (AYP) trains and funds Kenyans to teach community yoga classes. Preliminary research with a small sample of AYP teachers suggested the program had a positive impact. This study used concept mapping to explore the experiences of a larger sample. Participants brainstormed statements about how practicing and/or teaching yoga changed them. They sorted statements into self-defined piles and rated them in terms of perceived importance. Multidimensional scaling (MDS) of sort data calculated statement coordinates wherein each statement is placed in proximity to other statements as a function of how frequently statements are sorted together by participants. These results are then and mapped in a two-dimensional space. Hierarchical cluster analysis (HCA) of these data identified clusters (i.e., concepts) among statements. Cluster average importance ratings gave the concept map depth and indicated concept importance. Bridging analysis and researchers' conceptual understanding of yoga literature facilitated HCA interpretive decisions. Of 72 AYP teachers, 52 and 48 teachers participated in brainstorming and sorting/rating activities, respectively. Teachers brainstormed 93 statements about how they had changed. The resultant MDS statement map had adequate validity (stress value = .29). HCA created a 12-cluster solution with the following concepts of perceived change: Identity as a Yoga Teacher; Prosocial Development; Existential Possibility; Genuine Positive Regard; Value and Respect for Others (highest importance); Presence, Acceptance, and Competence; Service and Trust; Non-judgment and Emotion Regulation (lowest importance); Engagement and Connection; Interpersonal Effectiveness; Psychosocial Functioning; and Physical Competence and Security. Teachers perceived the AYP as facilitating change across physical, mental, and spiritual domains. Additional research is needed to quantify and compare this change to other health promotion program outcomes.

Hypoxia diminishes the protective function of white-matter astrocytes in the developing brain.

PubMed

Agematsu, Kota; Korotcova, Ludmila; Morton, Paul D; Gallo, Vittorio; Jonas, Richard A; Ishibashi, Nobuyuki

2016-01-01

White-matter injury after surgery is common in neonates with cerebral immaturity secondary to in utero hypoxia. Astrocytes play a central role in brain protection; however, the reaction of astrocytes to hypothermic circulatory arrest (HCA) remains unknown. We investigated the role of astrocytes in white-matter injury after HCA and determined the effects of preoperative hypoxia on this role, using a novel mouse model. Mice were exposed to hypoxia from days 3 to 11, which is equivalent to the third trimester in humans (prehypoxia, n = 49). Brain slices were transferred to a chamber perfused by cerebrospinal fluid. Oxygen-glucose deprivation (OGD) was performed to simulate ischemia-reperfusion/reoxygenation resulting from circulatory arrest under hypothermia. Astrocyte reactions were compared with preoperative normoxia (prenormoxia; n = 45). We observed astrocyte activation after 25°C ischemia-reperfusion/reoxygenation in prenormoxia (P < .01). Astrocyte number after OGD correlated with caspase-3(+) cells (rho = .77, P = .001), confirming that astrogliosis is an important response after HCA. At 3 hours after OGD, astrocytes in prenormoxia had already proliferated and become activated (P < .05). Conversely, astrocytes that developed under hypoxia did not display these responses. At 20 hours after ischemia-reperfusion/reoxygenation, astrogliosis was not observed in prehypoxia, demonstrating that hypoxia altered the response of astrocytes to insult. In contrast to prenormoxia, caspase-3(+) cells in prehypoxia increased after ischemia reperfusion/reoxygenation, compared with control (P < .01). Caspase-3(+) cells were more common with prehypoxia than with prenormoxia (P < .001), suggesting that lack of astrogliosis permits increased white-matter injury. Preoperative hypoxia alters the neuroprotective function of astrocytes. Restoring this function before surgery may be a therapeutic option to reduce postoperative white-matter injury in the immature brain. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Functional Association of Arabidopsis CAX1 and CAX3 Is Required for Normal Growth and Ion Homeostasis1

PubMed Central

Cheng, Ning-Hui; Pittman, Jon K.; Shigaki, Toshiro; Lachmansingh, Jinesh; LeClere, Sherry; Lahner, Brett; Salt, David E.; Hirschi, Kendal D.

