Energy policy - compromise or change?

International Nuclear Information System (INIS)

Lewitz, J.C.

1998-01-01

Is there a contrast between compromise and change? In the author's opinion, there is not. Society changes. Sometimes, change is brought about more easily on the basis of a compromise. A pluralistic society needs compromises in order to participate in change with convictions of its own. To reach a compromise including a large part of one's conviction, the public must be convinced. This is achieved most easily by somebody who is well informed, educated, and trained. In this respect, not only specialized knowledge counts, but also the ability to handle the language and to know how to speak, and the behavior in public. Expert knowledge is acquired at the university, in the execution of one's profession, and in advanced training. Knowledge may be enhanced, for instance, by dealing with the arguments used by the other side. This will help in arguing one's own point more effectively. Individual talks, and events at which information and knowledge are disseminated, enable persons to assume an opinion based on their comprehension. Many uniform opinions create a majority opinion. (orig.) [de

6 CFR 13.46 - Compromise or settlement.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Compromise or settlement. 13.46 Section 13.46 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.46 Compromise or settlement. (a) Parties may Make offers of compromise or settlement at any time...

Retinol binding protein 4, obesity, and insulin resistance in adolescents

Directory of Open Access Journals (Sweden)

Ronaldi Noor

2017-02-01

Full Text Available Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4, secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated. Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56. We measured subjects’ body mass index (BMI and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR index. Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05. Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05. Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.

Career Compromises: Framings and Their Implications.

Science.gov (United States)

Gati, Itamar; Houminer, Daphna; Aviram, Tamar

1998-01-01

Career compromise was investigated in three framings (alternatives, aspect importance, within-aspect preference). Young adults and school counselors rated hypothetical stories. Results of four studies with different designs (Average N=106) supported the hypothesis. The alternatives framing was associated with greater compromise and decision…

A novel lung slice system with compromised antioxidant defenses

Energy Technology Data Exchange (ETDEWEB)

Hardwick, S.J.; Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries PLC, Cheshire (England))

1990-04-01

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

A novel lung slice system with compromised antioxidant defenses

International Nuclear Information System (INIS)

Hardwick, S.J.; Adam, A.; Cohen, G.M.; Smith, L.L.

1990-01-01

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 μM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP + , and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14 CO 2 from D-[ 14 C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

OpenAIRE

Hutchison, Samantha K.; Harrison, Cheryce; Stepto, Nigel; Meyer, Caroline; Teede, Helena J.

2008-01-01

OBJECTIVE?Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating ...

Cyber indicators of compromise: a domain ontology for security information and event management

Science.gov (United States)

2017-03-01

heuristics, mapping, and detection. CybOX is aimed at supporting a broad range of important cyber security domains to include [31]: • Digital...REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE CYBER INDICATORS OF COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND...Distribution is unlimited. CYBER INDICATORS OF COMPROMISE: A DOMAIN ONTOLOGY FOR SECURITY INFORMATION AND EVENT MANAGEMENT Marsha D. Rowell

Dental management of medically compromised patients

Directory of Open Access Journals (Sweden)

Sherly Horax

2016-06-01

Full Text Available These days, treatment in dentistry is no longer for patient without complication, but also for patient with bad medical record. With correct treatment management in handling medical condition of patient, not only for dental treatment but also their systematic disease, all the dental staff also can improve for the better quality of life of the patient. Patient with medical compromised start to realize that  keeping good oral hygiene is so important for their lives, therefore dental staff need to improve their science and technology and also for facing patient with medical compromised. This article will discuss and suggest various treatment consideration and protocol for the patient of with medical compromised.

TRAF4 and Castration-Resistant Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0536 TITLE: TRAF4 and Castration-Resistant Prostate Cancer PRINCIPAL INVESTIGATOR: Ping Yi CONTRACTING...Castration Resistant prostate cancer 5b. GRANT NUMBER W81XWH-15-1-0536 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ping Yi 5d. PROJECT NUMBER 5e. TASK...to be a critical player in castration-resistant prostate cancers . It was suggested that the function of AR in CRPC is not to turn on the same

Compromise in cooperative game and the VIKOR method

Directory of Open Access Journals (Sweden)

Opricović Serafim

2009-01-01

Full Text Available Five approaches in conflict resolution are distinguished, based on cooperativeness and aggressiveness in resolving conflict. Compromise based on cooperativeness is emphasized here as a solution in conflict resolution. Cooperative game theory oriented towards aiding the conflict resolution is considered and the compromise value for TU(transferable utility-game is presented. The method VIKOR could be applied to determine compromise solution of a multicriteria decision making problem with noncommensurable and conflicting criteria. Compromise is considered as an intermediate state between conflicting objectives or criteria reached by mutual concession. The applicability of the cooperative game theory and the VIKOR method for conflict resolution is illustrated.

Resistance to lambda-cyhalothrin in Spanish field populations of Ceratitis capitata and metabolic resistance mediated by P450 in a resistant strain.

Science.gov (United States)

Arouri, Rabeh; Le Goff, Gaelle; Hemden, Hiethem; Navarro-Llopis, Vicente; M'saad, Mariem; Castañera, Pedro; Feyereisen, René; Hernández-Crespo, Pedro; Ortego, Félix

2015-09-01

The withdrawal of malathion in the European Union in 2009 resulted in a large increase in lambda-cyhalothrin applications for the control of the Mediterranean fruit fly, Ceratitis capitata, in Spanish citrus crops. Spanish field populations of C. capitata have developed resistance to lambda-cyhalothrin (6-14-fold), achieving LC50 values (129-287 ppm) higher than the recommended concentration for field treatments (125 ppm). These results contrast with the high susceptibility to lambda-cyhalothrin found in three Tunisian field populations. We have studied the mechanism of resistance in the laboratory-selected resistant strain W-1Kλ (205-fold resistance). Bioassays with synergists showed that resistance was almost completely suppressed by the P450 inhibitor PBO. The study of the expression of 53 P450 genes belonging to the CYP4, CYP6, CYP9 and CYP12 families in C. capitata revealed that CYP6A51 was overexpressed (13-18-fold) in the resistant strain. The W-1Kλ strain also showed high levels of cross-resistance to etofenprox (240-fold) and deltamethrin (150-fold). Field-evolved resistance to lambda-cyhalothrin has been found in C. capitata. Metabolic resistance mediated by P450 appears to be the main resistance mechanism in the resistant strain W-1Kλ. The levels of cross-resistance found may compromise the effectiveness of other pyrethroids for the control of this species. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

22 CFR 213.25 - Standards for compromise.

Science.gov (United States)

2010-04-01

... proceedings. In evaluating the acceptability of the offer, the CFO may consider, among other factors, the... applicable exemptions available to the debtor under State and Federal law in determining the Government's ability to enforce collection. (b) USAID may compromise a claim, or recommend acceptance of a compromise...

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

Science.gov (United States)

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

20 CFR 255.18 - Compromise of overpayments.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compromise of overpayments. 255.18 Section 255.18 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT... standards which the Board applies in exercising its authority under 31 U.S.C. 3711 to compromise an...

16 CFR 1.96 - Compromise of penalty.

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Compromise of penalty. 1.96 Section 1.96 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL... may compromise any penalty or proposed penalty at any time, with leave of court when necessary, taking...

Arabidopsis MAP kinase 4 negatively regulates systemic acquired resistance

DEFF Research Database (Denmark)

Petersen, M.; Brodersen, P.; Naested, H.

2000-01-01

Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) revels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern...... of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression....

In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.

Science.gov (United States)

Schader, Susan M; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Colby-Germinario, Susan P; Wainberg, Mark A

2012-02-01

Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use of a microbicide may, however, lead to the development of drug resistance in users that are already, or become, infected with HIV-1. In such cases, the efficacy of treatments may be compromised since the same (or similar) antiretrovirals used in treatments are being developed as microbicides. To help predict which drug resistance mutations may develop in the context of suboptimal use, HIV-1 primary isolates of different subtypes and different baseline resistance profiles were used to infect primary cells in vitro in the presence of increasing suboptimal concentrations of the two candidate microbicide antiretrovirals dapivirine (DAP) and tenofovir (TFV) alone or in combination. Infections were ongoing for 25 weeks, after which reverse transcriptase genotypes were determined and scrutinized for the presence of any clinically recognized reverse transcriptase drug resistance mutations. Results indicated that suboptimal concentrations of DAP alone facilitated the emergence of common nonnucleoside reverse transcriptase inhibitor resistance mutations, while suboptimal concentrations of DAP plus TFV gave rise to fewer mutations. Suboptimal concentrations of TFV alone did not frequently result in the development of resistance mutations. Sensitivity evaluations for stavudine (d4T), nevirapine (NVP), and lamivudine (3TC) revealed that the selection of resistance as a consequence of suboptimal concentrations of DAP may compromise the potential for NVP to be used in treatment, a finding of potential relevance in developing countries.

V3-independent competitive resistance of a dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100.

Directory of Open Access Journals (Sweden)

Yosuke Maeda

Full Text Available A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The resistant variant displayed competitive resistance to the CXCR4 inhibitor AMD3100, indicating that the resistant variant had a higher affinity for CXCR4 than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the resistant variant harbored amino acid substitutions in the V2, C2, and C4 regions, but no remarkable changes in the V3 loop. Site-directed mutagenesis confirmed that the changes in the C2 and C4 regions were principally involved in the reduced sensitivity to AMD3100. Furthermore, the change in the C4 region was associated with increased sensitivity to soluble CD4, and profoundly enhanced the entry efficiency of the virus. Therefore, it is likely that the resistant variant acquired the higher affinity for CD4/CXCR4 by the changes in non-V3 regions. Taken together, a CXCR4 inhibitor-resistant HIV-1 can evolve using a non-V3 pathway.

Gamma processing of Arabic bread for immune system-compromised cancer patients

International Nuclear Information System (INIS)

Grecz, N.; Brannon, R.; Jaw, R.; Al-Harithy, R.; Hahn, E.W.

1985-01-01

Arabic bread prepared from local Saudi flour contained a total of up to 105 4 organisms per g. Most of these were bacterial spores that survived the baking process (1.3 x 10 2 to 3.5 x 10 3 ) and a small number of yeasts and molds (10 to 40 cells per g). The organisms in Arabic bread appear to be harmless to healthy individuals. However, for immune system-compromised cancer patients and bone marrow transplant recipients, it is prudent to irradiate the bread to reduce microbial contamination. The decimal reduction doses (10% survival) for the most radiation-resistant organisms (spore formers) in bread were 0.11 to 0.15 Mrad. Accordingly, 0.6 Mrad was sufficient to reduce the number of spores in Arabic bread by a factor of 10,000, i.e., to <1/g. This treatment constitutes radiation pasteurization (radicidation), and to this extent, provides a margin of microbiological safety. Sensory evaluation by the nine-point hedonic scale showed no detectable loss of organoleptic quality of bread up to 0.6 Mrad, while irradiation to 2.5 Mrad induced unacceptable organoleptic changes

Strained Compromises?

DEFF Research Database (Denmark)

Ibsen, Christian Lyhne

The Danish version of flexicurity is not only about a balance between labour market flexibility and social security. Arguably, it is also series of more or less stable underlying compromises between social partners about the main mechanisms and aims of labour market regulation which – supposedly...... – should be focused on employment rather than jobs and competition on quality rather than on labour costs. However, most studies on Danish flexicurity have been carried out under favourable economic conditions with social partners almost naturally agreeing to the merits of the model – at least in principle...

The human gut microbiota as a reservoir for antimicrobial resistance genes

NARCIS (Netherlands)

Bülow, E.

2015-01-01

In the last decades, the emergence and spread of resistant opportunistic pathogens is compromising the effectiveness of antimicrobial therapies. Understanding the emergence and global spread of drug-resistant microorganisms is thus crucial to combat antimicrobial resistance. The human gut harbors a

Compromised data from social media to big data

CERN Document Server

Redden, Joanna; Langlois, Ganaele

2015-01-01

There has been a data rush in the past decade brought about by online communication and, in particular, social media (Facebook, Twitter, Youtube, among others), which promises a new age of digital enlightenment. But social data is compromised: it is being seized by specific economic interests, it leads to a fundamental shift in the relationship between research and the public good, and it fosters new forms of control and surveillance. Compromised Data: From Social Media to Big Data explores how we perform critical research within a compromised social data framework. The expert, international l

Transgenic Cavendish bananas with resistance to Fusarium wilt tropical race 4.

Science.gov (United States)

Dale, James; James, Anthony; Paul, Jean-Yves; Khanna, Harjeet; Smith, Mark; Peraza-Echeverria, Santy; Garcia-Bastidas, Fernando; Kema, Gert; Waterhouse, Peter; Mengersen, Kerrie; Harding, Robert

2017-11-14

Banana (Musa spp.) is a staple food for more than 400 million people. Over 40% of world production and virtually all the export trade is based on Cavendish banana. However, Cavendish banana is under threat from a virulent fungus, Fusarium oxysporum f. sp. cubense tropical race 4 (TR4) for which no acceptable resistant replacement has been identified. Here we report the identification of transgenic Cavendish with resistance to TR4. In our 3-year field trial, two lines of transgenic Cavendish, one transformed with RGA2, a gene isolated from a TR4-resistant diploid banana, and the other with a nematode-derived gene, Ced9, remain disease free. Transgene expression in the RGA2 lines is strongly correlated with resistance. Endogenous RGA2 homologs are also present in Cavendish but are expressed tenfold lower than that in our most resistant transgenic line. The expression of these homologs can potentially be elevated through gene editing, to provide non-transgenic resistance.

Flow-based Compromise Detection

NARCIS (Netherlands)

Hofstede, R.J.

2016-01-01

Brute-force attacks are omnipresent and manyfold on the Internet, and aim at compromising user accounts by issuing large numbers of authentication attempts on applications and daemons. Widespread targets of such attacks are Secure SHell (SSH) and Web applications, for example. The impact of

Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.

Science.gov (United States)

Wise, Sarah K; Laury, Adrienne M; Katz, Elizabeth H; Den Beste, Kyle A; Parkos, Charles A; Nusrat, Asma

2014-05-01

Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier. Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure. Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. © 2014 ARS-AAOA, LLC.

IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

Science.gov (United States)

Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

2014-01-01

Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

41 CFR 105-55.019 - Compromise of claims.

Science.gov (United States)

2010-07-01

... and a recommendation for the acceptance of the compromise offer. Justice Department approval is not... exercise the authorities in this section. (b) Unless otherwise provided by law, when the principal balance... Department of Justice. GSA will evaluate the compromise offer, using the factors set forth in § 105-55.020...

Arsenite promotes centrosome abnormalities under a p53 compromised status induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

International Nuclear Information System (INIS)

Liao, W.-T.; Yu, H.-S.; Lin Pinpin; Chang, Louis W.

2010-01-01

Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus an interaction between arsenite and cigarette smoking in lung carcinogenesis was suspected. In the present study, we investigated the interactions of a tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK) and arsenite on lung cell transformation. BEAS-2B, an immortalized human lung epithelial cell line, was selected to test the centrosomal abnormalities and colony formation by NNK and arsenite. We found that NNK, alone, could enhance BEAS-2B cell growth at 1-5 μM. Under NNK exposure, arsenite was able to increase centrosomal abnormality as compared with NNK or arsenite treatment alone. NNK treatment could also reduce arsenite-induced G2/M cell cycle arrest and apoptosis, these cellular effects were found to be correlated with p53 dysfunction. Increased anchorage-independent growth (colony formation) of BEAS-2B cells cotreated with NNK and arsenite was also observed in soft agar. Our present investigation demonstrated that NNK could provide a p53 compromised status. Arsenite would act specifically on this p53 compromised status to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenite under tobacco-specific carcinogen co-exposure.

Combating QR-Code-Based Compromised Accounts in Mobile Social Networks.

Science.gov (United States)

Guo, Dong; Cao, Jian; Wang, Xiaoqi; Fu, Qiang; Li, Qiang

2016-09-20

Cyber Physical Social Sensing makes mobile social networks (MSNs) popular with users. However, such attacks are rampant as malicious URLs are spread covertly through quick response (QR) codes to control compromised accounts in MSNs to propagate malicious messages. Currently, there are generally two types of methods to identify compromised accounts in MSNs: one type is to analyze the potential threats on wireless access points and the potential threats on handheld devices' operation systems so as to stop compromised accounts from spreading malicious messages; the other type is to apply the method of detecting compromised accounts in online social networks to MSNs. The above types of methods above focus neither on the problems of MSNs themselves nor on the interaction of sensors' messages, which leads to the restrictiveness of platforms and the simplification of methods. In order to stop the spreading of compromised accounts in MSNs effectively, the attacks have to be traced to their sources first. Through sensors, users exchange information in MSNs and acquire information by scanning QR codes. Therefore, analyzing the traces of sensor-related information helps to identify the compromised accounts in MSNs. This paper analyzes the diversity of information sending modes of compromised accounts and normal accounts, analyzes the regularity of GPS (Global Positioning System)-based location information, and introduces the concepts of entropy and conditional entropy so as to construct an entropy-based model based on machine learning strategies. To achieve the goal, about 500,000 accounts of Sina Weibo and about 100 million corresponding messages are collected. Through the validation, the accuracy rate of the model is proved to be as high as 87.6%, and the false positive rate is only 3.7%. Meanwhile, the comparative experiments of the feature sets prove that sensor-based location information can be applied to detect the compromised accounts in MSNs.

Combating QR-Code-Based Compromised Accounts in Mobile Social Networks

Directory of Open Access Journals (Sweden)

Dong Guo

2016-09-01

Full Text Available Cyber Physical Social Sensing makes mobile social networks (MSNs popular with users. However, such attacks are rampant as malicious URLs are spread covertly through quick response (QR codes to control compromised accounts in MSNs to propagate malicious messages. Currently, there are generally two types of methods to identify compromised accounts in MSNs: one type is to analyze the potential threats on wireless access points and the potential threats on handheld devices’ operation systems so as to stop compromised accounts from spreading malicious messages; the other type is to apply the method of detecting compromised accounts in online social networks to MSNs. The above types of methods above focus neither on the problems of MSNs themselves nor on the interaction of sensors’ messages, which leads to the restrictiveness of platforms and the simplification of methods. In order to stop the spreading of compromised accounts in MSNs effectively, the attacks have to be traced to their sources first. Through sensors, users exchange information in MSNs and acquire information by scanning QR codes. Therefore, analyzing the traces of sensor-related information helps to identify the compromised accounts in MSNs. This paper analyzes the diversity of information sending modes of compromised accounts and normal accounts, analyzes the regularity of GPS (Global Positioning System-based location information, and introduces the concepts of entropy and conditional entropy so as to construct an entropy-based model based on machine learning strategies. To achieve the goal, about 500,000 accounts of Sina Weibo and about 100 million corresponding messages are collected. Through the validation, the accuracy rate of the model is proved to be as high as 87.6%, and the false positive rate is only 3.7%. Meanwhile, the comparative experiments of the feature sets prove that sensor-based location information can be applied to detect the compromised accounts in MSNs.

Insulin Resistance in Alzheimer's Disease

Science.gov (United States)

Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

2014-01-01

Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

Functional characterization of the antibiotic resistance reservoir in the human microflora

DEFF Research Database (Denmark)

Sommer, Morten; Church, George M; Dantas, Gautam

2010-01-01

The increasing levels of multi-drug resistance in human pathogenic bacteria are compromising our ability to treat infectious disease. Since antibiotic resistance determinants are readily exchanged between bacteria through lateral gene transfer, there is an increasing interest in investigating res...

Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases.

Directory of Open Access Journals (Sweden)

Craig B Wilen

2011-04-01

Full Text Available HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5 virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4 in place of or in addition to CCR5 (R5X4 remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals.

New wheat-rye 5DS-4RS·4RL and 4RS-5DS·5DL translocation lines with powdery mildew resistance.

Science.gov (United States)

Fu, Shulan; Ren, Zhenglong; Chen, Xiaoming; Yan, Benju; Tan, Feiquan; Fu, Tihua; Tang, Zongxiang

2014-11-01

Powdery mildew is one of the serious diseases of wheat (Triticum aestivum L., 2 n = 6 × = 42, genomes AABBDD). Rye (Secale cereale L., 2 n = 2 × = 14, genome RR) offers a rich reservoir of powdery mildew resistant genes for wheat breeding program. However, extensive use of these resistant genes may render them susceptible to new pathogen races because of co-evolution of host and pathogen. Therefore, the continuous exploration of new powdery mildew resistant genes is important to wheat breeding program. In the present study, we identified several wheat-rye addition lines from the progeny of T. aestivum L. Mianyang11 × S. cereale L. Kustro, i.e., monosomic addition lines of the rye chromosomes 4R and 6R; a disomic addition line of 6R; and monotelosomic or ditelosomic addition lines of the long arms of rye chromosomes 4R (4 RL) and 6R (6 RL). All these lines displayed immunity to powdery mildew. Thus, we concluded that both the 4 RL and 6 RL arms of Kustro contain powdery mildew resistant genes. It is the first time to discover that 4 RL arm carries powdery mildew resistant gene. Additionally, wheat lines containing new wheat-rye translocation chromosomes were also obtained: these lines retained a short arm of wheat chromosome 5D (5 DS) on which rye chromosome 4R was fused through the short arm 4 RS (designated 5 DS-4 RS · 4 RL; 4 RL stands for the long arm of rye chromosome 4R); or they had an extra short arm of rye chromosome 4R (4 RS) that was attached to the short arm of wheat chromosome 5D (5 DS) (designated 4 RS-5 DS · 5 DL; 5 DL stands for the long arm of wheat chromosome 5D). These two translocation chromosomes could be transmitted to next generation stably, and the wheat lines containing 5 DS-4 RS · 4 RL chromosome also displayed immunity to powdery mildew. The materials obtained in this study can be used for wheat powdery mildew resistant breeding program.

32 CFR 310.50 - Lost, stolen, or compromised information.

Science.gov (United States)

2010-07-01

... Official for Privacy within 24 hours of discovering that a breach of personally identifiable information... Privacy Office of the breach within 48 hours upon being notified that a loss, theft, or compromise has... (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Privacy Act Violations § 310.50 Lost, stolen, or compromised...

Physically Compromised and Physically Talented Children in Northeastern Slovenia

Directory of Open Access Journals (Sweden)

Planinšec Jurij

2012-12-01

Full Text Available The aim of our research was to determine the share of physically compromised and physically talented children in northeastern Slovenia. The sample comprised 621 children aged nine to eleven years, among which there were 316 girls (M=10; SD=0.8 and 305 boys (M=10; SD=0.81. In order to assess their motor skills, seven different tests were used, mostly from Eurofit test battery, which covered explosive power, repetitive power balance, eye–hand coordination, speed of simple movements, whole body coordination, and endurance. The assessment was made for each physical fitness test separately. The cut-off points for determination of physically compromised and physically talented children were set at -1SD and +1SD, respectively. The results of all physical fitness tests showed that the share of physically compromised children exceeded ten percent for both genders. The largest number of boys and girls were physically compromised with regard to endurance and balance, respectively. On the other hand, boys proved to be most physically talented with regard to endurance, and girls with regard to explosive power. Gender differences were most obvious with regard to general endurance, as 21 per cent of the boys were physically compromised as opposed to 13 per cent of the girls. As for physical talent, we observed less gender-related differences. The results indicate increasing differences in physical fitness among children from northeastern Slovenia. The implementation of curricular and extracurricular sports activities should aim at reducing the number of physically compromised children. On the other hand, it would make sense to encourage physically talented children to get involved in organized forms of exercise.

Mechanisms linking brain insulin resistance to Alzheimer's disease

Science.gov (United States)

Matioli, Maria Niures P.S.; Nitrini, Ricardo

2015-01-01

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection. PMID:29213950

Mechanisms linking brain insulin resistance to Alzheimer's disease

Directory of Open Access Journals (Sweden)

Maria Niures P.S. Matioli

Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

Outcomes of Soft Tissue Reconstruction for Traumatic Lower Extremity Fractures with Compromised Vascularity.

Science.gov (United States)

Badash, Ido; Burtt, Karen E; Leland, Hyuma A; Gould, Daniel J; Rounds, Alexis D; Azadgoli, Beina; Patel, Ketan M; Carey, Joseph N

2017-10-01

Traumatic lower extremity fractures with compromised arterial flow are limb-threatening injuries. A retrospective review of 158 lower extremities with traumatic fractures, including 26 extremities with arterial injuries, was performed to determine the effects of vascular compromise on flap survival, successful limb salvage and complication rates. Patients with arterial injuries had a larger average flap surface area (255.1 vs 144.6 cm2, P = 0.02) and a greater number of operations (4.7 vs 3.8, P = 0.01) than patients without vascular compromise. Patients presenting with vascular injury were also more likely to require fasciotomy [odds ratio (OR): 6.5, confidence interval (CI): 2.3-18.2] and to have a nerve deficit (OR: 16.6, CI: 3.9-70.0), fracture of the distal third of the leg (OR: 2.9, CI: 1.15-7.1) and intracranial hemorrhage (OR: 3.84, CI: 1.1-12.9). After soft tissue reconstruction, patients with arterial injuries had a higher rate of amputation (OR: 8.5, CI: 1.3-53.6) and flap failure requiring a return to the operating room (OR: 4.5, CI: 1.5-13.2). Arterial injury did not correlate with infection or overall complication rate. In conclusion, arterial injuries resulted in significant complications for patients with lower extremity fractures requiring flap coverage, although limb salvage was still effective in most cases.

Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

Science.gov (United States)

Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

Respiratory Failure Associated with the Lipodystrophy Syndrome in an HIV-Positive Patient with Compromised Lung Function

Directory of Open Access Journals (Sweden)

Natasha Press

2001-01-01

Full Text Available Protease inhibitors, used as treatment in human immunodeficiency virus (HIV infection, are associated with a syndrome of peripheral lipodystrophy, central adiposity, hyperlipidemia and insulin resistance. An HIV-positive patient with chronic obstructive pulmonary disease is presented who developed the lipodystrophy syndrome that is associated with the use of protease inhibitors. It is postulated that the lipodystrophy syndrome further compromised his lung function, leading to respiratory failure. Patients who have pulmonary disease and are taking protease inhibitors require monitoring of clinical status and pulmonary function tests.

Insecticide Resistance Reducing Effectiveness of Malaria Control

Centers for Disease Control (CDC) Podcasts

Malaria prevention is increasingly insecticide based. Dr. John Gimnig, an entomologist with the Division of Parasitic Diseases, CDC, discusses evidence that mosquito resistance to insecticides, which is measured in the laboratory, could compromise malaria prevention in the field.

Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

Science.gov (United States)

Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

2017-01-01

Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin.

Directory of Open Access Journals (Sweden)

Sheena D Singh

2009-07-01

Full Text Available Candida albicans is the leading fungal pathogen of humans, causing life-threatening disease in immunocompromised individuals. Treatment of candidiasis is hampered by the limited number of antifungal drugs whose efficacy is compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. We previously established that the molecular chaperone Hsp90, which regulates the form and function of diverse client proteins, potentiates resistance to the azoles in C. albicans and in the model yeast Saccharomyces cerevisiae. Genetic studies in S. cerevisiae revealed that Hsp90's role in azole resistance is to enable crucial cellular responses to the membrane stress exerted by azoles via the client protein calcineurin. Here, we demonstrate that Hsp90 governs cellular circuitry required for resistance to the only new class of antifungals to reach the clinic in decades, the echinocandins, which inhibit biosynthesis of a critical component of the fungal cell wall. Pharmacological or genetic impairment of Hsp90 function reduced tolerance of C. albicans laboratory strains and resistance of clinical isolates to the echinocandins and created a fungicidal combination. Compromising calcineurin function phenocopied compromising Hsp90 function. We established that calcineurin is an Hsp90 client protein in C. albicans: reciprocal co-immunoprecipitation validated physical interaction; Hsp90 inhibition blocked calcineurin activation; and calcineurin levels were depleted upon genetic reduction of Hsp90. The downstream effector of calcineurin, Crz1, played a partial role in mediating calcineurin-dependent stress responses activated by echinocandins. Hsp90's role in echinocandin resistance has therapeutic potential given that genetic compromise of C. albicans HSP90 expression enhanced the efficacy of an echinocandin in a murine model of disseminated candidiasis. Our results identify the first Hsp90 client protein in C. albicans, establish an entirely

Silencing of the Rice Gene LRR1 Compromises Rice Xa21 Transcript Accumulation and XA21-Mediated Immunity.

Science.gov (United States)

Caddell, Daniel F; Park, Chang-Jin; Thomas, Nicholas C; Canlas, Patrick E; Ronald, Pamela C

2017-12-01

The rice immune receptor XA21 confers resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. We previously demonstrated that an auxilin-like protein, XA21 BINDING PROTEIN 21 (XB21), positively regulates resistance to Xoo. To further investigate the function of XB21, we performed a yeast two-hybrid screen. We identified 22 unique XB21 interacting proteins, including LEUCINE-RICH REPEAT PROTEIN 1 (LRR1), which we selected for further analysis. Silencing of LRR1 in the XA21 genetic background (XA21-LRR1Ri) compromises resistance to Xoo compared with control XA21 plants. XA21-LRR1Ri plants have reduced Xa21 transcript levels and reduced expression of genes that serve as markers of XA21-mediated activation. Overexpression of LRR1 is insufficient to alter resistance to Xoo in rice lines lacking XA21. Taken together, our results indicate that LRR1 is required for wild-type Xa21 transcript expression and XA21-mediated immunity.

Dealing with antimicrobial resistance - the Danish experience

DEFF Research Database (Denmark)

Bager, Flemming; Aarestrup, Frank Møller; Wegener, Henrik Caspar

2000-01-01

(DANMAP), which monitors resistance among bacteria from food animals, food and humans. A programme to monitor all use of prescription medicine in food animals at the herd level is presently being implemented. Another initiative was the elaboration of a series of practical recommendations to veterinarians...... on the prudent use of antimicrobials in order to reduce the development of resistance without compromising therapeutic efficacy. Our experience with avoparcin shows that a restrictive policy on the use of antimicrobials can curb the development of resistance. However, the occurrence and persistence of specific...

Compromise decision support problems for hierarchical design involving uncertainty

Science.gov (United States)

Vadde, S.; Allen, J. K.; Mistree, F.

1994-08-01

In this paper an extension to the traditional compromise Decision Support Problem (DSP) formulation is presented. Bayesian statistics is used in the formulation to model uncertainties associated with the information being used. In an earlier paper a compromise DSP that accounts for uncertainty using fuzzy set theory was introduced. The Bayesian Decision Support Problem is described in this paper. The method for hierarchical design is demonstrated by using this formulation to design a portal frame. The results are discussed and comparisons are made with those obtained using the fuzzy DSP. Finally, the efficacy of incorporating Bayesian statistics into the traditional compromise DSP formulation is discussed and some pending research issues are described. Our emphasis in this paper is on the method rather than the results per se.

Infective endocarditis caused by multidrug-resistant Streptococcus mitis in a combined immunocompromised patient: an autopsy case report.

Science.gov (United States)

Matsui, Natsuko; Ito, Makoto; Kuramae, Hitoshi; Inukai, Tomomi; Sakai, Akiyoshi; Okugawa, Masaru

2013-04-01

An autopsy case of infective endocarditis caused by multidrug-resistant Streptococcus mitis was described in a patient with a combination of factors that compromised immune status, including autoimmune hemolytic anemia, post-splenectomy state, prolonged steroid treatment, and IgA deficiency. The isolated S. mitis strain from blood culture was broadly resistant to penicillin, cephalosporins, carbapenem, macrolides, and fluoroquinolone. Recurrent episodes of bacterial infections and therapeutic use of several antibiotics may underlie the development of multidrug resistance for S. mitis. Because clinically isolated S. mitis strains from chronically immunocompromised patients have become resistant to a wide spectrum of antibiotics, appropriate antibiotic regimens should be selected when treating invasive S. mitis infections in these compromised patients.

Near-infrared spectroscopy for detection of vascular compromise in paediatric supracondylar fractures

International Nuclear Information System (INIS)

Skowno, Justin J; De Lima, Jonathan; Quick, Tom J; Carpenter, Eleanor C; Gibbons, Paul J; Little, David G

2014-01-01

Children suffering supracondylar fractures of the humerus are at risk of vascular compromise, which is currently assessed clinically, although other modalities such as angiography, pulse oximetry, Doppler ultrasound and magnetic resonance angiography have been used. We sought to ascertain whether tissue haemoglobin oxygenation (StO 2 ) measurement could distinguish between patients with and without clinical vascular compromise following supracondylar fractures of the humerus. We prospectively observed StO 2  using near-infrared spectroscopy in 29 paediatric patients with supracondylar fractures requiring operative manipulation. The injured and uninjured volar forearm compartments were monitored immediately before and after fracture reduction. The relationship between StO 2  in the injured and uninjured limb, and the presence of pre-operative vascular compromise was assessed. Seven out of 29 children presented with vascular compromise. Patients with clinical vascular compromise had significantly lower pre-reduction StO 2  (63.5% ± 15%, mean ± standard deviation), compared to those without compromise (80.9% ± 10%). StO 2  normalized following surgery in all children with vascular compromise. These improvements in muscle StO 2  were associated, in all patients, with the clinical return of pulses and resolution of neurological symptoms if present. StO 2  monitoring can identify patients with clinical vascular compromise, can identify the return of adequate perfusion following operative correction of supracondylar fractures, and may be a useful adjunct to clinical assessment. (paper)

Oxidant resistance in a yeast mutant deficient in the Sit4 phosphatase

DEFF Research Database (Denmark)

López-Mirabal, H Reynaldo; Winther, Jakob R; Kielland-Brandt, Morten C

2008-01-01

Resistance to thiol oxidation can arise from mutations altering redox homeostasis. A Saccharomyces cerevisiae sit4-110 mutant is here described, which was isolated as resistant to the thiol-specific oxidant dipyridyl disulfide (DPS) and which contains a single-residue substitution in the SIT4 gene...

When data representation compromise data security

DEFF Research Database (Denmark)

Simonsen, Eivind Ortind; Dahl, Mads Ronald

WHEN DATA REPRESENTATION COMPROMISE DATA SECURITY The workflow of transforming data into informative representations makes extensive usage of computers and software. Scientists have a conventional tradition for producing publications that include tables and graphs as data representations....... These representations can be used for multiple purposes such as publications in journals, teaching and conference material. But when created, stored and distributed in a digital form there is a risk of compromising data security. Data beyond the once used specifically to create the representation can be included...... on the internet over many years? A new legislation proposed in 2012 by the European Commission on protection of personal data will be implemented from 2015. The new law will impose sanction options ranging from a warning to a fine up to 100.000.000 EUR. We argue that this new law will lead to especially...

Tax Administration: IRS Should Evaluate the Changes to Its Offer in Compromise Program

National Research Council Canada - National Science Library

2002-01-01

...) Offer in Compromise (OIC) Program. An offer in compromise is an agreement between a taxpayer and the IRS to settle or compromise the taxpayer's tax liability for less than the full amount owed...

The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis.

Science.gov (United States)

Ibrahim, Sulaiman S; Riveron, Jacob M; Stott, Robert; Irving, Helen; Wondji, Charles S

2016-01-01

Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Objections to the Libertarian Stem Cell Compromise

Directory of Open Access Journals (Sweden)

Walter E. Block

2010-11-01

Full Text Available In Block (2010 I offered a compromise between the pro choice position that fervently supports stem cell research, and the pro life philosophy which bitterly opposes it. The compromise was a contest: allow would be researchers to create as many fertilized eggs as they wished. But, also, these should be offered up to would be parents to adopt all of these “children” as they wanted. If and only if there were any unadopted fetuses remaining in the laboratories of the nation would it be licit, on libertarian grounds, for research on them to take place. In the present paper I respond to several objections to this “modest proposal.”

7 CFR 1956.68 - Compromise or adjustment without debtor's signature.

Science.gov (United States)

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Compromise or adjustment without debtor's signature... Loan Programs and Multi-Family Housing § 1956.68 Compromise or adjustment without debtor's signature... made to obtain the debtor's signature and the date(s) of such effort. (c) The specific reasons why it...

32 CFR 842.99 - Compromise, termination, and suspension of collection.

Science.gov (United States)

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Compromise, termination, and suspension of collection. 842.99 Section 842.99 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR... States (31 U.S.C. 3701, 3711-3719) § 842.99 Compromise, termination, and suspension of collection. This...

Enhanced 2,4-D Metabolism in Two Resistant Papaver rhoeas Populations from Spain

Directory of Open Access Journals (Sweden)

Joel Torra

2017-09-01

Full Text Available Corn poppy (Papaver rhoeas, the most problematic broadleaf weed in winter cereals in Southern Europe, has developed resistance to the widely-used herbicide, 2,4-D. The first reported resistance mechanism in this species to 2,4-D was reduced translocation from treated leaves to the rest of the plant. However, the presence of other non-target site resistance (NTSR mechanisms has not been investigated up to date. Therefore, the main objective of this research was to reveal if enhanced 2,4-D metabolism is also present in two Spanish resistant (R populations to synthetic auxins. With this aim, HPLC experiments at two 2,4-D rates (600 and 2,400 g ai ha−1 were conducted to identify and quantify the metabolites produced and evaluate possible differences in 2,4-D degradation between resistant (R and susceptible (S plants. Secondarily, to determine the role of cytochrome P450 in the resistance response, dose-response experiments were performed using malathion as its inhibitor. Three populations were used: S, only 2,4-D R (R-703 and multiple R to 2,4-D and ALS inhibitors (R-213. HPLC studies indicated the presence of two hydroxy metabolites in these R populations in shoots and roots, which were not detected in S plants, at both rates. Therefore, enhanced metabolism becomes a new NTSR mechanism in these two P. rhoeas populations from Spain. Results from the dose-response experiments also showed that pre-treatment of R plants with the cytochrome P450 (P450 inhibitor malathion reversed the phenotype to 2,4-D from resistant to susceptible in both R populations. Therefore, it could be hypothesized that a malathion inhibited P450 is responsible of the formation of the hydroxy metabolites detected in the metabolism studies. This and previous research indicate that two resistant mechanisms to 2,4-D could be present in populations R-703 and R-213: reduced translocation and enhanced metabolism. Future experiments are required to confirm these hypotheses

Genome Comparison of Erythromycin Resistant Campylobacter from Turkeys Identifies Hosts and Pathways for Horizontal Spread of erm(B Genes

Directory of Open Access Journals (Sweden)

Diego Florez-Cuadrado

2017-11-01

Full Text Available Pathogens in the genus Campylobacter are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in Campylobacter is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene erm(B between strains. Here, we evaluate resistance to six antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni from turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni were screened for the presence of the erm(B gene, that has not previously been identified in isolates from turkeys. The genomes of two positive C. coli isolates were sequenced and in both isolates the erm(B gene clustered with resistance determinants against aminoglycosides plus tetracycline, including aad9, aadE, aph(2″-IIIa, aph(3′-IIIa, and tet(O genes. Comparative genomic analysis identified identical erm(B sequences among Campylobacter from turkeys, Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.

Acute gastrointestinal compromise in neonates with congenital diaphragmatic hernia prior to repair.

Science.gov (United States)

Fox, Catherine; Stewart, Michael; King, Sebastian K; Patel, Neil

2016-12-01

Congenital diaphragmatic hernia (CDH) affects 1 in 3000 live births. Modern management strategies include delayed repair of the diaphragm to permit pre-operative optimization of cardiorespiratory status. We describe a cohort of neonates in whom early emergency operative intervention was required for potentially fatal intestinal compromise. A retrospective review was performed of all neonatal CDH patients managed at a tertiary center in an 8-year period (2005-2012). A total of 126 CDH patients were managed during the 8-year period. Five neonates (male - 1; gestation 37+4-39+7; birth weight 2.9-3.7kg; left CDH - 5) required emergency operative intervention for presumed gastrointestinal compromise. All five neonates demonstrated systemic hypotension despite inotropic support, raised serum lactate (>2mmol/L), and abnormal radiographic findings. Operative intervention occurred within 3days of birth (1-3days). Findings included gastric volvulus, jejunal volvulus, and perforated caecum. All patients underwent primary diaphragmatic repair without a patch. Temporary ileostomy was required in 1 patient. All patients remain alive. Gastrointestinal compromise is a rare, but potentially catastrophic, complication of CDH. Emergency operative intervention may be required in a select cohort of patients. Early deterioration following birth should alert clinicians to the possibility of significant intestinal pathology. Level IV case series with no comparison group. Copyright © 2016 Elsevier Inc. All rights reserved.

Neratinib resistance and cross-resistance to other HER2-targeted drugs due to increased activity of metabolism enzyme cytochrome P4503A4.

Science.gov (United States)

Breslin, Susan; Lowry, Michelle C; O'Driscoll, Lorraine

2017-02-28

Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to neratinib was assessed. Cellular phenotype changes were evaluated using migration, invasion and anoikis assays. Immunoblotting for HER family members and drug efflux pumps, as well as enzyme activity assays were performed. Neratinib resistance conferred cross-resistance to trastuzumab, lapatinib and afatinib. Furthermore, the efficacy of neratinib was reduced in trastuzumab- and lapatinib-resistant cells. Neratinib-resistant cells were more aggressive than their drug-sensitive counterparts, with increased CYP3A4 activity identified as a novel mechanism of neratinib resistance. The potential of increased CYP3A4 activity as a biomarker and/or target to add value to neratinib warrants investigation.

10 CFR 15.41 - When a claim may be compromised.

Science.gov (United States)

2010-01-01

... it has not been referred to DOJ for litigation. (b) Unless otherwise provided by law, when the... with the DOJ. The NRC will evaluate the compromise offer, using the factors set forth in this part. If an offer to compromise any debt in excess of $100,000 is acceptable to the NRC, the NRC shall refer...