2005-01-01

Cation levels within the cytosol are coordinated by a network of transporters. Here, we examine the functional roles of calcium exchanger 1 (CAX1), a vacuolar H+/Ca2+ transporter, and the closely related transporter CAX3. We demonstrate that like CAX1, CAX3 is also localized to the tonoplast. We show that CAX1 is predominately expressed in leaves, while CAX3 is highly expressed in roots. Previously, using a yeast assay, we demonstrated that an N-terminal truncation of CAX1 functions as an H+/Ca2+ transporter. Here, we use the same yeast assay to show that full-length CAX1 and full-length CAX3 can partially, but not fully, suppress the Ca2+ hypersensitive yeast phenotype and coexpression of full-length CAX1 and CAX3 conferred phenotypes not produced when either transporter was expressed individually. In planta, CAX3 null alleles were modestly sensitive to exogenous Ca2+ and also displayed a 22% reduction in vacuolar H+-ATPase activity. cax1/cax3 double mutants displayed a severe reduction in growth, including leaf tip and flower necrosis and pronounced sensitivity to exogenous Ca2+ and other ions. These growth defects were partially suppressed by addition of exogenous Mg2+. The double mutant displayed a 42% decrease in vacuolar H+/Ca2+ transport, and a 47% decrease in H+-ATPase activity. While the ionome of cax1 and cax3 lines were modestly perturbed, the cax1/cax3 lines displayed increased PO43−, Mn2+, and Zn2+ and decreased Ca2+ and Mg2+ in shoot tissue. These findings suggest synergistic function of CAX1 and CAX3 in plant growth and nutrient acquisition. PMID:16055687

48 CFR 1436.602-4 - Selection authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Selection authority. 1436.602-4 Section 1436.602-4 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR SPECIAL...-4 Selection authority. The HCA is authorized to serve as the designated selection authority. ...

48 CFR 2936.602-4 - Selection Authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Selection Authority. 2936.602-4 Section 2936.602-4 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL... Selection Authority. The HCA is authorized to serve as the designated Selection Authority in accordance with...

48 CFR 2825.302 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. 2825.302 Section 2825.302 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Balance of Payments Program 2825.302 Policy. The HCA, or designee at a level not lower than the...

48 CFR 2825.302 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. 2825.302 Section 2825.302 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Balance of Payments Program 2825.302 Policy. The HCA, or designee at a level not lower than the...

48 CFR 3001.403 - Individual deviations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Individual deviations... from the FAR and HSAR 3001.403 Individual deviations. Unless precluded by law, executive order, or other regulation, the HCA is authorized to approve individual deviation (except with respect to (FAR) 48...

48 CFR 302.101 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Acquisition and Logistics Management. PSC: Director, Strategic Acquisition Service. SAMHSA: Director, Division... delegations of HCA authority through the Contracting Officer level. (e) Program Manager is a federal employee... designated in writing to act as a Program Manager for a group of related major or non-major IT or...

48 CFR 1509.406-3 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PLANNING CONTRACTOR QUALIFICATIONS Debarment, Suspension and Ineligibility 1509.406-3 Procedures. (a... who do not appear on the GSA Consolidated List; e.g., those who are ineligible based on a settlement...) Obtain the HCA's recommendation prior to reaching a voluntary exclusion settlement with a Contractor in...

48 CFR 1445.302 - Contracts with foreign governments or international organizations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Government Property 1445.302 Contracts with foreign governments or international organizations. The HCA... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contracts with foreign governments or international organizations. 1445.302 Section 1445.302 Federal Acquisition Regulations System...

48 CFR 1445.302 - Contracts with foreign governments or international organizations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Government Property 1445.302 Contracts with foreign governments or international organizations. The HCA... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contracts with foreign governments or international organizations. 1445.302 Section 1445.302 Federal Acquisition Regulations System...