Evaluation of instant cup noodle, irradiated for immuno-compromised patients

International Nuclear Information System (INIS)

Lee, Ji-Hye; Kim, Jae-Kyung; Park, Jae-Nam; Yoon, Young-Min; Sung, Nak-Yun; Kim, Jae-Hun; Song, Beom-Seok; Yook, Hong-Sun; Kim, Byeong-Keun; Lee, Ju-Woon

2012-01-01

In the present study, initial microbial load of instant cup noodle (ICN) was investigated and gamma irradiation applied to develop immuno-compromised patients food for their safe consumption. The initial microbial population of dried vegetable and meat, and noodle was below the detection limit (1 log CFU/g); however, that of seasoning powder was just above 4 log CFU/g. Moreover, rehydrated-ICN with water at 100 °C still show above 3 log CFU/g of microbial load, which indicates the need for an additional process to control microbial safety of the seasoning powder. The total aerobic bacteria in seasoning powder and rehydrated-ICN could be controlled with 17 kGy gamma irradiation. This result referred 17 kGy gamma irradiation could reach ‘practical sterility’ of ICN. The overall difference in sensory properties between the non-irradiated and irradiated ICN was insignificant. Thus, gamma irradiation could improve the microbial quality of ICN, and reduce the risk of infection posed by the seasoning powder, without any adverse effects on their sensory quality. These results suggest that gamma-irradiated ICN can be used as a snack food for immuno-compromised patients.

Evaluation of instant cup noodle, irradiated for immuno-compromised patients

Science.gov (United States)

Lee, Ji-Hye; Kim, Jae-Kyung; Park, Jae-Nam; Yoon, Young-Min; Sung, Nak-Yun; Kim, Jae-Hun; Song, Beom-Seok; Yook, Hong-Sun; Kim, Byeong-Keun; Lee, Ju-Woon

2012-08-01

In the present study, initial microbial load of instant cup noodle (ICN) was investigated and gamma irradiation applied to develop immuno-compromised patients food for their safe consumption. The initial microbial population of dried vegetable and meat, and noodle was below the detection limit (1 log CFU/g); however, that of seasoning powder was just above 4 log CFU/g. Moreover, rehydrated-ICN with water at 100 °C still show above 3 log CFU/g of microbial load, which indicates the need for an additional process to control microbial safety of the seasoning powder. The total aerobic bacteria in seasoning powder and rehydrated-ICN could be controlled with 17 kGy gamma irradiation. This result referred 17 kGy gamma irradiation could reach 'practical sterility' of ICN. The overall difference in sensory properties between the non-irradiated and irradiated ICN was insignificant. Thus, gamma irradiation could improve the microbial quality of ICN, and reduce the risk of infection posed by the seasoning powder, without any adverse effects on their sensory quality. These results suggest that gamma-irradiated ICN can be used as a snack food for immuno-compromised patients.

Strained Compromises? Danish Flexicurity During Crisis

DEFF Research Database (Denmark)

Ibsen, Christian Lyhne

2011-01-01

The Danish concept of flexicurity in a ‘Golden Triangle’ of low job protection, high income security and high employment security is not only about a balance between labor market flexibility and social security. Arguably, it is also a series of more or less stable underlying compromises between...

TNFα-Induced Mucin 4 Expression Elicits Trastuzumab Resistance in HER2-Positive Breast Cancer.

Science.gov (United States)

Mercogliano, María F; De Martino, Mara; Venturutti, Leandro; Rivas, Martín A; Proietti, Cecilia J; Inurrigarro, Gloria; Frahm, Isabel; Allemand, Daniel H; Deza, Ernesto Gil; Ares, Sandra; Gercovich, Felipe G; Guzmán, Pablo; Roa, Juan C; Elizalde, Patricia V; Schillaci, Roxana

2017-02-01

Although trastuzumab administration improved the outcome of HER2-positive breast cancer patients, resistance events hamper its clinical benefits. We demonstrated that TNFα stimulation in vitro induces trastuzumab resistance in HER2-positive breast cancer cell lines. Here, we explored the mechanism of TNFα-induced trastuzumab resistance and the therapeutic strategies to overcome it. Trastuzumab-sensitive breast cancer cells, genetically engineered to stably overexpress TNFα, and de novo trastuzumab-resistant tumors, were used to evaluate trastuzumab response and TNFα-blocking antibodies effectiveness respectively. Immunohistochemistry and antibody-dependent cell cytotoxicity (ADCC), together with siRNA strategy, were used to explore TNFα influence on the expression and function of its downstream target, mucin 4 (MUC4). The clinical relevance of MUC4 expression was studied in a cohort of 78 HER2-positive breast cancer patients treated with adjuvant trastuzumab. TNFα overexpression turned trastuzumab-sensitive cells and tumors into resistant ones. Histopathologic findings revealed mucin foci in TNFα-producing tumors. TNFα induced upregulation of MUC4 that reduced trastuzumab binding to its epitope and impaired ADCC. Silencing MUC4 enhanced trastuzumab binding, increased ADCC, and overcame trastuzumab and trastuzumab-emtansine antiproliferative effects in TNFα-overexpressing cells. Accordingly, administration of TNFα-blocking antibodies downregulated MUC4 and sensitized de novo trastuzumab-resistant breast cancer cells and tumors to trastuzumab. In HER2-positive breast cancer samples, MUC4 expression was found to be an independent predictor of poor disease-free survival (P = 0.008). We identified TNFα-induced MUC4 expression as a novel trastuzumab resistance mechanism. We propose MUC4 expression as a predictive biomarker of trastuzumab efficacy and a guide to combination therapy of TNFα-blocking antibodies with trastuzumab. Clin Cancer Res; 23(3); 636-48. �

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

Science.gov (United States)

Reyna, Sara M; Ghosh, Sangeeta; Tantiwong, Puntip; Meka, C S Reddy; Eagan, Phyllis; Jenkinson, Christopher P; Cersosimo, Eugenio; Defronzo, Ralph A; Coletta, Dawn K; Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.

Large resistive-switching phenomena observed in Ag/Si3N4/Al memory cells

International Nuclear Information System (INIS)

Kim, Hee-Dong; An, Ho-Myoung; Kim, Kyoung Chan; Seo, Yujeong; Kim, Tae Geun; Nam, Ki-Hyun; Chung, Hong-Bay; Lee, Eui Bok

2010-01-01

An effective resistive-switching effect has been observed in silicon nitride (Si 3 N 4 ) dielectrics in Ag/Si 3 N 4 /Al memory cells. The ratio of the low resistance to high resistance state was larger than 10 7 at ±1.2 V for a 10 nm thick Si 3 N 4 layer. This switching behavior is attributed to a change in the conductivity of the Si 3 N 4 dielectrics, depending on whether nitride-related traps are filled with electrons under positive biases or unfilled under negative biases. This assertion is experimentally confirmed from the relationship between the amount of charges trapped in the Si 3 N 4 layer and the corresponding changes in its resistance with respect to bias voltages. In addition, the formation or dissolution of the conductive path is confirmed by conductive atomic force microscopy current images

Securing Single Points of Compromise (SPoC)

Energy Technology Data Exchange (ETDEWEB)

Belangia, David Warren [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-06-25

Securing the Single Points of Compromise that provide central services to the institution’s environment is paramount to success when trying to protect the business. (Fisk, 2014) Time Based Security mandates protection (erecting and ensuring effective controls) that last longer than the time to detect and react to a compromise. When enterprise protections fail, providing additional layered controls for these central services provides more time to detect and react. While guidance is readily available for securing the individual critical asset, protecting these assets as a group is not often discussed. Using best business practices to protect these resources as individual assets while leveraging holistic defenses for the group increases the opportunity to maximize protection time, allowing detection and reaction time for the SPoCs that is commensurate with the inherent risk of these centralized services.

A model of antibiotic-resistant bacterial epidemics in hospitals

OpenAIRE

Webb, Glenn F.; D'Agata, Erika M. C.; Magal, Pierre; Ruan, Shigui

2005-01-01

The emergence of drug-resistant strains of bacteria is an increasing threat to society, especially in hospital settings. Many antibiotics that were formerly effective in combating bacterial infections in hospital patients are no longer effective because of the evolution of resistant strains, which compromises medical care worldwide. In this article, we formulate a two-level population model to quantify key elements in nosocomial (hospital-acquired) infections. At the bacteria level, patients ...

Improving cylinder-type LiFePO4 battery performance via control of internal resistance

Science.gov (United States)

Purwanto, Agus; Jumari, Arif; Nizam, Muhammad; Widiyandari, Hendri; Sudaryanto; Deswita; Azmin Mohamad, Ahmad

2018-04-01

Strategies for controlling the internal resistance to improve battery performance were systematically investigated. Electrode densification of LiFePO4 cathodes significantly reduced the internal resistance of the prepared batteries. Densification by reduction to 31.25% of initial thickness resulted in optimal electrochemical performance of the prepared LiFePO4 batteries. The addition of KS 6 graphite material improved the conductivity of the cathodes, which was indicated by a lowering of the internal resistance. The internal resistance was decreased from 73 to 54 when the KS6/AB ratio was varied from 3 to 1. Another factor in controlling the internal resistance was the location of a welded aluminum tab in the cathode. The welding of an aluminum tab in a small gap in the cathode significantly reduced the internal resistance. Thus, three main factors can be performed during fabrication to reduce the internal resistance of a LiFePO4 battery: cathode densification, KS-6 graphite addition, and the arrangement of an aluminum tab welded to the cathode. By optimizing these factors, high-performance LFP batteries were produced.

Antimicrobial resistance of F4+ Escherichia coli isolated from Swine in Italy.

Science.gov (United States)

Luppi, A; Bonilauri, P; Dottori, M; Gherpelli, Y; Biasi, G; Merialdi, G; Maioli, G; Martelli, P

2015-02-01

Four-hundred and forty-two F4+ pathogenic Escherichia coli were isolated in a period of 10 years (2002-2011), from pigs that were suffering from diarrhoea belonging to Italian swine herds. The strains were analysed for their susceptibility to 12 antimicrobials using the disc diffusion method. During the study period, a statistically significant proportion of isolates resistant to enrofloxacin (14.5-89.3%), marbofloxacin (5.4-60.7%), flumequine (49.1-92.9%), danofloxacin (21.6-80%), florfenicol (9.8-64.3%), thiamphenicol (50-92%) and cefquinome (3.8-44%) was recorded. An increase in resistance (not statistically significant) to gentamicin (63.6-85.7%), apramycin (61.8-82.1%), trimethoprim-sulphamethoxazole (75-89.3%), tetracycline (97-100%) and erythromycin (92.4-100%) was also observed. Based on antimicrobial multiresistance, the strains were collected into three groups: I. resistant to 2-5 antimicrobials; II. resistant to 6-8 antimicrobials; III. resistant to 9-12 antimicrobials. The number of isolates belonging to the first group showed a statistically significant decrease (P < 0.05; R(2)  = 0.896; r = -0.9608), while the isolates belonging to the second and third groups showed a statistically significant increase in resistance (P < 0.05; R(2)  = 0.753; r = 0.8890 and P < 0.05; R(2)  = 0.727; r = 0.8701, respectively) over the period of study. The results of this study suggest the need for continued monitoring of the development of resistance. © 2013 Blackwell Verlag GmbH.

The overexpression of MRP4 is related to multidrug resistance in osteosarcoma cells

Directory of Open Access Journals (Sweden)

Zhonghui He

2015-01-01

Full Text Available Doxorubicin (Adriamycin, ADM is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs are members of a superfamily of ATP-binding cassette (ABC transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient′s primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05. In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05. Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells.

Alchemy or Science? Compromising Archaeology in the Deep Sea

Science.gov (United States)

Adams, Jonathan

2007-06-01

In the torrid debate between archaeology and treasure hunting, compromise is often suggested as the pragmatic solution, especially for archaeology carried out either in deep water or beyond the constraints that commonly regulate such activities in territorial seas. Both the wisdom and the need for such compromise have even been advocated by some archaeologists, particularly in forums such as the internet and conferences. This paper argues that such a compromise is impossible, not in order to fuel confrontation but simply because of the nature of any academic discipline. We can define what archaeology is in terms of its aims, theories, methods and ethics, so combining it with an activity founded on opposing principles must transform it into something else. The way forward for archaeology in the deep sea does not lie in a contradictory realignment of archaeology’s goals but in collaborative research designed to mesh with emerging national and regional research and management plans.

Differential diagnosis of the signal-compromised lunate in MRI

International Nuclear Information System (INIS)

Schmitt, R.; Christopoulos, G.; Coblenz, G.; Froehner, S.; Brunner, H.; Kalb, K.; Krimmer, H.; Lanz, U.

2005-01-01

Purpose: To define both the underlying pathology and diagnostic criteria in lunates presenting with conspicuous signal pattern in MRI. Materials and Methods: The retrospective evaluation of 2940 MRI examinations revealed 203 patients with signal alterations of the lunate. All MRI examinations were performed on 1.5-Tesla platforms using dedicated surface coils and an intravenous contrast agent. To establish a definitive diagnosis, a total of 252 MRI examinations (49 follow-ups), 22 CT examinations and 4 arthroscopic studies were obtained in addition to the obligatory conventional radiographs. Results: Incorporating all clinical data, radiographs and MRI examinations succeeded in assigning a diagnosis in 136 signal-compromised lunates (67.0%), whereas additional diagnostic procedures or follow-up examinations were required for the definitive diagnosis in 57 cases (33.0%). The most frequent entities were 51 cases of Kienboeck's disease (25.1%), 47 cases of ulnolunate-(triquetral) impaction syndromes (23.2%) and 44 cases of intra-osseous ganglion cysts (21.7%). Other pathologies included 23 degenerative, 19 traumatic and 10 inflammatory changes as well as 9 congenital conditions. For MRI assessment of the altered lunate, the most important parameters were location and morphology as well as involvement of the articular and osseous structures of the carpus. Conclusion: The lunate may be affected by different pathological states of the wrist. In total, only one quarter of the signal-compromised lunate represented Kienboeck's disease. (orig.)

Strained Compromises? Danish Flexicurity During Crisis

Directory of Open Access Journals (Sweden)

Christian Lyhne Ibsen

2011-01-01

Full Text Available The Danish concept of flexicurity in a `Golden Triangle´ of low job protection, high income security and high employment security is not only about a balance between labor market flexibility and social security. Arguably, it is also a series of more or less stable underlying compromises between social partners about the main mechanisms and aims of labor market regulation which - supposedly - should be focused on employment rather than jobs, and competition on quality rather than on labor costs. However, the `Golden Triangle´ - this article argues - seems in need of complementary concepts. The article therefore introduces, `centralized decentralization´ - a concept that directs our attention to forms of flexibility and security primarily for people in work. Most studies on Danish flexicurity have been carried out under favorable economic conditions. In light of the economic slump hitting Denmark in 2008, this article investigates if and how the recession challenged these compromises by comparing two rounds of case-based interviews in three metalworking companies in 2007 and 2009. It is shown that practice has indeed changed - albeit modestly - due to worsened economic circumstances. For example the case studies show that the hypothesized preference for external numerical flexibility is perhaps too crude as employers use different ways to restructure employment. Especially the examples of de facto concessionary bargaining to save jobs are important here - although the extent of concessions is modest. The evidence thus suggests that the `Golden Triangle´ flexicurity compromises are indeed strained by the economic cycle and that responses to impetus for restructuring are far more nuanced than sometimes portrayed. It is argues that more company studies across national labor markets and industrial relations institutions will enhance our understanding of the dynamics during times of restructuring.

EMERGING ANTIMICROBIAL RESISTANCE IN HOSPITAL A THREAT TO PUBLIC HEALTH

Directory of Open Access Journals (Sweden)

Vichal Rastogi

2013-01-01

Full Text Available Background: Antimicrobial resistance(AMR threatens the health of many throughout the world, since both old and new infectious diseases remain a formidable public health threat. When pathogenic microorganisms can multiply beyond some critical mass in the face of invading antimicrobials, treatment outcome is compromised. This phenomenon is referred as antimicrobial resistance (AMR. Objective: This retrospective study was conducted to assess the overall antimicrobial resistance in bacterial isolates from tertiary care hospitals as majority of patients here receive empirical antibiotics therapy. Method: This retrospective study was carried out in teaching hospital, Greater Noida to determine prevalence of multidrug resistance in patients in relation to empirical antibiotic therapy in hospital. Various samples (pus,urine,blood were collected for bacterial culture and antibiotic sensitivity. Results: Total 500 bacterial strains isolated from ICU, surgery, obstetrics & gynaecology and orthopaedics and their sensitivity pattern was compared in this study. The highest number of resistant bacterias were of pseudomonas sp. i.e. 21(33.87% followed by 16(25.80% of staphylococcus aureus, 12(19.35% of Escherichia coli, Klebseilla sp & Proteus vulgaris were 05(8.06% each & Citrobacter sp. 03(4.83%. Total 62(12.4% bacterial isolates were found to be resistant to multiple drugs. The 31 (50% of these resistant bacteria were prevalent in ICU, 12(19.35% in Surgery, 11(17.74% in Gynaecology, 08(12.90% in Orthopaedics.. All the bacterial strains were resistant to common antibiotics like Penicillin, Amoxicillin, Doxycycline & Cotrimoxazole and some were even resistant to Imipenem. Conclusion: Therefore we have outlined the nature of the antimicrobial resistance problem as an important health issue for national and international community. It is advised to avoid use of empirical antibiotics therapy.

Recombinations in staphylococcal cassette chromosome mec elements compromise the molecular detection of methicillin resistance in Staphylococcus aureus

KAUST Repository

Hill-Cawthorne, Grant A.

2014-06-27

Clinical laboratories are increasingly using molecular tests for methicillin-resistant Staphylococcus aureus (MRSA) screening. However, primers have to be targeted to a variable chromosomal region, the staphylococcal cassette chromosome mec (SCCmec). We initially screened 726 MRSA isolates from a single UK hospital trust by recombinase polymerase amplification (RPA), a novel, isothermal alternative to PCR. Undetected isolates were further characterised using multilocus sequence, spa typing and whole genome sequencing. 96% of our tested phenotypically MRSA isolates contained one of the six orfX-SCCmec junctions our RPA test and commercially available molecular tests target. However 30 isolates could not be detected. Sequencing of 24 of these isolates demonstrated recombinations within the SCCmec element with novel insertions that interfered with the RPA, preventing identification as MRSA. This result suggests that clinical laboratories cannot rely solely upon molecular assays to reliably detect all methicillin-resistance. The presence of significant recombinations in the SCCmec element, where the majority of assays target their primers, suggests that there will continue to be isolates that escape identification. We caution that dependence on amplification-based molecular assays will continue to result in failure to diagnose a small proportion (?4%) of MRSA isolates, unless the true level of SCCmec natural diversity is determined by whole genome sequencing of a large collection of MRSA isolates. © 2014 Hill-Cawthorne et al.

Recombinations in staphylococcal cassette chromosome mec elements compromise the molecular detection of methicillin resistance in Staphylococcus aureus.

Directory of Open Access Journals (Sweden)

Grant A Hill-Cawthorne

Full Text Available Clinical laboratories are increasingly using molecular tests for methicillin-resistant Staphylococcus aureus (MRSA screening. However, primers have to be targeted to a variable chromosomal region, the staphylococcal cassette chromosome mec (SCCmec. We initially screened 726 MRSA isolates from a single UK hospital trust by recombinase polymerase amplification (RPA, a novel, isothermal alternative to PCR. Undetected isolates were further characterised using multilocus sequence, spa typing and whole genome sequencing. 96% of our tested phenotypically MRSA isolates contained one of the six orfX-SCCmec junctions our RPA test and commercially available molecular tests target. However 30 isolates could not be detected. Sequencing of 24 of these isolates demonstrated recombinations within the SCCmec element with novel insertions that interfered with the RPA, preventing identification as MRSA. This result suggests that clinical laboratories cannot rely solely upon molecular assays to reliably detect all methicillin-resistance. The presence of significant recombinations in the SCCmec element, where the majority of assays target their primers, suggests that there will continue to be isolates that escape identification. We caution that dependence on amplification-based molecular assays will continue to result in failure to diagnose a small proportion (∼4% of MRSA isolates, unless the true level of SCCmec natural diversity is determined by whole genome sequencing of a large collection of MRSA isolates.

Recombinations in staphylococcal cassette chromosome mec elements compromise the molecular detection of methicillin resistance in Staphylococcus aureus

KAUST Repository

Hill-Cawthorne, Grant A.; Hudson, Lyndsey O.; Abd El Ghany, Moataz; Piepenburg, Olaf; Nair, Mridul; Dodgson, Andrew; Forrest, Matthew S.; Clark, Taane G.; Pain, Arnab

2014-01-01

Clinical laboratories are increasingly using molecular tests for methicillin-resistant Staphylococcus aureus (MRSA) screening. However, primers have to be targeted to a variable chromosomal region, the staphylococcal cassette chromosome mec (SCCmec). We initially screened 726 MRSA isolates from a single UK hospital trust by recombinase polymerase amplification (RPA), a novel, isothermal alternative to PCR. Undetected isolates were further characterised using multilocus sequence, spa typing and whole genome sequencing. 96% of our tested phenotypically MRSA isolates contained one of the six orfX-SCCmec junctions our RPA test and commercially available molecular tests target. However 30 isolates could not be detected. Sequencing of 24 of these isolates demonstrated recombinations within the SCCmec element with novel insertions that interfered with the RPA, preventing identification as MRSA. This result suggests that clinical laboratories cannot rely solely upon molecular assays to reliably detect all methicillin-resistance. The presence of significant recombinations in the SCCmec element, where the majority of assays target their primers, suggests that there will continue to be isolates that escape identification. We caution that dependence on amplification-based molecular assays will continue to result in failure to diagnose a small proportion (?4%) of MRSA isolates, unless the true level of SCCmec natural diversity is determined by whole genome sequencing of a large collection of MRSA isolates. © 2014 Hill-Cawthorne et al.

Abscisic acid negatively regulates post-penetration resistance of Arabidopsis to the biotrophic powdery mildew fungus.

Science.gov (United States)

Xiao, Xiang; Cheng, Xi; Yin, Kangquan; Li, Huali; Qiu, Jin-Long

2017-08-01

Pytohormone abscisic acid (ABA) plays important roles in defense responses. Nonetheless, how ABA regulates plant resistance to biotrophic fungi remains largely unknown. Arabidopsis ABA-deficient mutants, aba2-1 and aba3-1, displayed enhanced resistance to the biotrophic powdery mildew fungus Golovinomyces cichoracearum. Moreover, exogenously administered ABA increased the susceptibility of Arabidopsis to G. cichoracearum. Arabidopsis ABA perception components mutants, abi1-1 and abi2-1, also displayed similar phenotypes to ABA-deficient mutants in resistance to G. cichoracearum. However, the resistance to G. cichoracearum is not changed in downstream ABA signaling transduction mutants, abi3-1, abi4-1, and abi5-1. Microscopic examination revealed that hyphal growth and conidiophore production of G. cichoracearum were compromised in the ABA deficient mutants, even though pre-penetration and penetration growth of the fungus were not affected. In addition, salicylic acid (SA) and MPK3 are found to be involved in ABA-regulated resistance to G. cichoracearum. Our work demonstrates that ABA negatively regulates post-penetration resistance of Arabidopsis to powdery mildew fungus G. cichoracearum, probably through antagonizing the function of SA.

Insecticide Resistance Reducing Effectiveness of Malaria Control

Centers for Disease Control (CDC) Podcasts

2007-01-24

Malaria prevention is increasingly insecticide based. Dr. John Gimnig, an entomologist with the Division of Parasitic Diseases, CDC, discusses evidence that mosquito resistance to insecticides, which is measured in the laboratory, could compromise malaria prevention in the field.  Created: 1/24/2007 by Emerging Infectious Diseases.   Date Released: 3/13/2007.

Does low self-esteem predict health compromising behaviours among adolescents?

Science.gov (United States)

Mcgee, R; Williams, S

2000-10-01

It is often believed that low self-esteem is associated with such health-compromising behaviours in adolescence as substance use, early sexual activity, eating problems and suicidal ideation. Surprisingly, there is little longitudinal research addressing this issue. This longitudinal study examines the predictive association between both global and academic self-esteem from ages 9 to 13 years, and a variety of health compromising behaviours at age 15, in a large sample of young New Zealanders. Levels of global self-esteem significantly predicted adolescent report of problem eating, suicidal ideation, and multiple health compromising behaviours. Earlier levels of self-esteem were unrelated to later substance use and early sexual activity. The findings are discussed in terms of their implications for efforts to raise self-esteem among young people. Copyright 2000 The Association for Professionals in Services for Adolescents.

COMPROMISE EFFECT ON CONSUMERS’ BEHAVIOR

Directory of Open Access Journals (Sweden)

Markus Surkamta Eric Santosa

2016-09-01

Full Text Available The way consumers think about the products they will buy determines their buying behavior. The decision to buy a particular product is obviously in accordance with the buyer’s attitude. The buyers will also feel more comfortable if their behavior meets with the approval and expectations of the people close to them. While the development of a certain attitude has no effect on subjective judgment, the effect of compromise is likely to make a contribution to its development. Since it is still unclear, this study’s main purposed is to clarify this. In addition, while an attitude is theorized as being a predictor of behavior, through behavioral intention, the study’s secondary purpose is to boost the earlier findings. Likewise, in accordance with the theory of planned behavior, the study will also examine the other predictors of behavioral intention, in relation to the behavioral intention itself. A sample consisting of a 100 respondents was compiled by using the convenience and judgment technique. The data were analyzed using Amos 16.0 and SPSS 16.0. As expected, the compromise effect had a significant influence on whether the customers’ attitude or the subjective norm was the main determinant. Likewise, the customers’ attitude, the subjective norm and perceived behavioral control were confirmed as good predictors of customers’ behavioral intentions.

Identification of bacterial blight resistance genes Xa4 in Pakistani ...

African Journals Online (AJOL)

SERVER

2008-03-04

Mar 4, 2008 ... Bacterial blight (BB) caused by Xanthomonas oryzae pv oryzae (Xoo) is a major biotic constraint in the irrigated rice belts. Genetic resistance is the most effective and economical control for bacterial blight. Molecular survey was conducted to identify the rice germplasm/lines for the presence of Xa4, a.

MUTUAL CONCESSIONS - SPECIFIC ELEMENT OF THE COMPROMISE/TRANSACTION CONTRACT

Directory of Open Access Journals (Sweden)

Georgeta-Bianca Spîrchez

2012-11-01

Full Text Available Given the usefulness and practical importance of the compromise contract conclusion and of the amicably dispute resolution, within the business world, we aim to analyze, in what follows, the concrete means by which these kind of settlement are achieved. Two questions become legitimate in the context of concerns about mutual concessions which the parties make in a compromise contract. These questions are the following: “What are the mutual concessions? Do mutual concessions mean equivalent concessions?” and “How mutual concessions are required to complete a valid settlement? Is the requirement of mutual concessions grounded?”

Knowledge is power: averting safety-compromising events in the OR.

Science.gov (United States)

Catalano, Kathleen

2008-12-01

Surgical procedures can be unpredictable, and safety-compromising events can jeopardize patient safety. Perioperative nurses should be watchful for factors that can contribute to safety-compromising events, as well as the errors that can follow, and know how to avert them if possible. Knowledge is power and increased awareness of patient safety issues and the resources that are available to both health care practitioners and consumers can help perioperative nurses ward off patient safety problems before they occur.

Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

Science.gov (United States)

Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

2004-06-20

Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

Vatican is lone opponent of world conference's compromises on abortion.

Science.gov (United States)

1994-09-07

Three years in the making, the draft program of action of the 1994 International Conference on Population and Development sets nonbinding policy guidelines to contain the world's population at 7.27 billion in 2015. Although the Vatican was pleased to see Pakistan put forward a compromise formula developed to appease Catholic and Muslim objectors of abortion, the Church was unprepared to accept the compromise immediately and requested further discussion. The Vatican's rejection drew a strong chorus of vocal disapproval from other conference delegates. Even Iran accepted the draft as a "perfect text," while Sweden grudgingly accepted it as a "rock-bottom compromise." With no Catholic countries objecting to the compromise, the Vatican stood alone in its refusal to compromise with the rest of the world's leaders and peoples. Germany, speaking for the European Union, warned that enough concessions had already been made. The rationale for Vatican opposition was unclear since the section explicitly rejects abortion as a means of family planning and urges countries to minimize both the incidence of unsafe abortion and abortion overall by improving family planning. Prevention of unwanted pregnancies must be given highest priority and women should have ready access to compassionate counselling, with abortion never promoted as a means of family planning. Moreover, there is no longer a reference to sexual health education, a plea to governments to review their laws and policies on abortion, and a call to consider women's health rather than relying upon criminal codes and punitive measures. Participants said the Vatican objected to a phrase stating that abortions, where legal, should be safe, while the Church representative argued that any suggestion that abortion is safe contradicts church doctrine on the sanctity of life.

Adolescent Health-Compromising Behaviors: Motivating School Counselors.

Science.gov (United States)

Nagel, Liza; Scherer, David G.; Lee, William

2000-01-01

Investigated middle and high school counselors' perceptions of adolescent health-compromising behaviors and motivations to intervene. Data from a survey based on protection motivation theory showed differences in counselors' perceptions of the severity of risk-taking behaviors. Perceptions were highly correlated with intentions to seek out…

Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.

Science.gov (United States)

Sabdia, S; Greer, R M; Prior, T; Kumar, S

2015-05-01

The aim of this study was to explore the association between the cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise. This retrospective cross sectional study was conducted at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum and neonatal outcomes. Babies born by caesarean section or instrumental delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60 (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery, emergency delivery for failure to progress, emergency caesarean section for other reasons or elective caesarean section). The percentage of infants with a cerebro-umbilical ratio cerebro-umbilical ratio between the 10th-90th centile and 9.6% of infants with a cerebro-umbilical ratio > 90th centile required delivery for the same indication (p cerebro-umbilical ratio was associated with an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI 1.41-2.92), p cerebro-umbilical ratio measured at 35-37 weeks is associated with a greater risk of intrapartum compromise. This is a relatively simple technique which could be used to risk stratify women in diverse healthcare settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

The medically compromised patient: Are dental implants a feasible option?

Science.gov (United States)

Vissink, A; Spijkervet, Fkl; Raghoebar, G M

2018-03-01

In healthy subjects, dental implants have evolved to be a common therapy to solve problems related to stability and retention of dentures as well as to replace failing teeth. Although dental implants are applied in medically compromised patients, it is often not well known whether this therapy is also feasible in these patients, whether the risk of implant failure and developing peri-implantitis is increased, and what specific preventive measures, if any, have to be taken when applying dental implants in these patients. Generally speaking, as was the conclusion by the leading review of Diz, Scully, and Sanz on placement of dental implants in medically compromised patients (J Dent, 41, 2013, 195), in a few disorders implant survival may be lower, and the risk of a compromised peri-implant health and its related complications be greater, but the degree of systemic disease control outweighs the nature of the disorder rather than the risk accompanying dental implant treatment. So, as dental implant treatment is accompanied by significant functional benefits and improved oral health-related quality of life, dental implant therapy is a feasible treatment in almost any medically compromised patient when the required preventive measures are taken and follow-up care is at a high level. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain.

Science.gov (United States)

Sinha, Manish; Dola, Vasanth R; Agarwal, Pooja; Srivastava, Kumkum; Haq, Wahajul; Puri, Sunil K; Katti, Seturam B

2014-07-15

Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β(3)- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target. Copyright © 2014 Elsevier Ltd. All rights reserved.

31 CFR 902.2 - Bases for compromise.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Bases for compromise. 902.2 Section 902.2 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FEDERAL CLAIMS... necessary to further an enforcement principle, such as the Government's willingness to pursue aggressively...

[Antimicrobial susceptibility and drug-resistance genes of Yersinia spp. of retailed poultry in 4 provinces of China].

Science.gov (United States)

Peng, Z X; Zou, M Y; Xu, J; Guan, W Y; Li, Y; Liu, D R; Zhang, S S; Hao, Q; Yan, S F; Wang, W; Yu, D M; Li, F Q

2018-04-06

Objective: To monitor the antimicrobial resistance and drug-resistance genes of Yersinia enterocolitis , Y. intermedia and Y. frederiksenii recovered from retailed fresh poultry of 4 provinces of China. Methods: The susceptibility of 25 isolated Yersinia spp. to 14 classes and 25 kinds of antibiotics was determined by broth microdilution method according to CLSI (Clinical and Laboratory Standards Institute). The antibiotic resistance genes were predicted with antibiotic resistance genes database (ARDB) using whole genome sequences of Yersinia spp. Results: In all 22 Y. enterocolitis tested, 63.7% (14 isolates), 22.8% (5 isolates), 4.6% and 4.6% of 1 isolates exhibited the resistance to cefoxitin, ampicillin-sulbactam, nitrofurantoin and trimethoprim-sulfamethoxazole, respectively. All the 25 isolates were multi-drug resistant to more than 3 antibiotics, while 64.0% of isolates were resistant to more than 4 antibiotics. A few Y. enterocolitis isolates of this study were intermediate to ceftriaxone and ciprofloxacin. Most Yersinia spp. isolates contained antibiotic resistance genes mdtG, ksgA, bacA, blaA, rosAB and acrB , and 5 isolates recovered from fresh chicken also contained dfrA 1, catB 2 and ant 3 ia . Conclusion: The multi-drug resistant Yersinia spp. isolated from retailed fresh poultry is very serious in the 4 provinces of China, and their contained many kinds of drug-resistance genes.

Factors influencing treatment decision-making for maintaining or extracting compromised teeth.

Science.gov (United States)

Lang-Hua, Bich Hue; McGrath, Colman P J; Lo, Edward C M; Lang, Niklaus P

2014-01-01

To evaluate treatment decision-making with respect to maintaining periodontally compromised teeth among dentists with or without postgraduate qualifications in implant dentistry. A series of patient scenarios with varying degrees of periodontal disease levels was presented to dental practitioners. Practitioners' decision-making outcome was determined, and intention to retain the compromised teeth was analyzed in bivariate and regression analyses (accounting for postgraduate implant training, gender, years in dental practice, and implant placement experience). This study involved 30 dental practitioners with postgraduate implant qualifications (GDPP), 33 dental practitioners without postgraduate implant qualifications (GDP), and 27 practitioners undergoing training for postgraduate implant qualifications (GDPT). Variations in treatment decision-making were evident between the three groups. Differences in treatment approaches to retaining compromised teeth were apparent. Furthermore, variations in rehabilitation of extracted scenarios existed in terms of use of implant and number of implants need for rehabilitation. Accounting for dentist and practice factors in regression analyses, GDPP/GDPT were three times as likely to retain periodontally compromised upper molar, with or without pain, compared to GDP (without pain OR 3.10, 95%CI 1.04, 10.62 P = 0.04; with pain OR 3.08, 95%CI 1.09, 8.14 P = 0.03). Variations in treatment decision-making with respect to retaining periodontally compromised teeth exist between dental practitioners with and those without postgraduate training in implant dentistry. Furthermore differences in management approaches in how they would retain the teeth or rehabilitate the dental arch were apparent. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Fuzzy compromise: An effective way to solve hierarchical design problems

Science.gov (United States)

Allen, J. K.; Krishnamachari, R. S.; Masetta, J.; Pearce, D.; Rigby, D.; Mistree, F.

1990-01-01

In this paper, we present a method for modeling design problems using a compromise decision support problem (DSP) incorporating the principles embodied in fuzzy set theory. Specifically, the fuzzy compromise decision support problem is used to study hierarchical design problems. This approach has the advantage that although the system modeled has an element of uncertainty associated with it, the solution obtained is crisp and precise. The efficacy of incorporating fuzzy sets into the solution process is discussed in the context of results obtained for a portal frame.

Mechanical Properties and Thermal Shock Resistance Analysis of BNNT/Si3N4 Composites

Science.gov (United States)

Wang, Shouren; Wang, Gaoqi; Wen, Daosheng; Yang, Xuefeng; Yang, Liying; Guo, Peiquan

2018-04-01

BNNT/Si3N4 ceramic composites with different weight amount of BNNT fabricated by hot isostatic pressing were introduced. The mechanical properties and thermal shock resistance of the composites were investigated. The results showed that BNNT-added ceramic composites have a finer and more uniform microstructure than that of BNNT-free Si3N4 ceramic because of the retarding effect of BNNT on Si3N4 grain growth. The addition of 1.5 wt.% BNNT results in simultaneous increase in flexural strength, fracture toughness, and thermal shock resistance. The analysis of the results indicates that BNNT brings many thermal transport channels in the microstructure, increasing the efficiency of thermal transport, therefore results in increase of thermal shock resistance. In addition, BNNT improves the residual flexural strength of composites by crack deflection, bridging, branching and pinning, which increase the crack propagation resistance.

The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis

DEFF Research Database (Denmark)

Nicolini, Franck E; Ibrahim, Amr R; Soverini, Simona

2013-01-01

The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64...... patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according...... to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315...

Antimicrobial resistance mechanisms among Campylobacter.

Science.gov (United States)

Wieczorek, Kinga; Osek, Jacek

2013-01-01

Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

Molecular mechanisms of cisplatin resistance in cervical cancer.

Science.gov (United States)

Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

2016-01-01

Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical Studies of Deleobuvir and Faldaprevir.

Directory of Open Access Journals (Sweden)

Kristi L Berger

Full Text Available The resistance profile of anti-hepatitis C virus (HCV agents used in combination is important to guide optimal treatment regimens. We evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants among HCV genotype (GT-1a and -1b-infected patients treated with faldaprevir (HCV protease inhibitor, deleobuvir (HCV polymerase non-nucleoside inhibitor, and ribavirin in multiple clinical studies.HCV NS3/4A and NS5B population sequencing (Sanger method was performed on all baseline plasma samples (n = 1425 NS3; n = 1556 NS5B and on post-baseline plasma samples from patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b. Persistence and time to loss of resistance-associated variants (RAVs was estimated using Kaplan-Meier analysis.Faldaprevir RAVs (NS3 R155 and D168 and deleobuvir RAVs (NS5B 495 and 496 were rare (90%. Virologic relapse was associated with RAVs in both NS3 and NS5B (53% GT-1b; 52% GT-1b; some virologic relapses had NS3 RAVs only (47% GT-1a; 17% GT-1b. Median time to loss of GT-1b NS5B P495 RAVs post-treatment (5 months was less than that of GT-1b NS3 D168 (8.5 months and GT-1a R155 RAVs (11.5 months.Faldaprevir and deleobuvir RAVs are more prevalent among virologic failures than at baseline. Treatment response was not compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499 at baseline (wild-type in GT-1a, polymorphism in GT-1b may reduce response to this deleobuvir-based regimen.

45 CFR 1177.12 - Compromise, suspension and termination.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Compromise, suspension and termination. 1177.12 Section 1177.12 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON...) debts arising from GAO audit exceptions. ...

15 CFR 19.7 - When will Commerce entities compromise a Commerce debt?

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false When will Commerce entities compromise a Commerce debt? 19.7 Section 19.7 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To Collect Commerce Debts § 19.7 When will Commerce entities compromise...

Impact of Resistance Training on Skeletal Muscle Mitochondrial Biogenesis, Content, and Function

Directory of Open Access Journals (Sweden)

Thomas Groennebaek

2017-09-01

Full Text Available Skeletal muscle metabolic and contractile properties are reliant on muscle mitochondrial and myofibrillar protein turnover. The turnover of these specific protein pools is compromised during disease, aging, and inactivity. Oppositely, exercise can accentuate muscle protein turnover, thereby counteracting decay in muscle function. According to a traditional consensus, endurance exercise is required to drive mitochondrial adaptations, while resistance exercise is required to drive myofibrillar adaptations. However, concurrent practice of traditional endurance exercise and resistance exercise regimens to achieve both types of muscle adaptations is time-consuming, motivationally demanding, and contended to entail practice at intensity levels, that may not comply with clinical settings. It is therefore of principle interest to identify effective, yet feasible, exercise strategies that may positively affect both mitochondrial and myofibrillar protein turnover. Recently, reports indicate that traditional high-load resistance exercise can stimulate muscle mitochondrial biogenesis and mitochondrial respiratory function. Moreover, fatiguing low-load resistance exercise has been shown capable of promoting muscle hypertrophy and expectedly entails greater metabolic stress to potentially enhance mitochondrial adaptations. Consequently, fatiguing low-load resistance exercise regimens may possess the ability to stimulate muscle mitochondrial adaptations without compromising muscle myofibrillar accretion. However, the exact ability of resistance exercise to drive mitochondrial adaptations is debatable, not least due to some methodological challenges. The current review therefore aims to address the evidence on the effects of resistance exercise on skeletal muscle mitochondrial biogenesis, content and function. In prolongation, a perspective is taken on the specific potential of low-load resistance exercise on promoting mitochondrial adaptations.

Transient heat stress compromises the resistance of wheat (Poales: Poaceae) seedlings to Hessian fly (Diptera: Cecidomyiidae) infestation.

Science.gov (United States)

Currie, Yaleaka; Moch, John; Underwood, Joshua; Kharabsheh, Hamzah; Quesenberry, Amy; Miyagi, Risa; Thomas, Carolyn; Boney, Melanie; Woods, Samantha; Chen, Ming-Shun; Zhu, Lieceng

2014-02-01

Heat stress exerts a profound impact on the resistance of plants to parasites. In this research, we investigated the impact of an acute transient heat stress on the resistance of the wheat line 'Molly,' which contains the R gene H13, to an avirulent Hessian fly (Mayetiola destructor (Say)) population. We found that a significant portion of Molly seedlings stressed at 40 degrees C for 6 h during or after the initial Hessian fly larval attack became susceptible to otherwise avirulent insects, whereas unstressed control plants remained 100% resistant. Specifically, 77.8, 73.3, 83.3, and 46.7% of plants heat stressed at 0, 6,12, and 24 h, respectively, after the initial larval attack became susceptible. Biochemical analysis revealed that heat stress caused a transient decrease in 12-oxo-phytodienoic acid, but an increase in salicylic acid accumulation in Molly plants. The change in phytohormones after heat stress and Hessian fly infestation was not observed in 'Newton,' a near-isogenic but Hessian fly susceptible wheat line. Instead, heat stress caused a relatively prolonged reduction in palmitoleic acid. The role of phytohormones in heat-induced loss of wheat resistance was discussed.

Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

OpenAIRE

de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

2009-01-01

Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

Identification and evaluation of two diagnostic markers linked to Fusarium wilt resistance (race 4) in banana (Musa spp.).

Science.gov (United States)

Wang, Wei; Hu, Yulin; Sun, Dequan; Staehelin, Christian; Xin, Dawei; Xie, Jianghui

2012-01-01

Fusarium wilt caused by the fungus Fusarium oxysporum f. sp. cubense race 4 (FOC4) results in vascular tissue damage and ultimately death of banana (Musa spp.) plants. Somaclonal variants of in vitro micropropagated banana can hamper success in propagation of genotypes resistant to FOC4. Early identification of FOC4 resistance in micropropagated banana plantlets is difficult, however. In this study, we identified sequence-characterized amplified region (SCAR) markers of banana associated with resistance to FOC4. Using pooled DNA from resistant or susceptible genotypes and 500 arbitrary 10-mer oligonucleotide primers, 24 random amplified polymorphic DNA (RAPD) products were identified. Two of these RAPD markers were successfully converted to SCAR markers, called ScaU1001 (GenBank accession number HQ613949) and ScaS0901 (GenBank accession number HQ613950). ScaS0901 and ScaU1001 could be amplified in FOC4-resistant banana genotypes ("Williams 8818-1" and Goldfinger), but not in five tested banana cultivars susceptible to FOC4. The two SCAR markers were then used to identify a somaclonal variant of the genotype "Williams 8818-1", which lost resistance to FOC4. Hence, the identified SCAR markers can be applied for a rapid quality control of FOC4-resistant banana plantlets immediately after the in vitro micropropagation stage. Furthermore, ScaU1001 and ScaS0901 will facilitate marker-assisted selection of new banana cultivars resistant to FOC4.

Super-resolution microscopy reveals the insulin-resistance-regulated reorganization of GLUT4 on plasma membranes.

Science.gov (United States)

Gao, Lan; Chen, Junling; Gao, Jing; Wang, Hongda; Xiong, Wenyong

2017-01-15

GLUT4 (also known as SLC2A4) is essential for glucose uptake in skeletal muscles and adipocytes, which play central roles in whole-body glucose metabolism. Here, using direct stochastic optical reconstruction microscopy (dSTORM) to investigate the characteristics of plasma-membrane-fused GLUT4 at the single-molecule level, we have demonstrated that insulin and insulin resistance regulate the spatial organization of GLUT4 in adipocytes. Stimulation with insulin shifted the balance of GLUT4 on the plasma membrane toward a more dispersed configuration. In contrast, insulin resistance induced a more clustered distribution of GLUT4 and increased the mean number of molecules per cluster. Furthermore, our data demonstrate that the F 5 QQI motif and lipid rafts mediate the maintenance of GLUT4 clusters on the plasma membrane. Mutation of F 5 QQI (F 5 QQA-GLUT4) induced a more clustered distribution of GLUT4; moreover, destruction of lipid rafts in adipocytes expressing F 5 QQA-GLUT4 dramatically decreased the percentage of large clusters and the mean number of molecules per cluster. In conclusion, our data clarify the effects of insulin stimulation or insulin resistance on GLUT4 reorganization on the plasma membrane and reveal new pathogenic mechanisms of insulin resistance. © 2017. Published by The Company of Biologists Ltd.

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

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Yu-Chieh Chen

2013-03-01

Full Text Available Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms.

Roles of Melatonin in Fetal Programming in Compromised Pregnancies

Science.gov (United States)

Chen, Yu-Chieh; Sheen, Jiunn-Ming; Tiao, Miao-Meng; Tain, You-Lin; Huang, Li-Tung

2013-01-01

Compromised pregnancies such as those associated with gestational diabetes mellitus, intrauterine growth retardation, preeclampsia, maternal undernutrition, and maternal stress may negatively affect fetal development. Such pregnancies may induce oxidative stress to the fetus and alter fetal development through the epigenetic process that may affect development at a later stage. Melatonin is an oxidant scavenger that reverses oxidative stress during the prenatal period. Moreover, the role of melatonin in epigenetic modifications in the field of developmental programming has been studied extensively. Here, we describe the physiological function of melatonin in pregnancy and discuss the roles of melatonin in fetal programming in compromised pregnancies, focusing on its involvement in redox and epigenetic mechanisms. PMID:23466884

The impact of purchase quantity on the compromise effect: The balance heuristic

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Yin-Hui Cheng

2012-07-01

Full Text Available Most prior research on the compromise effect has focused on single rather than multiple choices. This research investigates the potential effects of purchase quantity on the compromise effect. We propose that the share of the middle option in a trinary choice set decreases as the purchase quantity increases, because people tend to employ a balance heuristic to distribute their multiple choices among the available options to achieve a balanced state and to satisfy their variety-seeking tendency. Furthermore, we propose that the need for justification and an optimal stimulation level moderate the relationship between the number of purchase items and the compromise effect. These proposed hypotheses are supported by results from three experiments.

47 CFR 1.1915 - Exploration of compromise.

Science.gov (United States)

2010-10-01

... justification of the offer and addressing the bases for compromise at 31 CFR 902.2. Debtors will provide full.... Unless otherwise provided by law, when the principal balance of a debt, exclusive of interest, penalties... evaluate an offer, using the factors set forth in 31 CFR 902.2 and, as appropriate, refer the offer with...

Antibiotic resistance in Burkholderia species.

Science.gov (United States)

Rhodes, Katherine A; Schweizer, Herbert P

2016-09-01

The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Copyright © 2016 Elsevier Ltd. All rights reserved.

36 CFR 1011.7 - When will the Presidio Trust compromise a debt?

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false When will the Presidio Trust... Procedures To Collect Presidio Trust Debts § 1011.7 When will the Presidio Trust compromise a debt? (a... debt owed to the Presidio Trust that is not recovered as the result of a compromise will be reported to...

Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy

Science.gov (United States)

Kendziorra, Emil; Ahlborn, Kerstin; Spitzner, Melanie; Rave-Fränk, Margret; Emons, Georg; Gaedcke, Jochen; Kramer, Frank; Wolff, Hendrik A.; Becker, Heinz; Beissbarth, Tim; Ebner, Reinhard; Ghadimi, B.Michael; Pukrop, Tobias; Ried, Thomas; Grade, Marian

2011-01-01

A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference-mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a β-catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G2/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by γH2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy. PMID:21983179

Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line

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Isabella Massimi

2015-01-01

Full Text Available Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4 overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα. In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293 to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.

TM4SF1 Promotes Gemcitabine Resistance of Pancreatic Cancer In Vitro and In Vivo.

Directory of Open Access Journals (Sweden)

Jia Cao

Full Text Available TM4SF1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC and affects the development of this cancer. Also, multidrug resistance (MDR is generally associated with tumor chemoresistance in pancreatic cancer. However, the correlation between TM4SF1 and MDR remains unknown. This research aims to investigate the effect of TM4SF1 on gemcitabine resistance in PDAC and explore the possible molecular mechanism between TM4SF1 and MDR.The expression of TM4SF1 was evaluated in pancreatic cancer cell lines and human pancreatic duct epithelial (HPDE cell lines by quantitative RT-PCR. TM4SF1 siRNA transfection was carried out using Hiperfect transfection reagent to knock down TM4SF1. The transcripts were analyzed by quantitative RT-PCR, RT-PCR and western blotting for further study. The cell proliferation and apoptosis were obtained to investigate the sensitivity to gemcitabine of pancreatic cancer cells after silencing TM4SF1 in vitro. We demonstrated that cell signaling of TM4SF1 mediated chemoresistance in cancer cells by assessing the expression of multidrug resistance (MDR genes using quantitative RT-PCR. In vivo, we used orthotopic pancreatic tumor models to investigate the effect of proliferation after silencing TM4SF1 by a lentivirus-mediated shRNA in MIA PaCa-2 cell lines.The mRNA expression of TM4SF1 was higher in seven pancreatic cancer cell lines than in HPDE cell lines. In three gemcitabine-sensitive cell lines (L3.6pl, BxPC-3, SU86.86, the expression of TM4SF1 was lower than that in four gemcitabine-resistant cell lines (MIA PaCa-2, PANC-1, Hs766T, AsPC-1. We evaluated that TM4SF1 was a putative target for gemcitabine resistance in pancreatic cancer cells. Using AsPC-1, MIA PaCa-2 and PANC-1, we investigated that TM4SF1 silencing affected cell proliferation and increased the percentages of cell apoptosis mediated by treatment with gemcitabine compared with cells which were treated with negative control. This resistance was associated

Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1

Science.gov (United States)

Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Kagaayi, Joseph; Kizza, Allan; Pillay, Visva; Laeyendecker, Oliver; Reynolds, Steven J.; Eshleman, Susan H.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.

2009-01-01

Background Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4+ T cells, potentially complicating future treatment. Methods Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4+ T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. PMID:19338474

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

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Chen, Yanmin; Lv, Ping; Du, Mengkai; Liang, Zhaoxia; Zhou, Menglin; Chen, Danqing

2017-07-01

Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

Is patient confidentiality compromised with the electronic health record?: a position paper.

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Wallace, Ilse M

2015-02-01

In order for electronic health records to fulfill their expected benefits, protection of privacy of patient information is key. Lack of trust in confidentiality can lead to reluctance in disclosing all relevant information, which could have grave consequences. This position paper contemplates whether patient confidentiality is compromised by electronic health records. The position that confidentiality is compromised was supported by the four bioethical principles and argued that despite laws and various safeguards to protect patients' confidentiality, numerous data breaches have occurred. The position that confidentiality is not compromised was supported by virtue ethics and a utilitarian viewpoint and argued that safeguards keep information confidential and the public feels relatively safe with the electronic health record. The article concludes with an ethically superior position that confidentiality is compromised with the electronic health record. Although organizational and governmental ways of enhancing the confidentiality of patient information within the electronic health record facilitate confidentiality, the ultimate responsibility of maintaining confidentiality rests with the individual end-users and their ethical code of conduct. The American Nurses Association Code of Ethics for nurses calls for nurses to be watchful with data security in electronic communications.

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

International Nuclear Information System (INIS)

Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

2013-01-01

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

Energy Technology Data Exchange (ETDEWEB)

Fujii, Masakazu, E-mail: masakazu731079@yahoo.co.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoguchi, Toyoshi, E-mail: toyoshi@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Batchuluun, Battsetseg, E-mail: battsetseg.batchuluun@gmail.com [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sugiyama, Naonobu, E-mail: nao1@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kobayashi, Kunihisa, E-mail: nihisak@fukuoka-u.ac.jp [Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino, Fukuoka 818-8502 (Japan); Sonoda, Noriyuki, E-mail: noriyuki@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takayanagi, Ryoichi, E-mail: takayana@intmed3.med.kyushu-u.ac.jp [Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2013-08-16

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.

Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

Science.gov (United States)

Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

2017-02-01

From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

Aggressive chemotherapy and the selection of drug resistant pathogens.

Directory of Open Access Journals (Sweden)

Silvie Huijben

2013-09-01

Full Text Available Drug resistant pathogens are one of the key public health challenges of the 21st century. There is a widespread belief that resistance is best managed by using drugs to rapidly eliminate target pathogens from patients so as to minimize the probability that pathogens acquire resistance de novo. Yet strong drug pressure imposes intense selection in favor of resistance through alleviation of competition with wild-type populations. Aggressive chemotherapy thus generates opposing evolutionary forces which together determine the rate of drug resistance emergence. Identifying treatment regimens which best retard resistance evolution while maximizing health gains and minimizing disease transmission requires empirical analysis of resistance evolution in vivo in conjunction with measures of clinical outcomes and infectiousness. Using rodent malaria in laboratory mice, we found that less aggressive chemotherapeutic regimens substantially reduced the probability of onward transmission of resistance (by >150-fold, without compromising health outcomes. Our experiments suggest that there may be cases where resistance evolution can be managed more effectively with treatment regimens other than those which reduce pathogen burdens as fast as possible.

The characteristics of surface oxidation and corrosion resistance of nitrogen implanted zircaloy-4

International Nuclear Information System (INIS)

Tang, G.; Choi, B.H.; Kim, W.; Jung, K.S.; Kwon, H.S.; Lee, S.J.; Lee, J.H.; Song, T.Y.; Shon, D.H.; Han, J.G.

1997-01-01

This work is concerned with the development and application of ion implantation techniques for improving the corrosion resistance of zircaloy-4. The corrosion resistance in nitrogen implanted zircaloy-4 under a 120 keV nitrogen ion beam at an ion dose of 3 x 10 17 cm -2 depends on the implantation temperature. The characteristics of surface oxidation and corrosion resistance were analyzed with the change of implantation temperature. It is shown that as implantation temperature rises from 100 to 724 C, the colour of specimen surface changes from its original colour to light yellow at 100 C, golden at 175 C, pink at 300 C, blue at 440 C and dark blue at 550 C. As the implantation temperature goes above 640 C, the colour of surface changes to light black, and the surface becomes a little rough. The corrosion resistance of zircaloy-4 implanted with nitrogen is sensitive to the implantation temperature. The pitting potential of specimens increases from 176 to 900 mV (SCE) as the implantation temperature increases from 100 to 300 C, and decreases from 900 to 90 mV(SCE) as the implantation temperature increases from 300 to 640 C. The microstructure, the distribution of oxygen, nitrogen and carbon elements, the oxide grain size and the feature of the precipitation in the implanted surface were investigated by optical microscope, TEM, EDS, XRD and AES. The experimental results reveal that the ZrO 2 is distributed mainly on the outer surface. The ZrN is distributed under the ZrO 2 layer. The characteristics of the distribution of ZrO 2 and ZrN in the nitrogen-implanted zircaloy-4 is influenced by the implantation temperature of the sample, and in turn the corrosion resistance is influenced. (orig.)

Integer goal programming approach for finding a compromise ...

African Journals Online (AJOL)

In second model the cost and time spent on repairing the components are considered as two different objectives. Selective maintenance operation is used to select the repairable components and a multi-objective goal programming algorithm is proposed to obtain compromise selection of repairable components for the two ...

Regenerative Needs Following Alveolar Ridge Preservation Procedures in Compromised and Noncompromised Extraction Sockets: A Cone Beam Computed Tomography Study.

Science.gov (United States)

Koutouzis, Theofilos; Lipton, David

2016-01-01

The aim of this study was to evaluate the necessity for additional regenerative procedures following healing of compromised and noncompromised extraction sockets with alveolar ridge preservation procedures through the use of virtual implant imaging software. The cohort was comprised of 87 consecutive patients subjected to a single maxillary tooth extraction with an alveolar ridge preservation procedure for subsequent implant placement. Patients were divided into two main groups based on the integrity of the buccal bone plate following teeth extraction. Patients in the compromised socket (CS) group (n = 52) had partial or complete buccal bone plate loss, and patients in the noncompromised socket (NCS) group (n = 35) exhibited no bone loss of their socket walls following tooth extraction. Following 4 to 6 months of healing, all patients had a cone beam computed tomography (CBCT) study. Root-formed implants were placed virtually in an ideal prosthetic position. The number of implants per group and location (anterior, premolar, molar) exhibiting exposed buccal implant surface was calculated. In the CS group, 5 out of 19 anterior implants (26.3%), 4 out of 14 premolar implants (28.5%), and 7 out of 19 molar implants (36.8%) had exposed buccal surfaces. In the NCS group, 4 out of 9 anterior implants (44.4%), 2 out of 9 premolar implants (22.2%), and 4 out of 17 molar implants (23.5%) had exposed buccal surfaces. There were no statistically significant differences for intragroup and intergroup comparisons (χ² test, P > .05). This study failed to find statistically significant differences in the frequency of implants with exposed buccal surfaces placed virtually, following treatment of compromised and noncompromised sockets. A high proportion (22% to 44%) of sites had implants that potentially needed additional regenerative procedures.

Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

DEFF Research Database (Denmark)

Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

2013-01-01

Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

Level of CYP4G19 Expression Is Associated with Pyrethroid Resistance in Blattella germanica

Directory of Open Access Journals (Sweden)

Guang-zhou Guo

2010-01-01

Full Text Available German cockroaches have become a large problem in the Shenzhen area because of their pesticide resistance, especially to pyrethroid. A pyrethroid called “Jia Chong Qing” to prevent pests for a long time were found to be resistant to “Jia Chong Qing” with resistance index of 3.88 measured using RT-PCR and immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein expression levels in the wild strain were substantially higher than that of a sensitive strain. dsRNA segments derived from the target gene CYP4G19 were prepared using in vitro transcription and were microinjected into abdomens of the wild strain. Two to eight days after injection, the result showed that CYP4G19 mRNA expressions were significantly reduced in the groups injected with dsRNAs.

Antimicrobial Resistance Profiles of Listeria monocytogenes and Listeria innocua Isolated from Ready-to-Eat Products of Animal Origin in Spain.

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Escolar, Cristina; Gómez, Diego; Del Carmen Rota García, María; Conchello, Pilar; Herrera, Antonio

2017-06-01

The objective of this work was to investigate the antimicrobial resistance in Listeria spp. isolated from food of animal origin. A total of 50 Listeria strains isolated from meat and dairy products, consisting of 7 Listeria monocytogenes and 43 Listeria innocua strains, were characterized for antimicrobial susceptibility against nine antimicrobials. The strains were screened by real-time PCR for the presence of antimicrobial resistance genes: tet M, tet L, mef A, msr A, erm A, erm B, lnu A, and lnu B. Multidrug resistance was identified in 27 Listeria strains, 4 belonging to L. monocytogenes. Resistance to clindamycin was the most common resistance phenotype and was identified in 45 Listeria strains; the mechanisms of resistance are still unknown. A medium prevalence of resistance to tetracycline (15 and 9 resistant and intermediate strains) and ciprofloxacin (13 resistant strains) was also found. Tet M was detected in Listeria strains with reduced susceptibility to tetracycline, providing evidence that both L. innocua and L. monocytogenes displayed acquired resistance. The presence of antimicrobial resistance genes in L. innocua and L. monocytogenes indicates that these genes may be transferred to commensal and pathogenic bacteria via the food chain; besides this, antibiotic resistance in L. monocytogenes could compromise the effective treatment of listeriosis in humans.

Robust Public Key Cryptography — A New Cryptosystem Surviving Private Key Compromise

Science.gov (United States)

Shaik, Cheman

A weakness of the present-day public key cryptosystems is that these cryptosystems do not survive private-key compromise attacks resulting from an internal breach of trust. In a competitive business environment, private key compromise is a common incident that voids the strength of public key cryptosystems such as RSA and ECC. Bribing corporate employees to disclose their secret keys and inadvertently disclosing secret information are among a plethora of practical attacks that occur at the implementation level. Once a breach of trust takes place and subsequently the private key is revealed, any public key cryptosystem fails to secure electronic data in Internet communications. The revealed key may be used by an attacker to decipher the intercepted data at an intermediary router. This weakness of public key cryptography calls for an additional security measure that enables encryptions to survive private key compromise attacks.

Rin4 causes hybrid necrosis and race-specific resistance in an interspecific lettuce hybrid.

Science.gov (United States)

Jeuken, Marieke J W; Zhang, Ningwen W; McHale, Leah K; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W; Visser, Richard G F; Niks, Rients E

2009-10-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis.

Transient Social-Ecological Stability: the Effects of Invasive Species and Ecosystem Restoration on Nutrient Management Compromise in Lake Erie

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Eric D. Roy

2010-03-01

Full Text Available Together, lake ecosystems and local human activity form complex social-ecological systems (SESs characterized by feedback loops and discontinuous change. Researchers in diverse fields have suggested that complex systems do not have single stable equilibria in the long term because of inevitable perturbation. During this study, we sought to address the general question of whether or not stable social-ecological equilibria exist in highly stressed and managed lacustrine systems. Using an integrated human-biophysical model, we investigated the impacts of a species invasion and ecosystem restoration on SES equilibrium, defined here as a compromise in phosphorus management among opposing stakeholders, in western Lake Erie. Our integrated model is composed of a calibrated ecological submodel representing Sandusky Bay, and a phosphorus management submodel that reflects the societal benefits and costs of phosphorus regulation. These two submodels together form a dynamic feedback loop that includes freshwater ecology, ecosystem services, and phosphorus management. We found that the invasion of dreissenid mussels decreased ecosystem resistance to eutrophication, necessitating increased phosphorus management to preserve ecosystem services and thus creating the potential for a shift in social-ecological equilibrium. Additionally, our results suggest that net benefits in the region following the invasion of dreissenids may never again reach the pre-invasion level if on-site phosphorus control is the sole management lever. Further demonstrating transient system stability, large-scale wetland restoration shifted points of management compromise to states characterized by less on-site phosphorus management and higher environmental quality, resulting in a significant increase in net benefits in the region. We conclude that lacustrine SESs are open and dynamic, and we recommend that future models of these systems emphasize site-specific perturbation over

High-throughput screening identifies Ceefourin 1 and Ceefourin 2 as highly selective inhibitors of multidrug resistance protein 4 (MRP4).

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Cheung, Leanna; Flemming, Claudia L; Watt, Fujiko; Masada, Nanako; Yu, Denise M T; Huynh, Tony; Conseil, Gwenaëlle; Tivnan, Amanda; Polinsky, Alexander; Gudkov, Andrei V; Munoz, Marcia A; Vishvanath, Anasuya; Cooper, Dermot M F; Henderson, Michelle J; Cole, Susan P C; Fletcher, Jamie I; Haber, Michelle; Norris, Murray D

2014-09-01

Multidrug resistance protein 4 (MRP4/ABCC4), a member of the ATP-binding cassette (ABC) transporter superfamily, is an organic anion transporter capable of effluxing a wide range of physiologically important signalling molecules and drugs. MRP4 has been proposed to contribute to numerous functions in both health and disease; however, in most cases these links remain to be unequivocally established. A major limitation to understanding the physiological and pharmacological roles of MRP4 has been the absence of specific small molecule inhibitors, with the majority of established inhibitors also targeting other ABC transporter family members, or inhibiting the production, function or degradation of important MRP4 substrates. We therefore set out to identify more selective and well tolerated inhibitors of MRP4 that might be used to study the many proposed functions of this transporter. Using high-throughput screening, we identified two chemically distinct small molecules, Ceefourin 1 and Ceefourin 2, that inhibit transport of a broad range of MRP4 substrates, yet are highly selective for MRP4 over other ABC transporters, including P-glycoprotein (P-gp), ABCG2 (Breast Cancer Resistance Protein; BCRP) and MRP1 (multidrug resistance protein 1; ABCC1). Both compounds are more potent MRP4 inhibitors in cellular assays than the most widely used inhibitor, MK-571, requiring lower concentrations to effect a comparable level of inhibition. Furthermore, Ceefourin 1 and Ceefourin 2 have low cellular toxicity, and high microsomal and acid stability. These newly identified inhibitors should be of great value for efforts to better understand the biological roles of MRP4, and may represent classes of compounds with therapeutic application. Copyright © 2014 Elsevier Inc. All rights reserved.

Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans

DEFF Research Database (Denmark)

Brejning, Jeanette; Nørgaard, Steffen; Schøler, Lone Vedel

2014-01-01

NDG-4 is a predicted transmembrane acyltransferase protein that acts in the distribution of lipophilic factors. Consequently, ndg-4 mutants lay eggs with a pale appearance due to lack of yolk, and they are resistant to sterility caused by dietary supplementation with the long-chain omega-6 polyun...

Identifying genetic relatives without compromising privacy.

Science.gov (United States)

He, Dan; Furlotte, Nicholas A; Hormozdiari, Farhad; Joo, Jong Wha J; Wadia, Akshay; Ostrovsky, Rafail; Sahai, Amit; Eskin, Eleazar

2014-04-01

The development of high-throughput genomic technologies has impacted many areas of genetic research. While many applications of these technologies focus on the discovery of genes involved in disease from population samples, applications of genomic technologies to an individual's genome or personal genomics have recently gained much interest. One such application is the identification of relatives from genetic data. In this application, genetic information from a set of individuals is collected in a database, and each pair of individuals is compared in order to identify genetic relatives. An inherent issue that arises in the identification of relatives is privacy. In this article, we propose a method for identifying genetic relatives without compromising privacy by taking advantage of novel cryptographic techniques customized for secure and private comparison of genetic information. We demonstrate the utility of these techniques by allowing a pair of individuals to discover whether or not they are related without compromising their genetic information or revealing it to a third party. The idea is that individuals only share enough special-purpose cryptographically protected information with each other to identify whether or not they are relatives, but not enough to expose any information about their genomes. We show in HapMap and 1000 Genomes data that our method can recover first- and second-order genetic relationships and, through simulations, show that our method can identify relationships as distant as third cousins while preserving privacy.

Phorbol esters induce interleukin 2 mRNA in sensitive but not in resistant EL4 cells

International Nuclear Information System (INIS)

Harrison, J.R.; Lynch, K.R.; Sando, J.J.

1986-01-01

Phorbol ester (PE) sensitive EL4 cells are growth-inhibited and produce interleukin 2 (IL2) when treated with PE. Resistant EL4 cells lack both responses. To determine whether the defect in resistant cells occurs pre or post-transcriptionally, an assay for IL2 mRNA was developed using a synthetic oligonucleotide to mouse IL2 as a probe. Total RNA (15 μg) from cells +/- PE was electrophoresed, blotted onto a cationic nylon membrane, and probed with radiolabeled oligomer. This probe hybridized to a 1.1 kb band in RNA from PE-treated sensitive cells. This RNA was detectable within 3h of PE administration, was clearly visible by 6h, and peaked by 9 to 12h. No bands hybridizing with the IL2 probe were detected in RNA isolated from unstimulated cells or from resistant EL4 cells at any time following PE stimulation. Since levels of the protooncogene c-myc have been shown to decrease in a number of cell lines during differentiation and growth inhibition, total RNA from EL4 cells was probed with a nick-translated plasmid containing the protein coding region of the c-myc gene. In PE sensitive cells, levels of c-myc RNA are markedly reduced by 3h. In a pilot experiment with resistant cells, c-myc levels appeared to remain constant. These results demonstrate that PE induced IL2 mRNA in PE sensitive but not resistant EL4 cells. Sensitive and resistant EL4 cell lines provide a useful model for the investigation of the regulation of gene expression by PE

High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

Science.gov (United States)

Saravanan, Shanmugam; Gomathi, Selvamurthi; Delong, Allison; Kausalya, Bagavathi; Sivamalar, Sathasivam; Poongulali, Selvamuthu; Brooks, Katherine; Kumarasamy, Nagalingeswaran; Balakrishnan, Pachamuthu; Solomon, Sunil S; Cu-Uvin, Susan; Kantor, Rami

2018-05-24

Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

MCPA (4-Chloro-2-ethylphenoxyacetate) resistance in hemp-nettle (Galeopsis tetrahit L.).

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Weinberg, Tsafrir; Stephenson, Gerald R; McLean, Michael D; Hall, J Christopher

2006-11-29

The physiological basis for MCPA resistance in a hemp-nettle (Galeopsis tetrahit L.) biotype, obtained from a MCPA-resistant field population, was investigated. Dose-response studies revealed that the resistance factor for MCPA, based on GR50 comparisons of total dry weight of resistant (R) and susceptible (S) plants, was 3.3. Resistance factors for fluroxypyr, dicamba, 2,4-D, glyphosate, and chlorsulfuron were 8.2, 1.7, 1.6, 0.7, and 0.6, respectively. MCPA resistance was not due to differences in absorption, because both R and S biotypes absorbed 54% of applied [14C]MCPA 72 h after treatment. However, R plants exported less (45 vs 58% S) recovered 14C out of treated leaves to the apical meristem (6 vs 13% S) and root (32 vs 38% S). In both biotypes, approximately 20% of the 14C recovered in planta was detected as MCPA metabolites. However, less of the 14C recovered in the roots of R plants was MCPA. Therefore, two different mechanisms protect R hemp-nettle from MCPA phytotoxicity: a lower rate of MCPA translocation and a higher rate of MCPA metabolism in the roots. In support of these results, genetic studies indicated that the inheritance of MCPA resistance is governed by at least two nuclear genes with additive effects.

Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

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Patricia Fernandez

2014-10-01

Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

Salivary changes in medically compromised patients: A clinical and biochemical study

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Yehoshuva R Tummuru

2017-01-01

Full Text Available Introduction: Medically compromised patients require special attention when dental procedures are performed on them. These individuals may require modified or slightly altered techniques. Aims and Objectives: The present study was taken up with two main objectives. The first one being examining and recording various oral manifestations in medically compromised patients, and the second objective was to collect samples of saliva from such patients and to analyze and establish any salivary changes in such medically compromised patients. Materials and Methods: A total of 100 patients were selected for the study. These patients were divided into four groups of 25 patients each: diabetes mellitus group, chronic renal failure group, liver cirrhosis group and control group. All the selected patients were subjected to a detailed general and intra oral examinations and the relevant data was recorded on a specially designed proforma; salivary analysis was done to know the flow rate, pH, total salivary proteins, sodium, potassium, and LDH levels. Results: From the findings, it can be inferred that salivary changes namely changes in salivary pH, salivary flow rates, salivary sodium, salivary potassium, salivary total proteins, and salivary lactate dehydrogenase are significant in medically compromised patients namely uncontrolled diabetes mellitus, chronic renal failure, cirrhosis of liver compared to the control group. Conclusion: pH of saliva was elevated in chronic renal failure patients. Salivary flow rates and sodium were decreased in diabetes mellitus, chronic renal failure, and cirrhosis of liver patients. There was a significant elevation of salivary potassium in chronic renal failure patients. LDH elevation was significant in uncontrolled diabetes mellitus.

Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death.

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Wang, Yan; Cordewener, Jan H G; America, Antoine H P; Shan, Weixing; Bouwmeester, Klaas; Govers, Francine

2015-09-01

L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

Breeding of new variety Yangfumai 4 with high resistance to wheat yellow mosaic disease

International Nuclear Information System (INIS)

He Zhentian; Chen Xiulan; Zhang Rong; Wang Jianhua; Wang Jinrong; Liu Jian

2011-01-01

To control the infection of wheat yellow mosaic disease,new wheat variety with high-yield, disease-resistant was selected. Ningmai 9, which carries yellow mosaic disease resistant genes, was used as original material. Combination of conventional breeding technique and radiation methods, a new wheat variety Yangfumai 4 was developed during 1996-2007, and registered in 2008. The new wheat variety with high yield and resistance to yellow mosaic disease is suitable to plant in the Yangtze River region. (authors)

Molecular mechanisms of cisplatin resistance in cervical cancer

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Zhu H

2016-06-01

Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

Improved ductility and oxidation resistance of cast Ti–6Al–4V alloys by microalloying

International Nuclear Information System (INIS)

Luan, J.H.; Jiao, Z.B.; Chen, G.; Liu, C.T.

2014-01-01

Highlights: • Modified Ti64 alloys with improved ductility and oxidation resistance are developed. • B improves the ductility by refining grain size and enhancing boundary cohesion. • Y enhances the oxidation resistance by possibly slowing down the oxidation kinetics. - Abstract: The effects of B and Y on the mechanical properties and oxidation behavior of cast Ti–6Al–4V alloys were systematically investigated, and the new alloys with improved ductility and oxidation resistance are developed by the microalloying approach. The results indicate that boron is beneficial for improving the ductility by not only grain-size refinement but also grain-boundary enhancement, while yttrium is effective in increasing the oxidation resistance through possibly slowing down the oxidation kinetics. The improved properties, together with their high strength, make the microalloyed cast Ti–6Al–4V alloys competitive for practical engineering applications

Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity

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Bruno M. Simões

2015-09-01

Full Text Available Breast cancers (BCs typically express estrogen receptors (ERs but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.

26 CFR 301.6331-3 - Restrictions on levy while offers to compromise are pending.

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2010-04-01

... are pending. 301.6331-3 Section 301.6331-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... for Collection of Taxes § 301.6331-3 Restrictions on levy while offers to compromise are pending. Cross-reference. For provisions relating to the making of levies while an offer to compromise is pending...

Transmitted antiretroviral drug resistance in New York State, 2006-2008: results from a new surveillance system.

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Adam C Readhead

Full Text Available HIV transmitted drug resistance (TDR is a public health concern because it has the potential to compromise antiretroviral therapy (ART at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system.We conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses.Of 13,109 new HIV diagnoses, 9,785 (75% had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43% had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%-12.1% had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%-7.0%, 4.3% (3.6%-4.9% and 2.9% (2.4%-3.4%, respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204. Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77-1.30. TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%-7.9% and 1.4% (1.0%-1.8%, respectively.TDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.

NS5A Sequence Heterogeneity and Mechanisms of Daclatasvir Resistance in Hepatitis C Virus Genotype 4 Infection.

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Zhou, Nannan; Hernandez, Dennis; Ueland, Joseph; Yang, Xiaoyan; Yu, Fei; Sims, Karen; Yin, Philip D; McPhee, Fiona

2016-01-15

Daclatasvir is an NS5A inhibitor approved for treatment of infection due to hepatitis C virus (HCV) genotypes (GTs) 1-4. To support daclatasvir use in HCV genotype 4 infection, we examined a diverse genotype 4-infected population for HCV genotype 4 subtype prevalence, NS5A polymorphisms at residues associated with daclatasvir resistance (positions 28, 30, 31, or 93), and their effects on daclatasvir activity in vitro and clinically. We performed phylogenetic analysis of genotype 4 NS5A sequences from 186 clinical trial patients and 43 sequences from the European HCV database, and susceptibility analyses of NS5A polymorphisms and patient-derived NS5A sequences by using genotype 4 NS5A hybrid genotype 2a replicons. The clinical trial patients represented 14 genotype 4 subtypes; most prevalent were genotype 4a (55%) and genotype 4d (27%). Daclatasvir 50% effective concentrations for 10 patient-derived NS5A sequences representing diverse phylogenetic clusters were ≤0.080 nM. Most baseline sequences had ≥1 NS5A polymorphism at residues associated with daclatasvir resistance; however, only 3 patients (1.6%) had polymorphisms conferring ≥1000-fold daclatasvir resistance in vitro. Among 46 patients enrolled in daclatasvir trials, all 20 with baseline resistance polymorphisms achieved a sustained virologic response. Circulating genotype 4 subtypes are genetically diverse. Polymorphisms conferring high-level daclatasvir resistance in vitro are uncommon before therapy, and clinical data suggest that genotype 4 subtype and baseline polymorphisms have minimal impact on responses to daclatasvir-containing regimens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Microstructural stability of heat-resistant high-pressure die-cast Mg-4Al-4Ce alloy

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei; Zhang, Jinghuai; Li, Guoqiang; Feng, Yan; Su, Minliang; Wu, Ruizhi; Zhang, Zhongwu [Harbin Engineering Univ. (China). Key Laboratory of Superlight Material and Surface Technology; Jiao, Yufeng [Jiamusi Univ. (China). College of Materials Science and Engineering

2017-05-15

The thermal stability of Al-RE (rare earth) intermetallic phases with individual RE for heat-resistant high-pressure die-casting Mg-Al-RE alloys is investigated. The results of this study show that the main strengthening phase of Mg-4Al-4Ce alloy is Al{sub 11}Ce{sub 3}, whose content is about 5 wt.% according to quantitative X-ray diffraction phase analysis. The Al{sub 11}Ce{sub 3} phase appears to have high thermal stability at 200 C and 300 C, while phase morphology change with no phase structure transition could occur for Al{sub 11}Ce{sub 3} when the temperature reaches 400 C. Furthermore, besides the kinds of rare earths and temperature, stress is also an influencing factor in the microstructural stability of Mg-4Al-4Ce alloy.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

OpenAIRE

Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

2014-01-01

Introduction: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failu...

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

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Nadia Bakkour

2007-10-01

Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK

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Katayama, Ryohei; Khan, Tahsin M.; Benes, Cyril; Lifshits, Eugene; Ebi, Hiromichi; Rivera, Victor M.; Shakespeare, William C.; Iafrate, A. John; Engelman, Jeffrey A.; Shaw, Alice T.

2011-01-01

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion oncogene represents a molecular target in a small subset of non-small cell lung cancers (NSCLCs). This fusion leads to constitutive ALK activation with potent transforming activity. In a pivotal phase 1 clinical trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitumor activity in the majority of patients with NSCLC harboring ALK fusions. However, despite these remarkable initial responses, cancers eventually develop resistance to crizotinib, usually within 1 y, thereby limiting the potential clinical benefit. To determine how cancers acquire resistance to ALK inhibitors, we established a model of acquired resistance to crizotinib by exposing a highly sensitive EML4-ALK–positive NSCLC cell line to increasing doses of crizotinib until resistance emerged. We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene. Cells resistant to higher doses (1 μM) also developed a gatekeeper mutation, L1196M, within the kinase domain, rendering EML4-ALK insensitive to crizotinib. This gatekeeper mutation was readily detected using a unique and highly sensitive allele-specific PCR assay. Although crizotinib was ineffectual against EML4-ALK harboring the gatekeeper mutation, we observed that two structurally different ALK inhibitors, NVP-TAE684 and AP26113, were highly active against the resistant cancer cells in vitro and in vivo. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitor 17-AAG. Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations. PMID:21502504

The Akt inhibitor ISC-4 synergizes with cetuximab in 5-FU-resistant colon cancer.

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Joshua E Allen

Full Text Available Phenylbutyl isoselenocyanate (ISC-4 is an Akt inhibitor with demonstrated preclinical efficacy against melanoma and colon cancer. In this study, we sought to improve the clinical utility of ISC-4 by identifying a synergistic combination with FDA-approved anti-cancer therapies, a relevant and appropriate disease setting for testing, and biomarkers of response. We tested the activity of ISC-4 and 19 FDA-approved anticancer agents, alone or in combination, against the SW480 and RKO human colon cancer cell lines. A synergistic interaction with cetuximab was identified and validated in a panel of additional colon cancer cell lines, as well as the kinetics of synergy. ISC-4 in combination with cetuximab synergistically reduced the viability of human colon cancer cells with wild-type but not mutant KRAS genes. Further analysis revealed that the combination therapy cooperatively decreased cell cycle progression, increased caspase-dependent apoptosis, and decreased phospho-Akt in responsive tumor cells. The synergism between ISC-4 and cetuximab was retained independently of acquired resistance to 5-FU in human colon cancer cells. The combination demonstrated synergistic anti-tumor effects in vivo without toxicity and in the face of resistance to 5-FU. These results suggest that combining ISC-4 and cetuximab should be explored in patients with 5-FU-resistant colon cancer harboring wild-type KRAS.

The Yttrium Effect on Nanoscale Structure, Mechanical Properties, and High-Temperature Oxidation Resistance of (Ti0.6Al0.4)1- x Y x N Multilayer Coatings

Science.gov (United States)

Wang, Jingxian; Yazdi, Mohammad Arab Pour; Lomello, Fernando; Billard, Alain; Kovács, András; Schuster, Frédéric; Guet, Claude; White, Timothy J.; Wouters, Yves; Pascal, Céline; Sanchette, Frédéric; Dong, ZhiLi

2017-09-01

As machine tool coating specifications become increasingly stringent, the fabrication of protective titanium aluminum nitride (Ti-Al-N) films by physical vapor deposition (PVD) is progressively more demanding. Nanostructural modification through the incorporation of metal dopants can enhance coating mechanical properties. However, dopant selection and their near-atomic-scale role in performance optimization is limited. Here, yttrium was alloyed in multilayered Ti-Al-N films to tune microstructures, microchemistries, and properties, including mechanical characteristics, adhesion, wear resistance, and resilience to oxidation. By regulating processing parameters, the multilayer period (Λ) and Y content could be adjusted, which, in turn, permitted tailoring of grain nucleation and secondary phase formation. With the composition fixed at x = 0.024 in (Ti0.6Al0.4)1- x Y x N and Λ increased from 5.5 to 24 nm, the microstructure transformed from acicular grains with 〈111〉 preferred orientation to equiaxed grains with 〈200〉 texture, while the hardness (40.8 ± 2.8 GPa to 29.7 ± 4.9 GPa) and Young's modulus (490 ± 47 GPa to 424 ± 50 GPa) concomitantly deteriorated. Alternately, when Λ = 5.5 nm and x in (Ti0.6Al0.4)1- x Y x N was raised from 0 to 0.024, the hardness was enhanced (28.7 ± 7.3 GPa to 40.8 ± 2.8 GPa) while adhesion and wear resistance were not compromised. The Ti-Al-N adopted a rock-salt type structure with Y displacing either Ti or Al and stabilizing a secondary wurtzite phase. Moreover, Y effectively retarded coating oxidation at 1073 K (800 °C) in air by inhibiting grain boundary oxygen diffusion.

Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells.

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Zhou, Kairui; Shi, Xiaoli; Huo, Jinling; Liu, Weihua; Yang, Dongxiao; Yang, Tengjiao; Qin, Tiantian; Wang, Cong

2017-08-01

Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc). In these drug-resistant cell lines, we found the cell motility was enhanced and BMP4 was up-regulated relative to their respective parental cell lines. Consistent with in vitro assays, migration potential and BMP4 expression were increased in EC109/Taxol nude mice. Furthermore, to address whether BMP4 was required to enhance the metastatic in EC109/Taxol cells, the pharmacological inhibitor of BMP signaling dorsomorphin was used; meanwhile, we found that the migration and invasion abilities were inhibited. Moreover, the canonical Smad signaling pathway was investigated. Overall, our studies demonstrated that BMP4 participates in the regulation of invasion and migration by EC109/Taxol cells, and inhibition of BMP4 may be a novel strategy to interfere with metastasis in cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Simple PCR assays improve the sensitivity of HIV-1 subtype B drug resistance testing and allow linking of resistance mutations.

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Jeffrey A Johnson

Full Text Available BACKGROUND: The success of antiretroviral therapy is known to be compromised by drug-resistant HIV-1 at frequencies detectable by conventional bulk sequencing. Currently, there is a need to assess the clinical consequences of low-frequency drug resistant variants occurring below the detection limit of conventional genotyping. Sensitive detection of drug-resistant subpopulations, however, requires simple and practical methods for routine testing. METHODOLOGY: We developed highly-sensitive and simple real-time PCR assays for nine key drug resistance mutations and show that these tests overcome substantial sequence heterogeneity in HIV-1 clinical specimens. We specifically used early wildtype virus samples from the pre-antiretroviral drug era to measure background reactivity and were able to define highly-specific screening cut-offs that are up to 67-fold more sensitive than conventional genotyping. We also demonstrate that sequencing the mutation-specific PCR products provided a direct and novel strategy to further detect and link associated resistance mutations, allowing easy identification of multi-drug-resistant variants. Resistance mutation associations revealed in mutation-specific amplicon sequences were verified by clonal sequencing. SIGNIFICANCE: Combined, sensitive real-time PCR testing and mutation-specific amplicon sequencing provides a powerful and simple approach that allows for improved detection and evaluation of HIV-1 drug resistance mutations.