48 CFR 2930.201-5 - Waiver.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Waiver. 2930.201-5 Section 2930.201-5 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL CONTRACTING REQUIREMENTS COST ACCOUNTING STANDARDS ADMINISTRATION CAS Program Requirements 2930.201-5 Waiver. (a) The HCA is...

48 CFR 2901.603-3 - Appointment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... all warrants above the micro-purchase threshold. In addition, appointments may be made for specific... functions. (a) Purchase Cards (micro-purchase threshold). Purchase cardholders will be appointed in accordance with the DOL Guidelines for Purchase Card Use and the Agency/Office procedures approved by the HCA...

48 CFR 303.303 - Reporting suspected antitrust violations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Reporting suspected antitrust violations. 303.303 Section 303.303 Federal Acquisition Regulations System HEALTH AND HUMAN... Antitrust Violations 303.303 Reporting suspected antitrust violations. (h) The HCA shall provide a copy of...

48 CFR 303.303 - Reporting suspected antitrust violations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Reporting suspected antitrust violations. 303.303 Section 303.303 Federal Acquisition Regulations System HEALTH AND HUMAN... Antitrust Violations 303.303 Reporting suspected antitrust violations. (h) The HCA shall provide a copy of...

48 CFR 3432.407 - Interest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Interest. 3432.407 Section... CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 3432.407 Interest. The HCA is designated as the official who may authorize advance payments without interest under FAR 32.407...

48 CFR 3432.407 - Interest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Interest. 3432.407 Section... CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 3432.407 Interest. The HCA is designated as the official who may authorize advance payments without interest under FAR 32.407...

48 CFR 3432.407 - Interest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Interest. 3432.407 Section... CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 3432.407 Interest. The HCA is designated as the official who may authorize advance payments without interest under FAR 32.407...

48 CFR 3432.407 - Interest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Interest. 3432.407 Section... CONTRACTING REQUIREMENTS CONTRACT FINANCING Advance Payments for Non-Commercial Items 3432.407 Interest. The HCA is designated as the official who may authorize advance payments without interest under FAR 32.407...

Honor Thy Parents: An Ethnic Multigroup Analysis of Filial Responsibility, Health Perceptions, and Caregiving Decisions.

PubMed

Santoro, Maya S; Van Liew, Charles; Holloway, Breanna; McKinnon, Symone; Little, Timothy; Cronan, Terry A

2016-08-01

The present study explores patterns of parity and disparity in the effect of filial responsibility on health-related evaluations and caregiving decisions. Participants who identified as White, Black, Hispanic, or Asian/Pacific Islander read a vignette about an older man needing medical care. They were asked to imagine that they were the man's son and answer questions regarding their likelihood of hiring a health care advocate (HCA) for services related to the father's care. A multigroup (ethnicity) path analysis was performed, and an intercept invariant multigroup model fits the data best. Direct and indirect effect estimation showed that filial responsibility mediated the relationship between both the perceived severity of the father's medical condition and the perceived need for medical assistance and the likelihood of hiring an HCA only for White and Hispanic participants, albeit differently. The findings demonstrate that culture and ethnicity affect health evaluations and caregiving decision making. © The Author(s) 2015.

Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin.

PubMed

Engels, Christina; Schwab, Clarissa; Zhang, Jianbo; Stevens, Marc J A; Bieri, Corinne; Ebert, Marc-Olivier; McNeill, Kristopher; Sturla, Shana J; Lacroix, Christophe

2016-11-07

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering agents.

PubMed

Chiaramonte, Niccolò; Bua, Silvia; Ferraroni, Marta; Nocentini, Alessio; Bonardi, Alessandro; Bartolucci, Gianluca; Durante, Mariaconcetta; Lucarini, Laura; Chiapponi, Donata; Dei, Silvia; Manetti, Dina; Teodori, Elisabetta; Gratteri, Paola; Masini, Emanuela; Supuran, Claudiu T; Romanelli, Maria Novella

2018-05-10

Two series of 2-benzylpiperazines have been prepared and tested for the inhibition of physiologically relevant isoforms of human carbonic anhydrases (hCA, EC 4.2.1.1). The new compounds carry on one nitrogen atom of the piperazine ring a sulfamoylbenzamide group as zinc-binding moiety, and different alkyl/acyl/sulfonyl groups on the other nitrogen. Regio- and stero-isomers are described. The majority of these compounds showed Ki values in the low-medium nanomolar range against hCA I, II and IV, but not IX. In many instances interaction with the enzyme was enantioselective. The binding mode has been studied by means of X-ray crystallography and molecular modelling. Two compounds, evaluated in rabbit models of glaucoma, were able to significantly reduce intraocular pressure, making them interesting candidates for further studies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A reappraisal of retrograde cerebral perfusion.