Sustainable Development Compromise[d] in the Planning of Metro Vancouver’s Agricultural Lands—the Jackson Farm Case

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Meg Holden

2013-11-01

Full Text Available This research provides analysis of the case of the Jackson Farm development application, embedded within the particular dynamics of the municipal, regional, and provincial sustainability land use policy culture of the Metro Vancouver region, in Canada. Within a culture of appreciation of the increasing need for sustainability in land use policy, including the protection of agricultural lands at the provincial level through the Agricultural Land Reserve (ALR, to urban intensification and protection of the green zone at the regional scale, lies a political conflict that comes into focus in individual land use decisions, within municipalities struggling for autonomy. This case is neither driven strictly by “the politics of the highest bidder” nor by policy failure; the case of the Jackson Farm is instead a case of the challenges of implementing inter-governmental coordination and collaborative governance in a context of both significant sustainability policy and urban growth. The process can be seen to follow an ecological modernization agenda, seeking “win–win” alternatives rather than recognizing that typical compromises, over time, may tip the direction of development away from sustainability policy goals. Understanding the twists, turns, and eventual compromise reached in the case of the Jackson Farm brings to light the implications of the shift in the regional planning culture which may necessitate a less flexible, more structured prioritization of competing goals within plans and policies in order to meet sustainability goals. We highlight this, and present an alternative implementation process within the existing policy regime with potential to aid the specific goal of agricultural land protection.

Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

Energy Technology Data Exchange (ETDEWEB)

Komura, Jun-ichiro, E-mail: junkom@med.tohoku.ac.jp [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ikehata, Hironobu [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Mori, Toshio [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan); Ono, Tetsuya [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

2012-03-10

During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.

Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

International Nuclear Information System (INIS)

Komura, Jun-ichiro; Ikehata, Hironobu; Mori, Toshio; Ono, Tetsuya

2012-01-01

During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: ► Global genome repair of (6-4) photoproducts is fully active in mitotic cells. ► DNA in condensed mitotic chromatin does not seem inaccessible or inert. ► Mitotic transcriptional repression may impair transcription-coupled repair.

Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer

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Nafi, Siti Norasikin Mohd; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Haider, Syed; Li, Ji-Liang; Bridges, Esther; Capala, Jacek; Ioannis, Roxanis; Harris, Adrian L; Kong, Anthony

2014-01-01

The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response. There was also increased nuclear HER4 staining in the tumours from BT474 xenograft mice and human patients treated with trastuzumab. Furthermore, nuclear HER4 predicted poor clinical response to trastuzumab monotherapy in patients undergoing a window study and was shown to be an independent poor prognostic factor in HER2 positive breast cancer. Our data suggest that HER4 plays a key role in relation to trastuzumab resistance in HER2 positive breast cancer. Therefore, our study provides novel findings that HER4 activation, cleavage and nuclear translocation influence trastuzumab sensitivity and resistance in HER2 positive breast cancer. Nuclear HER4 could be a potential prognostic and predictive biomarker and understanding the role of HER4 may provide strategies to overcome trastuzumab resistance in HER2 positive breast cancer. PMID:25153719

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

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Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I.; Griffin, Timothy M.; Barlic-Dicen, Jana

2014-01-01

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.—Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Rin4 Causes Hybrid Necrosis and Race-Specific Resistance in an Interspecific Lettuce Hybrid[W

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Jeuken, Marieke J.W.; Zhang, Ningwen W.; McHale, Leah K.; Pelgrom, Koen; den Boer, Erik; Lindhout, Pim; Michelmore, Richard W.; Visser, Richard G.F.; Niks, Rients E.

2009-01-01

Some inter- and intraspecific crosses may result in reduced viability or sterility in the offspring, often due to genetic incompatibilities resulting from interactions between two or more loci. Hybrid necrosis is a postzygotic genetic incompatibility that is phenotypically manifested as necrotic lesions on the plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and Lactuca saligna) hybrids that correlated with resistance to downy mildew. Segregation analysis revealed a specific allelic combination at two interacting loci to be responsible. The allelic interaction had two consequences: (1) a quantitative temperature-dependent autoimmunity reaction leading to necrotic lesions, lethality, and quantitative resistance to an otherwise virulent race of Bremia lactucae; and (2) a qualitative temperature-independent race-specific resistance to an avirulent race of B. lactucae. We demonstrated by transient expression and silencing experiments that one of the two interacting genes was Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene products, and their interactions result in hypersensitive resistance to Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting allele of Rin4 in lettuce showed that three residues were critical for hybrid necrosis. PMID:19855048

WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines.

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Sikora, Matthew J; Jacobsen, Britta M; Levine, Kevin; Chen, Jian; Davidson, Nancy E; Lee, Adrian V; Alexander, Caroline M; Oesterreich, Steffi

2016-09-20

Invasive lobular carcinoma (ILC) of the breast typically presents with clinical biomarkers consistent with a favorable response to endocrine therapies, and over 90 % of ILC cases express the estrogen receptor (ER). However, a subset of ILC cases may be resistant to endocrine therapies, suggesting that ER biology is unique in ILC. Using ILC cell lines, we previously demonstrated that ER regulates a distinct gene expression program in ILC cells, and we hypothesized that these ER-driven pathways modulate the endocrine response in ILC. One potential novel pathway is via the Wnt ligand WNT4, a critical signaling molecule in mammary gland development regulated by the progesterone receptor. The ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used to assess WNT4 gene expression and regulation, as well as the role of WNT4 in estrogen-regulated proliferation. To assess these mechanisms in the context of endocrine resistance, we developed novel ILC endocrine-resistant long-term estrogen-deprived (ILC-LTED) models. ILC and ILC-LTED cell lines were used to identify upstream regulators and downstream signaling effectors of WNT4 signaling. ILC cells co-opted WNT4 signaling by placing it under direct ER control. We observed that ER regulation of WNT4 correlated with use of an ER binding site at the WNT4 locus, specifically in ILC cells. Further, WNT4 was required for endocrine response in ILC cells, as WNT4 knockdown blocked estrogen-induced proliferation. ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. In the latter case, WNT4 expression was driven by activated nuclear factor kappa-B signaling in ILC-LTED cells. In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. CDKN1A knockdown partially reversed the effects of WNT4 knockdown. WNT4 drives a novel signaling pathway in ILC cells, with a

Sterile diets for the immuno-compromised: Is there a need?

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Butterweck, Joseph S.

1995-02-01

There is a general misunderstanding in the radiation processing industry about the use of sterile diets in the medical profession. Sterile diets are used on a limited basis in hospitals that specialize in cancer treatment and organ transplants. These patients are severely immuno-compromised. There are many other patients that are immuno-compromised that do not require sterile diets. These patients may require a diet that is pathogen-free and are aslo "low-microbial diets". Nosocomial infections have become a major issue in US hospitals. The "infection control committee" is the focus group responsible to assure nosocomial infections incidence are below the hospital goals. Application of ionizing radiation to sterilize diets has not been chosen because the product is not available at a reasonable total cost. This paper will discuss the hospitals views.

Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4.

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Todaro, M; Lombardo, Y; Francipane, M G; Alea, M Perez; Cammareri, P; Iovino, F; Di Stefano, A B; Di Bernardo, C; Agrusa, A; Condorelli, G; Walczak, H; Stassi, G

2008-04-01

We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2. Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptotic proteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 acts as an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a novel treatment for epithelial cancers.

Weather resistance of CaSO4 ṡ 1/2H2O-based sand-fixation material

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Liu, Xin; Tie, Shengnian

2017-07-01

Searching for an economical and effective sand-fixing material and technology is of great importance in Northwest China. This paper described the use of a semihydrated gypsum-(CaSO4 ṡ 1/2H2O-)based composite as a sand-fixing material. Its morphology and composition were characterized by SEM, and its water resistance, freezing-thawing resistance and wind erosion resistance were tested in the field. The results indicated that semihydrated gypsum-(CaSO4 ṡ 1/2H2O-)based sand-fixing composite has good water resistance and water-holding capacity. Its strength is maintained at 1.42 MPa after 50 freezing and thawing cycles, and its wind erosion increases with increasing wind speed and slope. Its compressive strength starts to decrease after nine months of field tests with no change in appearance, but it still satisfies the requirements of fixation technology. This sand-fixing material should have wide application owing to its good weather resistance.

MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4

International Nuclear Information System (INIS)

Wei, Xueju; Wang, Weibin; Wang, Lanlan; Zhang, Yuanyuan; Zhang, Xian; Chen, Mingtai; Wang, Fang; Yu, Jia; Ma, Yanni; Sun, Guotao

2016-01-01

Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21

Experimental study on the resistance to hydrogen embrittlement of NIFS-V4Cr4Ti alloy

International Nuclear Information System (INIS)

Chen Jiming; Xu Zengyu; Den Ying; Muroga, T.

2002-01-01

SWIP (Southwestern Institute of Physics) has joined an international collaboration on the hydrogen embrittlement resistance evaluation of the vanadium alloy. This paper presents some experiments on the tensile properties and Charpy impact properties of the NIFS-V4Cr4Ti alloy with high-level hydrogen concentration. The experiment results show different properties against hydrogen embrittlement in static tension and impact load. The critical hydrogen concentration required to embrittle the alloy was about 215 - 310 mg·kg -1 on static tension load, but less than 130 mg·kg -1 on impact loading

Multi drug resistant tuberculosis presenting as anterior mediastinal mass

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Parmarth Chandane

2016-01-01

Full Text Available Enlargement of the mediastinal lymphatic glands is a common presentation of intrathoracic tuberculosis (TB in children. However, usually, the mediastinal TB nodes enlarge to 2.8 ± 1.0 cm. In this report, we describe a case of anterior mediastinal lymphnode TB seen as huge mass (7 cm on computed tomography (CT thorax without respiratory or food pipe compromise despite anterior mediastinum being an enclosed space. CT guided biopsy of the mass cultured Mycobacterium TB complex which was resistant to isoniazide, rifampicin, streptomycin ofloxacin, moxifloxacin, and pyrazinamide. Hence, we report primary multi drug resistant TB presenting as anterior mediastinal mass as a rare case report.

Peripheral insulin resistance in ILK-depleted mice by reduction of GLUT4 expression.

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Hatem-Vaquero, Marco; Griera, Mercedes; García-Jerez, Andrea; Luengo, Alicia; Álvarez, Julia; Rubio, José A; Calleros, Laura; Rodríguez-Puyol, Diego; Rodríguez-Puyol, Manuel; De Frutos, Sergio

2017-08-01

The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycemia and insulinemia concurrently with a reduction of the expression and membrane presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wild-type littermates (WT). Tolerance tests and insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK, suggesting a similar stage to prediabetes in humans. Under randomly fed conditions, no differences between cKD-ILK and WT were observed in the expression of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other hand, the glucose uptake capacity in response to exogenous insulin was impaired when ILK was blocked in vivo and in vitro , although IR/IRS/AKT phosphorylation states were increased but not different between groups. We conclude that ILK depletion modifies the transcription of GLUT4, which results in reduced peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular target and a prognostic biomarker of insulin resistance. © 2017 Society for Endocrinology.

Chemical suppressors of mlo-mediated powdery mildew resistance

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Wu, Hongpo; Kwaaitaal, Mark; Strugala, Roxana; Schaffrath, Ulrich; Bednarek, Paweł

2017-01-01

Loss-of-function of barley mildew locus o (Mlo) confers durable broad-spectrum penetration resistance to the barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). Given the importance of mlo mutants in agriculture, surprisingly few molecular components have been identified to be required for this type of resistance in barley. With the aim to identify novel cellular factors contributing to mlo-based resistance, we devised a pharmacological inhibitor screen. Of the 41 rationally chosen compounds tested, five caused a partial suppression of mlo resistance in barley, indicated by increased levels of Bgh host cell entry. These chemicals comprise brefeldin A (BFA), 2′,3′-dideoxyadenosine (DDA), 2-deoxy-d-glucose, spermidine, and 1-aminobenzotriazole. Further inhibitor analysis corroborated a key role for both anterograde and retrograde endomembrane trafficking in mlo resistance. In addition, all four ribonucleosides, some ribonucleoside derivatives, two of the five nucleobases (guanine and uracil), some guanine derivatives as well as various polyamines partially suppress mlo resistance in barley via yet unknown mechanisms. Most of the chemicals identified to be effective in partially relieving mlo resistance in barley also to some extent compromised powdery mildew resistance in an Arabidopsis mlo2 mlo6 double mutant. In summary, our study identified novel suppressors of mlo resistance that may serve as valuable probes to unravel further the molecular processes underlying this unusual type of disease resistance. PMID:29127104

Water soluble and metal-containing electron beam resist poly(sodium 4-styrenesulfonate)

International Nuclear Information System (INIS)

Abbas, Arwa Saud; Alqarni, Sondos; Shokouhi, Babak Baradaran; Yavuz, Mustafa; Cui, Bo

2014-01-01

Popular electron beam resists such as PMMA, ZEP and HSQ all use solvent or base solutions for processing, which may attack the sub-layers or substrate that are made out of organic semiconducting materials. In this study we show that water soluble poly(sodium 4-styrenesulfonate), or sodium PSS, can be used as a negative electron beam resist developed in water. Moreover, since PSS contains metal sodium, its dry etching resistance is much higher than PMMA. It is notable that sodium PSS’s sensitivity and contrast is still far inferior to organic resists such as PMMA, thus it is not suitable for patterning dense and high-resolution structures. Nevertheless, feature size down to 40 nm was achieved for sparse patterns. Lastly, using very low energy (here 2 keV) electron beam lithography and liftoff process using water only, patterning of metal layer on an organic conductive material P3HT was achieved. The metallization of an organic conducting material may find applications in organic semiconductor devices such as OLED. (paper)

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

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Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-05-01

We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

Fire resistant polyamide based on 1-(diorganooxyphosphonyl)methyl-2,4- and -2,6diamino benzene

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Mikroyannidis, J. A. (Inventor); Kourtides, D. A. (Inventor)

1986-01-01

1-(Diorganooxyphosphonyl)methyl2,4- and-2,6diamino benzenes are reacted with polyacylhalides and optionally comonomers to produce polyamides which have desirable heat and fire resistance properties. These polymers are used to form fibers and fabrics where fire resistance properties are important, e.g., aircraft equipment and structures.

Transportin-SR is required for proper splicing of resistance genes and plant immunity.

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Shaohua Xu

2011-06-01

Full Text Available Transportin-SR (TRN-SR is a member of the importin-β super-family that functions as the nuclear import receptor for serine-arginine rich (SR proteins, which play diverse roles in RNA metabolism. Here we report the identification and cloning of mos14 (modifier of snc1-1, 14, a mutation that suppresses the immune responses conditioned by the auto-activated Resistance (R protein snc1 (suppressor of npr1-1, constitutive 1. MOS14 encodes a nuclear protein with high similarity to previously characterized TRN-SR proteins in animals. Yeast two-hybrid assays showed that MOS14 interacts with AtRAN1 via its N-terminus and SR proteins via its C-terminus. In mos14-1, localization of several SR proteins to the nucleus was impaired, confirming that MOS14 functions as a TRN-SR. The mos14-1 mutation results in altered splicing patterns of SNC1 and another R gene RPS4 and compromised resistance mediated by snc1 and RPS4, suggesting that nuclear import of SR proteins by MOS14 is required for proper splicing of these two R genes and is important for their functions in plant immunity.

Loss of ABCB4 attenuates the caspase-dependent apoptosis regulating resistance to 5-Fu in colorectal cancer.

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Hu, Hanqing; Wang, Meng; Guan, Xu; Yuan, Ziming; Liu, Zheng; Zou, Chaoxia; Wang, Guiyu; Gao, Xu; Wang, Xishan

2018-02-28

The adenosine triphosphate-binding cassette (ABC) is a large group of proteins involved in material transportation, cellular homeostasis, and closely associated with chemoresistance. ATP-binding cassette protein B4 (ABCB4) is a member of ABCs which has a similar structure to ABCB1, but fewer researches were performed. The present study is aimed to investigate the putative mechanism of ABCB4 in 5-fluorouracil (5-Fu) resistance. Then, we found that ABCB4 was significantly down-regulated in the 5-Fu resistant HCT8 cell lines by polymerase chain reaction (PCR) and Western blot. The knockdown of ABCB4 by small interfering RNA decreased the apoptosis by 5-Fu in resistant HCT8R cell lines without influencing the proliferation. Also, we found a lower expression of cleaved caspase and PARP by Western blot after the knockdown of ABCB4. However, the knockdown of ABCB4 did not influence the proliferation and apoptosis. Furthermore, the histological detection of ABCB4 mRNA level in human colorectal cancer tissues and even in the recurrent tissues after 5-Fu single-agent chemotherapy was employed to provide more concrete evidence that ABCB4 may be a tumor suppressor gene to regulate chemoresistance in colorectal cancer. Moreover, a 109-patient cohort revealed that ABCB4 predicted a poor recurrence-free survival and overall survival. In summary, ABCB4 was down-regulated in the 5-Fu resistant cells and knockdown of ABCB4 alleviated the cell apoptosis and predicts a shorter recurrence-free survival and overall survival. © 2018 The Author(s).

A Compromise Programming Model for Highway Maintenance Resources Allocation Problem

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Hui Xiong

2012-01-01

Full Text Available This paper formulates a bilevel compromise programming model for allocating resources between pavement and bridge deck maintenances. The first level of the model aims to solve the resource allocation problems for pavement management and bridge deck maintenance, without considering resource sharing between them. At the second level, the model uses the results from the first step as an input and generates the final solution to the resource-sharing problem. To solve the model, the paper applies genetic algorithms to search for the optimal solution. We use a combination of two digits to represent different maintenance types. Results of numerical examples show that the conditions of both pavements and bridge decks are improved significantly by applying compromise programming, rather than conventional methods. Resources are also utilized more efficiently when the proposed method is applied.

Efflux pumps as antimicrobial resistance mechanisms.

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Poole, Keith

2007-01-01

Antibiotic resistance continues to hamper antimicrobial chemotherapy of infectious disease, and while biocide resistance outside of the laboratory is as yet unrealized, in vitro and in vivo episodes of reduced biocide susceptibility are not uncommon. Efflux mechanisms, both drug-specific and multidrug, are important determinants of intrinsic and/or acquired resistance to these antimicrobials in important human pathogens. Multidrug efflux mechanisms are generally chromosome-encoded, with their expression typically resultant from mutations in regulatory genes, while drug-specific efflux mechanisms are encoded by mobile genetic elements whose acquisition is sufficient for resistance. While it has been suggested that drug-specific efflux systems originated from efflux determinants of self-protection in antibiotic-producing Actinomycetes, chromosomal multidrug efflux determinants, at least in Gram-negative bacteria, are appreciated as having an intended housekeeping function unrelated to drug export and resistance. Thus, it will be important to elucidate the intended natural function of these efflux mechanisms in order, for example, to anticipate environmental conditions or circumstances that might promote their expression and, so, compromise antimicrobial chemotherapy. Given the clinical significance of antimicrobial exporters, it is clear that efflux must be considered in formulating strategies for treatment of drug-resistant infections, both in the development of new agents, for example, less impacted by efflux or in targeting efflux directly with efflux inhibitors.

Fine Mapping of the Dominant Potyvirus Resistance Gene Pvr7 Reveals a Relationship with Pvr4 in Capsicum annuum.

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Venkatesh, Jelli; An, Jeongtak; Kang, Won-Hee; Jahn, Molly; Kang, Byoung-Cheorl

2018-01-01

Pepper mottle virus (PepMoV) is the most common potyvirus infection of pepper plants and causes significant yield losses. The Pvr7 gene from Capsicum chinense PI159236 and the Pvr4 gene from C. annuum CM334 both have been reported to confer dominant resistance to PepMoV. The Pvr7 locus conferring resistance to PepMoV in C. annuum '9093' was previously mapped to chromosome 10. To develop a high-resolution map of the Pvr7 locus in 9093, we constructed an intraspecific F 2 mapping population consisting of 916 individuals by crossing PepMoV-resistant C. annuum '9093' and the PepMoV-susceptible C. annuum 'Jeju'. To delimit the Pvr7 target region, single-nucleotide polymorphism (SNP) markers derived from the Pvr4 region were used for genotyping the F 2 population. Molecular mapping delimited the Pvr7 locus to a physical interval of 258 kb, which was the same region as Pvr4 on chromosome 10. Three SNP markers derived from Pvr4 mapping perfectly cosegregated with PepMoV resistance. Sequencing analyses of the Pvr7 flanking markers and the Pvr4-specific gene indicated that Pvr7 and Pvr4 are the same gene. Resistance spectrum analysis of 9093 against pepper potyviruses showed that 9093 has a resistance spectrum similar to that of cultivar CM334. These combined results demonstrate that, unlike previously thought, the dominant PepMoV resistance in 9093 could be derived from C. annuum 'CM334', and that Pvr4 and Pvr7 should be considered as the same locus.

Increased plasma levels of FABP4 and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus.

Science.gov (United States)

Li, Yuan-yuan; Xiao, Rui; Li, Cai-ping; Huangfu, Jian; Mao, Jiang-feng

2015-02-08

The aim of this study was to investigate the relationship between plasma fatty acid binding protein 4 (FABP4), phosphatase and tensin homolog (PTEN), and insulin resistance in patients with gestational diabetes mellitus (GDM). Plasma FABP4 and PTEN were determined by ELISA in GDM patients (GDM group, n=30) and in euglycemic pregnant women (control group, n=30). The clinical features, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were compared between the 2 groups. The influence of risk factors on insulin resistance, including BMI, lipid profiles, FABP4, and PTEN, were further investigated by multiple-factor stepwise regression analysis. Higher levels of BMI, ΔBMI, triglyceride (TG), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting insulin, HOMA-IR, FABP4, PTEN, and lower level of high-density lipoprotein cholesterol (HDL-C) were found in the GDM patients than in the controls (all Pinsulin resistance. GDM patients have more severe insulin resistance compared to euglycemic pregnant women. Higher levels of plasma FABP4 and PTEN are associated with increased insulin resistance and may participate in the pathogenesis of insulin resistance during gestation.

Nutritional Modulation of Insulin Resistance

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Martin O. Weickert

2012-01-01

Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

Science.gov (United States)

Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

2017-04-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

The compromised gut in the neonate : Diagnostic and clinical aspects

NARCIS (Netherlands)

Schurink, Maarten

2016-01-01

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease predominantly occurring in preterm infants, causing significant patient morbidity and mortality. It is characterized by loss of bowel wall integrity due to ischemia (lack of oxygen due to a compromised blood flow) and

Molecular cytogenetic characterization of a new wheat-rye 4R chromosome translocation line resistant to powdery mildew.

Science.gov (United States)

An, Diaoguo; Zheng, Qi; Zhou, Yilin; Ma, Pengtao; Lv, Zhenling; Li, Lihui; Li, Bin; Luo, Qiaoling; Xu, Hongxing; Xu, Yunfeng

2013-07-01

Rye is an important and valuable gene resource for wheat improvement. However, due to extensive growing of cultivars with disease resistance genes from short arm of rye chromosome 1R and coevolution of pathogen virulence and host resistance, these cultivars successively lost resistance to pathogens. Identification and deployment of new resistance gene sources in rye are, therefore, of especial importance and urgency. A new wheat-rye line, designated as WR41-1, was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. It was proved to be a new wheat-rye T4BL·4RL and T7AS·4RS translocation line using sequential genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization (mc-FISH), and expressed sequence tag-simple sequence repeat (EST-SSR) marker analysis. WR41-1 showed high levels of resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 13 of 23 Bgt isolates tested at the seedling stage. According to its resistant pattern to 23 different Bgt isolates, WR41-1 may possess new gene(s) for resistance to powdery mildew, which differed from previously identified and known powdery mildew genes from rye (Pm7, Pm8, Pm17, and Pm20). In addition, WR41-1 was cytologically stable, had a desirable fertility, and is expected to be useful in wheat improvement.

Non-host Plant Resistance against Phytophthora capsici Is Mediated in Part by Members of the I2 R Gene Family in Nicotiana spp.

Science.gov (United States)

Vega-Arreguín, Julio C; Shimada-Beltrán, Harumi; Sevillano-Serrano, Jacobo; Moffett, Peter

2017-01-01

The identification of host genes associated with resistance to Phytophthora capsici is crucial to developing strategies of control against this oomycete pathogen. Since there are few sources of resistance to P. capsici in crop plants, non-host plants represent a promising source of resistance genes as well as excellent models to study P. capsici - plant interactions. We have previously shown that non-host resistance to P. capsici in Nicotiana spp. is mediated by the recognition of a specific P. capsici effector protein, PcAvr3a1 in a manner that suggests the involvement of a cognate disease resistance (R) genes. Here, we have used virus-induced gene silencing (VIGS) and transgenic tobacco plants expressing dsRNA in Nicotiana spp. to identify candidate R genes that mediate non-host resistance to P. capsici . Silencing of members of the I2 multigene family in the partially resistant plant N. edwardsonii and in the resistant N. tabacum resulted in compromised resistance to P. capsici . VIGS of two other components required for R gene-mediated resistance, EDS1 and SGT1 , also enhanced susceptibility to P. capsici in N. edwardsonii , as well as in the susceptible plants N. benthamiana and N. clevelandii . The silencing of I2 family members in N. tabacum also compromised the recognition of PcAvr3a1. These results indicate that in this case, non-host resistance is mediated by the same components normally associated with race-specific resistance.

Whatever It Takes: Health Compromising Behaviors in Female Athletes

Science.gov (United States)

Waldron, Jennifer J.; Krane, Vikki

2005-01-01

The power and performance model of sport stresses a sport ethic of doing "whatever it takes" to win (Coakley, 2004). Uncritical acceptance of this model may lead to various health-compromising behaviors. Employing achievement goal theory, we examine why female athletes may adopt the power and performance approach. An ego motivational climate and a…

48 CFR 239.7102-2 - Compromising emanations-TEMPEST or other standard.

Science.gov (United States)

2010-10-01

... INFORMATION TECHNOLOGY Security and Privacy for Computer Systems 239.7102-2 Compromising emanations—TEMPEST or... requiring activity is responsible for providing to the contracting officer— (a) The required protections, i...

Characteristics of Resistance Spot Welded Ti6Al4V Titanium Alloy Sheets

Directory of Open Access Journals (Sweden)

Xinge Zhang

2017-10-01

Full Text Available Ti6Al4V titanium alloy is applied extensively in the aviation, aerospace, jet engine, and marine industries owing to its strength-to-weight ratio, excellent high-temperature properties and corrosion resistance. In order to extend the application range, investigations on welding characteristics of Ti6Al4V alloy using more welding methods are required. In the present study, Ti6Al4V alloy sheets were joined using resistance spot welding, and the weld nugget formation, mechanical properties (including tensile strength and hardness, and microstructure features of the resistance spot-welded joints were analyzed and evaluated. The visible indentations on the weld nugget surfaces caused by the electrode force and the surface expulsion were severe due to the high welding current. The weld nugget width at the sheets’ faying surface was mainly affected by the welding current and welding time, and the welded joint height at weld nugget center was chiefly associated with electrode force. The maximum tensile load of welded joint was up to 14.3 kN in the pullout failure mode. The hardness of the weld nugget was the highest because of the coarse acicular α′ structure, and the hardness of the heat-affected zone increased in comparison to the base metal due to the transformation of the β phase to some fine acicular α′ phase.

A libertarian perspective on the stem cell debate: compromising the uncompromisible.

Science.gov (United States)

Block, Walter

2010-08-01

The present paper attempts to forge a compromise between those who maintain that stem cell research is out-and-out murder of young helpless human beings and those who favor this practice. The compromise is predicated upon the libertarian theory of private property rights. Starting out with the premise that not only the fetus but even the fertilized egg is a human being, with all rights thereto, it offers a competition between those who fertilize eggs for research and those who wish to adopt them. If and only if the former win this competition will they be allowed to use these very young human beings for the purposes they have constructed them. This is justified on grounds of avoiding child abuse.

HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

DEFF Research Database (Denmark)

Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

2016-01-01

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

Anthropogenic noise compromises antipredator behaviour in European eels.

Science.gov (United States)

Simpson, Stephen D; Purser, Julia; Radford, Andrew N

2015-02-01

Increases in noise-generating human activities since the Industrial Revolution have changed the acoustic landscape of many terrestrial and aquatic ecosystems. Anthropogenic noise is now recognized as a major pollutant of international concern, and recent studies have demonstrated impacts on, for instance, hearing thresholds, communication, movement and foraging in a range of species. However, consequences for survival and reproductive success are difficult to ascertain. Using a series of laboratory-based experiments and an open-water test with the same methodology, we show that acoustic disturbance can compromise antipredator behaviour--which directly affects survival likelihood--and explore potential underlying mechanisms. Juvenile European eels (Anguilla anguilla) exposed to additional noise (playback of recordings of ships passing through harbours), rather than control conditions (playback of recordings from the same harbours without ships), performed less well in two simulated predation paradigms. Eels were 50% less likely and 25% slower to startle to an 'ambush predator' and were caught more than twice as quickly by a 'pursuit predator'. Furthermore, eels experiencing additional noise had diminished spatial performance and elevated ventilation and metabolic rates (indicators of stress) compared with control individuals. Our results suggest that acoustic disturbance could have important physiological and behavioural impacts on animals, compromising life-or-death responses. © 2014 John Wiley & Sons Ltd.

Creating clones, kids & chimera: liberal democratic compromise at the crossroads.

Science.gov (United States)

Adams, Nathan A

2004-01-01

The objective of this article is to find middle ground between the supporters and opponents of biotechnology by perpetuating the existing legal compromise pertaining to the complete range of health and welfare doctrines relevant to the biotechnological industry. The author aspires neither to add to nor detract from this liberal democratic consensus, but to preserve its constitutive balance between positivism and natural law and over-regulation and under-regulation in the hopes of stabilizing new political fault lines developing around the few biotechnological innovations already grabbing headlines. The most feasible solution is to extend the existing liberal democratic compromise with respect to equal protection, reproductive rights, the First Amendment, human subject experimentation, patent law, and parental rights. This includes banning or monopolizing certain biotechnologies and extending substantive special respect to the ex vivo living human embryo. Biotechnology must not be left to regulate itself.

Improving the corrosion resistance of Mg–4.0Zn–0.2Ca alloy by micro-arc oxidation

Energy Technology Data Exchange (ETDEWEB)

Xia, Y.H. [The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Zhang, B.P., E-mail: zhangbp@sxicc.ac.cn [National Engineering Laboratory for Carbon Fiber Technology, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001 (China); Lu, C.X. [National Engineering Laboratory for Carbon Fiber Technology, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001 (China); Geng, L. [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

2013-12-01

In this paper, corrosion resistance of the Mg–4.0Zn–0.2Ca alloy was modified by micro-arc oxidation (MAO) process. The microstructure and phase constituents of MAO layer were characterized by SEM, XRD and X-ray photoelectron spectroscopy (XPS). The corrosion resistance of MAO treated Mg–4.0Zn–0.2Ca alloy in the simulated body fluid were characterized by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The microstructure results indicated that a kind of ceramic film was composed by MgO and MgF{sub 2} was formed on the surface of Mg–4.0Zn–0.2Ca alloy after MAO treatment. The electrochemical test reveals that the corrosion resistance of MAO treated samples increase 1 order of magnitude. The mechanical intensity test showed that the MAO treated samples has suitable mechanical properties. - Highlights: • Ceramic layer which is composited by MgO and MgF{sub 2} is prepared to improve the corrosion resistance of Mg–4.0Zn–0.2Ca alloy. • MAO treatment does not affect the mechanical properties of the Mg–4.0Zn–0.2Ca alloy. • After 30-day immersion in SBF, the mechanical properties of MAO coated samples are still enough for bone fixed.

Improving the corrosion resistance of Mg–4.0Zn–0.2Ca alloy by micro-arc oxidation

International Nuclear Information System (INIS)

Xia, Y.H.; Zhang, B.P.; Lu, C.X.; Geng, L.

2013-01-01

In this paper, corrosion resistance of the Mg–4.0Zn–0.2Ca alloy was modified by micro-arc oxidation (MAO) process. The microstructure and phase constituents of MAO layer were characterized by SEM, XRD and X-ray photoelectron spectroscopy (XPS). The corrosion resistance of MAO treated Mg–4.0Zn–0.2Ca alloy in the simulated body fluid were characterized by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The microstructure results indicated that a kind of ceramic film was composed by MgO and MgF 2 was formed on the surface of Mg–4.0Zn–0.2Ca alloy after MAO treatment. The electrochemical test reveals that the corrosion resistance of MAO treated samples increase 1 order of magnitude. The mechanical intensity test showed that the MAO treated samples has suitable mechanical properties. - Highlights: • Ceramic layer which is composited by MgO and MgF 2 is prepared to improve the corrosion resistance of Mg–4.0Zn–0.2Ca alloy. • MAO treatment does not affect the mechanical properties of the Mg–4.0Zn–0.2Ca alloy. • After 30-day immersion in SBF, the mechanical properties of MAO coated samples are still enough for bone fixed

Geographical gradient of the eIF4E alleles conferring resistance to potyviruses in pea (Pisum) germplasm.

Science.gov (United States)

Konečná, Eva; Šafářová, Dana; Navrátil, Milan; Hanáček, Pavel; Coyne, Clarice; Flavell, Andrew; Vishnyakova, Margarita; Ambrose, Mike; Redden, Robert; Smýkal, Petr

2014-01-01

The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the eIF4E gene to identify novel genetic diversity. Germplasm of 2803 pea accessions was screened for eIF4E intron 3 length polymorphism, resulting in the detection of four eIF4E(A-B-C-S) variants, whose distribution was geographically structured. The eIF4E(A) variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, eIF4E(B), was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The eIF4E(C) variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The eIF4E(S) variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (eIF4E(A-1-2-3-4-5-6-7), eIF4E(B-1), eIF4E(C-2)) conferred resistance to the P1 PSbMV pathotype. This work identified novel eIF4E alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible eIF4E(S1) allele. Despite high variation present in wild Pisum accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis to study the co-evolution of potyviruses and the

No-compromise reptation quantum Monte Carlo

International Nuclear Information System (INIS)

Yuen, W K; Farrar, Thomas J; Rothstein, Stuart M

2007-01-01

Since its publication, the reptation quantum Monte Carlo algorithm of Baroni and Moroni (1999 Phys. Rev. Lett. 82 4745) has been applied to several important problems in physics, but its mathematical foundations are not well understood. We show that their algorithm is not of typical Metropolis-Hastings type, and we specify conditions required for the generated Markov chain to be stationary and to converge to the intended distribution. The time-step bias may add up, and in many applications it is only the middle of a reptile that is the most important. Therefore, we propose an alternative, 'no-compromise reptation quantum Monte Carlo' to stabilize the middle of the reptile. (fast track communication)

Pulmonary, neurological and hepatic compromise in paragonimiasis: case report

International Nuclear Information System (INIS)

Uriza Carrasco, Alfonso Jose; Cuervo Valencia, Catalina; Valencia M, Andres Mauricio; Echeverri Toro, Lina Maria

2011-01-01

Paragonimiasis is a parasitic infectious disease, frequently with pulmonary abnormalities, although erratic parasite migration can compromise other organs. this disease is endemic in areas of southeast Asia, but it has been described in other tropical and subtropical regions. In this article, we report a case of indigenous patient with pulmonary abnormalities by Paragonimiasis, neurologic and hepatic abnormalities too.

IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

Science.gov (United States)

Ramos, Juan Carlos; Ruiz, Phillip; Ratner, Lee; Reis, Isildinha M.; Brites, Carlos; Pedroso, Celia; Byrne, Gerald E.; Toomey, Ngoc L.; Andela, Valentine; Harhaj, Edward W.; Lossos, Izidore S.

2007-01-01

Adult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-α) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 10; 60%) more often than did sensitive variants (1 of 9; 11%). This finding was independent of the disease form. Elevated expression of the putative c-Rel target, interferon regulatory factor-4 (IRF-4), was observed in 10 (91%) of 11 nonresponders and in all tested patients with c-Rel+ tumors and occurred in the absence of the HTLV-1 oncoprotein Tax. In contrast, tumors in complete responders did not express c-Rel or IRF-4. Gene rearrangement studies demonstrated the persistence of circulating T-cell clones in long-term survivors maintained on antiviral therapy. The expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with antiviral resistance. These molecular features may help guide treatment. AZT and IFN-α is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely. PMID:17138822

Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance.

Science.gov (United States)

Liu, Simu; Bartnikas, Lisa M; Volko, Sigrid M; Ausubel, Frederick M; Tang, Dingzhong

2016-01-01

Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

Mutation of the glucosinolate biosynthesis enzyme cytochrome P450 83A1 monooxygenase increases camalexin accumulation and powdery mildew resistance

Directory of Open Access Journals (Sweden)

Simu eLiu

2016-03-01

Full Text Available Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1, which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

Would Enforcing Competition Law Compromise Industry Policy Objectives?

OpenAIRE

Evenett, Simon J.

2005-01-01

One recurring concern in the debate over the efficacy of enacting competition laws in developing countries is that its enforcement may compromise important industrial policy goals. This concern has been raised in regional fora and in multilateral organizations such as the World Trade Organization, where officials have considered the pros and cons of including competition provisions in international trade agreements. However, the concern is broader and often national debates over the merits of...

The potyviral suppressor of RNA silencing confers enhanced resistance to multiple pathogens

International Nuclear Information System (INIS)

Pruss, Gail J.; Lawrence, Christopher B.; Bass, Troy; Li Qingshun Q.; Bowman, Lewis H.; Vance, Vicki

2004-01-01

Helper component-protease (HC-Pro) is a plant viral suppressor of RNA silencing, and transgenic tobacco expressing HC-Pro has increased susceptibility to a broad range of viral pathogens. Here we report that these plants also exhibit enhanced resistance to unrelated heterologous pathogens. Tobacco mosaic virus (TMV) infection of HC-Pro-expressing plants carrying the N resistance gene results in fewer and smaller lesions compared to controls without HC-Pro. The resistance to TMV is compromised but not eliminated by expression of nahG, which prevents accumulation of salicylic acid (SA), an important defense signaling molecule. HC-Pro-expressing plants are also more resistant to tomato black ring nepovirus (TBRV) and to the oomycete Peronospora tabacina. Enhanced TBRV resistance is SA-independent, whereas the response to P. tabacina is associated with early induction of markers characteristic of SA-dependent defense. Thus, a plant viral suppressor of RNA silencing enhances resistance to multiple pathogens via both SA-dependent and SA-independent mechanisms

The potyviral suppressor of RNA silencing confers enhanced resistance to multiple pathogens.

Science.gov (United States)

Pruss, Gail J; Lawrence, Christopher B; Bass, Troy; Li, Qingshun Q; Bowman, Lewis H; Vance, Vicki

2004-03-01

Helper component-protease (HC-Pro) is a plant viral suppressor of RNA silencing, and transgenic tobacco expressing HC-Pro has increased susceptibility to a broad range of viral pathogens. Here we report that these plants also exhibit enhanced resistance to unrelated heterologous pathogens. Tobacco mosaic virus (TMV) infection of HC-Pro-expressing plants carrying the N resistance gene results in fewer and smaller lesions compared to controls without HC-Pro. The resistance to TMV is compromised but not eliminated by expression of nahG, which prevents accumulation of salicylic acid (SA), an important defense signaling molecule. HC-Pro-expressing plants are also more resistant to tomato black ring nepovirus (TBRV) and to the oomycete Peronospora tabacina. Enhanced TBRV resistance is SA-independent, whereas the response to P. tabacina is associated with early induction of markers characteristic of SA-dependent defense. Thus, a plant viral suppressor of RNA silencing enhances resistance to multiple pathogens via both SA-dependent and SA-independent mechanisms.

Macronutrient manipulations of cheese resulted in lower energy content without compromising its satiating capacity

DEFF Research Database (Denmark)

Hansen, Thea Toft; Sjödin, Anders Mikael; Ritz, Christian

2018-01-01

Manipulation of food’s macronutrient composition in order to reduce energy content without compromising satiating capacity may be helpful in body weight control. For cheeses, substituting fat with protein may provide such opportunity. We aimed at examining the acute effect of cheeses with different...... macronutrient compositions on accumulated energy intake and subjective appetite sensation. A total of thirty-nine normal-weight (average BMI 24·4 kg/m2) men and women completed the partly double-blind, randomised crossover study with high-protein/low-fat (HP/LF, 696 kJ), high-protein/high-fat (HP/HF, 976 k...

Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

Science.gov (United States)

Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

2018-06-01

Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Food supply confers calcifiers resistance to ocean acidification

KAUST Repository

Ramajo, Laura; Pé rez-Leó n, Elia; Hendriks, Iris E.; Marbà , Nú ria; Krause-Jensen, Dorte; Sejr, Mikael K.; Blicher, Martin E.; Lagos, Nelson A.; Olsen, Ylva S.; Duarte, Carlos M.

2016-01-01

Invasion of ocean surface waters by anthropogenic CO2 emitted to the atmosphere is expected to reduce surface seawater pH to 7.8 by the end of this century compromising marine calcifiers. A broad range of biological and mineralogical mechanisms allow marine calcifiers to cope with ocean acidification, however these mechanisms are energetically demanding which affect other biological processes (trade-offs) with important implications for the resilience of the organisms against stressful conditions. Hence, food availability may play a critical role in determining the resistance of calcifiers to OA. Here we show, based on a meta-analysis of existing experimental results assessing the role of food supply in the response of organisms to OA, that food supply consistently confers calcifiers resistance to ocean acidification.

Food supply confers calcifiers resistance to ocean acidification

KAUST Repository

Ramajo, Laura

2016-01-18

Invasion of ocean surface waters by anthropogenic CO2 emitted to the atmosphere is expected to reduce surface seawater pH to 7.8 by the end of this century compromising marine calcifiers. A broad range of biological and mineralogical mechanisms allow marine calcifiers to cope with ocean acidification, however these mechanisms are energetically demanding which affect other biological processes (trade-offs) with important implications for the resilience of the organisms against stressful conditions. Hence, food availability may play a critical role in determining the resistance of calcifiers to OA. Here we show, based on a meta-analysis of existing experimental results assessing the role of food supply in the response of organisms to OA, that food supply consistently confers calcifiers resistance to ocean acidification.

Principles of treatment planning for compromised first permanent molars in mixed dentition period: A review article

Directory of Open Access Journals (Sweden)

Behrad Tanbakuchi

2017-02-01

Full Text Available Background and Aims: The first permanent molar is susceptible to caries, endodontic complications and developmental anomalies. Compromised teeth with poor prognosis could cause the clinician to face dilemmas. The aim of this review article was to assess recent guidelines on the treatment planning of compromised first permanent molars in mixed dentition period. Materials and Methods: The design of the study was based on review of literature by searching the MEDLINE, Web of science and Google scholar. Key words (permanent first molar, extraction, treatment plan were used. This search was limited to the English articles published after the year 2000. Conclusion: A number of factors influenced decision-making process regarding compromised first permanent molars including the restorative status of the tooth, dental age of the patient, degree of crowding and occlusal relationships were assessed. The ideal time for removal of these teeth was 8-9 years of age. However, the current evidence for managing compromised first permanent molars demands clinical trials.

Recombinant Promoter (MUASCsV8CP) Driven Totiviral Killer Protein 4 (KP4) Imparts Resistance Against Fungal Pathogens in Transgenic Tobacco

Science.gov (United States)

Deb, Debasish; Shrestha, Ankita; Maiti, Indu B.; Dey, Nrisingha

2018-01-01

Development of disease-resistant plant varieties achieved by engineering anti-microbial transgenes under the control of strong promoters can suffice the inhibition of pathogen growth and simultaneously ensure enhanced crop production. For evaluating the prospect of such strong promoters, we comprehensively characterized the full-length transcript promoter of Cassava Vein Mosaic Virus (CsVMV; -565 to +166) and identified CsVMV8 (-215 to +166) as the highest expressing fragment in both transient and transgenic assays. Further, we designed a new chimeric promoter ‘MUASCsV8CP’ through inter-molecular hybridization among the upstream activation sequence (UAS) of Mirabilis Mosaic Virus (MMV; -297 to -38) and CsVMV8, as the core promoter (CP). The MUASCsV8CP was found to be ∼2.2 and ∼2.4 times stronger than the CsVMV8 and CaMV35S promoters, respectively, while its activity was found to be equivalent to that of the CaMV35S2 promoter. Furthermore, we generated transgenic tobacco plants expressing the totiviral ‘Killer protein KP4’ (KP4) under the control of the MUASCsV8CP promoter. Recombinant KP4 was found to accumulate both in the cytoplasm and apoplast of plant cells. The agar-based killing zone assays revealed enhanced resistance of plant-derived KP4 against two deuteromycetous foliar pathogenic fungi viz. Alternaria alternata and Phoma exigua var. exigua. Also, transgenic plants expressing KP4 inhibited the growth progression of these fungi and conferred significant fungal resistance in detached-leaf and whole plant assays. Taken together, we establish the potential of engineering “in-built” fungal stress-tolerance in plants by expressing KP4 under a novel chimeric caulimoviral promoter in a transgenic approach. PMID:29556246

Physiological Responses to N-NO3 and N-NH4 of Triazine Resistant and Susceptible Plants of Horseweed (Erigeron canadensis L.

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Ryszard Stanek

2013-12-01

Full Text Available Triazine resistant and susceptible biotypes of horseweed (Erigeron canadensis L. were grown under controlled conditions in nutrient solution with NH4 or NO3 ions as nitrogen source. Indicators such as: dry matter, CO2 assimilation, chloroplasts activity, dark respiration and the content of K, Ca, Mg in the above ground parts displayed lower levels when plants were fed with NH4 than with NO ions. Reduction of these indicators was stronger for the triazine susceptible plants which grew better than their resistant counterparts when fed with N-NO3. The triazine resistant plants grown with N-NH4 contained more protein-N and K than the susceptible ones. Chloroplasts of the resistant plants were also less sensitive to NH4CL treatment. It is concluded that the resistant plants appear to be more tolerant to NH4 ions as compared with their susceptible counterparts. For this reason application of ammonium forms of nitrogen fertilization in horticultural practice could favour spreading of triazine resistant horseweed.

Effects of protein kinase C activators on phorbol ester-sensitive and -resistant EL4 thymoma cells.

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Sansbury, H M; Wisehart-Johnson, A E; Qi, C; Fulwood, S; Meier, K E

1997-09-01

Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.

Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.

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Le Bacquer, Olivier; Petroulakis, Emmanuel; Paglialunga, Sabina; Poulin, Francis; Richard, Denis; Cianflone, Katherine; Sonenberg, Nahum

2007-02-01

The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome.

First report of the infection of insecticide-resistant malaria vector mosquitoes with an entomopathogenic fungus under field conditions

NARCIS (Netherlands)

Howard, Annabel F. V.; N'Guessan, Raphael; Koenraadt, Constantianus J. M.; Asidi, Alex; Farenhorst, Marit; Akogbéto, Martin; Knols, Bart G. J.; Takken, Willem

2011-01-01

Insecticide-resistant mosquitoes are compromising the ability of current mosquito control tools to control malaria vectors. A proposed new approach for mosquito control is to use entomopathogenic fungi. These fungi have been shown to be lethal to both insecticide-susceptible and

The global status of insect resistance to neonicotinoid insecticides.

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Bass, Chris; Denholm, Ian; Williamson, Martin S; Nauen, Ralf

2015-06-01

The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management. Copyright © 2015 Elsevier Inc. All rights reserved.

Crack behavior of oxidation resistant coating layer on Zircaloy-4 for accident tolerant fuel claddings

International Nuclear Information System (INIS)

Park, Jung Hwan; Kim, Eui Jung; Jung, Yang Il; Park, Dong Jun; Kim, Hyun Gil; Park, Jeong Yong; Yang, Jae Ho

2016-01-01

Terrani et al. reported the oxidation resistance of Fe-based alloys for protecting zirconium alloys from the rapid oxidation in a high-temperature steam environment. Kim and co-workers also reported the corrosion behavior of Cr coated zirconium alloy using a plasma spray and laser beam scanning. Cracks are developed by tensile stress, and this significantly deteriorates the oxidation resistance. This tensile stress is possibly generated by the thermal cycle or bending or the irradiation growth of zirconium. In this study, Cr was deposited by AIP on to Zircaloy-4 plate, and the crack behavior of Cr coated Zircaloy-4 under uni-axial tensile strain was observed. In addition, the strain of the as-deposited state was calculated by iso-inclination method. Coating began to crack at 8% of applied strain. It is assumed that a well-densified structure by AIP tends to be resistant to cracking under tensile strain.

Crack behavior of oxidation resistant coating layer on Zircaloy-4 for accident tolerant fuel claddings

Energy Technology Data Exchange (ETDEWEB)

Park, Jung Hwan; Kim, Eui Jung; Jung, Yang Il; Park, Dong Jun; Kim, Hyun Gil; Park, Jeong Yong; Yang, Jae Ho [KAERI, Daejeon (Korea, Republic of)

2016-05-15

Terrani et al. reported the oxidation resistance of Fe-based alloys for protecting zirconium alloys from the rapid oxidation in a high-temperature steam environment. Kim and co-workers also reported the corrosion behavior of Cr coated zirconium alloy using a plasma spray and laser beam scanning. Cracks are developed by tensile stress, and this significantly deteriorates the oxidation resistance. This tensile stress is possibly generated by the thermal cycle or bending or the irradiation growth of zirconium. In this study, Cr was deposited by AIP on to Zircaloy-4 plate, and the crack behavior of Cr coated Zircaloy-4 under uni-axial tensile strain was observed. In addition, the strain of the as-deposited state was calculated by iso-inclination method. Coating began to crack at 8% of applied strain. It is assumed that a well-densified structure by AIP tends to be resistant to cracking under tensile strain.

Increased autophagy in CD4(+) T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance

NARCIS (Netherlands)

van Loosdregt, Jorg; Rossetti, Maura; Spreafico, Roberto; Moshref, Maryam; Olmer, Merissa; Williams, Gary W; Kumar, Pavanish; Copeland, Dana; Pischel, Ken; Lotz, Martin; Albani, Salvatore

2016-01-01

Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4(+) T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4(+) T cells in the autoimmune

The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors.

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Keith P Romano

Full Text Available Hepatitis C virus (HCV infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors--telaprevir, danoprevir, vaniprevir and MK-5172--in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus.

Secretion of salivary statherin is compromised in uncontrolled diabetic patients

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Masahiro Izumi

2015-06-01

Conclusions and general significance: The results show that synthesis and secretion of statherin is reduced in diabetics and this reduction is salivary gland specific. As compromised salivary statherin secretion leads to increased oral health risk, this study indicates that routine oral health assessment of these patients is warranted.

Influence of political opposition and compromise on conservation outcomes in the Tongass National Forest, Alaska.

Science.gov (United States)

Beier, Colin M

2008-12-01

To understand how a highly contentious policy process influenced a major conservation effort, I examined the origins, compromises, and outcomes of the Alaska National Interest Lands Conservation Act of 1980 (ANILCA) for the Tongass National Forest. Tongass wilderness designation was among the most controversial issues in the ANILCA debate, and it faced strong opposition from influential lawmakers, land managers, and Alaska residents. To investigate the influence of this opposition on Tongass conservation outcomes, I conducted a gap analysis of Tongass reserves and a policy analysis of the ANILCA debate and traced the influence of specific interests through the amendments, negotiations, and resulting compromises needed to enact ANILCA. Overall, I found that Tongass reserves comprise a broadly representative cross-section of ecosystems and species habitats in southeastern Alaska. Redrawn reserve boundaries, industry subsidies, and special access regulations reflected compromises to minimize the impact of wilderness conservation on mining, timber, and local stakeholder interests, respectively. Fragmentation of the Admiralty Island National Monument-the most ecologically valuable and politically controversial reserve-resulted from compromises with Alaskan Native (indigenous peoples of Alaska) corporations and timber interests. Despite language to accommodate "reasonable access" to wilderness reserves, ongoing access limitations highlight the concerns of Alaska residents that opposed ANILCA several decades ago. More broadly, the Tongass case suggests that early and ambitious conservation action may offset strong political opposition; compromises needed to establish key reserves often exacerbate development impacts in unprotected areas; and efforts to minimize social conflicts are needed to safeguard the long-term viability of conservation measures.

Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia

International Nuclear Information System (INIS)

Kuroda, Satoshi; Sakuragi, Mitsugi; Motomiya, Mineo; Nakagawa, Tango; Mitsumori, Kenji; Tsuru, Mitsuo; Takigawa, Shugo; Kamiyama, Hiroyasu; Abe, Hiroshi.

1990-01-01

To evaluate the efficacy of tests for selecting patients with hemodynamic compromise, measurement of cerebral blood volume (CBV) with 99m Tc-RBC single photon emission computed tomography (SPECT) was performed in thirteen patients with occlusive cerebrovascular disease, and was compared with results obtained by 133 Xe SPECT and acetazolamide (Diamox) test. All patients in our study suffered TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery, although plain CT scan or MRI revealed no or, if any, only localized infarcted lesions. Regional cerebral blood volume (rCBV) was measured with 99m Tc-RBC SPECT and regional cerebral blood flow (rCBF) was measured with 133 Xe SPECT before and after intravenous injection of 10 - 12 mg/kg acetazolamide (Diamox). Our results suggest that the ipsilateral rCBV/rCBF (mean transit time) is a more sensitive index of the cerebral perfusion reserve than the use of only rCBV or rCBF of the ipsilateral hemisphere. Also, the ipsilateral rCBV/rCBF is significantly correlated (r= -0.72) with the Diamox reactivity of rCBF, which is considered to represent the cerebral vasodilatory capacity in patients with chronic cerebral ischemia. Postoperative SPECT study revealed remarkable improvement of ipsilateral rCBV/rCBF and Diamox reactivity in four patients who underwent EC/IC bypass surgery to improve the hemodynamic compromise. In conclusion, our results suggest that the measurement of rCBV/rCBF with 133 Xe SPECT and 99m Tc-RBC SPECT is useful for detecting the hemodynamic compromise in patients with occlusive cerebrovascular disease. (author)

A 4-year surveillance of antimicrobial resistance patterns of Acinetobacter baumanni in a university-affiliated hospital in China.

Science.gov (United States)

Xu, Ting; Xia, Wenying; Rong, Guodong; Pan, Shiyang; Huang, Peijun; Gu, Bing

2013-08-01

To investigate the changes in resistance of Acinetobacter baumanni (A. baumannii) to different antimicrobial agents and the association of resistance rates with several independent factors: specimen origin, hospital wards, patients' gender and age, from 2008 to 2011. Bacterial isolates were isolated from January 2008 to December 2011 in the First Affiliated Hospital of Nanjing Medical University. Antimicrobial susceptibility testing was determined by the Kirby-Bauer Disk Diffusion Agar method as recommended by CLSI. Data were managed by the software WHONET 5.4 and analyzed by SPSS 17.0 software. The proportion of A. baumannii in our hospital increased from 7.0% in 2008 to 18.8% in 2011, becoming the most frequent pathogen in gram-negative isolates. 79.9% of A. baumannii were cultured from respiratory tract and geriatrics showed the highest isolation rate of A. baumannii during 4 years. The resistance rates to 12 antibiotics significantly increased from 2008 to 2011, from 14.8% to 90.8% to imipenem, and from 23.3% to 91.1% to meropenem. Statistical analysis demonstrated that the specimen origin, hospital wards, patients' gender and age were associated with resistance rate in varying degrees. The 4-year surveillance of antimicrobial susceptibility demonstrated the rapid increase of drug-resistant strains of A. baumannii, and revealed several factors related with resistance rate. Knowing the antimicrobial resistance patterns will help guide the empirical therapy and strengthen interventional infection control measures in China.

Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

Science.gov (United States)

Xu, Peng-Tao; Song, Zhen; Zhang, Wen-Cheng; Jiao, Bo; Yu, Zhi-Bin

2015-01-01

Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

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Peng-Tao Xu

2015-01-01

Full Text Available Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

Role of fluttering dislocations in the thermal interface resistance between a silicon crystal and plastic solid 4He

Science.gov (United States)

Amrit, Jay; Ramiere, Aymeric; Volz, Sebastian

2018-01-01

A quantum solid (solid 4He) in contact with a classical solid defines a new class of interfaces. In addition to its quantum nature, solid 4He is indeed a very plastic medium. We examine the thermal interface resistance upon solidification of superfluid 4He in contact with a silicon crystal surface (111) and show that dislocations play a crucial role in the thermal interface transport. The growth of solid 4He and the measurements are conducted at the minimum of the melting curve of helium (0.778 K and ˜25 bar ). The results display a first-order transition in the Kapitza resistance from a value of RK ,L=(80 ±8 ) c m2K /W at a pressure of 24.5 bar to a value of RK ,S=(41.7 ±8 ) c m2K /W after the formation of solid helium at ˜25.2 bar . The drop in RK ,S is only of a factor of ˜2 , although transverse phonon modes in solid 4He now participate in heat transmission at the interface. We provide an explanation for the measured RK ,S by considering the interaction of thermal phonons with vibrating dislocations in solid 4He. We demonstrate that this mechanism, also called fluttering, induces a thermal resistance RF l∝NdT-6 , where T is the temperature and Nd is the density of dislocations. We estimate that for dislocation densities on the order of ˜107c m-2 , RF l predominates over the boundary resistance RK ,S. These fundamental findings shed light on the role of dislocations and provide a quantitative explanation for previous experiments which showed no measurable change in the Kapitza resistance between Cu and superfluid 4He upon solidification of the latter. This demonstrates the possibility of using dislocations as an additional means to tailor thermal resistances at interfaces, formed especially with a plastic material.

Progressive resistance training in elderly hiv-positive patients: does it work?

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Paula Maria Loiola de Souza

2008-01-01

Full Text Available BACKGROUND: Elderly people present alterations in body composition and physical fitness, compromising their quality of life. Chronic diseases, including HIV/AIDS, worsen this situation. Resistance exercises are prescribed to improve fitness and promote healthier and independent aging. Recovery of strength and physical fitness is the goal of exercise in AIDS wasting syndrome. OBJECTIVE: This study describes a case series of HIV-positive elderly patients who participated in a progressive resistance training program and evaluates their body composition, muscular strength, physical fitness and the evolution of CD4+ and CD8+ cell counts. METHODS: Subjects were prospectively recruited for nine months. The training program consisted of three sets of 8-12 repetitions of leg press, seated row, lumbar extension and chest press, performed with free weight machines hts, twice/week for one year. Infectious disease physicians followed patients and reported all relevant clinical data. Body composition was assessed by anthropometric measures and dual-energy x-ray absorptiometry before and after the training program. RESULTS: Fourteen patients, aged 62-71 years old, of both genders, without regular physical activity who had an average of nine years of HIV/AIDS history were enrolled. The strengths of major muscle groups increased (74%-122%, p=0.003-0.021 with a corresponding improvement in sit-standing and walking 2.4 m tests (p=0.003. There were no changes in clinical conditions and body composition measures, but triceps and thigh skinfolds were significantly reduced (p=0.037. In addition, there were significant increases in the CD4+ counts (N=151 cells; p=0.008 and the CD4+/CD8+ ratio (0.63 to 0.81, p=0.009. CONCLUSION: Resistance training increased strength, improved physical fitness, reduced upper and lower limb skinfolds, and were associated with an improvement in the CD4+ and CD4+/CD8+ counts in HIV positive elderly patients without significant side effects.

Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein.

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Vesa Kirjavainen

Full Text Available Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS O-antigen (O-ag and outer core (OC do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp, an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host.

First report of the infection of insecticide-resistant malaria vector mosquitoes with an entomopathogenic fungus under field conditions

NARCIS (Netherlands)

Howard, A.F.V.; N'Guessan, R.; Koenraadt, C.J.M.; Asidi, A.; Farenhorst, M.; Akogbeto, M.; Knols, B.G.J.; Takken, W.

2011-01-01

Background: Insecticide-resistant mosquitoes are compromising the ability of current mosquito control tools to control malaria vectors. A proposed new approach for mosquito control is to use entomopathogenic fungi. These fungi have been shown to be lethal to both insecticide-susceptible and

Non-destructive reversible resistive switching in Cr doped Mott insulator Ca2RuO4: Interface vs bulk effects

KAUST Repository

Shen, Shida; Williamson, Morgan; Cao, Gang; Zhou, Jianshi; Goodenough, John; Tsoi, Maxim

2017-01-01

A non-destructive reversible resistive switching is demonstrated in single crystals of Cr-doped Mott insulator Ca2RuO4. An applied electrical bias was shown to reduce the DC resistance of the crystal by as much as 75%. The original resistance

The Leukotriene B4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis

Science.gov (United States)

Secatto, Adriana; Soares, Elyara Maria; Locachevic, Gisele Aparecida; Assis, Patricia Aparecida; Paula-Silva, Francisco Wanderlei Garcia; Serezani, Carlos Henrique; de Medeiros, Alexandra Ivo; Faccioli, Lúcia Helena

2014-01-01

The bioactive lipid mediator leukotriene B4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype. PMID:24465479

KP4 to control Ustilago tritici in wheat: Enhanced greenhouse resistance to loose smut and changes in transcript abundance of pathogen related genes in infected KP4 plants.

Science.gov (United States)

Quijano, Carolina Diaz; Wichmann, Fabienne; Schlaich, Thomas; Fammartino, Alessandro; Huckauf, Jana; Schmidt, Kerstin; Unger, Christoph; Broer, Inge; Sautter, Christof

2016-09-01

Ustilago tritici causes loose smut, which is a seed-borne fungal disease of wheat, and responsible for yield losses up to 40%. Loose smut is a threat to seed production in developing countries where small scale farmers use their own harvest as seed material. The killer protein 4 (KP4) is a virally encoded toxin from Ustilago maydis and inhibits growth of susceptible races of fungi from the Ustilaginales. Enhanced resistance in KP4 wheat to stinking smut, which is caused by Tilletia caries, had been reported earlier. We show that KP4 in genetically engineered wheat increased resistance to loose smut up to 60% compared to the non-KP4 control under greenhouse conditions. This enhanced resistance is dose and race dependent. The overexpression of the transgene kp4 and its effect on fungal growth have indirect effects on the expression of endogenous pathogen defense genes.

KP4 to control Ustilago tritici in wheat: Enhanced greenhouse resistance to loose smut and changes in transcript abundance of pathogen related genes in infected KP4 plants

Directory of Open Access Journals (Sweden)

Carolina Diaz Quijano

2016-09-01

Full Text Available Ustilago tritici causes loose smut, which is a seed-borne fungal disease of wheat, and responsible for yield losses up to 40%. Loose smut is a threat to seed production in developing countries where small scale farmers use their own harvest as seed material. The killer protein 4 (KP4 is a virally encoded toxin from Ustilago maydis and inhibits growth of susceptible races of fungi from the Ustilaginales. Enhanced resistance in KP4 wheat to stinking smut, which is caused by Tilletia caries, had been reported earlier. We show that KP4 in genetically engineered wheat increased resistance to loose smut up to 60% compared to the non-KP4 control under greenhouse conditions. This enhanced resistance is dose and race dependent. The overexpression of the transgene kp4 and its effect on fungal growth have indirect effects on the expression of endogenous pathogen defense genes.

Decoupling of a tight-fit transceiver phased array for human brain imaging at 9.4T: Loop overlapping rediscovered.

Science.gov (United States)

Avdievich, Nikolai I; Giapitzakis, Ioannis-Angelos; Pfrommer, Andreas; Henning, Anke

2018-02-01

To improve the decoupling of a transceiver human head phased array at ultra-high fields (UHF, ≥ 7T) and to optimize its transmit (Tx) and receive (Rx) performance, a single-row eight-element (1 × 8) tight-fit transceiver overlapped loop array was developed and constructed. Overlapping the loops increases the RF field penetration depth but can compromise decoupling by generating substantial mutual resistance. Based on analytical modeling, we optimized the loop geometry and relative positioning to simultaneously minimize the resistive and inductive coupling and constructed a 9.4T eight-loop transceiver head phased array decoupled entirely by overlapping loops. We demonstrated that both the magnetic and electric coupling between adjacent loops is compensated at the same time by overlapping and nearly perfect decoupling (below -30 dB) can be obtained without additional decoupling strategies. Tx-efficiency and SNR of the overlapped array outperformed that of a common UHF gapped array of similar dimensions. Parallel Rx-performance was also not compromised due to overlapping the loops. As a proof of concept we developed and constructed a 9.4T (400 MHz) overlapped transceiver head array based on results of the analytical modeling. We demonstrated that at UHF overlapping loops not only provides excellent decoupling but also improves both Tx- and Rx-performance. Magn Reson Med 79:1200-1211, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Fludarabine-mediated circumvention of cytarabine resistance is associated with fludarabine triphosphate accumulation in cytarabine-resistant leukemic cells.

Science.gov (United States)

Yamamoto, Shuji; Yamauchi, Takahiro; Kawai, Yasukazu; Takemura, Haruyuki; Kishi, Shinji; Yoshida, Akira; Urasaki, Yoshimasa; Iwasaki, Hiromichi; Ueda, Takanori

2007-02-01

The combination of cytarabine (ara-C) with fludarabine is a common approach to treating resistant acute myeloid leukemia. Success depends on a fludarabine triphosphate (F-ara-ATP)-mediated increase in the active intracellular metabolite of ara-C, ara-C 5'-triphosphate (ara-CTP). Therapy-resistant leukemia may exhibit ara-C resistance, the mechanisms of which might induce cross-resistance to fludarabine with reduced F-ara-ATP formation. The present study evaluated the effect of combining ara-C and fludarabine on ara-C-resistant leukemic cells in vitro. Two variant cell lines (R1 and R2) were 8-fold and 10-fold more ara-C resistant, respectively, than the parental HL-60 cells. Reduced deoxycytidine kinase activity was demonstrated in R1 and R2 cells, and R2 cells also showed an increase in cytosolic 5'-nucleotidase II activity. Compared with HL-60 cells, R1 and R2 cells produced smaller amounts of ara-CTP. Both variants accumulated less F-ara-ATP than HL-60 cells and showed cross-resistance to fludarabine nucleoside (F-ara-A). R2 cells, however, accumulated much smaller amounts of F-ara-ATP and were more F-ara-A resistant than R1 cells. In HL-60 and R1 cells, F-ara-A pretreatment followed by ara-C incubation produced F-ara-ATP concentrations sufficient for augmenting ara-CTP production, thereby enhancing ara-C cytotoxicity. No potentiation was observed in R2 cells. Nucleotidase might preferentially degrade F-ara-A monophosphate over ara-C monophosphate, leading to reduced F-ara-ATP production and thereby compromising the F-ara-A-mediated potentiation of ara-C cytotoxicity in R2 cells. Thus, F-ara-A-mediated enhancement of ara-C cytotoxicity depended on F-ara-ATP accumulation in ara-C-resistant leukemic cells but ultimately was associated with the mechanism of ara-C resistance.

Autobiographical memory compromise in Alzheimer's disease: a cognitive and clinical overview.

Science.gov (United States)

El Haj, Mohamad; Roche, Jean; Gallouj, Karim; Gandolphe, Marie-Charlotte

2017-12-01

Autobiographical memory refers to memory for personal information. The compromise of autobiographical memory in Alzheimer's disease (AD) results in a loss of knowledge about events and facts that defined the patients' life, and consequently, degradation of their self-knowledge and sense of identity. The compromise of autobiographical memory in AD can be attributed to a diminished subjective experience of memory and a diminished sense of the self. Our review provides a comprehensive overview of cognitive and clinical processes that may be involved in difficulties to retrieve autobiographical memories in Alzheimer's disease. Our review also proposes a theoretical model according to which, the diminished ability to retrieve contextual information and the overgenerality of recall result in a diminished subjective experience of past and future thinking. Besides its theoretical contribution, our review proposes clinical applicability for evaluation and rehabilitation of autobiographical memory in AD.

Orthodontic space closure using simple mechanics in compromised first molar extraction spaces: Case series

Directory of Open Access Journals (Sweden)

Prashant M Dhole

2018-01-01

Full Text Available Orthodontic treatments involving missing or compromised first permanent molars are often challenging cases to treat considering the loss of potential anchor tooth. The case series presents orthodontic treatment in three patients with mutilated/absent first permanent molars. The treatment goals were to be accomplished by extraction of compromised teeth and retention of healthy dentition. The diagnosis and problem list needed extractions to accomplish the treatment goals. The possibility of extracting compromised first permanent molars instead of other healthy teeth was considered. A setup was done to determine the final occlusion in asymmetric extraction cases. Fixed appliances were used with simple mechanics without any additional anchorage devices. Case-based retention protocols were followed. All the three patients achieved the predetermined treatment objectives of improved esthetics and healthy and stable functional occlusion. The simple and efficient mechanics and finishing techniques for comprehensive orthodontic treatment with first molar extractions presented in the report should help clinicians when treating similar patients.

Mutations in the P-Type Cation-Transporter ATPase 4, PfATP4, Mediate Resistance to Both Aminopyrazole and Spiroindolone Antimalarials

Science.gov (United States)

2015-01-01

Aminopyrazoles are a new class of antimalarial compounds identified in a cellular antiparasitic screen with potent activity against Plasmodium falciparum asexual and sexual stage parasites. To investigate their unknown mechanism of action and thus identify their target, we cultured parasites in the presence of a representative member of the aminopyrazole series, GNF-Pf4492, to select for resistance. Whole genome sequencing of three resistant lines showed that each had acquired independent mutations in a P-type cation-transporter ATPase, PfATP4 (PF3D7_1211900), a protein implicated as the novel Plasmodium spp. target of another, structurally unrelated, class of antimalarials called the spiroindolones and characterized as an important sodium transporter of the cell. Similarly to the spiroindolones, GNF-Pf4492 blocks parasite transmission to mosquitoes and disrupts intracellular sodium homeostasis. Our data demonstrate that PfATP4 plays a critical role in cellular processes, can be inhibited by two distinct antimalarial pharmacophores, and supports the recent observations that PfATP4 is a critical antimalarial target. PMID:25322084

INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, Haiwen; Li, Hongliang, E-mail: honglianglity@sina.com; Chen, Qi

2016-08-26

Docetaxel efficiency in the therapy of prostate cancer (PCa) patients is limited due to the development of chemoresistance. Recent studies have implied a role of INPP4B in tumor chemoresistance, while the effects of INPP4B on docetaxel resistance in PCa have not been elucidated. In the present study, the docetaxel-resistant human PCa cell lines PC3-DR and DU-145-DR were established from the parental cell lines PC3 and DU-145, and the expression and role of INPP4B in docetaxel-resistant PCa cells were investigated. The results demonstrated that INPP4B expression was significantly downregulated in docetaxel-resistant cells. Overexpression of INPP4B increased the sensitivity to docetaxel and promoted cell apoptosis in PC3-DR and DU-145-DR cells. In addition, INPP4B overexpression downregulated the expression of the mesenchymal markers fibronectin, N-cadherin, and vimentin, and upregulated the expression level of the epithelial maker E-cadherin. Furthermore, INPP4B overexpression markedly inhibited the PI3K/Akt pathway. We also found that IGF-1, the inhibitor of PI3K/Akt, markedly blocked the change in EMT markers induced by overexpression of INPP4B, and reversed the resistance of PC3-DR and DU-145-DR cells to docetaxel, which is sensitized by Flag-INPP4B. In summary, the presented data indicate that INPP4B is crucial for docetaxel-resistant PCa cell survival, potentially by regulating EMT through the PI3K/Akt signaling pathway. - Highlights: • INPP4B is downregulated in docetaxel-resistant PCa cells. • INPP4B inhibits cell proliferation. • INPP4B induces cell apoptosis. • INPP4B inhibits PCa cell EMT.

Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

Science.gov (United States)

Skelton, Joshua J; Simpson, David M; Peterson, Mark A; Riechers, Dean E

2017-07-26

The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U 50 = 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M 50 = 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

Sterilization of freeze dried manila clam (Ruditapea philippinarum) porridge for immuno-compromised patients

Energy Technology Data Exchange (ETDEWEB)

Song, Beom Seok; Park, Jae Nam [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

2017-02-15

This study was conducted to evaluate the combined effect of gamma irradiation and different conditions (vacuum packaging, antioxidant and freezing) on the microbiological and sensory characteristics of freeze dried Manila clam porridge (MCP) for immuno-compromised patient food. McP can be sterilized at 1 kGy to 10 kGy. the initial counts of total aerobic bacteria and yeast molds in the non-irradiated MCP were 2.4±0.5 and 1.2±0.3 log CFU g{sup -}'1, respectively, but gamma irradiation significantly decreased the total aerobic bacteria to below the detection limit (1 log CFU g{sup -1}) (5 kGy). Moreover, gamma irradiation effectively eliminated yeasts/molds at dose below than 1 kGy. However, gamma irradiation accelerated the increase of lipid oxidation and therefore, decreased the sensory characteristics of MCP as irradiation dose increased. to improve the sensory qualities of gamma irradiated MCP, combination treatment (vacuum packaging, 0.1% vitamin c) were applied. there was no significant difference in the overall acceptance scores between the combined-treatment sample (5.6 points) and the non-irradiated samples (6.0). the results indicate that combination treatment (vacuum packaging, 0.1% vitamin c) may help to maintain the quality of MCP. therefore, it considered that irradiation of MCP with combined treatment and this is an effective method for the consumption as a special purpose food such as for space travel or immuno-compromised patients.

Sterilization of freeze dried manila clam (Ruditapea philippinarum) porridge for immuno-compromised patients

International Nuclear Information System (INIS)

Song, Beom Seok; Park, Jae Nam

2017-01-01

This study was conducted to evaluate the combined effect of gamma irradiation and different conditions (vacuum packaging, antioxidant and freezing) on the microbiological and sensory characteristics of freeze dried Manila clam porridge (MCP) for immuno-compromised patient food. McP can be sterilized at 1 kGy to 10 kGy. the initial counts of total aerobic bacteria and yeast molds in the non-irradiated MCP were 2.4±0.5 and 1.2±0.3 log CFU g"-'1, respectively, but gamma irradiation significantly decreased the total aerobic bacteria to below the detection limit (1 log CFU g"-"1) (5 kGy). Moreover, gamma irradiation effectively eliminated yeasts/molds at dose below than 1 kGy. However, gamma irradiation accelerated the increase of lipid oxidation and therefore, decreased the sensory characteristics of MCP as irradiation dose increased. to improve the sensory qualities of gamma irradiated MCP, combination treatment (vacuum packaging, 0.1% vitamin c) were applied. there was no significant difference in the overall acceptance scores between the combined-treatment sample (5.6 points) and the non-irradiated samples (6.0). the results indicate that combination treatment (vacuum packaging, 0.1% vitamin c) may help to maintain the quality of MCP. therefore, it considered that irradiation of MCP with combined treatment and this is an effective method for the consumption as a special purpose food such as for space travel or immuno-compromised patients

Electrical resistivity anisotropy of osmium single crystals in the range 4,2 to 300 K

International Nuclear Information System (INIS)

Volkenshtejn, N.V.; Dyakina, V.P.; Dyakin, V.V.; Startsev, V.E.; Cherepanov, V.I.; Azhazha, V.M.; Kovtun, G.P.; Elenskij, V.A.; AN Ukrainskoj SSR, Kharkov. Fiziko-Tekhnicheskij Inst.)

1981-01-01

Electrical resistivity and size effect anisotropies of pure osmium single crystals with rhosub(273.2/rhosub(4.2)2600 were investigated in the temperature range 4.2 to 300 K. It is found that the electrical resistivity anisotropy (αT)=rhosub( )/rhosub( ) is less than unit and has a maximum at T approximately 50 K; the size effect anisotropy (rho1)sub( )/(rho1)sub( ) is 0.39+-0.07 at T=4.2 K; at liquid helium temperature, the dependence of thin samples is controlled by the scattering of conduction electrons by the surface of the sample. The results are discussed for the specific shape of the Fermi surface geometry of osmium with an account for the scattering processes of conduction electrons by phonons and by surface of the sample

GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance

DEFF Research Database (Denmark)

Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian

2012-01-01

To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both...... than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate....... The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage....

4-N, 4-S & 4-O Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pKa on Activity vs. Chloroquine Resistant Malaria+, #

OpenAIRE

Natarajan, Jayakumar K.; Alumasa, John; Yearick, Kimberly; Ekoue-Kovi, Kekeli A.; Casabianca, Leah B.; de Dios, Angel C.; Wolf, Christian; Roepe, Paul D.

2008-01-01

Using predictions from heme – quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure – function principles. We vary side chain length for both monoethyl and diethyl 4N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position, and vary side chain length for these analogues. We introduce an additio...

Involvement of steatosis-induced glucagon resistance in hyperglucagonaemia

DEFF Research Database (Denmark)

Suppli, Malte P; Lund, Asger; Bagger, Jonatan I

2016-01-01

diabetes per se - is the main driver behind fasting hyperglucagonaemia. We hypothesise that in the majority of type 2 diabetic individuals hepatic sensitivity to glucagon is compromised due to hepatic steatosis, and that this provides a feedback mechanism acting at the level of pancreatic alpha cells...... recognised to play a significant role in type 2 diabetic pathophysiology. However, the mechanisms underlying disturbances in the regulation of glucagon remain unclear. Glucagon constitutes the primary stimulus for hepatic glucose production and, thus, upholds adequate blood glucose levels during fasting......, leading to elevated levels of glucagon. Here we present our hypothesis and propose a way to test it. If our hypothesis holds true, hepatic glucagon resistance would constitute a parallel to the obesity-induced insulin resistance in muscle and liver tissue, and underpin a central role for glucagon...

Fine mapping of the rice bacterial blight resistance gene Xa-4 and its co-segregation marker

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

An F2 population developed from the Xa-4 near isogenic lines,IR24 and IRBB4,was used for fine mapping of the rice bacterial blight resistance gene,Xa-4.Some restriction fragment length polymorphism (RFLP) markers on the high-density map constructed by Harushima et al.and the amplified DNA fragments homologous to the conserved domains of plant disease resistance (R) genes were used to construct the genetic linkage map around the gene Xa-4 by scoring susceptible individuals in the population.Xa-4 was mapped between the RFLP marker G181 and the polymerase chain reaction (PCR) marker M55.The R gene homologous fragment marker RS13 was found co-segregating with Xa-4 by analyzing all the plants in the population.This result opened an approach to map-based cloning of this gene,and marker RS13 can be applied to molecular marker-assisted selection of Xa-4 in rice breeding programs.

Synergistic effects of sodium 
ascorbate and acetone to restore compromised bond strength 
after enamel bleaching.

Science.gov (United States)

Boruziniat, Alireza; Manafi, Safa; Cehreli, Zafer C

To evaluate the effect of a new experimental solution containing sodium ascorbate (SA) and acetone on reversing compromised bonding to enamel immediately after bleaching. The buccal surface of intact, extracted human premolars (n = 60) was bleached. The teeth were then randomly assigned to 6  groups according to the type of pretreatment applied prior to adhesive procedures: 10% SA in acetone-water solution applied for 1 and 5 min (groups 1 and 2, respectively); aqueous solution of 10% SA applied for 10 min (group 3); 100% acetone applied for 10 min (group 4); no pretreatment (negative control; group 5). An additional group (positive control; group 6) comprised unbleached teeth (n = 12). Two composite microcylinders were bonded on each specimen for evaluation of microshear bond strength (MBS) and failure modes. Data were analyzed using the one-way ANOVA and Tukey's post-hoc and chi-square tests at P = 0.05. Groups 1 and 2 yielded similar MBS values to groups 4 and 6 (positive control). The mean MBS of groups 3 and 5 (negative control) were similar, and significantly lower than that of the positive control group. The application of 10% SA in an acetone-water solution prior to bonding procedures can restore compromised enamel bond strength to its unbleached state within a clinically acceptable time of 1 min.

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example

International Nuclear Information System (INIS)

Rosewall, Tara; Alasti, Hamideh; Bayley, Andrew; Yan, Jing

2017-01-01

Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2 = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were −0.4 to 1.8 mm (LR), −1.2 to 5.2 mm (SI) and −1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

Compromised Global and Regional Cerebral Blood Flow in Congestive Heart Failure

Energy Technology Data Exchange (ETDEWEB)

Kim, J. S.; Kim, J. J.; Im, K. C.; Moon, D. H. [College of Medicine, Univ. of Ulsan, Seoul (Korea, Republic of)

2003-07-01

It has been known that cerebral perfusion is maintained in patients with congestive heart failure (CHF) by a complex series of compensatory mechanisms. However cognitive impairment is a common problem experienced by patients with CHF and may result from deranged cerebral perfusion. We prospectively investigated the global and regional CBF of patients with CHF and compared the results with that of normal controls. Thirty two patients (M/F: 22/10, 4211 yr) with CHF (LVEF=218.1%) and 10 healthy controls (M/F: 6/4, 398 yr) were prospectively studied. No patients had cerebrovascular disease or other disease affecting cognitive function. All patients and normal controls underwent radionuclide angiography including cerebral hemispheres and aortic arch, and brain perfusion SPECT using Tc-99m ECD. Global CBF was measured non-invasively by the application of Patlak plot graphical analysis. Quantitative rCBF images were obtained from SPECT image using global CBF values, regional/global count ratios, and Lassen's linearization correction algorithm. Difference of regional CBF between CHF and normal control were assessed using a SPM99 without global count normalization (uncorrected p<0.0001, extent threshold>100 voxels). Global CBF (41.54.7 ml/min/100g) of the patients with CHF were significantly lower than those (49.15.7 ml/min/100g) of controls (p<0.001). Regional CBF was significantly decreased in frontal, temporal and parietal neocortex of both cerebral hemispheres compared to normal controls. Regional rCBF of basal ganglia, thalamus, and brain stem were preserved, even though global CBF was variably compromised. Our study show that global CBF is significantly decreased in CHF and regional CBF of frontal, parietal and temporal neocortex is compromised preferentially. Further studies would be needed to investigate the relationship of rCBF change and cognitive impairment in patients with CHF.

Non-destructive reversible resistive switching in Cr doped Mott insulator Ca2RuO4: Interface vs bulk effects

Science.gov (United States)

Shen, Shida; Williamson, Morgan; Cao, Gang; Zhou, Jianshi; Goodenough, John; Tsoi, Maxim

2017-12-01

A non-destructive reversible resistive switching is demonstrated in single crystals of Cr-doped Mott insulator Ca2RuO4. An applied electrical bias was shown to reduce the DC resistance of the crystal by as much as 75%. The original resistance of the sample could be restored by applying an electrical bias of opposite polarity. We have studied this resistive switching as a function of the bias strength, applied magnetic field, and temperature. A combination of 2-, 3-, and 4-probe measurements provide a means to distinguish between bulk and interfacial contributions to the switching and suggests that the switching is mostly an interfacial effect. The switching was tentatively attributed to electric-field driven lattice distortions which accompany the impurity-induced Mott transition. This field effect was confirmed by temperature-dependent resistivity measurements which show that the activation energy of this material can be tuned by an applied DC electrical bias. The observed resistance switching can potentially be used for building non-volatile memory devices like resistive random access memory.

Non-destructive reversible resistive switching in Cr doped Mott insulator Ca2RuO4: Interface vs bulk effects

KAUST Repository

Shen, Shida

2017-12-29

A non-destructive reversible resistive switching is demonstrated in single crystals of Cr-doped Mott insulator Ca2RuO4. An applied electrical bias was shown to reduce the DC resistance of the crystal by as much as 75%. The original resistance of the sample could be restored by applying an electrical bias of opposite polarity. We have studied this resistive switching as a function of the bias strength, applied magnetic field, and temperature. A combination of 2-, 3-, and 4-probe measurements provide a means to distinguish between bulk and interfacial contributions to the switching and suggests that the switching is mostly an interfacial effect. The switching was tentatively attributed to electric-field driven lattice distortions which accompany the impurity-induced Mott transition. This field effect was confirmed by temperature-dependent resistivity measurements which show that the activation energy of this material can be tuned by an applied DC electrical bias. The observed resistance switching can potentially be used for building non-volatile memory devices like resistive random access memory.

Inhibition of Androgen Receptor Function and Level in Castration-Resistant Prostate Cancer Cells by 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone.