PubMed

Ueda, Yuichi

2013-05-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients.

A reappraisal of retrograde cerebral perfusion

PubMed Central

2013-01-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

Forms of work organization and associations with shoulder disorders: Results from a French working population.

PubMed

Bodin, Julie; Garlantézec, Ronan; Costet, Nathalie; Descatha, Alexis; Fouquet, Natacha; Caroly, Sandrine; Roquelaure, Yves

2017-03-01

The aim of this study was to identify forms of work organization in a French region and to study associations with the occurrence of symptomatic and clinically diagnosed shoulder disorders in workers. Workers were randomly included in this cross-sectional study from 2002 to 2005. Sixteen organizational variables were assessed by a self-administered questionnaire: i.e. shift work, job rotation, repetitiveness of tasks, paced work/automatic rate, work pace dependent on quantified targets, permanent controls or surveillance, colleagues' work and customer demand, and eight variables measuring decision latitude. Five forms of work organization were identified using hierarchical cluster analysis (HCA) of variables and HCA of workers: low decision latitude with pace constraints, medium decision latitude with pace constraints, low decision latitude with low pace constraints, high decision latitude with pace constraints and high decision latitude with low pace constraints. There were significant associations between forms of work organization and symptomatic and clinically-diagnosed shoulder disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

High Content Analysis technology for evaluating the joint toxicity of sunset yellow and sodium sulfite in vitro.

PubMed

Qu, Daofeng; Gu, Yanpei; Feng, Lifang; Han, Jianzhong

2017-10-15

Foods contain various additives that affect our daily lives. At present, food additive safety evaluation standards are based on the toxicity of single additives, but food additives are often used in combination and may have additive, synergistic or antagonistic actions. The current study investigated the toxicity of food additives and mechanisms of damage in HepG2 cells using High Content Analysis (HCA). We used the CCK-8 assay to determine cell viability, providing an experimental basis for determining the safety of food additives. All of the food additives tested were observed to decrease the growth of HepG2 cells in a dose-dependent manner. Sunset yellow and sodium sulfite had IC50 values of 1.06, and 0.30g/L at 24h, respectively. HCA showed that both sunset yellow and sodium sulfite had synergistic effects on cell number, membrane permeability, mitochondrial membrane potential, intracellular calcium level, oxidative stress, and high dose group DNA damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity of novel silicate and borate-based glass structures on in vitro bioactivity and degradation behaviour.

PubMed

Mancuso, Elena; Bretcanu, Oana; Marshall, Martyn; Dalgarno, Kenneth W

2017-10-15

Three novel glass compositions, identified as NCL2 (SiO 2 -based), NCL4 (B 2 O 3 -based) and NCL7 (SiO 2 -based), along with apatite-wollastonite (AW) were processed to form sintered dense pellets, and subsequently evaluated for their in vitro bioactive potential, resulting physico-chemical properties and degradation rate. Microstructural analysis showed the carbonated hydroxyapatite (HCA) precipitate morphology following SBF testing to be composition-dependent. AW and the NCL7 formulation exhibited greater HCA precursor formation than the NCL2 and NCL4-derived pellets. Moreover, the NCL4 borate-based samples showed the highest biodegradation rate; with silicate-derived structures displaying the lowest weight loss after SBF immersion. The results of this study suggested that glass composition has significant influence on apatite-forming ability and also degradation rate, indicating the possibility to customise the properties of this class of materials towards the bone repair and regeneration process.