Science.gov (United States)

Masoodi, Khalid Z; Eisermann, Kurtis; Yang, Zhenyu; Dar, Javid A; Pascal, Laura E; Nguyen, Minh; O'Malley, Katherine; Parrinello, Erica; Feturi, Firuz G; Kenefake, Alex N; Nelson, Joel B; Johnston, Paul A; Wipf, Peter; Wang, Zhou

2017-10-01

The androgen receptor (AR) plays a critical role in the development of castration-resistant prostate cancer (CRPC) as well as in the resistance to the second-generation AR antagonist enzalutamide and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Novel agents targeting AR may inhibit the growth of prostate cancer cells resistant to enzalutamide and/or abiraterone. Through a high-throughput/high-content screening of a 220,000-member small molecule library, we have previously identified 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone (IMTPPE) (SID 3712502) as a novel small molecule capable of inhibiting AR transcriptional activity and protein level in C4-2 prostate cancer cells. In this study, we show that IMTPPE inhibits AR-target gene expression using real-time polymerase chain reaction, Western blot, and luciferase assays. IMTPPE inhibited proliferation of AR-positive, but not AR-negative, prostate cancer cells in culture. IMTPPE inhibited the transcriptional activity of a mutant AR lacking the ligand-binding domain (LBD), indicating that IMTPPE inhibition of AR is independent of the LBD. Furthermore, animal studies showed that IMTPPE inhibited the growth of 22Rv1 xenograft tumor, a model for enzalutamide-resistant prostate cancer. These findings suggest that IMTPPE is a potential lead compound for developing clinical candidates for the treatment of CRPC, including those resistant to enzalutamide. Copyright © 2017 Endocrine Society.

Iran. Nuclear crisis: the continuous compromise?

International Nuclear Information System (INIS)

Cherief, Hamza

2016-01-01

The author comments and discusses the content and implications of the Joint Comprehensive Plan of Action which has been adopted in July 2015 by the Republic of Iran and the members of the E3/EU+3 group. According to this text, a flexible normative and institutional framework is defined, according to which negotiation must prevail on the reinstatement of economic sanctions. While significantly lowering objectives related to non proliferation, this plan aims (through various arrangements which are discussed by the author) at maintaining Iran under the threshold of nuclear power. The author also comments various aspects related to the implementation of this Plan of Action, and outlines that they rely on the search for a continuous compromise: negotiations and involvement of international bodies are foreseen before application of sanctions

Microbial corrosion resistance of galvanized coatings with 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one as a biocidal ingredient in electrolytes

International Nuclear Information System (INIS)

Zhai, Xiaofan; Myamina, Maria; Duan, Jizhou; Hou, Baorong

2013-01-01

Highlights: •Addition of DCOIT to zinc electrolyte increases current efficiency. •Zn deposited from electrolytes with DCOIT inhibits growth and metabolism of SRB. •DCOIT on coating surfaces influences the coating structure and morphology. •EIS and polarization results show good microbial-corrosion resistance in SRB. -- Abstract: Electrodeposition of galvanized coatings from electrolyte containing 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) can increase microbial corrosion resistance. Coatings were found to inhibit the growth and metabolism of sulphate-reducing bacteria (SRB). Open circuit potentials and corrosion rates of coupons revealed DCOIT effectively influences the coating property. Energy diffraction spectrum and infrared absorption spectra were used to detect DCOIT on the coating surface. Scanning electron microscopy and X-ray diffraction revealed morphological and structural modifications. Electrochemical impedance spectroscopy and polarization techniques determined the corrosion behaviour of coatings in SRB. Results showed coatings formed from electrolytes with DCOIT have improved microbial corrosion resistance and bactericidal action

Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

Science.gov (United States)

Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

2007-11-01

Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

Study of prevalence and effects of insulin resistance in patients with chronic hepatitis C genotype 4.

Science.gov (United States)

Amer, A F; Baddour, M M; Elshazly, M A; Fadally, G; Hanafi, N F; Assar, S L

2016-02-01

There is strong epidemiological evidence linking hepatitis C virus (HCV) infection and diabetes. Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. Insulin resistance [homeostasis model assessmentinsulin resistance (HOMA-IR) score > 3.0] was detected in 31 of 100 nondiabetic patients. The relationship between elevated HOMA-IR and baseline viral load and degree of fibrosis was statistically significant (r = 0.218 and r = 0.223). Follow-up of patients with complete early virological response until the end of treatment showed a statistically significant decrease in HOMA-IR score. Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool.

A method for identifying compromised clients based on DNS traffic analysis

DEFF Research Database (Denmark)

Stevanovic, Matija; Pedersen, Jens Myrup; D’Alconzo, Alessandro

2017-01-01

DNS is widely abused by Internet criminals in order to provide reliable communication within malicious network infrastructure as well as flexible and resilient hosting of malicious content. This paper presents a novel detection method that can be used for identifying potentially compromised clien...

Reversible Resistance Switching Effect in Amorphous Ge1Sb4Te7 Thin Films without Phase Transformation

International Nuclear Information System (INIS)

Hua-Jun, Sun; Li-Song, Hou; Yi-Qun, Wu; Xiao-Dong, Tang

2009-01-01

We demonstrate a reversible resistance switching effect that does not rely on amorphous-crystalline phase transformation in a nanoscale capacitor-like cell using Ge 1 Sb 4 Te 7 films as the working material. The polarity and amplitude of the applied electric voltage switches the cell resistance between low- and high-resistance states, as revealed in the current-voltage characteristics of the film by conductive atomic force microscopy (CAFM). This reversible SET/RESET switching effect is induced by voltage pulses and their polarity. The change of electrical resistance due to the switching effect is approximately two orders of magnitude

Complete genome sequence of hypervirulent and outbreak-associated Acinetobacter baumannii strain LAC-4: epidemiology, resistance genetic determinants and potential virulence factors

Science.gov (United States)

Ou, Hong-Yu; Kuang, Shan N.; He, Xinyi; Molgora, Brenda M.; Ewing, Peter J.; Deng, Zixin; Osby, Melanie; Chen, Wangxue; Xu, H. Howard

2015-01-01

Acinetobacter baumannii is an important human pathogen due to its multi-drug resistance. In this study, the genome of an ST10 outbreak A. baumannii isolate LAC-4 was completely sequenced to better understand its epidemiology, antibiotic resistance genetic determinants and potential virulence factors. Compared with 20 other complete genomes of A. baumannii, LAC-4 genome harbors at least 12 copies of five distinct insertion sequences. It contains 12 and 14 copies of two novel IS elements, ISAba25 and ISAba26, respectively. Additionally, three novel composite transposons were identified: Tn6250, Tn6251 and Tn6252, two of which contain resistance genes. The antibiotic resistance genetic determinants on the LAC-4 genome correlate well with observed antimicrobial susceptibility patterns. Moreover, twelve genomic islands (GI) were identified in LAC-4 genome. Among them, the 33.4-kb GI12 contains a large number of genes which constitute the K (capsule) locus. LAC-4 harbors several unique putative virulence factor loci. Furthermore, LAC-4 and all 19 other outbreak isolates were found to harbor a heme oxygenase gene (hemO)-containing gene cluster. The sequencing of the first complete genome of an ST10 A. baumannii clinical strain should accelerate our understanding of the epidemiology, mechanisms of resistance and virulence of A. baumannii. PMID:25728466

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

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Balamurugan Periaswamy

Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

Parental care compromises feeding in the pumpkinseed ( Lepomis gibbosus)

Science.gov (United States)

Zięba, G.; Dukowska, M.; Przybylski, M.; Fox, M. G.; Smith, C.

2018-04-01

Providing parental care is potentially costly. Costs can arise through elevated energy expenditure or from an increased risk of mortality. A cost of parental care can also occur because a parent is compromised in their ability to forage. We used pumpkinseed Lepomis gibbosus, a fish with an alternative male mating strategy, to test whether parental males differed in their feeding in comparison with females and cuckolder males. To address this question, we examined the stomach contents of female, cuckolder male, and parental male pumpkinseed during the breeding season over an entire diel cycle. We showed that parental males had a lower total weight of food in their stomachs in comparison with females, while cuckolder males did not. Parental males also had a lower weight and number of chironomids in their stomachs. The temporal pattern of feeding of parental males diverged from that of females, and they had a lower probability of pupal chironomids in their stomachs, which implies spatial segregation in foraging. Parental males had a greater probability of conspecific eggs in their stomachs than females, while the probability of egg cannibalism did not differ between cuckolder males and females. Overall, these finding meet predictions in accordance with an assumption that parental care and territoriality can compromise feeding.

7 CFR 4290.1710 - Secretary's authority to collect or compromise claims.

Science.gov (United States)

2010-01-01

... BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Miscellaneous § 4290.1710... consideration as he or she deems reasonable, collect or compromise all claims relating to obligations he or she...

Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

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Zheng Gong

Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean.

Science.gov (United States)

Burt, Andrew J; William, H Manilal; Perry, Gregory; Khanal, Raja; Pauls, K Peter; Kelly, James D; Navabi, Alireza

2015-01-01

Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris). Alleles at the Co-4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08) where Co-4 is localized. Three SCAR markers with known linkage to Co-4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK-4 loci found in previous studies. It is possible that the Co-4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases.

Effects of Nitrogen Implantation on the Resistance to Localized Corrosion of Zircaloy-4 in a Chloride Solution

International Nuclear Information System (INIS)

Lee, Sung Joon; Kwon, Hyuk Sang; Kim, Wan; Choi, Byung Ho

1996-01-01

The influences of ion dose and substrate temperature on the resistance to localized corrosion of nitrogen-implanted Zircaloy-4 are examined in terms of potentiodynamic anodic polarization tests in deaerated 4M NaCl solution at 80 .deg. C. Nitrogen implantations into the Zircaloy-4 were performed under conditions of varying the ion dose from 3 x 10 17 to 1.2 x 10 18 ions/cm 2 and of maintaining the substrate temperatures respectively at 100, 200, and 300 .deg. C by controlling the current density of ion beam. The resistance to localized corrosion of Zircaloy-4 was significantly increased with increasing the ion dose when implanted at substrate temperatures above 200 .deg. C. However, it was not almost improved by implantation at 100 .deg. C. Specifically, the pitting potential increased from 350mV (vs. SCE) for the unimplanted to values of 900 to about 1400mV (vs. SCE) for the implanted alloy depending on the nitrogen dose. This significant improvement in the resistance to localized corrosion of the implanted Zircaloy-4 was found to be associate with the formation of compound layers of ZrO 2 + ZrN during the implantation. The galvanostatic anodization tests on the nitrogen-implanted Zircaloy-4 in 1M H 2 SO 4 at 20 .deg. C demonstrated that an increase in the ion dose and also in the substrate temperature increased the thickness of the compound layer of ZrO 2 + ZrN, and hence increased the pitting potential of the alloy. The low resistance to localized and general corrosion of the alloy implanted at 100 .deg. C was attributed to the increase in surface defect density and also to thinner implanted layer compared with those formed at higher temperatures

Transcriptome profiling of resistant and susceptible Cavendish banana roots following inoculation with Fusarium oxysporum f. sp. cubense tropical race 4

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Li Chun-yu

2012-08-01

Full Text Available Abstract Background Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4, is considered the most lethal disease of Cavendish bananas in the world. The disease can be managed in the field by planting resistant Cavendish plants generated by somaclonal variation. However, little information is available on the genetic basis of plant resistance to Foc TR4. To a better understand the defense response of resistant banana plants to the Fusarium wilt pathogen, the transcriptome profiles in roots of resistant and susceptible Cavendish banana challenged with Foc TR4 were compared. Results RNA-seq analysis generated more than 103 million 90-bp clean pair end (PE reads, which were assembled into 88,161 unigenes (mean size = 554 bp. Based on sequence similarity searches, 61,706 (69.99% genes were identified, among which 21,273 and 50,410 unigenes were assigned to gene ontology (GO categories and clusters of orthologous groups (COG, respectively. Searches in the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG mapped 33,243 (37.71% unigenes to 119 KEGG pathways. A total of 5,008 genes were assigned to plant-pathogen interactions, including disease defense and signal transduction. Digital gene expression (DGE analysis revealed large differences in the transcriptome profiles of the Foc TR4-resistant somaclonal variant and its susceptible wild-type. Expression patterns of genes involved in pathogen-associated molecular pattern (PAMP recognition, activation of effector-triggered immunity (ETI, ion influx, and biosynthesis of hormones as well as pathogenesis-related (PR genes, transcription factors, signaling/regulatory genes, cell wall modification genes and genes with other functions were analyzed and compared. The results indicated that basal defense mechanisms are involved in the recognition of PAMPs, and that high levels of defense-related transcripts may contribute to Foc TR4 resistance in

CLINICAL CASE OF TREATMENT WITH RIBOSOMAL COMPLEX IN CHILD WITH COMPROMISED IMMUNITY

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A.A. Alekseeva

2011-01-01

Full Text Available The leading pathology in children is acute respiratory infections (ARI according to the expert data of WHO. The incidence of prolonged and recurrent types of ARI increases during recent years. Patients with these diseases subsequently form the group of children with compromised immunity. Immunogens and immunomodulators are the drugs of nonspecific prophylaxis which are used for the prevention of ARI. The group of bacterial immunomodulators is big but most well-studied systemic drug from this group is Ribomunyl. Ribosomal complex is effective and safe in pediatric practice. The article presents the clinical case of treatment with ribosomal complex in immunocompronised child with allergic pathology.Key words: children with compromised immunity, allergy, acute respiratory infections, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 211–215

Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

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Magdalena Radwanska

2007-05-01

Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

Energy Technology Data Exchange (ETDEWEB)

Chen, Liang [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Tang, Yanping [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Wang, Jian [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Yan, Zhongjie [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China); Xu, Ruxiang, E-mail: RuxiangXu@yahoo.com [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)

2013-06-14

Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

The Effects of Dilute Sulfuric Acid on Sheet Resistance and Transmittance in Poly(3,4-thylenedioxythiophene: Poly(styrenesulfonate Films

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Teen-Hang Meen

2013-01-01

Full Text Available The conductivity of poly(3,4-thylenedioxythiophene: poly(styrenesulfonate (PEDOT: PSS films by adding various molar concentrations of sulfuric acid (H2SO4 was improved and studied in this paper. The sheet resistance of the doped PEDOT: PSS film was enhanced with increasing the ratio of H2SO4, but it drops after the maximum sheet resistance. The reason for this phenomenon is resulting from the fact that the H2SO4 preferentially react with the sorbitol which is so-called the pinacol rearrangement. The nonconductive anions of some PSS− were substituted by the conductive anions of hydrogen sulfate (HSO4- when the residual H2SO4 reacted with PSS. In addition to the substitution reaction, PEDOT chains were increasingly aggregated with increasing the ratio of H2SO4. After doped H2SO4, the sheet resistance of H2SO4-doped PEDOT: PSS film is improved nearly 36%; the surface roughness is reduced from 1.268 nm to 0.822 nm and the transmittance is up to 91.9% in the visible wavelength range from 400 to 700 nm.

[Systematic review of antimicrobial resistance in Enterobacteriaceae isolates from Colombian hospitals].

Science.gov (United States)

González, Leidy; Cortés, Jorge Alberto

2014-01-01

Bacterial resistance is a public health problem worldwide that seriously compromises the possibility to treat infections. To identify levels of resistance to antibiotic markers in Enterobacteriaceae isolates from Colombian hospitals. A systematic literature survey was done including articles indexed in Medline, Embase and LILACS. A manual search was made of Colombian scientific journals and other publications on infectious disease that were not available electronically. In total, 43 observational studies and epidemiological reports were identified with information about resistance among Enterobacteriaceae isolates in Colombian hospitals, mainly from Bogotá, Cali and Medellín. The resistance rate of Escherichia coli ranges from 3 to 11%, 5 to 20% and from 0.2 to 0.8% for piperacillin-tazobactam, third generation cephalosporins and carbapenems, respectively. For Klebsiella pneumoniae resistance rates ranges from 21.8 to 48.1% to piperacillin-tazobactam, 20 to 35% to broad-spectrum cephalosporins and 3 to 8% to carbapenems, with significant variations by cities, levels of care and clinical settings. The spread of bacterial resistance in Enterobacteriaceae isolated in Colombian hospitals is a growing problem that calls for priority action to cut the chains of transmission.

Antimalarial activity of novel 4-aminoquinolines active against drug resistant strains.

Science.gov (United States)

Kondaparla, Srinivasarao; Soni, Awakash; Manhas, Ashan; Srivastava, Kumkum; Puri, Sunil K; Katti, S B

2017-02-01

In the present study we have synthesized a new class of 4-aminoquinolines and evaluated against Plasmodium falciparum in vitro (3D7-sensitive strain & K1-resistant strain) and Plasmodium yoelii in vivo (N-67 strain). Among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against K1 strain as compared to CQ. In addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against N-67 strain when administered orally. Further, biophysical studies suggest that this series of compounds act on heme polymerization target. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of distinct specificity determinants in resistance protein Cf-4 allows construction of a Cf-9 mutant that confers recognition of avirulence protein AVR4

NARCIS (Netherlands)

Hoorn, Van der R.A.L.; Roth, R.; Wit, De P.J.G.M.

2001-01-01

The tomato resistance genes Cf-4 and Cf-9 confer specific, hypersensitive response-associated recognition of Cladosporium carrying the avirulence genes Avr4 and Avr9, respectively. Cf-4 and Cf-9 encode type I transmembrane proteins with extracellular leucine-rich repeats (LRRs). Compared with Cf-9,

Metabolic engineering of geranic acid in maize to achieve fungal resistance is compromised by novel glycosylation patterns.

Science.gov (United States)

Yang, Ting; Stoopen, Geert; Yalpani, Nasser; Vervoort, Jacques; de Vos, Ric; Voster, Alessandra; Verstappen, Francel W A; Bouwmeester, Harro J; Jongsma, Maarten A

2011-07-01

Many terpenoids are known to have antifungal properties and overexpression of these compounds in crops is a potential tool in disease control. In this study, 15 different mono- and sesquiterpenoids were tested in vitro against two major pathogenic fungi of maize (Zea mays), Colletotrichum graminicola and Fusarium graminearum. Among all tested terpenoids, geranic acid showed very strong inhibitory activity against both fungi (MICLippia dulcis under the control of a ubiquitin promoter. The volatile and non-volatile metabolite profiles of leaves from transgenic and control lines were compared. The headspaces collected from intact seedlings of transgenic and control plants were not significantly different, although detached leaves of transgenic plants emitted 5-fold more geranyl acetate compared to control plants. Non-targeted LC-MS profiling and LC-MS-MS identification of extracts from maize leaves revealed that the major significantly different non-volatile compounds were 2 geranic acid derivatives, a geraniol dihexose and 4 different types of hydroxyl-geranic acid-hexoses. A geranic acid glycoside was the most abundant, and identified by NMR as geranoyl-6-O-malonyl-β-d-glucopyranoside with an average concentration of 45μM. Fungal bioassays with C. graminicola and F. graminearum did not reveal an effect of these changes in secondary metabolite composition on plant resistance to either fungus. The results demonstrate that metabolic engineering of geraniol into geranic acid can rely on the existing default pathway, but branching glycosylation pathways must be controlled to achieve accumulation of the aglycones. Copyright © 2011 Elsevier Inc. All rights reserved.

Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean.

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Andrew J Burt

Full Text Available Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris. Alleles at the Co-4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08 where Co-4 is localized. Three SCAR markers with known linkage to Co-4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK-4 loci found in previous studies. It is possible that the Co-4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases.

Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase.

Science.gov (United States)

Zhao, Yu; Majid, Mona C; Soll, Jennifer M; Brickner, Joshua R; Dango, Sebastian; Mosammaparast, Nima

2015-06-12

Repair of DNA alkylation damage is critical for genomic stability and involves multiple conserved enzymatic pathways. Alkylation damage resistance, which is critical in cancer chemotherapy, depends on the overexpression of alkylation repair proteins. However, the mechanisms responsible for this upregulation are unknown. Here, we show that an OTU domain deubiquitinase, OTUD4, is a positive regulator of ALKBH2 and ALKBH3, two DNA demethylases critical for alkylation repair. Remarkably, we find that OTUD4 catalytic activity is completely dispensable for this function. Rather, OTUD4 is a scaffold for USP7 and USP9X, two deubiquitinases that act directly on the AlkB proteins. Moreover, we show that loss of OTUD4, USP7, or USP9X in tumor cells makes them significantly more sensitive to alkylating agents. Taken together, this work reveals a novel, noncanonical mechanism by which an OTU family deubiquitinase regulates its substrates, and provides multiple new targets for alkylation chemotherapy sensitization of tumors. © 2015 The Authors.

Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

LENUS (Irish Health Repository)

Gasch, Claudia

2017-01-01

It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

NARCIS (Netherlands)

Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

2016-01-01

The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

[Tuberculosis in compromised hosts].

Science.gov (United States)

2003-11-01

Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

Tracking Weight Change, Insulin Resistance, Stress, and Aerobic Fitness over 4 Years of College

Science.gov (United States)

Hopper, Mari K.; Moninger, Shana Lynn

2017-01-01

Objective: To determine if weight gain is accompanied by development of insulin resistance (IR) during 4 years in college. Participants: Two cohorts of college students were enrolled in fall semesters 2009 and 2010 and tracked for 4 years. Methods: Following a 12-hour fast, subjects reported for measurement of body mass index (BMI), perceived…

Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting.

Science.gov (United States)

Musicha, Patrick; Feasey, Nicholas A; Cain, Amy K; Kallonen, Teemu; Chaguza, Chrispin; Peno, Chikondi; Khonga, Margaret; Thompson, Sarah; Gray, Katherine J; Mather, Alison E; Heyderman, Robert S; Everett, Dean B; Thomson, Nicholas R; Msefula, Chisomo L

2017-06-01

Efforts to treat Escherichia coli infections are increasingly being compromised by the rapid, global spread of antimicrobial resistance (AMR). Whilst AMR in E. coli has been extensively investigated in resource-rich settings, in sub-Saharan Africa molecular patterns of AMR are not well described. In this study, we have begun to explore the population structure and molecular determinants of AMR amongst E. coli isolates from Malawi. Ninety-four E. coli isolates from patients admitted to Queen's Hospital, Malawi, were whole-genome sequenced. The isolates were selected on the basis of diversity of phenotypic resistance profiles and clinical source of isolation (blood, CSF and rectal swab). Sequence data were analysed using comparative genomics and phylogenetics. Our results revealed the presence of five clades, which were strongly associated with E. coli phylogroups A, B1, B2, D and F. We identified 43 multilocus STs, of which ST131 (14.9%) and ST12 (9.6%) were the most common. We identified 25 AMR genes. The most common ESBL gene was bla CTX-M-15 and it was present in all five phylogroups and 11 STs, and most commonly detected in ST391 (4/4 isolates), ST648 (3/3 isolates) and ST131 [3/14 (21.4%) isolates]. This study has revealed a high diversity of lineages associated with AMR, including ESBL and fluoroquinolone resistance, in Malawi. The data highlight the value of longitudinal bacteraemia surveillance coupled with detailed molecular epidemiology in all settings, including low-income settings, in describing the global epidemiology of ESBL resistance. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The presence of plasmid-mediated resistance genes among uropathogenes isolated from diabetic and non-diabetic patients with chronic pyelonephritis

Directory of Open Access Journals (Sweden)

O.I. Chub

2014-10-01

Full Text Available Increased multidrug resistance of extended-spectrum beta-lactamases (ESBLs compromises the efficacy of treatment of urinary tract infections. The objective of this study is to determine the prevalence of ESBL-producing uropathogens from patients with chronic pyelonephritis (CP and to evaluate the risk factors of these types of infections. Screening for the presence of plasmid-mediated ESBL was performed by polymerase chain reaction. Out of 105 patients, 22 (20.9% revealed strains with resistance genes: 11 (36.7%, 11 (36.7% and 8 (26.7% were identified to carry bla(TEM, bla(SHV and bla(CTX-M beta-lactamase genes, respectively. We have demonstrated that prevalence of the resistance among patients with CP combined with type 2 DM was 31.3%, while among patients with CP without type 2 DM was 27.4%; however the difference between these groups was not significant. The main factors related with appearance of plasmid-mediated resistance genes were age range above 55 years, Chronic Kidney Disease stage ІІІ and ІV, in-patient treatment history, history of using antibiotics last year. Isolation and detection of ESBL-producing strains are essential fоr the sеlection оf the mоst effеctive antibiоtic for the empiric trеatment.

ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

OpenAIRE

Weese, J.S.; Gigu?re, S.; Guardabassi, L.; Morley, P.S.; Papich, M.; Ricciuto, D.R.; Sykes, J.E.

2015-01-01

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the...

Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

International Nuclear Information System (INIS)

Geelen, Caroline MM van; Pennarun, Bodvael; Le, Phuong TK; Vries, Elisabeth GE de; Jong, Steven de

2011-01-01

rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948

Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

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de Vries Elisabeth GE

2011-01-01

Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

Analyses of natural variation indicates that the absence of RPS4/RRS1 and amino acid change in RPS4 cause loss of their functions and resistance to pathogens.

Science.gov (United States)

Narusaka, Mari; Iuchi, Satoshi; Narusaka, Yoshihiro

2017-03-04

A pair of Arabidopsis thaliana resistance proteins, RPS4 and RRS1, recognizes the cognate Avr effector from the bacterial pathogens Pseudomonas syringae pv. tomato expressing avrRps4 (Pst-avrRps4), Ralstonia solanacearum, and the fungal pathogen Colletotrichum higginsianum and leads to defense signaling activation against the pathogens. In the present study, we analyzed 14 A. thaliana accessions for natural variation in Pst-avrRps4 and C. higginsianum susceptibility, and found new compatible and incompatible Arabidopsis-pathogen interactions. We first found that A. thaliana accession Cvi-0 is susceptible to Pst-avrRps4. Interestingly, the genome sequence assembly indicated that Cvi-0 lost both RPS4 and RRS1, but not RPS4B and RRS1B, compared to the reference genome sequence from A. thaliana accession Col-0. On the other hand, the natural variation analysis of RPS4 alleles from various Arabidopsis accessions revealed that one amino-acid change, Y950H, is responsible for the loss of resistance to Pst-avrRps4 and C. higginsianum in RLD-0. Our data indicate that the amino acid change, Y950H, in RPS4 resulted in the loss of both RPS4 and RRS1 functions and resistance to pathogens.

Control of Antimicrobial Resistance Requires an Ethical Approach

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Ben Parsonage

2017-11-01

Full Text Available Ethical behavior encompasses actions that benefit both self and society. This means that tackling antimicrobial resistance (AMR becomes an ethical obligation, because the prospect of declining anti-infectives affects everyone. Without preventive action, loss of drugs that have saved lives over the past century, will condemn ourselves, people we know, and people we don’t know, to unacceptable risk of untreatable infection. Policies aimed at extending antimicrobial life should be considered within an ethical framework, in order to balance the choice, range, and quality of drugs against stewardship activities. Conserving availability and effectiveness for future use should not compromise today’s patients. Practices such as antimicrobial prophylaxis for healthy people ‘at risk’ should receive full debate. There are additional ethical considerations for AMR involving veterinary care, agriculture, and relevant bio-industries. Restrictions for farmers potentially threaten the quality and quantity of food production with economic consequences. Antibiotics for companion animals do not necessarily spare those used for humans. While low-income countries cannot afford much-needed drugs, pharmaceutical companies are reluctant to develop novel agents for short-term return only. Public demand encourages over-the-counter, internet, black market, and counterfeit drugs, all of which compromise international control. Prescribers themselves require educational support to balance therapeutic choice against collateral damage to both body and environment. Predicted mortality due to AMR provides justification for international co-operation, commitment and investment to support surveillance and stewardship along with development of novel antimicrobial drugs. Ethical arguments for, and against, control of antimicrobial resistance strategies are presented and discussed in this review.

Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

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Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

2014-08-01

The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Barley yellow mosaic virus VPg is the determinant protein for breaking eIF4E-mediated recessive resistance in barley plants

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Huangai Li

2016-09-01

Full Text Available In this study, we investigated the barley yellow mosaic virus (BaYMV, genus Bymovirus factor(s responsible for breaking eIF4E-mediated recessive resistance genes (rym4/5/6 in barley. Genome mapping analysis using chimeric infectious cDNA clones between rym5-breaking (JT10 and rym5-non-breaking (JK05 isolates indicated that genome-linked viral protein (VPg is the determinant protein for breaking the rym5 resistance. Likewise, VPg is also responsible for overcoming the resistances of rym4 and rym6 alleles. Mutational analysis identified that amino acids Ser-118, Thr-120 and His-142 in JT10 VPg are the most critical residues for overcoming rym5 resistance in protoplasts. Moreover, the rym5-non-breaking JK05 could accumulate in the rym5 protoplasts when eIF4E derived from a susceptible barley cultivar was expressed from the viral genome. Thus, the compatibility between VPg and host eIF4E determines the ability of BaYMV to infect barley plants.

Happenstance and compromise: a gendered analysis of students' computing degree course selection

Science.gov (United States)

Lang, Catherine

2010-12-01

The number of students choosing to study computing at university continues to decline this century, with an even sharper decline in female students. This article presents the results of a series of interviews with university students studying computing courses in Australia that uncovered the influence of happenstance and compromise on course choice. This investigation provides an insight into the contributing factors into the continued downturn of student diversity in computing bachelor degree courses. Many females interviewed made decisions based on happenstance, many males interviewed had chosen computing as a compromise course, and family helped in the decision-making to a large degree in both genders. The major implication from this investigation is the finding that students of both genders appear to be socialised away from this discipline, which is perceived as a support or insurance skill, not a career in itself, in all but the most technical-oriented (usually male) student.

Is ridge preservation/augmentation at periodontally compromised extraction sockets safe? A retrospective study.

Science.gov (United States)

Kim, Jung-Ju; Ben Amara, Heithem; Schwarz, Frank; Kim, Hae-Young; Lee, Jung-Won; Wikesjö, Ulf M E; Koo, Ki-Tae

2017-10-01

This study aimed to evaluate the safety of ridge preservation/augmentation procedures when performed at compromised extraction sockets. Patients subject to ridge preservation/augmentation at periodontally compromised sockets at Seoul National University Dental Hospital (SNUDH) were evaluated in a chart review. Tooth extractions due to acute infection were not included in our study as chronically formed lesions are the only lesions that can be detected from radiographic images. If inflammatory symptoms persisted following ridge preservation/augmentation and antimicrobial and anti-inflammatory therapy, the patient was categorized as a re-infection case and implanted biomaterial removed. Of 10,060 patients subject to tooth extractions at SNUDH, 2011 through 2015, 297 cases meeting inclusion criteria were reviewed. The severity and type of lesions were not specific because extracting data was only done by radiographic images and chart records. The review identified eight patients exhibiting inflammatory symptoms that required additional antimicrobial and anti-inflammatory therapy. Within this group, re-infection occurred in two patients requiring biomaterials removal. The final safety rate for the ridge preservation/augmentation was 99.3%. None of the demographic factors, systemic conditions or choice of biomaterial affected the safety of ridge preservation/augmentation. Alveolar ridge preservation/augmentation at periodontally compromised sockets appears safe following thorough removal of infectious source. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of whey protein supplementation on resistance exercise-induced changes in muscle strength, lean mass, and function in mobility-limited older adults

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Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass. Further studies are required to determine whether this effect extends to functionally compromised older adults. The objectives of the study were to compare the effects of whey protein concent...

Modulation of TRAIL resistance in colon carcinoma cells : Different contributions of DR4 and DR5

NARCIS (Netherlands)

van Geelen, Caroline M. M.; Pennarun, Bodvael; Le, Phuong T. K.; de Vries, Elisabeth G. E.; de Jong, Steven

2011-01-01

Background: rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether

Corporate corruption of the environment: sustainability as a process of compromise.

Science.gov (United States)

Nyberg, Daniel; Wright, Christopher

2013-09-01

A key response to environmental degradation, climate change and declining biodiversity has been the growing adoption of market principles in an effort to better value the social good of nature. Through concepts such as 'natural capitalism' and 'corporate environmentalism', nature is increasingly viewed as a domain of capitalist endeavour. In this article, we use convention theory and a pluralist understanding of social goods to investigate how the social good of the environment is usurped by the alternate social good of the market. Through analysis of interviews with sustainability managers and corporate documentation, we highlight how organizational actors employ compromise to temporally settle disputes between competing claims about environmental activities. Our findings contribute to an understanding of the processes of empirically grounded critique and the under-theorized concept of compromise between social goods. Rather than protecting the environment, the corporate promotion of sustainability facilitates the corruption of the social good of the environment and its conversion into a market commodity. © London School of Economics and Political Science 2013.

The Novel Gene VpPR4-1 from Vitis pseudoreticulata Increases Powdery Mildew Resistance in Transgenic Vitis vinifera L.

Science.gov (United States)

Dai, Lingmin; Wang, Dan; Xie, Xiaoqing; Zhang, Chaohong; Wang, Xiping; Xu, Yan; Wang, Yuejin; Zhang, Jianxia

2016-01-01

Pathogenesis-related proteins (PRs) can lead to increased resistance of the whole plant to pathogen attack. Here, we isolate and characterize a PR-4 protein (VpPR4-1) from a wild Chinese grape Vitis pseudoreticulata which shows greatly elevated transcription following powdery mildew infection. Its expression profiles under a number of abiotic stresses were also investigated. Powdery mildew, salicylic acid, and jasmonic acid methyl ester significantly increased the VpPR4-1 induction while NaCl and heat treatments just slightly induced VpPR4-1 expression. Abscisic acid and cold treatment slightly affected the expression level of VpPR4-1. The VpPR4-1 gene was overexpressed in 30 regenerated V. vinifera cv. Red Globe via Agrobacterium tumefaciens-mediated transformation and verified by the Western blot. The 26 transgenic grapevines exhibited higher expression levels of PR-4 protein content than wild-type vines and six of them were inoculated with powdery mildew which showed that the growth of powdery mildew was repressed. The powdery mildew-resistance of Red Globe transformed with VpPR4-1 was enhanced inoculated with powdery mildew. Moreover, other powdery mildew resistant genes were associated with feedback regulation since VpPR4-1 is in abundance. This study demonstrates that PR-4 protein in grapes plays a vital role in defense against powdery mildew invasion.

Effects of solution treatment on mechanical properties and corrosion resistance of 4A duplex stainless steel

Energy Technology Data Exchange (ETDEWEB)

Lu, Panpan; Wang, Aiqin; Wang, Wenyan [Henan Univ. of Science and Technology, Luoyang (China). School of Material Science and Engineering; Xie, Jingpei [Henan Univ. of Science and Technology, Luoyang (China). Collaborative Innovation Center of Nonferrous Metals

2018-02-15

In this study, 4A duplex stainless steels were prepared via remelting in an intermediate frequency furnace and subsequently solution treated at different temperatures. The effects of solution treatment on the mechanical properties and corrosion resistance of 4A duplex stainless steel were investigated. Microstructures were characterized via optical microscopy and scanning electron microscopy. The mechanical properties were evaluated via hardness test, tensile test, and impact test experiments. The point corrosion resistance was studied via chemical immersion and potentiodynamic anodic polarization. The results showed that with increasing solution temperature in the range of 1223 - 1423 K, the tensile strength and hardness first decreased and then increased, and minimum values were obtained at 1323 K. The σ phase precipitated at the boundaries of the α/γ phases in samples solution treated at 1223 K, decreasing both impact energy and pitting potential of the experimental steels. When experimental steels were solution treated at 1373 K for 2 h, a suitable volume fraction of α/γ was uniformly distributed throughout the microstructure, and the steels exhibited optimal mechanical properties and pitting corrosion resistance.

Normobaric hypoxia increases the growth hormone response to maximal resistance exercise in trained men.

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Filopoulos, Dean; Cormack, Stuart J; Whyte, Douglas G

2017-08-01

This study examined the effect of hypoxia on growth hormone (GH) release during an acute bout of high-intensity, low-volume resistance exercise. Using a single-blinded, randomised crossover design, 16 resistance-trained males completed two resistance exercise sessions in normobaric hypoxia (HYP; inspiratory oxygen fraction, (FiO 2 ) 0.12, arterial oxygen saturation (SpO 2 ) 82 ± 2%) and normoxia (NOR; FiO 2 0.21, SpO 2 98 ± 0%). Each session consisted of five sets of three repetitions of 45° leg press and bench press at 85% of one repetition maximum. Heart rate, SpO 2 , and electromyographic activity (EMG) of the vastus lateralis muscle were measured throughout the protocol. Serum lactate and GH levels were determined pre-exposure, and at 5, 15, 30 and 60 min post-exercise. Differences in mean and integrated EMG between HYP and NOR treatments were unclear. However, there was an important increase in the peak levels and area under the curve of both lactate (HYP 5.8 ± 1.8 v NOR 3.9 ± 1.1 mmol.L -1 and HYP 138.7 ± 33.1 v NOR 105.8 ± 20.8 min.mmol.L -1 ) and GH (HYP 4.4 ± 3.1 v NOR 2.1 ± 2.5 ng.mL -1 and HYP 117.7 ± 86.9 v NOR 72.9 ± 85.3 min.ng.mL -1 ) in response to HYP. These results suggest that performing high-intensity resistance exercise in a hypoxic environment may provide a beneficial endocrine response without compromising the neuromuscular activation required for maximal strength development.

4-N, 4-S & 4-O Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pKa on Activity vs. Chloroquine Resistant Malaria+, #

Science.gov (United States)

Natarajan, Jayakumar K.; Alumasa, John; Yearick, Kimberly; Ekoue-Kovi, Kekeli A.; Casabianca, Leah B.; de Dios, Angel C.; Wolf, Christian; Roepe, Paul D.

2009-01-01

Using predictions from heme – quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure – function principles. We vary side chain length for both monoethyl and diethyl 4N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position, and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4N, 4S and 4O derivatives vs. μ-oxo dimeric heme, measure binding constants for monomeric vs. dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs. CQR malaria. PMID:18512900

Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China.

Science.gov (United States)

Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi

2018-04-01

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.

Identification of Differentially-Expressed Genes in Response to Mycosphaerella fijiensis in the Resistant Musa Accession 'Calcutta-4' Using Suppression Subtractive Hybridization.

Science.gov (United States)

Sánchez Timm, Eduardo; Hidalgo Pardo, Lisette; Pacheco Coello, Ricardo; Chávez Navarrete, Tatiana; Navarrete Villegas, Oscar; Santos Ordóñez, Efrén

2016-01-01

Bananas and plantains are considered an important crop around the world. Banana production is affected by several constraints, of which Black Sigatoka Disease, caused by the fungus Mycosphaerella fijiensis, is considered one of the most important diseases in banana plantations. The banana accession 'Calcutta-4' has a natural resistance to Black Sigatoka; however, the fruit is not valuable for commercialization. Gene identification and expression studies in 'Calcutta-4' might reveal possible gene candidates for resistant to the disease and elucidate mechanisms for resistance. A subtracted cDNA library was generated from leaves after 6, 9 and 12 days inoculated with M. fijiensis conidia on greenhouse banana plants of the accession 'Calcutta-4'. Bioinformatic analysis revealed 99 good quality sequences. Blast2go analysis revealed that 31% of the sequences could not be categorized and, according to the Biological Process Category, 32 and 28 ESTs are related to general metabolic and cellular processes, respectively; while 10 ESTs response to stimulus. Seven sequences were redundant and one was similar to genes that may be involved in pathogen resistance including the putative disease resistance protein RGA1. Genes encoding zinc finger domains were identified and may play an important role in pathogen resistance by inducing the expression of downstream genes. Expression analysis of four selected genes was performed using RT-qPCR during the early stage of the disease development at 6, 9, 12 and 15 days post inoculation showing a peak of up regulation at 9 or 12 days post inoculation. Three of the four genes showed an up-regulation of expression in 'Calcutta-4' when compared to 'Williams' after inoculation with M. fijiensis, suggesting a fine regulation of specific gene candidates that may lead to a resistance response. The genes identified in early responses in a plant-pathogen interaction may be relevant for the resistance response of 'Calcutta-4' to Black Sigatoka

Identification of Differentially-Expressed Genes in Response to Mycosphaerella fijiensis in the Resistant Musa Accession 'Calcutta-4' Using Suppression Subtractive Hybridization.

Directory of Open Access Journals (Sweden)

Eduardo Sánchez Timm

Full Text Available Bananas and plantains are considered an important crop around the world. Banana production is affected by several constraints, of which Black Sigatoka Disease, caused by the fungus Mycosphaerella fijiensis, is considered one of the most important diseases in banana plantations. The banana accession 'Calcutta-4' has a natural resistance to Black Sigatoka; however, the fruit is not valuable for commercialization. Gene identification and expression studies in 'Calcutta-4' might reveal possible gene candidates for resistant to the disease and elucidate mechanisms for resistance. A subtracted cDNA library was generated from leaves after 6, 9 and 12 days inoculated with M. fijiensis conidia on greenhouse banana plants of the accession 'Calcutta-4'. Bioinformatic analysis revealed 99 good quality sequences. Blast2go analysis revealed that 31% of the sequences could not be categorized and, according to the Biological Process Category, 32 and 28 ESTs are related to general metabolic and cellular processes, respectively; while 10 ESTs response to stimulus. Seven sequences were redundant and one was similar to genes that may be involved in pathogen resistance including the putative disease resistance protein RGA1. Genes encoding zinc finger domains were identified and may play an important role in pathogen resistance by inducing the expression of downstream genes. Expression analysis of four selected genes was performed using RT-qPCR during the early stage of the disease development at 6, 9, 12 and 15 days post inoculation showing a peak of up regulation at 9 or 12 days post inoculation. Three of the four genes showed an up-regulation of expression in 'Calcutta-4' when compared to 'Williams' after inoculation with M. fijiensis, suggesting a fine regulation of specific gene candidates that may lead to a resistance response. The genes identified in early responses in a plant-pathogen interaction may be relevant for the resistance response of 'Calcutta-4' to

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

Science.gov (United States)

Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum; Sharma, Manish; Nielsen, Morten A; Alifrangis, Michael; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

2016-10-21

Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.

Science.gov (United States)

Tanimoto, Azusa; Yamada, Tadaaki; Nanjo, Shigeki; Takeuchi, Shinji; Ebi, Hiromichi; Kita, Kenji; Matsumoto, Kunio; Yano, Seiji

2014-07-15

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.

Towards a legitimate compromise?: An exploration of Integrated Reporting in the Netherlands

NARCIS (Netherlands)

van Bommel, K.

2014-01-01

Purpose – The purpose of this paper is to examine the multiplicity of views on integrated reporting and to consider the possibility of, and impediments to, reconciling these multiple rationales (“orders of worth”) and thus gain legitimacy through a compromise. This sheds light on the understanding

Safety and Efficacy of Alginate Adhesion Barrier Gel in Compromised Intestinal Anastomosis

NARCIS (Netherlands)

Chaturvedi, A.; Yauw, S.T.K.; Lomme, R.M.L.M.; Hendriks, T.; Goor, H. van

2017-01-01

BACKGROUND: For any anti-adhesive barrier developed for abdominal surgery, the use under conditions in which anastomotic healing is compromised needs to be investigated. The current study evaluates the effect of a new ultrapure alginate gel on early healing of high-risk anastomoses in the ileum and

Microstructure and Wear Resistance of Composite Coating by Laser Cladding Al/TiN on the Ti-6Al-4V Substrate

Science.gov (United States)

Zhang, H. X.; Yu, H. J.; Chen, C. Z.

2015-05-01

The composite coatings were fabricated by laser cladding Al/TiN pre-placed powders on Ti-6Al-4V substrate for enhancing wear resistance and hardness of the substrate. The composite coatings were analyzed by means of X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). The sliding wear tests were performed by MM200 wear test machine. The hardness of the coatings was tested by HV-1000 hardness tester. After laser cladding, it was found that there was a good metallurgical bond between the coating and the substrate. The composite coatings were mainly composed of the matrix of β-Ti (Al) and the reinforcements of titanium nitride (TiN), Ti3Al, TiAl and Al3Ti. The hardness and wear resistance of the coatings on four samples were greatly improved, among which sample 4 exhibited the highest hardness and best wear resistance. The hardness of the coating on sample 4 was approximately 2.5 times of the Ti-6Al-4V substrate. And the wear resistance of sample 4 was four times of the substrate.

Catecholate-siderophore produced by As-resistant bacterium effectively dissolved FeAsO_4 and promoted Pteris vittata growth

International Nuclear Information System (INIS)

Liu, Xue; Yang, Guang-Mei; Guan, Dong-Xing; Ghosh, Piyasa; Ma, Lena Q.

2015-01-01

The impact of siderophore produced by arsenic-resistant bacterium Pseudomonas PG12 on FeAsO_4 dissolution and plant growth were examined. Arsenic-hyperaccumulator Pteris vittata was grown for 7 d in 0.2-strength Fe-free Hoagland solution containing FeAsO_4 mineral and PG12-siderophore or fungal-siderophore desferrioxamine B (DFOB). Standard siderophore assays indicated that PG12-siderophore was catecholate-type. PG12-siderophore was more effective in promoting FeAsO_4 dissolution, and Fe and As plant uptake than DFOB. Media soluble Fe and As in PG12 treatment were 34.6 and 3.07 μM, 1.6- and 1.4-fold of that in DFOB. Plant Fe content increased from 2.93 to 6.24 g kg"−"1 in the roots and As content increased from 14.3 to 78.5 mg kg"−"1 in the fronds. Besides, P. vittata in PG12 treatment showed 2.6-times greater biomass than DFOB. While P. vittata fronds in PG12 treatment were dominated by AsIII, those in DFOB treatment were dominated by AsV (61–77%). This study showed that siderophore-producing arsenic-resistant rhizobacteria may have potential in enhancing phytoremediation of arsenic-contaminated soils. - Graphical abstract: As-induced root exudate phytate enhanced FeAsO_4 dissolution, and As uptake and plant growth of Pteris vittata. Display Omitted - Highlights: • Arsenic-resistant rhizobacterium Pseudomonas PG12 was from rhizosphere of As-hyperaccumulator Pteris vittata. • PG12 was effective in producing catecholate-type siderophore with high affinity with Fe. • PG12-produced siderophore increased Fe and As uptake and growth in P. vittata. - Siderophores produced by arsenic-resistant bacteria were effective in solubilizing FeAsO_4 mineral and enhancing plant growth of As-hyperaccumulator Pteris vittata.

Fibre reinforcement in a structurally compromised endodontically treated molar: a case report

Directory of Open Access Journals (Sweden)

Renita Soares

2016-05-01

Full Text Available The reconstruction of structurally compromised posterior teeth is a rather challenging procedure. The tendency of endodontically treated teeth (ETT to fracture is considerably higher than vital teeth. Although posts and core build-ups followed by conventional crowns have been generally employed for the purpose of reconstruction, this procedure entails sacrificing a considerable amount of residual sound enamel and dentin. This has drawn the attention of researchers to fibre reinforcement. Fibre-reinforced composite (FRC, designed to replace dentin, enables the biomimetic restoration of teeth. Besides improving the strength of the restoration, the incorporation of glass fibres into composite resins leads to favorable fracture patterns because the fibre layer acts as a stress breaker and stops crack propagation. The following case report presents a technique for reinforcing a badly broken-down ETT with biomimetic materials and FRC. The proper utilization of FRC in structurally compromised teeth can be considered to be an economical and practical measure that may obviate the use of extensive prosthetic treatment.

Striking a Balance between Program Requirements and GT Principles: Writing a compromised GT proposal

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Sherry L. Xie, Ph.D. Candidate

2009-06-01

Full Text Available Glaser’s term “compromised GT proposal” (2001, p.114 refers to the type of Grounded Theory (GT proposal that is written in order to conform to the requirements of a standardized qualitative research proposal. A GT proposal needs only to supply information on the area of interest, the data source and a statement of method to the effect that the researcher begin to collect, code and analyse the data and let the theory emerge. Thus, the proposal may only occupy “a page or two” (Glaser, 2001, p. 111. Whilst being consistent with the methodology, a GT proposal sometimes has to give way to the format specified by a PhD program or committee even though the format was not defined for a GT proposal and in some areas, conflicts with GT principles; for example, the format may require a literature review. This short paper reports on my experience of writing a compromised GT proposal as a first-time GT researcher. It describes how both Glaser’s advice on writing compromised GT research proposals and the characteristics of the substantive area of the proposed research were used to satisfy program requirements while still maintaining GT fundamentals.

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

International Nuclear Information System (INIS)

Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

2005-01-01

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

Mapping insecticide resistance and characterization of resistance mechanisms in Anopheles arabiensis (Diptera: Culicidae) in Ethiopia.

Science.gov (United States)

Alemayehu, Eba; Asale, Abebe; Eba, Kasahun; Getahun, Kefelegn; Tushune, Kora; Bryon, Astrid; Morou, Evangelia; Vontas, John; Van Leeuwen, Thomas; Duchateau, Luc; Yewhalaw, Delenasaw

2017-09-02

The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae (s.s.) and An. arabiensis may compromise the current vector control interventions and threatens the global malaria control and elimination efforts. Insecticide resistance was monitored in several study sites in Ethiopia from 2013 to 2015 using papers impregnated with discriminating concentrations of DDT, deltamethrin, bendiocarb, propoxur, malathion, fenitrothion and pirimiphos-methyl, following the WHO insecticide susceptibility test procedure. Mosquitoes sampled from different localities for WHO bioassay were morphologically identified as An. gambiae (s.l.) using standard taxonomic keys. Samples were identified to species using species-specific polymerase chain reaction (PCR) and screened for the presence of target site mutations L1014F, L1014S and N1575Y in the voltage gated sodium channel (VGSC) gene and G119S in the acethylcholinesterase (AChE) gene using allele-specific PCR. Biochemical assays were performed to assess elevated levels of acetylcholinesterases, carboxylcholinesterases, glutathione-S-transferases (GSTs) and cytochrome P450s monooxygenases in wild populations of An. arabiensis, compared to the fully susceptible Sekoru An. arabiensis laboratory strain. Populations of An. arabiensis were resistant to DDT and deltamethrin but were susceptible to fenitrothion in all the study sites. Reduced susceptibility to malathion, pirimiphos-methyl, propoxur and bendiocarb was observed in some of the study sites. Knockdown resistance (kdr L1014F) was detected in all mosquito populations with allele frequency ranging from 42 to 91%. Elevated levels of glutathione-S-transferases (GSTs) were detected in some of the mosquito populations. However, no elevated levels of monooxygenases and esterases were detected in any of the populations assessed. Anopheles arabiensis populations from all surveyed sites in Ethiopia exhibited resistance against DDT and pyrethroids

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

M Hashem Abdel

2011-11-01

Full Text Available Abstract Background Hepatitis C virus (HCV is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4 in the world; this study investigated effects of HCV genotype-4 (HCV-4 on prevalence of insulin resistance in chronic hepatitis C (CHC and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23. Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

Molecular characterization and expression profile of partial TLR4 gene in association to mastitis in crossbred cattle.

Science.gov (United States)

Panigrahi, Manjit; Sharma, Arjava; Bhushan, Bharat

2014-01-01

Crossbred cattle are more prone to mastitis in comparison to indigenous cattle. Toll-like receptor 4 (TLR4) recognizes pathogen ligands, for example, lipopolysaccharide (LPS) endotoxin from Escherichia coli and mediates signaling to initiate innate and adaptive immune responses. Mutations in TLR4 can compromise the host immune response to certain pathogens, so it may be a potential candidate for marker assisted selection to enhance mastitis resistance in dairy cattle. Hence, in this study role of bovine TLR4 gene in mastitis resistance was investigated by association as well as expression profiling analysis in crossbred cattle. The animals were divided into mastitis affected and unaffected groups on the basis of history of animals and California Mastitis Test (CMT). PCR-SSCP and Sequence analysis revealed three genotypes of coreceptor binding region 1 (CRBR1) fragment of TLR4 gene namely AA, AB, and BB in both groups of cattle. The logistic regression model did not show any significant effect of these genotypes on the occurrence of clinical mastitis. Moreover, in vitro challenge of peripheral blood mononuclear cells (PBMCs) with LPS failed to show any association of the genotypes with TLR4 gene expression. In a nutshell, in the present study enough evidence was not found for association of the SNP variants of CRBR1 fragment of TLR4 gene with mastitis susceptibility in crossbred cattle.

Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

DEFF Research Database (Denmark)

Houthuijzen, Julia M; Oosterom, Ilse; Hudson, Brian D

2017-01-01

Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts....... M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance....

Wave resistance calculation method combining Green functions based on Rankine and Kelvin source

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LI Jingyu

2017-12-01

Full Text Available [Ojectives] At present, the Boundary Element Method(BEM of wave-making resistance mostly uses a model in which the velocity distribution near the hull is solved first, and the pressure integral is then calculated using the Bernoulli equation. However,the process of this model of wave-making resistance is complex and has low accuracy.[Methods] To address this problem, the present paper deduces a compound method for the quick calculation of ship wave resistance using the Rankine source Green function to solve the hull surface's source density, and combining the Lagally theorem concerning source point force calculation based on the Kelvin source Green function so as to solve the wave resistance. A case for the Wigley model is given.[Results] The results show that in contrast to the thin ship method of the linear wave resistance theorem, this method has higher precision, and in contrast to the method which completely uses the Kelvin source Green function, this method has better computational efficiency.[Conclusions] In general, the algorithm in this paper provides a compromise between precision and efficiency in wave-making resistance calculation.

Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.

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Choi, Won-Suk; Jeong, Ju Hwan; Kwon, Jin Jung; Ahn, Su Jeong; Lloren, Khristine Kaith S; Kwon, Hyeok-Il; Chae, Hee Bok; Hwang, Jungwon; Kim, Myung Hee; Kim, Chul-Joong; Webby, Richard J; Govorkova, Elena A; Choi, Young Ki; Baek, Yun Hee; Song, Min-Suk

2018-01-01

Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA subtypes using gene-fragmented random mutagenesis. We generated libraries of mutant influenza viruses using reverse genetics (RG) and selected resistant variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison. We identified 37 amino acid substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4 in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or peramivir) as determined using a fluorescence-based NA inhibition assay. Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate that each NA subtype possesses unique NAI resistance markers, and knowledge of these substitutions in AIVs is important in facilitating antiviral susceptibility monitoring of NAI resistance in AIVs. IMPORTANCE The frequency of human infections with avian influenza viruses (AIVs) has increased in recent years. Despite the availability of vaccines, neuraminidase inhibitors (NAIs), as the only available class of drugs for AIVs in humans, have been constantly used for treatment, leading to the inevitable emergence

Stable gene transfer of CCR5 and CXCR4 siRNAs by sleeping beauty transposon system to confer HIV-1 resistance

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Akkina Ramesh

2008-07-01

Full Text Available Abstract Background Thus far gene therapy strategies for HIV/AIDS have used either conventional retroviral vectors or lentiviral vectors for gene transfer. Although highly efficient, their use poses a certain degree of risk in terms of viral mediated oncogenesis. Sleeping Beauty (SB transposon system offers a non-viral method of gene transfer to avoid this possible risk. With respect to conferring HIV resistance, stable knock down of HIV-1 coreceptors CCR5 and CXCR4 by the use of lentiviral vector delivered siRNAs has proved to be a promising strategy to protect cells from HIV-1 infection. In the current studies our aim is to evaluate the utility of SB system for stable gene transfer of CCR5 and CXCR4 siRNA genes to derive HIV resistant cells as a first step towards using this system for gene therapy. Results Two well characterized siRNAs against the HIV-1 coreceptors CCR5 and CXCR4 were chosen based on their previous efficacy for the SB transposon gene delivery. The siRNA transgenes were incorporated individually into a modified SB transfer plasmid containing a FACS sortable red fluorescence protein (RFP reporter and a drug selectable neomycin resistance gene. Gene transfer was achieved by co-delivery with a construct expressing a hyperactive transposase (HSB5 into the GHOST-R3/X4/R5 cell line, which expresses the major HIV receptor CD4 and and the co-receptors CCR5 and CXCR4. SB constructs expressing CCR5 or CXCR4 siRNAs were also transfected into MAGI-CCR5 or MAGI-CXCR4 cell lines, respectively. Near complete downregulation of CCR5 and CXCR4 surface expression was observed in transfected cells. During viral challenge with X4-tropic (NL4.3 or R5-tropic (BaL HIV-1 strains, the respective transposed cells showed marked viral resistance. Conclusion SB transposon system can be used to deliver siRNA genes for stable gene transfer. The siRNA genes against HIV-1 coreceptors CCR5 and CXCR4 are able to downregulate the respective cell surface proteins

Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer.

Science.gov (United States)

Cao, Ya-Lei; Zhuang, Ting; Xing, Bao-Heng; Li, Na; Li, Qin

2017-08-01

Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum-based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V-PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co-incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1-containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients. Copyright © 2017 John Wiley & Sons, Ltd.

Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK

International Nuclear Information System (INIS)

Fontana, Diletta; Ceccon, Monica; Gambacorti-Passerini, Carlo; Mologni, Luca

2015-01-01

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors. About 80% of ALK-positive anaplastic large-cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)-ALK, whereas 5% of non-small-cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases. However, several cases of resistance appeared in NSCLC patients, and ALK amino acid substitutions were identified as a leading cause of resistance to crizotinib. Second-generation ALK inhibitors have been developed in order to overcome crizotinib resistance. In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs. Since the biological activity of ALK mutations extends beyond the specific type of fusion, both NPM-ALK- and EML4-ALK-positive cellular models were used. Our data revealed that most mutants may be targeted by using different inhibitors. One relevant exception is represented by the G1202R substitution, which was highly resistant to all drugs (>10-fold increased IC 50 compared to wild type) and may represent the most challenging mutation to overcome. These results provide a prediction of cross-resistance of known crizotinib-resistant mutations against all second-generation tyrosine kinase inhibitors (TKIs) clinically available, and therefore could be a useful tool to help clinicians in the management of crizotinib-resistance cases

32 CFR 310.14 - Notification when information is lost, stolen, or compromised.

Science.gov (United States)

2010-07-01

... THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Systems of Records § 310.14... the individual of any loss, theft, or compromise (See also, § 310.50 for reporting of the breach to Senior Component Official for Privacy and the Defense Privacy Office). (1) The notification shall be made...

Osseous pseudo-myelomatose compromise, in leukemia chronic lymphoid

International Nuclear Information System (INIS)

Martinez Betancur, Octavio; Lopez de Goenaga, Maria Ines

2000-01-01

It was described a case of chronic lymphocytic leukemia in a 75 year old man, with pseudomyelomatosis osteolytic lesions in the skull, excluding other potential causes of osteolytic lesions in the clinical context of malignant lymphoproliferative neoplasm. The real frequency of osseous compromise in chronic lymphocytic leukemia is 10%. Lesions are defined as generalized osteoporosis and osteolysis with lacunar aspect, similar to myeloma lesions. Because histopathology in lymphoproliferative neoplasms may be similar, it might be difficult to diagnose chronic lymphocytic leukemia certainly, if the clinical manifestations are not considered. Differential diagnosis with other lymphoproliferative neoplasm is based basically in absolute lymphocytosis greater than 10 X 109/L, with lymphocytes with mature appearance

The triglyceride/high-density lipoprotein cholesterol ratio fails to predict insulin resistance in African-American women: an analysis of Jackson Heart Study.

Science.gov (United States)

Sumner, Anne E; Harman, Jane L; Buxbaum, Sarah G; Miller, Bernard V; Tambay, Anita V; Wyatt, Sharon B; Taylor, Herman A; Rotimi, Charles N; Sarpong, Daniel F

2010-12-01

Compared to whites, insulin-resistant African Americans have worse outcomes. Screening programs that could identify insulin resistance early enough for intervention to affect outcome often rely on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels. Racial differences in TG and HDL-C may compromise the efficacy of these programs in African Americans. A recommendation currently exists to use the TG/HDL-C ratio ≥2.0 to predict insulin resistance in African Americans. The validity of this recommendation needs examination. Therefore, our aim was to determine the ability of TG/HDL-C ratio to predict insulin resistance in African Americans. In 1,903 African Americans [895 men, 1,008 women, age 55 ± 12 years, mean ± standard deviation (SD), range 35-80 years, body mass index (BMI) 31.0 ± 6.4 kg/m(2), range 18.5-55 kg/m(2)] participating in the Jackson Heart Study, a population-based study of African Americans, Jackson, Mississippi tricounty region, insulin resistance was defined by the upper quartile (≥4.43) of homeostasis model assessment of insulin resistance (HOMA-IR). An area under the receiver operating characteristic curve (AUC-ROC) of >0.70 was required for prediction of insulin resistance by TG/HDL-C. The optimal test cutoff was determined by the Youden index. HOMA-IR was similar in men and women (3.40 ± 2.03 vs. 3.80 ± 2.46, P = 0.60). Women had lower TG (94 ± 49 vs. 109 ± 65 mg/dL P Heart Study can help determine the efficacy of screening programs in African-Americans.

The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum

DEFF Research Database (Denmark)

Bruun-Rasmussen, M.; Møller, I.S.; Tulinius, G.

2007-01-01

to linkage group VI together with other Potyvirus resistances. One of these, sbm1, confers resistance to strains of Pea seedborne mosaic virus and previously has been identified as a mutant allele of the eukaryotic translation initiation factor 4E gene (eIF4E). Sequence comparison of eIF4E from BYMV...... was overcome, and virus from these plants had a codon change causing an Arg to His change at position 116 of the predicted viral genome-linked protein (VPg). Accordingly, plants carrying the wlv resistance gene were infected upon inoculation with BYMV-W derived from cDNA with a His codon at position 116...

Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing

Science.gov (United States)

Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun

2016-07-01

Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various

Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

Science.gov (United States)

Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

2014-02-18

Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU.

The germinlike protein GLP4 exhibits superoxide dismutase activity and is an important component of quantitative resistance in wheat and barley

DEFF Research Database (Denmark)

Christensen, Anders Bentsen; Thordal-Christensen, Hans; Zimmermann, Grit

2004-01-01

Germinlike proteins (GLP) are encoded in plants by a gene family with proposed functions in plant development and defense. Genes of GLP subfamily 4 of barley (HvGLP4, formerly referred to as HvOxOLP) and the wheat orthologue TaGLP4 (formerly referred to as TaGLP2a) were previously found...... overexpression of TaGLP4 and HvGLP4 enhanced resistance against B. graminis in wheat and barley, whereas transient silencing by RNA interference reduced basal resistance in both cereals. The effect of GLP4 overexpression or silencing was strongly influenced by the genotype of the plant. The data suggest...

Soybean and sunflower oil-induced insulin resistance correlates with impaired GLUT4 protein expression and translocation specifically in white adipose tissue.

Science.gov (United States)

Poletto, Ana Cláudia; Anhê, Gabriel Forato; Eichler, Paula; Takahashi, Hilton Kenji; Furuya, Daniela Tomie; Okamoto, Maristela Mitiko; Curi, Rui; Machado, Ubiratan Fabres

2010-03-01

Free fatty acids are known for playing a crucial role in the development of insulin resistance. High fat intake is known for impairing insulin sensitivity; however, the effect of vegetable-oil injections have never been investigated. The present study investigated the effects of daily subcutaneous injections (100 microL) of soybean (SB) and sunflower (SF) oils, during 7 days. Both treated groups developed insulin resistance as assessed by insulin tolerance test. The mechanism underlying the SB- and SF-induced insulin resistance was shown to involve GLUT4. In SB- and SF-treated animals, the GLUT4 protein expression was reduced approximately 20% and 10 min after an acute in vivo stimulus with insulin, the plasma membrane GLUT4 content was approximately 60% lower in white adipose tissue (WAT). No effects were observed in skeletal muscle. Additionally, both oil treatments increased mainly the content of palmitic acid ( approximately 150%) in WAT, which can contribute to explain the GLUT4 regulations. Altogether, the present study collects evidence that those oil treatments might generate insulin resistance by targeting GLUT4 expression and translocation specifically in WAT. These alterations are likely to be caused due to the specific local increase in saturated fatty acids that occurred as a consequence of oil daily injections. 2010 John Wiley & Sons, Ltd.

4-N-, 4-S-, and 4-O-chloroquine analogues: influence of side chain length and quinolyl nitrogen pKa on activity vs chloroquine resistant malaria.

Science.gov (United States)

Natarajan, Jayakumar K; Alumasa, John N; Yearick, Kimberly; Ekoue-Kovi, Kekeli A; Casabianca, Leah B; de Dios, Angel C; Wolf, Christian; Roepe, Paul D

2008-06-26

Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs mu-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.

Molecular Phylogenetics of Transmitted Drug Resistance in Newly Diagnosed HIV Type 1 Individuals in Denmark, a Nation-Wide Study

DEFF Research Database (Denmark)

Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

2011-01-01

Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown...... resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V...

Molecular phylogenetics of transmitted drug resistance in newly diagnosed HIV Type 1 individuals in Denmark: a nation-wide study

DEFF Research Database (Denmark)

Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

2011-01-01

Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown...... resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V...

Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance.

Science.gov (United States)

Niu, Qi-Wen; Lin, Shih-Shun; Reyes, Jose Luis; Chen, Kuan-Chun; Wu, Hui-Wen; Yeh, Shyi-Dong; Chua, Nam-Hai

2006-11-01

Plant microRNAs (miRNAs) regulate the abundance of target mRNAs by guiding their cleavage at the sequence complementary region. We have modified an Arabidopsis thaliana miR159 precursor to express artificial miRNAs (amiRNAs) targeting viral mRNA sequences encoding two gene silencing suppressors, P69 of turnip yellow mosaic virus (TYMV) and HC-Pro of turnip mosaic virus (TuMV). Production of these amiRNAs requires A. thaliana DICER-like protein 1. Transgenic A. thaliana plants expressing amiR-P69(159) and amiR-HC-Pro(159) are specifically resistant to TYMV and TuMV, respectively. Expression of amiR-TuCP(159) targeting TuMV coat protein sequences also confers specific TuMV resistance. However, transgenic plants that express both amiR-P69(159) and amiR-HC-Pro(159) from a dimeric pre-amiR-P69(159)/amiR-HC-Pro(159) transgene are resistant to both viruses. The virus resistance trait is displayed at the cell level and is hereditable. More important, the resistance trait is maintained at 15 degrees C, a temperature that compromises small interfering RNA-mediated gene silencing. The amiRNA-mediated approach should have broad applicability for engineering multiple virus resistance in crop plants.

Mir-1307 regulates cisplatin resistance by targeting Mdm4 in breast cancer expressing wild type P53.

Science.gov (United States)

Wang, Xinyan; Zhu, Jianwei

2018-04-26

Many chemotherapy regimens are used to treat breast cancer; however, breast cancer cells often develop drug resistance that usually leads to relapse and poor prognosis. MicroRNAs (miRNAs) are short non-coding RNA molecules that post-transcriptionally regulate gene expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. We investigated the roles of miRNAs in the development of drug resistance in human breast cancer cells. MiRNA expression was detected in human breast cancer cell lines MCF-7 and MDA-MB-468 via real time PCR; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, cell viability, colony formation, and luciferase reporter gene assays; Western blot; and immunohistochemistry. MiR-1307 was downregulated while MDM4 was upregulated in MCF-7/cisplatin (CDDP) and MDA-MB-468/CDDP cells compared with parental MCF-7 and MDA-MB-468 cells. in vitro drug sensitivity assay demonstrated that overexpression of miR-1307 sensitized MCF-7/CDDP cells to CDDP. Luciferase activity assay with a reporter containing sequences from the 3' untranslated region of Mdm4 in MCF-7/CDDP cells suggested that Mdm4 was the direct target gene of miR-1307. Ectopic miR-1307 expression reduced the MDM4 protein level and sensitized MCF-7/CDDP cells to CDDP-induced apoptosis. Our findings suggest, for the first time, that miR-1307 could play a role in the development of CDDP resistance in breast cancer, at least in part by modulating apoptosis by targeting Mdm4. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

Science.gov (United States)

Charoenphandhu, Narattaphol; Suntornsaratoon, Panan; Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Teerapornpuntakit, Jarinthorn; Aeimlapa, Ratchaneevan; Chattipakorn, Nipon; Chattipakorn, Siriporn

2018-02-02

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Cytochrome P450 CYP4DE1 and CYP6CW3v2 contribute to ethiprole resistance in Laodelphax striatellus (Fallén).

Science.gov (United States)

Elzaki, M E A; Zhang, W; Han, Z

2015-06-01

Laodelphax striatellus Fallén (Hemiptera: Delphacidae), a destructive pest of rice, has developed high resistance to multiple insecticides, threatening the success of pest management programmes. The present study investigated ethiprole resistance mechanisms in a field population that is highly resistant to ethiprole. That population was used to establish a laboratory population that was subjected to further selection to produce a resistant strain. Target genes were cloned and compared between the resistant and the susceptible strains, the role of detoxification enzymes was examined, and the relative expression levels of 71 detoxification enzyme genes were tested using quantitative real time (RT)-PCR. The laboratory selection enhanced the resistance from 107-fold to 180-fold. The Rdl-type target site mutation seldom occurred in the resistant strain and is unlikely to represent the major mechanism underlying the observed resistance. Of the three important detoxification enzymes, only P450 monooxygenase was found to be associated with ethiprole resistance. Moreover, two genes, CYP4DE1 and CYP6CW3v2, were found to be overexpressed in the resistant strain. Furthermore, gene-silencing via a double-stranded RNA feeding test was carried out, and the results showed that the mRNA levels of CYP4DE1 and CYP6CW3v2 were reduced in the resistant strain, whereas ethiprole susceptibility was increased. These results suggest that CYP4DE1 and CYP6CW3v2 play an important role in ethiprole resistance in L. striatellus. © 2015 The Royal Entomological Society.

Detection of resistance, cross-resistance, and stability of resistance to new chemistry insecticides in Bemisia tabaci (Homoptera: Aleyrodidae).

Science.gov (United States)

Basit, Muhammad; Saeed, Shafqat; Saleem, Mushtaq Ahmad; Denholm, Ian; Shah, Maqbool

2013-06-01

Resistance levels in whitefly, Bemisia tabaci (Gennadius) collections from cotton and sunflower (up to four districts) for five neonicotinoids and two insect growth regulators (IGRs) were investigated for two consecutive years. Based on the LC50(s), all collections showed slight to moderate levels of resistance for the tested insecticides compared with the laboratory susceptible population. The data also indicated that cotton and sunflower collections had similar resistance levels. In comparison (four collections), Vehari collections showed higher resistance for acetamiprid, thiacloprid, and nitenpyram compared with those of others. Average resistance ratios for acetamiprid, thiacloprid, and nitenpyram ranged from 5- to 13-, 4- to 8-, and 9- to 13-fold, respectively. Multan and Vehari collections also exhibited moderate levels (9- to 16-fold) of resistance to buprofezin. Furthermore, toxicity of neonicotinoids against immature stages was equal to that of insect growth regulators. The data also suggested that resistance in the field populations was stable. After selection for four generations with bifenthrin (G1 to G4), resistance to bifenthrin increased to 14-fold compared with the laboratory susceptible population. Selection also increased resistance to fenpropathrin, lambdacyhalothrin, imidacloprid, acetamiprid, and diafenthuron. Cross-resistance and stability of resistance in the field populations is of some concern. Rotation of insecticides having no cross-resistance and targeting the control against immature stages may control the resistant insects, simultaneously reducing the selection pressure imposed.

QTL list: RXopJ4 resistance locus [PGDBj Registered plant list, Marker list, QTL list, Plant DB link and Genome analysis methods[Archive

Lifescience Database Archive (English)

Full Text Available QT62244 Solanum lycopersicum Solanaceae RXopJ4 resistance locus resistance to bacterial spot... disease resistance to bacterial spot disease (Xanthomonas perforans (Xp)) 3 J350 ... Chr06 ... 10.1007/s00122-012-2004-6 23117718

Effect of Si/Ge ratio on resistivity and thermopower in Gd{sub 5}Si{sub x}Ge{sub 4-x} magnetocaloric compounds

Energy Technology Data Exchange (ETDEWEB)

Raj Kumar, D.M. [Defence Metallurgical Research Laboratory, Kanchanbagh, Hyderabad 500058 (India); Manivel Raja, M., E-mail: mraja@dmrl.drdo.i [Defence Metallurgical Research Laboratory, Kanchanbagh, Hyderabad 500058 (India); Prabahar, K.; Chandrasekaran, V. [Defence Metallurgical Research Laboratory, Kanchanbagh, Hyderabad 500058 (India); Poddar, Asok; Ranganathan, R. [Saha Institute of Nuclear Physics, Kolkata 700064 (India); Suresh, K.G. [Indian Institute of Technology Bombay, Mumbai 400076 (India)

2011-07-15

The effect of Si/Ge ratio on resistivity and thermopower behavior has been investigated in the magnetocaloric ferromagnetic Gd{sub 5}Si{sub x}Ge{sub 4-x} compounds with x=1.7-2.3. Microstructural studies reveal the presence of Gd{sub 5}(Si,Ge){sub 4}-matrix phase (5:4-type) along with traces of secondary phases (5:5 or 5:3-type). The x=1.7 and 2.0 samples display the presence of a first order structural transition from orthorhombic to monoclinic phase followed by a magnetic transition of the monoclinic phase. The alloys with x=2.2 and 2.3 display only magnetic transitions of the orthorhombic phase. A low temperature feature apparent in the AC susceptibility and resistivity data below 100 K reflects an antiferromagnetic transition of secondary phase(s) present in these compounds. The resistivity behavior study correlates with microstructural studies. A large change in thermopower of -8 {mu}V/K was obtained at the magneto-structural transition for the x=2 compound. - Research highlights: Effect of Si/Ge ratio on microstructure, magneto-structural transitions, resistivity ({rho}) and thermopower S(T) behaviour has been investigated in Gd{sub 5}Si{sub x}Ge{sub 4-x} compounds with x=1.7, 2.0, 2.2 and 2.3. Microstructural studies reveal the presence of a Gd{sub 5}(Si,Ge){sub 4} -matrix phase (5:4-type) along with traces of secondary phases (5:5 or 5:3-type). The resistivity behaviour has shown good correlation with the microstructural studies. A large change in thermopower of -8{mu}V/K was obtained at the magneto-structural transition for the x=2 compound. The resistivity and change in thermopower values were high for the alloys with Si/Ge ratio {<=}1 compared to that of the alloys with Si/Ge ratio >1.

17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

Science.gov (United States)

Wieten, R W; Goorhuis, A; Jonker, E F F; de Bree, G J; de Visser, A W; van Genderen, P J J; Remmerswaal, E B M; Ten Berge, I J M; Visser, L G; Grobusch, M P; van Leeuwen, E M M

2016-06-01

The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r = -0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

Science.gov (United States)

Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

2014-01-01

First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

Comment on "Compromised birth outcomes and infant mortality among racial and ethnic groups"

NARCIS (Netherlands)

Van der Veen, WJ

Frisbie, Forbes, and Pullum (1996) show that it is meaningful to account for low birth weight, preterm delivery, and intrauterine growth-retardation when analyzing differences in compromised birth outcomes and infant mortality among racial and ethnic groups. I compare their findings for the 1987

Safety Evaluations of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI

Directory of Open Access Journals (Sweden)

Min Jeong Kim

2018-05-01

Full Text Available Over the past decade, a variety of lactic acid bacteria have been commercially available to and steadily used by consumers. However, recent studies have shown that some lactic acid bacteria produce toxic substances and display properties of virulence. To establish safety guidelines for lactic acid bacteria, the Food and Agriculture Organization of the United Nations (FAO/World Health Organization (WHO has suggested that lactic acid bacteria be characterized and proven safe for consumers’ health via multiple experiments (e.g., antibiotic resistance, metabolic activity, toxin production, hemolytic activity, infectivity in immune-compromised animal species, human side effects, and adverse-outcome analyses. Among the lactic acid bacteria, Bifidobacterium and Lactobacillus species are probiotic strains that are most commonly commercially produced and actively studied. Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI have been used in global functional food markets (e.g., China, Germany, Jordan, Korea, Lithuania, New Zealand, Poland, Singapore, Thailand, Turkey, and Vietnam as nutraceutical ingredients for decades, without any adverse events. However, given that the safety of some newly screened probiotic species has recently been debated, it is crucial that the consumer safety of each commercially utilized strain be confirmed. Accordingly, this paper details a safety assessment of B. bifidum BGN4 and B. longum BORI via the assessment of ammonia production, hemolysis of blood cells, biogenic amine production, antimicrobial susceptibility pattern, antibiotic resistance gene transferability, PCR data on antibiotic resistance genes, mucin degradation, genome stability, and possession of virulence factors. These probiotic strains showed neither hemolytic activity nor mucin degradation activity, and they did not produce ammonia or biogenic amines (i.e., cadaverine, histamine or tyramine. B. bifidum BGN4 and B. longum BORI produced a small

A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

KAUST Repository

Sheen, Patricia

2017-10-11

Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.

A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

KAUST Repository

Sheen, Patricia; Requena, David; Gushiken, Eduardo; Gilman, Robert H.; Antiparra, Ricardo; Lucero, Bryan; Lizá rraga, Pilar; Cieza, Basilio; Roncal, Elisa; Grandjean, Louis; Pain, Arnab; McNerney, Ruth; Clark, Taane G.; Moore, David; Zimic, Mirko

2017-01-01

Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.

Morgellons: contested illness, diagnostic compromise and medicalisation.

Science.gov (United States)

Fair, Brian

2010-05-01

The case of Morgellons illustrates how the emergence of a new medically contested illness intersected with and impacted on the diagnostic processes of an existing uncontested psychiatric condition, Delusional Parasitosis (DP). More specifically, the sociopolitical processes at play in the contested illness, Morgellons, dubiously reflect patient empowerment, as well the resilience and power of medical jurisdiction. This research offers insights into the contested illness and medicalisation literatures, and aims to bridge these two approaches towards the relationship between patient empowerment and medical authority, which I do through the notion of doctor-patient compromise. The data for this research come from a comprehensive qualitative analysis of Morgellons discourse through four key sources: the pro-Morgellons website Morgellons.org; the anti-Morgellons website Morgellonswatch.com; the popular media's portrayal of Morgellons; and the DP and Morgellons articles published in peer-reviewed medical journals, as made available on PubMed.

Addressing diversity in schools through dialogue and compromise

DEFF Research Database (Denmark)

Olsen, Tore Vincents

2018-01-01

This article evaluates a decentralized Danish model for dealing with cultural and religious diversity at individual schools. This evaluation is based upon normative theories of toleration, recognition and domination and examines whether the model implies compromise with the (liberal) educational...... values stipulated in the national legislation. The model, reconstructed from government publications, is based on reaching accommodation through dialogue between school staff and parents/students, with the pragmatic aim of facilitating the participation of students in everyday school activities....... The model is noteworthy because it appears to break with the widespread ‘retreat from multiculturalism’ predicated on the defence of liberal values, and because properly dealing with diversity at schools is important for ensuring students’ well-being and academic success....

Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Yunshan Wang

2013-12-01

Full Text Available CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.

Electrical resistance oscillations during plastic deformation in A Ti-Al-Nb-Zr alloy at 4·2 K

Science.gov (United States)

Nikiforenko, V. N.; Lavrentev, F. F.

1986-10-01

The serrated plastic flow in titanium alloy containing 5% Al, 2·5% Zr and 2% Nb has been investigated by measuring its electrical resistance and applying selective chemical etching. The electrical resistance was found to oscillate under active deformation at 4·2 K. Analysis of the possible causes seems to indicate a dominant role of break by dislocation pile-ups through obstacles, viz second phase precipitates and grain boundaries.

The pepper Bs4C proteins are localized to the endoplasmic reticulum (ER) membrane and confer disease resistance to bacterial blight in transgenic rice.

Science.gov (United States)

Wang, Jun; Zeng, Xuan; Tian, Dongsheng; Yang, Xiaobei; Wang, Lanlan; Yin, Zhongchao

2018-03-30

Transcription activator-like effector (TALE)-dependent dominant disease resistance (R) genes in plants, also referred to as executor R genes, are induced on infection by phytopathogenic bacteria of the genus Xanthomonas harbouring the corresponding TALE genes. Unlike the traditional R proteins, the executor R proteins do not determine the resistance specificity and may function broadly in different plant species. The executor R gene Bs4C-R in the resistant genotype PI 235047 of the pepper species Capsicum pubescens (CpBs4C-R) confers disease resistance to Xanthomonas campestris pv. vesicatoria (Xcv) harbouring the TALE genes avrBsP/avrBs4. In this study, the synthetic genes of CpBs4C-R and two other Bs4C-like genes, the susceptible allele in the genotype PI585270 of C. pubescens (CpBs4C-S) and the CaBs4C-R homologue gene in the cultivar 'CM334' of Capsicum annum (CaBs4C), were characterized in tobacco (Nicotiana benthamiana) and rice (Oryza sativa). The Bs4C genes induced cell death in N. benthamiana. The functional Bs4C-eCFP fusion proteins were localized to the endoplasmic reticulum (ER) membrane in the leaf epidermal cells of N. benthamiana. The Xa10 promoter-Bs4C fusion genes in transgenic rice conferred strain-specific disease resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight in rice, and were specifically induced by the Xa10-incompatible Xoo strain PXO99 A (pHM1avrXa10). The results indicate that the Bs4C proteins from pepper species function broadly in rice and the Bs4C protein-mediated cell death from the ER is conserved between dicotyledonous and monocotyledonous plants, which can be utilized to engineer novel and enhanced disease resistance in heterologous plants. © 2018 TEMASEK LIFE SCIENCES LABORATORY. MOLECULAR PLANT PATHOLOGY © 2018 JOHN WILEY & SONS LTD.

A prospective 4-year study of insulin resistance and adipokines in morbidly obese diabetic and non-diabetic patients after gastric banding.

Science.gov (United States)

Urbanavicius, Vaidotas; Juodeikis, Zygimantas; Dzenkeviciute, Vilma; Galkine, Aiste; Petrulioniene, Zaneta; Sapoka, Virginijus; Brimiene, Vilma; Vitkus, Dalius; Brimas, Gintautas

2017-06-01

There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m 2 . A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance

DEFF Research Database (Denmark)

Emanuelli, Brice; Eberlé, Delphine; Suzuki, Ryo

2008-01-01

, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin...

Management and design of hospital pens relative to behavior of the compromised dairy cow: A questionnaire survey of Iowa dairy farms

DEFF Research Database (Denmark)

Fogsgaard, Katrine Kop; Herskin, Mette S.; Gorden, Patrick J.

2016-01-01

on best prac-tices for housing and management of compromised cows. The purpose of this study was to providedescriptive information about management and husbandry practices of compromised cows on dairyfarms in Iowa. A questionnaire-based survey was designed to examine demographic information, designand...

Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis

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Sun Zujun

2012-05-01

Full Text Available Abstract Background Toll-like receptor 4 (TLR4 is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS, a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC treatment. However, the mechanisms responsible for cisplatin resistance are not well understood. Results The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88 were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs. OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS. Conclusions Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.

Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance.

Science.gov (United States)

Huang, Chien-Ning; Wang, Chau-Jong; Yang, Yi-Sun; Lin, Chih-Li; Peng, Chiung-Huei

2016-01-01

Diabetic nephropathy has a significant socioeconomic impact, but its mechanism is unclear and needs to be examined. Hibiscus sabdariffa polyphenols (HPE) inhibited high glucose-induced angiotensin II receptor-1 (AT-1), thus attenuating renal epithelial mesenchymal transition (EMT). Recently, we reported HPE inhibited dipeptidyl-peptidase-4 (DPP-4, the enzyme degrades type 1 glucagon-like peptide (GLP-1)), which mediated insulin resistance signals leading to EMT. Since free fatty acids can realistically bring about insulin resistance, using the palmitate-stimulated cell model in contrast with type 2 diabetic rats, in this study we examined if insulin resistance causes renal EMT, and the preventive effect of HPE. Our findings reveal that palmitate hindered 30% of glucose uptake. Treatment with 1 mg mL(-1) of HPE and the DPP-4 inhibitor linagliptin completely recovered insulin sensitivity and palmitate-induced signal cascades. HPE inhibited DPP-4 activity without altering the levels of DPP-4 and the GLP-1 receptor (GLP-1R). HPE decreased palmitate-induced phosphorylation of Ser307 of insulin receptor substrate-1 (pIRS-1 (S307)), AT-1 and vimentin, while increasing phosphorylation of phosphatidylinositol 3-kinase (pPI3K). IRS-1 knockdown revealed its essential role in mediating downstream AT-1 and EMT. In type 2 diabetic rats, it suggests that HPE concomitantly decreased the protein levels of DPP-4, AT-1, vimentin, and fibronectin, but reversed the in vivo compensation of GLP-1R. In conclusion, HPE improves insulin sensitivity by attenuating DPP-4 and the downstream signals, thus decreasing AT-1-mediated tubular-interstitial EMT. HPE could be an adjuvant to prevent diabetic nephropathy.

Relationship between Lower Tendency to Deceive in Aging and Inhibitory Compromise.

Science.gov (United States)

El Haj, Mohamad; Antoine, Pascal

2018-01-01

Deception can be associated with a heterogeneous network of concepts such as exaggeration, misleading, white lies, and faking. This paper assesses the tendency to deceive in aging. Our main aim was to assess whether older adults would demonstrate a low tendency to deceive. A total of 42 older adults (mean age 67.64 years, SD 7.87) and 45 younger adults (mean age 21.71 years, SD 2.66) were administered a deception scale including items such as "I sometimes tell lies if I have to" or "I never take things that don't belong to me." Participants were also administered an inhibition task. The results demonstrated a low tendency to deceive and low inhibition in older adults compared with younger ones. The low tendency to deceive in the older adults was significantly correlated with their diminished inhibitory ability. The low tendency to deceive in aging seems to be related to a difficulty in inhibiting an honest response. Since inhibitory compromise has been considered mainly to trigger negative consequences for cognition, the present paper illustrates how this age-related compromise can be associated with positive social outcomes, i.e., a low tendency to deceive. © 2017 S. Karger AG, Basel.

Characterization of gadolinium oxide thin films with CF{sub 4} plasma treatment for resistive switching memory applications

Energy Technology Data Exchange (ETDEWEB)

Wang, Jer-Chyi, E-mail: jcwang@mail.cgu.edu.tw [Department of Electronic Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan 333, Tao-Yuan, Taiwan (China); Ye, Yu-Ren [Department of Electronic Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan 333, Tao-Yuan, Taiwan (China); Lai, Chao-Sung, E-mail: cslai@mail.cgu.edu.tw [Department of Electronic Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan 333, Tao-Yuan, Taiwan (China); Lin, Chih-Ting [Department of Electronic Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan 333, Tao-Yuan, Taiwan (China); Lu, Hsin-Chun [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-Shan 333, Tao-Yuan, Taiwan (China); Wu, Chih-I [Graduated Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 106, Taiwan (China); Department of Electrical Engineering, National Taiwan University, Taipei 106, Taiwan (China); Wang, Po-Sheng [Graduated Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 106, Taiwan (China)

2013-07-01

The effect of the CF{sub 4} plasma treatment on the gadolinium oxide (Gd{sub x}O{sub y}) thin films for the resistive random access memory (RRAM) applications was investigated. The material properties of the fluorine incorporated Gd{sub x}O{sub y} films were analyzed by the X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS) and ultraviolet–visible spectroscopy (UV–VIS). Further, the set and reset voltages of the Pt/Gd{sub x}O{sub y}/W RRAM devices with the CF{sub 4} plasma treatment were effectively reduced to −1.15 and 2.1 V respectively owing to the low Schottky barrier height. The formation of Gd-F bonds can prevent the oxygen atoms from out-diffusing through Pt grain boundaries into the atmosphere, leading to the superior retention characteristics for over 10{sup 4} s. The CF{sub 4} plasma treated Gd{sub x}O{sub y} RRAMs can sustain a resistance ratio of 10{sup 2} for more than 800 times stable set/reset cycling, suitable for future low-voltage and high-performance nonvolatile memory operation.

Interaction of 2,4-D or Dicamba with Glufosinate for Control of Glyphosate-Resistant Giant Ragweed (Ambrosia trifida L. in Glufosinate-Resistant Maize (Zea mays L.

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Zahoor A. Ganie

2017-07-01

Full Text Available Glyphosate-resistant (GR giant ragweed is a problematic broadleaf weed in crops including maize and soybean in the Midwestern United States. Commercialization of crops with 2,4-D or dicamba and glufosinate resistance will allow post-emergence (POST applications of these herbicides. Therefore, information is needed on how 2,4-D/dicamba will interact with glufosinate in various rate combinations. The objectives of this study were to evaluate the interaction of glufosinate plus 2,4-D and/or dicamba for control of GR giant ragweed, and to determine their effect on GR giant ragweed density, biomass, maize injury, and yield. Field experiments were conducted in 2013 and 2014 in a field infested with GR giant ragweed in Nebraska, United States. The treatments included POST applications of glufosinate (450 or 590 g ai ha-1, 2,4-D, or dicamba at 280 or 560 g ae ha-1 applied alone and in tank-mixtures in glufosinate-resistant maize. The results showed that dicamba applied alone resulted in 56 to 62% and 73 to 83% control at 14 and 28 days after treatment (DAT, respectively, and ≥95% control at 60 DAT or at harvest compared to 17 to 30% and 57 to 73% control with 2,4-D applied alone at 280 and 560 g ai ha-1, respectively. Glufosinate tank-mixed with 2,4-D and/or dicamba consistently provided ≥89% control of GR giant ragweed, except that control with glufosinate plus 2,4-D varied from 80 to 92% at 60 DAT and at harvest. The comparison between the observed and expected control (determined by Colby’s equation suggested an additive interaction between glufosinate and 2,4-D or dicamba for control of GR giant ragweed. Contrast analysis also indicated that GR giant ragweed control with glufosinate plus 2,4-D or dicamba was either consistently higher or comparable with individual herbicides excluding 2,4-D applied alone. Herbicide programs, excluding 2,4-D at 280 g ae ha-1, resulted in ≥80% reduction in GR giant ragweed density. Tank-mixing glufosinate with

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

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Wang, Ruoxing [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States); Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States)

2012-10-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

International Nuclear Information System (INIS)

Wang, Ruoxing; Guo, Yan-Lin

2012-01-01

Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: ► Inhibition of Cdks slows down mESCs proliferation. ► mESCs display remarkable recovery capacity from short-term cell cycle interruption. ► Short-term cell cycle interruption does not compromise mESC self-renewal. ► Oct4 and Nanog are up-regulated via de novo synthesis by cell cycle interruption.

Control of glyphosate resistant hairy fleabane (Conyza bonariensis with dicamba and 2,4-D Controle de buva (Conyza bonariensis resistente ao glyphosate com dicamba e 2,4-D

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D.J. Soares

2012-06-01

Full Text Available Auxyn type herbicides such as dicamba and 2,4-D are alternative herbicides that can be used to control glyphosate-resistant hairy fleabane. With the forthcoming possibility of releasing dicamba-resistant and 2,4-D-resistant crops, use of these growth regulator herbicides will likely be an alternative that can be applied to the control of glyphosate resistant hairy fleabane (Conyza bonariensis. The objective of this research was to model the efficacy, through dose-response curves, of glyphosate, 2,4-D, isolated dicamba and glyphosatedicamba combinations to control a brazilian hairy fleabane population resistant to glyphosate. The greenhouse dose-response studies were conducted as a completely randomized experimental design, and the rates used for dose response curve construction were 0, 120, 240, 480, 720 and 960 g a.i. ha-1 for 2,4-D, dicamba and the dicamba combination, with glyphosate at 540 g a.e. ha-1. The rates for glyphosate alone were 0, 180, 360, 540, 720 and 960 g a.e. ha-1. Herbicides were applied when the plants were in a vegetative stage with 10 to 12 leaves and height between 12 and 15 cm. Hairy fleabane had low sensitivity to glyphosate, with poor control even at the 960 g a.e. ha-1 rate. Dicamba and 2,4-D were effective in controlling the studied hairy fleabane. Hairy fleabane responds differently to 2,4-D and dicamba. The combination of glyphosate and dicamba was not antagonistic to hairy fleabane control, and glyphosate may cause an additive effect on the control, despite the population resistance.Os herbicidas mimetizadores de auxinas como dicamba e 2,4-D são alternativas para o controle de buva resistente ao glyphosate. Com a possível futura liberação comercial de culturas resistentes ao dicamba e 2,4-D, a aplicação destes herbicidas reguladores de crescimento será uma provável alternativa de controle de buva resistente ao glyphosate. O objetivo desta pesquisa foi modelar por meio de curvas de dose-resposta a efic

In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection.

Science.gov (United States)

Giacobbi, Nicholas S; Sluis-Cremer, Nicolas

2017-07-01

Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the activity of DPV and MIV-150 is compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C. Copyright © 2017 American Society for Microbiology.

Political crisіs and compromise as the casual determinants in the process of political decisions making

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Shkuro Anton Sergiyovich

2013-12-01

Full Text Available There is a risk of certain ineffective results in the system of political decisions making. That’s why we should pay a special attention to the criteria of political crisis evaluation. Today the problem of national politics lies only in an adequate raising of questions about the way out of the political crisis using the mechanism of compromise achieving. The article is about the fundamental role of the crisis and the compromise and about their influence on the formation of the strategic development of policy.

Compromised Cerebral Blood Flow(CBF) in Congestive Heart Failure (CHB): non-invasive quantification with {sup 99m}Tc-ECD radionuclide angiography

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Seung; Kim, Jae Joong; Lim, Ki Chun; Lee, Hee Kyung; Moon, Dae Hyuk [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2002-07-01

Recent reports revealed that cerebral metabolism in CHF was abnormally deranged and proposed as a potential marker of disease severity. Since deranged cerebral metabolism in CHF may result from compromised cerebral perfusion, quantification of CHF may be useful for accurate risk stratification of CHF. Therefore, we investigated whether CHF in patients with CHF is compromised and correlated with clinical parameters. Fifteen patients (M/F:11/5, 45{+-}9yr) with CHF (LVEF<40%) and 7 healthy controls (M/F:5/2, 41{+-}8yr) were prospectively studied. All patients underwent radionuclide angiography including cerebral hemispheres and aortic arch using {sup 99m}Tc-ECD. Global CBF was measured non-invasively by the application of Patlak graphical plot analysis. All patients were also evaluated using a standardized protocol that included echocardiography and clinical evaluation. Global CBF (40.3{+-}5.2 ml/min/100g) of the patients with CHF were significantly lower than those (49.7{+-}2.4 ml/min/100g) of controls (p<0.01). Global CBF were correlated with NYHA functional class (r=-0.617, p=0.43), but not correlated with other clinical parameters such as age (r=-0.463, p=0.082), duration (r=0.237, p>0.1), systolic BP (r=-0.063, p>0.5), LVEF (r=-0.13, p>0.1), LV dimension(r=0.139, p>0.5), and PV pressure gradients (r=0.072, p>0.5). Cerebral perfusion of the patients with CHF was compromised and not correlated with cardiopulmonary hemodynamic parameters.

Using Resurrected Ancestral Proviral Proteins to Engineer Virus Resistance

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Asunción Delgado

2017-05-01

Full Text Available Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation such as cellular entry and replication. Pathogens and their hosts co-evolve. It follows that replacing a proviral factor with a functional ancestral form of the same protein could prevent viral propagation without fatally compromising organismal fitness. Here, we provide proof of concept of this notion. Thioredoxins serve as general oxidoreductases in all known cells. We report that several laboratory resurrections of Precambrian thioredoxins display substantial levels of functionality within Escherichia coli. Unlike E. coli thioredoxin, however, these ancestral thioredoxins are not efficiently recruited by the bacteriophage T7 for its replisome and therefore prevent phage propagation in E. coli. These results suggest an approach to the engineering of virus resistance. Diseases caused by viruses may have a devastating effect in agriculture. We discuss how the suggested approach could be applied to the engineering of plant virus resistance.

HIV-1 drug resistance prevalence, drug susceptibility and variant characterization in the Jacobi Medical Center paediatric cohort, Bronx, NY, USA.

Science.gov (United States)

de Mulder, M; York, V A; Wiznia, A A; Michaud, H A; Nixon, D F; Holguin, A; Rosenberg, M G

2014-03-01

With the advent of combined antiretroviral therapy (cART), perinatally HIV-infected children are surviving into adolescence and beyond. However, drug resistance mutations (DRMs) compromise viral control, affecting the long-term effectiveness of ART. The aims of this study were to detect and identify DRMs in a HIV-1 infected paediatric cohort. Paired plasma and dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected patients attending the Jacobi Medical Center, New York, USA. Clinical, virological and immunological data for these patients were analysed. HIV-1 pol sequences were generated from samples to identify DRMs according to the International AIDS Society (IAS) 2011 list. Forty-seven perinatally infected patients were selected, with a median age of 17.7 years, of whom 97.4% were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL and a mean CD4 count of 486 cells/μL at the time of sampling. Nineteen patients (40.4%) had achieved undetectable viraemia (40.5% had a CD4 count of > 500 cells/μL. Most of the patients (97.9%) had received cART, including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs to at least one drug class and 5.4% were triple resistant. The mean nucleotide similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were detected in plasma and 26 in DBSs, with 23 present in both. Although more perinatally HIV-1-infected children are reaching adulthood as a result of advances in cART, our study cohort presented a high prevalence of resistant viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM detection. © 2013 British HIV Association.

Effects of temephos resistance on life history traits of Aedes albopictus (Skuse (Diptera: Culicidae, a vector of arboviruses

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Junaid Rahim

2017-10-01

Full Text Available The effects of temephos resistance on the fitness cost of the wild populations of Aedes albopictus was evaluated. The larvae of two wild populations were exposed to the diagnostic dose of 0.02 mg and 0.012 mg/L. The larvae which survived after the 24 h exposure to diagnostic dose were considered as resistant and F1 generations were chosen for the comparisons of fitness parameters with the control strain, which includes larval developmental time, adult longevity, fecundity, wing length and hatchability. We found that temephos resistance had negative effects on larval developmental time which was longer for Gelugor strain among the populations with the median range of 10 days and a shorter longevity was observed with the median range of 13 days for males and 16 days for females. Whereas, an effective reduction of 29.8 and 38.6% was observed in fertility and fecundity of Gelugor strain as compared to control strain. In contrast, no clear differences were found in biological parameters of Balik Palau and USM strain, except fecundity and fertility with a reduction of 13.4 and 15.5%, respectively. Whereas, no significant differences were seen in the wing size between the populations with the mean length (mm of 2.40 for Gelugor, 2.44 for Balik Palau and 2.46 for USM control (p > 0.05. Present results indicated that the temephos resistance is associated with the developmental and reproduction potential of resistant population of A. albopictus and the fitness has been compromised. Keywords: Temephos, Insecticides resistance, Fitness cost, Aedes albopictus, Dengue

Seleção de linhagens de feijoeiro com tipo de grão carioca e com os alelos co-4 e co-5 de resistência à antracnose Selection of common bean strains with carioca grain type, and with the alleles co-4 and co-5 for anthracnose resistance

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Eduardo Henrique Keller Marcondes

2010-08-01

Full Text Available Objetivou-se, neste trabalho, identificar linhagens de feijão que reúnam, além da resistência à antracnose, alta produtividade de grãos do tipo carioca e resistência à mancha angular. Foram utilizadas 194 linhagens F5:6 extraídas de sete famílias segregantes, selecionadas do cruzamento entre os genitores H147 e B1. A linhagem H147 possui grãos tipo carioca, portadora do alelo Co-5, que confere resistência a várias raças de Colletotrichum lindemuthianum. A linhagem B1 também possui grãos tipo carioca e é portadora do alelo Co-4, que confere resistência a outro grupo de raças do mesmo patógeno. As linhagens foram avaliadas na safra das águas 2005/2006, em Lavras, com a cultivar Talismã e H147 como testemunhas, com base na produtividade e tipo de grãos. Foram selecionadas 99 linhagens, as quais foram avaliadas na safra da seca/2006, juntamente com a testemunha Talismã, com base na produtividade, tipo de grão e resistência à mancha angular. Dessas 99 linhagens, foram selecionadas 24, as quais foram avaliadas na safra de inverno/2006 em Lavras e Lambari, com base no tipo de grão e produtividade. Essas 24 linhagens foram inoculadas com a raça 321 de C. lindemuthianum, que quebra a resistência conferida pelo alelo Co-4, mas não o Co-5. Para verificar a presença do alelo Co4 foi utilizado um marcador SCAR que amplifica um fragmento de 950 pb por meio do primer SAS 13. Foi possível identificar 14 linhagens que possuem a pirâmide de alelos Co-4/Co-5 e entre elas, quatro destacaram-se em todos os caracteres avaliados.The objective of the research was to identify bean strains that possess at the same time resistance to anthracnose, high grain yield of Carioca grain type and resistance to angular leaf spot. 194 strains F5:6 were taken from seven segregating families derived from the cross H147 x B1. The H147 line has Carioca grain type and Co-5 resistance allele to several races of C. lindemuthianum. The B1 line also has the

Altered cultivar resistance of kimchi cabbage seedlings mediated by salicylic Acid, jasmonic Acid and ethylene.

Science.gov (United States)

Lee, Young Hee; Kim, Sang Hee; Yun, Byung-Wook; Hong, Jeum Kyu

2014-09-01

Two cultivars Buram-3-ho (susceptible) and CR-Hagwang (moderate resistant) of kimchi cabbage seedlings showed differential defense responses to anthracnose (Colletotrichum higginsianum), black spot (Alternaria brassicicola) and black rot (Xanthomonas campestris pv. campestris, Xcc) diseases in our previous study. Defense-related hormones salicylic acid (SA), jasmonic acid (JA) and ethylene led to different transcriptional regulation of pathogenesis-related (PR) gene expression in both cultivars. In this study, exogenous application of SA suppressed basal defenses to C. higginsianum in the 1st leaves of the susceptible cultivar and cultivar resistance of the 2nd leaves of the resistant cultivar. SA also enhanced susceptibility of the susceptible cultivar to A. brassicicola. By contrast, SA elevated disease resistance to Xcc in the resistant cultivar, but not in the susceptible cultivar. Methyl jasmonate (MJ) treatment did not affect the disease resistance to C. higginsianum and Xcc in either cultivar, but it compromised the disease resistance to A. brassicicola in the resistant cultivar. Treatment with 1-aminocyclopropane-1-carboxylic acid (ACC) ethylene precursor did not change resistance of the either cultivar to C. higginsianum and Xcc. Effect of ACC pretreatment on the resistance to A. brassicicola was not distinguished between susceptible and resistant cultivars, because cultivar resistance of the resistant cultivar was lost by prolonged moist dark conditions. Taken together, exogenously applied SA, JA and ethylene altered defense signaling crosstalk to three diseases of anthracnose, black spot and black rot in a cultivar-dependent manner.

Altered Cultivar Resistance of Kimchi Cabbage Seedlings Mediated by Salicylic Acid, Jasmonic Acid and Ethylene

Directory of Open Access Journals (Sweden)

Young Hee Lee

2014-09-01

Full Text Available Two cultivars Buram-3-ho (susceptible and CR-Hagwang (moderate resistant of kimchi cabbage seedlings showed differential defense responses to anthracnose (Colletotrichum higginsianum, black spot (Alternaria brassicicola and black rot (Xanthomonas campestris pv. campestris, Xcc diseases in our previous study. Defense-related hormones salicylic acid (SA, jasmonic acid (JA and ethylene led to different transcriptional regulation of pathogenesis-related (PR gene expression in both cultivars. In this study, exogenous application of SA suppressed basal defenses to C. higginsianum in the 1st leaves of the susceptible cultivar and cultivar resistance of the 2nd leaves of the resistant cultivar. SA also enhanced susceptibility of the susceptible cultivar to A. brassicicola. By contrast, SA elevated disease resistance to Xcc in the resistant cultivar, but not in the susceptible cultivar. Methyl jasmonate (MJ treatment did not affect the disease resistance to C. higginsianum and Xcc in either cultivar, but it compromised the disease resistance to A. brassicicola in the resistant cultivar. Treatment with 1-aminocyclopropane-1-carboxylic acid (ACC ethylene precursor did not change resistance of the either cultivar to C. higginsianum and Xcc. Effect of ACC pretreatment on the resistance to A. brassicicola was not distinguished between susceptible and resistant cultivars, because cultivar resistance of the resistant cultivar was lost by prolonged moist dark conditions. Taken together, exogenously applied SA, JA and ethylene altered defense signaling crosstalk to three diseases of anthracnose, black spot and black rot in a cultivar-dependent manner.

The Relationship of Fetuin-A, Adiponectin, Retinol Binding Protein-4 (RBP-4 and High Sensitivity C-Reactive Protein (hsCRP with Insulin Resistance (HOMA-IR in Obese Non Diabetic Men

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Imelda Novianti

2012-04-01

Full Text Available BACKGROUND: Central obesity is the accumulation of visceral (intra-abdominal fat and is strongly known to be associated with insulin resistance and type 2 diabetes mellitus (T2DM. Obesity can cause adipocyte hypertrophy that results in dysregulation of adipokine expression. The abnormal function of adipocytes may play an important role in the development of a chronic low-grade proinflammatory state associated with obesity. Adiponectin, retinol binding protein (RBP-4 and fetuin-A play a role in the pathophysiology of insulin resistance. Expression of fetuin-A is increased due to fat accumulation in the liver. Elevated concentration of fetuin-A in the circulation can impair insulin signaling in muscle and liver as well as suppress adiponectin secretion, although its molecular mechanism is still unclear. The aim of this study was to identify the relationship of fetuin-A, adiponectin, RBP-4 and hsCRP with insulin resistance in obese non diabetic men. METHODS: This was an observational study with a cross-sectional design. The study subjects were 64 men with non diabetic abdominal obesity, characterized by waist circumference of 98.47±5.88 cm and fasting blood glucose of 85.75±8.36 mg/dL. RESULTS: This study showed that fetuin-A was positively correlated with HOMA-IR in obese non diabetic men with insulin resistance (r=0.128; p=0.570, although not significant. Fetuin-A was found to be correlated with adiponectin, RBP-4 and hsCRP (r=0.150; p=0.233; r=0.050; p=0.711; r=-0.04; p=0.445, although not significant. CONCLUSIONS: The concentration of fetuin-A showed a tendency to be positively correlated with HOMA-IR and with RBP-4 in obese non diabetic men, although statistically not significant. The concentration of fetuin-A showed a tendency to be negatively correlated with adiponectin and hsCRP although statistically not significant. There was no interrelationship between fetuin-A, adiponectin, RBP-4, hsCRP and HOMA-IR. Elevated concentrations of fetuin

Proteomics of drug resistance in Candida glabrata biofilms.

Science.gov (United States)

Seneviratne, C Jayampath; Wang, Yu; Jin, Lijian; Abiko, Y; Samaranayake, Lakshman P

2010-04-01

Candida glabrata is a fungal pathogen that causes a variety of mucosal and systemic infections among compromised patient populations with higher mortality rates. Previous studies have shown that biofilm mode of the growth of the fungus is highly resistant to antifungal agents compared with the free-floating or planktonic mode of growth. Therefore, in the present study, we used 2-D DIGE to evaluate the differential proteomic profiles of C. glabrata under planktonic and biofilm modes of growth. Candida glabrata biofilms were developed on polystyrene surfaces and age-matched planktonic cultures were obtained in parallel. Initially, biofilm architecture, viability, and antifungal susceptibility were evaluated. Differentially expressed proteins more than 1.5-fold in DIGE analysis were subjected to MS/MS. The transcriptomic regulation of these biomarkers was evaluated by quantitative real-time PCR. Candida glabrata biofilms were highly resistant to the antifungals and biocides compared with the planktonic mode of growth. Candida glabrata biofilm proteome when compared with its planktonic proteome showed upregulation of stress response proteins, while glycolysis enzymes were downregulated. Similar trend could be observed at transcriptomic level. In conclusion, C. glabrata biofilms possess higher amount of stress response proteins, which may potentially contribute to the higher antifungal resistance seen in C. glabrata biofilms.

High-performance 4H-SiC junction barrier Schottky diodes with double resistive termination extensions

International Nuclear Information System (INIS)

Zheng Liu; Zhang Feng; Liu Sheng-Bei; Dong Lin; Liu Xing-Fang; Liu Bin; Yan Guo-Guo; Wang Lei; Zhao Wan-Shun; Sun Guo-Sheng; He Zhi; Fan Zhong-Chao; Yang Fu-Hua

2013-01-01

4H-SiC junction barrier Schottky (JBS) diodes with a high-temperature annealed resistive termination extension (HARTE) are designed, fabricated and characterized in this work. The differential specific on-state resistance of the device is as low as 3.64 mΩ·cm 2 with a total active area of 2.46 × 10 −3 cm 2 . Ti is the Schottky contact metal with a Schottky barrier height of 1.08 V and a low onset voltage of 0.7 V. The ideality factor is calculated to be 1.06. Al implantation annealing is performed at 1250°C in Ar, while good reverse characteristics are achieved. The maximum breakdown voltage is 1000 V with a leakage current of 9 × 10 −5 A on chip level. These experimental results show good consistence with the simulation results and demonstrate that high-performance 4H-SiC JBS diodes can be obtained based on the double HARTE structure. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice

OpenAIRE

Chen, Baoan; Cheng, Jian; Wu, Yanan; Gao, Feng; Xu, Wenlin; Shen, Huilin; Ding, Jiahua; Gao, Chong; Sun, Qian; Sun, Xinchen; Cheng, Hongyan; Li, Guohong; Chen, Wenji; Chen, Ningna; Liu, Lijie

2009-01-01

In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe3O4 (MNP-Fe3O4) combined with daunorubicin (DNR) in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 × 107 cells/each) respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice w...

Corrosion resistance characteristics of a Ti-6Al-4V alloy scaffold that is fabricated by electron beam melting and selective laser melting for implantation in vivo

Energy Technology Data Exchange (ETDEWEB)

Zhao, Bingjing; Wang, Hong [Department of Stomatology, General Hospital of the PLA, Beijing (China); Department of Stomatology, The Second Affiliated Stomatological Hospital of Liaoning Medical University (China); Qiao, Ning [College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing (China); Wang, Chao [School of Medicine, Nankai University, Tianjin 300071 (China); Hu, Min, E-mail: humin48@vip.163.com [Department of Stomatology, General Hospital of the PLA, Beijing (China)

2017-01-01

The purpose of this study is to determine the corrosion resistance of Ti-6Al-4V alloy fabricated with electron beam melting and selective laser melting for implantation in vivo. Ti-6Al-4V alloy specimens were fabricated with electron beam melting (EBM) and selective laser melting (SLM). A wrought form of Ti-6Al-4V alloy was used as a control. Surface morphology observation, component analysis, corrosion resistance experimental results, electrochemical impedance spectroscopy, crevice corrosion resistance experimental results, immersion test and metal ions precipitation analysis were processed, respectively. The thermal stability of EBM specimen was the worst, based on the result of open circuit potential (OCP) result. The result of electrochemical impedance spectroscopy indicated that the corrosion resistance of the SLM specimen was the best under the low electric potential. The result of potentiodynamic polarization suggested that the corrosion resistance of the SLM specimen was the best under the low electric potential (< 1.5 V) and EBM specimen was the best under the high electric potential (> 1.5 V).The crevice corrosion resistance of the EBM specimen was the best. The corrosion resistance of SLM specimen was the best, based on the result of immersion test. The content of Ti, Al and V ions of EBM, SLM and wrought specimens was very low. In general, the scaffolds that were fabricated with EBM and SLM had good corrosion resistance, and were suitable for implantation in vivo. - Highlights: • EBM and SLM Ti-6Al-4V alloy have good corrosion resistance, and both of them can be applied in vivo. • SLM Ti-6Al-4V alloy was more suitable for implantation in vivo than that of EBM Ti-6Al-4V alloy. • The crevice corrosion resistance of the EBM specimen is the best. • EBM and SLM specimens can form oxide film.

Constraining the brachial plexus does not compromise regional control in oropharyngeal carcinoma

International Nuclear Information System (INIS)

Robert, Mutter W; Wolden, Suzanne L; Lee, Nancy Y; Lok, Benjamin H; Dutta, Pinaki R; Riaz, Nadeem; Setton, Jeremy; Berry, Sean L; Goenka, Anuj; Zhang, Zhigang; Rao, Shyam S

2013-01-01

Accumulating evidence suggests that brachial plexopathy following head and neck cancer radiotherapy may be underreported and that this toxicity is associated with a dose–response. Our purpose was to determine whether the dose to the brachial plexus (BP) can be constrained, without compromising regional control. The radiation plans of 324 patients with oropharyngeal carcinoma (OPC) treated with intensity-modulated radiation therapy (IMRT) were reviewed. We identified 42 patients (13%) with gross nodal disease <1 cm from the BP. Normal tissue constraints included a maximum dose of 66 Gy and a D 05 of 60 Gy for the BP. These criteria took precedence over planning target volume (PTV) coverage of nodal disease near the BP. There was only one regional failure in the vicinity of the BP, salvaged with neck dissection (ND) and regional re-irradiation. There have been no reported episodes of brachial plexopathy to date. In combined-modality therapy, including ND as salvage, regional control did not appear to be compromised by constraining the dose to the BP. This approach may improve the therapeutic ratio by reducing the long-term risk of brachial plexopathy

Food insecure student clients of a university-based food bank have compromised health, dietary intake and academic quality.

Science.gov (United States)

Farahbakhsh, Jasmine; Hanbazaza, Mahitab; Ball, Geoff D C; Farmer, Anna P; Maximova, Katerina; Willows, Noreen D

2017-02-01

University and college students in wealthy countries may be vulnerable to financial food insecurity. If food insecure students have suboptimal health, their ability to learn and excel in their education could be compromised. This Canadian study examined the relationship of food security status to diet and self-perceived health and academic quality among students receiving emergency food hampers from the Campus Food Bank at University of Alberta. A convenience sample of 58 students completed a survey. Of participating students, 10.3% were food secure, 44.8% were moderately food insecure and 44.8% were severely food insecure. Overall, 32.8% rated their general health as fair/poor, 27.6% rated their mental health as fair/poor and 60.3% indicated at least one adverse academic outcome of not having enough money for food. Compared to other participating students, students with severe food insecurity had a greater likelihood of fair/poor general health (odds ratios (OR) 4.03, 95% confidence intervals (CI) 1.10-14.78); fair/poor mental health (OR 4.96, 95% CI 1.28-19.19); being unable to concentrate in class or during an exam (73.1% vs 40.6%, χ 2 = 6.12, P = 0.013); relying on food hampers (34.6% vs 9.7%, χ 2 = 5.57, P = 0.018); and, consuming fewer daily fruits, vegetables and legumes (2.12 vs 2.97 cup equivalents, P = 0.009). Food insecurity compromises students' health, diet and academic quality. Campus food banks are not the solution to student hunger. Governmental and university-based programmes and policies are needed to improve the food security situation of university students. © 2016 Dietitians Association of Australia.

Effect of physiological age on radiation resistance of some bacteria that are highly radiation resistant

International Nuclear Information System (INIS)

Keller, L.C.; Maxcy, R.B.

1984-01-01

Physiological age-dependent variation in radiation resistance was studied for three bacteria that are highly radiation resistant: Micrococcus radiodurans, Micrococcus sp. isolate C-3, and Moraxella sp. isolate 4. Stationary-phase cultures of M. radiodurans and isolate C-3 were much more resistant to gamma radiation than were log-phase cultures. This pattern of relative resistance was reversed for isolate 4. Resistance of isolate 4 to UV light was also greater during log phase, although heat resistance and NaCl tolerance after heat stresses were greater during stationary phase. Radiation-induced injury of isolate 4 compared with injury of Escherichia coli B suggested that the injury process, as well as the lethal process, was affected by growth phase. The hypothesis that growth rate affects radiation resistance was tested, and results were interpreted in light of the probable confounding effect of methods used to alter growth rates of bacteria. These results indicate that dose-response experiments should be designed to measure survival during the most resistant growth phase of the organism under study. The timing is particularly important when extrapolations of survival results might be made to potential irradiation processes for foods. 17 references

3-Aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione for circumvention of anticancer drug resistance.

Science.gov (United States)

Shchekotikhin, Andrey E; Shtil, Alexander A; Luzikov, Yuri N; Bobrysheva, Tatyana V; Buyanov, Vladimir N; Preobrazhenskaya, Maria N

2005-03-15

A series of 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione was synthesized by Mannich reaction or by the transamination of 3-dimethylaminomethyl 4,11-dihydroxy- or 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione. The potency of novel derivatives was tested on a National Cancer Institute panel of 60 human tumor cell lines as well as in cells with genetically defined determinants of cytotoxic drug resistance, P-glycoprotein (Pgp) expression, and p53 inactivation. Mannich derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione with an additional amino function in their side chain, demonstrated equal cytotoxicity against the parental K562 leukemia cells and their Pgp-positive subline, whereas the latter showed approximately 7-fold resistance to adriamycin, a Pgp transported drug. 3-(1-Piperazinyl)methyl and 3-(quinuclidin-3-yl)aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione killed HCT116 colon carcinoma cells (carrying wild type p53) and their p53-null variant within the similar range of concentrations. We conclude that Mannich modification of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione, especially when cyclic diamine (e.g., piperazine, quinuclidine) is used, confers an important feature to the resulting compounds, namely, the potency for tumor cells otherwise resistant to a variety of anticancer drugs.

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

NARCIS (Netherlands)

Gupta, Ravindra K.; Gregson, John; Parkin, Neil; Haile-Selassie, Hiwot; Tanuri, Amilcar; Andrade Forero, Liliana; Kaleebu, Pontiano; Watera, Christine; Aghokeng, Avelin; Mutenda, Nicholus; Dzangare, Janet; Hone, San; Hang, Zaw Zaw; Garcia, Judith; Garcia, Zully; Marchorro, Paola; Beteta, Enrique; Giron, Amalia; Hamers, Raph; Inzaule, Seth; Frenkel, Lisa M.; Chung, Michael H.; de Oliveira, Tulio; Pillay, Deenan; Naidoo, Kogie; Kharsany, Ayesha; Kugathasan, Ruthiran; Cutino, Teresa; Hunt, Gillian; Avila Rios, Santiago; Doherty, Meg; Jordan, Michael R.; Bertagnolio, Silvia

2018-01-01

Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether

Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen

International Nuclear Information System (INIS)

Blanquart, Christophe; Karouri, Salah-Eddine; Issad, Tarik

2009-01-01

The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.

The role of dentists on medically compromised children’s oral and dental prophylaxis in Hospital

Directory of Open Access Journals (Sweden)

Roosje Rosita Oewen

2008-12-01

Full Text Available Background: One of dentist’s main roles is to coordinate the management of medically compromised children. The term of medically compromised refers to those children who have medical conditions which affect the dental treatment or manifest as a specific oral and dental problem. Patient’s visit to Special Care for Dentistry Clinic Dr. Hasan Sadikin Hospital Bandung showed a remarkable increase. From under 10 new visit in 2003, now July–December 2008 showed 81 new visit. Purpose: This paper discusses several medical problems (cardiovascular, hematology, respiratory system, and genetic disorder in children and the role of dentist in the treatment of those patients in the hospital. Review: The increase of attention by all level to these medically compromised children in the hospital also increases the dentist’s role in supporting the prognosis of the disease and patient’s quality of life. The most important effort is oral and dental prophylaxis to prevent oral pathology which is caused by the manifestation of disease as well as the side effects of treatment. Conclusion: It is, concluded that role of the dentist in managing these patients is giving preventive efforts and dental treatment that may be improve patient’s quality of life. The preventive effort and dental treatment is customize according to the patients condition. Nevertheless, cooperation from the dentist and other professional is needed in treating these patients.

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

Directory of Open Access Journals (Sweden)

Roderick M. Card

2018-06-01

Full Text Available Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss, impedes the free trade and movement of animals, and has significant impact on pig health. Infection is generally treated with antibiotics of which pleuromutilins, such as tiamulin, are widely used for this purpose, but reports of resistance worldwide threaten continued effective control. In Brachyspira hyodysenteriae pleuromutilin resistance has been associated with mutations in chromosomal genes encoding ribosome-associated functions, however the dynamics of resistance acquisition are poorly understood, compromising stewardship efforts to preserve pleuromutilin effectiveness. In this study we undertook whole genome sequencing (WGS and phenotypic susceptibility testing of 34 UK field isolates and 3 control strains to investigate pleuromutilin resistance in Brachyspira hyodysenteriae. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A (tiamulin valnemulin antibiotic resistance, encoding a predicted ABC-F transporter. In vitro culture of isolates in the presence of inhibitory or sub-inhibitory concentrations of tiamulin showed that tva(A confers reduced pleuromutilin susceptibility that does not lead to clinical resistance but facilitates the development of higher-level resistance via mutations in genes encoding ribosome-associated functions. Genome sequencing of antibiotic-exposed isolates identified both new and previously described mutations in chromosomal genes associated with reduced pleuromutilin susceptibility, including the 23S rRNA gene and rplC, which encodes the L3 ribosomal protein. Interesting three antibiotic-exposed isolates harboured mutations in fusA, encoding Elongation Factor G, a gene not previously associated with pleuromutilin resistance. A longitudinal molecular epidemiological examination of two episodes of swine dysentery at the same farm indicated

The construction of a Solanum habrochaites LYC4 introgression line population and the identification of QTLs for resistance to Botrytis cinerea

NARCIS (Netherlands)

Finkers, H.J.; Heusden, van A.W.; Meijer-Dekens, R.G.; Kan, van J.A.L.; Maris, P.C.; Lindhout, P.

2007-01-01

Tomato (Solanum lycopersicum) is susceptible to grey mold (Botrytis cinerea). Partial resistance to this fungus has been identified in accessions of wild relatives of tomato such as Solanum habrochaites LYC4. In a previous F-2 mapping study, three QTLs conferring resistance to B. cinerea (Rbcq1,

Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

Science.gov (United States)

Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

2017-07-01

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure

DEFF Research Database (Denmark)

Schultze, Anna; Paredes, Roger; Sabin, Caroline

2014-01-01

during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log...... mutations on CD4 slopes in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test......-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. RESULTS: A total of 2731 patients experiencing a median of 1 (range 1-4) episodes were included in this analysis. The prevalence of any...

Selective up-regulation of protein kinase C eta in phorbol ester-sensitive versus -resistant EL4 mouse thymoma cells.

Science.gov (United States)

Resnick, M S; Luo, X; Vinton, E G; Sando, J J

1997-06-01

Stimulation of sensitive EL4 mouse thymoma cells (s-EL4) with phorbol esters results in production of interleukin 2 (IL-2), adherence to a plastic substrate, and growth inhibition, whereas a phorbol ester-resistant variant (r-EL4) fails to respond. Previous studies revealed substantially decreased expression of protein kinase C (PKC) epsilon in the r-EL4 versus s-EL4 cells. This work has been extended to examine the more recently described PKC isozymes. Western and Northern analyses revealed a marked decrease in PKC eta and theta in r-EL4 as compared to s-EL4 cells. Treatment of these lines with phorbol ester for 24 h resulted in down-regulation of all PKC isozymes examined except PKC eta, which was up-regulated in the s-EL4 cells at the time of maximal IL-2 production. Two newly isolated EL4 clones, resistant to phorbol ester-induced growth inhibition but still exhibiting the phorbol ester-induced adherence and IL-2 production, both expressed PKC eta and theta. Collectively, these observations suggest a dissociation of growth inhibition from adherence and IL-2 production pathways and a potential role for PKC eta in the latter.

Mitigating Reptile Road Mortality: Fence Failures Compromise Ecopassage Effectiveness

Science.gov (United States)

Baxter-Gilbert, James H.; Riley, Julia L.; Lesbarrères, David; Litzgus, Jacqueline D.

2015-01-01

Roadways pose serious threats to animal populations. The installation of roadway mitigation measures is becoming increasingly common, yet studies that rigorously evaluate the effectiveness of these conservation tools remain rare. A highway expansion project in Ontario, Canada included exclusion fencing and ecopassages as mitigation measures designed to offset detrimental effects to one of the most imperial groups of vertebrates, reptiles. Taking a multispecies approach, we used a Before-After-Control-Impact study design to compare reptile abundance on the highway before and after mitigation at an Impact site and a Control site from 1 May to 31 August in 2012 and 2013. During this time, radio telemetry, wildlife cameras, and an automated PIT-tag reading system were used to monitor reptile movements and use of ecopassages. Additionally, a willingness to utilize experiment was conducted to quantify turtle behavioral responses to ecopassages. We found no difference in abundance of turtles on the road between the un-mitigated and mitigated highways, and an increase in the percentage of both snakes and turtles detected dead on the road post-mitigation, suggesting that the fencing was not effective. Although ecopassages were used by reptiles, the number of crossings through ecopassages was lower than road-surface crossings. Furthermore, turtle willingness to use ecopassages was lower than that reported in previous arena studies, suggesting that effectiveness of ecopassages may be compromised when alternative crossing options are available (e.g., through holes in exclusion structures). Our rigorous evaluation of reptile roadway mitigation demonstrated that when exclusion structures fail, the effectiveness of population connectivity structures is compromised. Our project emphasizes the need to design mitigation measures with the biology and behavior of the target species in mind, to implement mitigation designs in a rigorous fashion, and quantitatively evaluate road

Mitigating reptile road mortality: fence failures compromise ecopassage effectiveness.

Directory of Open Access Journals (Sweden)

James H Baxter-Gilbert

Full Text Available Roadways pose serious threats to animal populations. The installation of roadway mitigation measures is becoming increasingly common, yet studies that rigorously evaluate the effectiveness of these conservation tools remain rare. A highway expansion project in Ontario, Canada included exclusion fencing and ecopassages as mitigation measures designed to offset detrimental effects to one of the most imperial groups of vertebrates, reptiles. Taking a multispecies approach, we used a Before-After-Control-Impact study design to compare reptile abundance on the highway before and after mitigation at an Impact site and a Control site from 1 May to 31 August in 2012 and 2013. During this time, radio telemetry, wildlife cameras, and an automated PIT-tag reading system were used to monitor reptile movements and use of ecopassages. Additionally, a willingness to utilize experiment was conducted to quantify turtle behavioral responses to ecopassages. We found no difference in abundance of turtles on the road between the un-mitigated and mitigated highways, and an increase in the percentage of both snakes and turtles detected dead on the road post-mitigation, suggesting that the fencing was not effective. Although ecopassages were used by reptiles, the number of crossings through ecopassages was lower than road-surface crossings. Furthermore, turtle willingness to use ecopassages was lower than that reported in previous arena studies, suggesting that effectiveness of ecopassages may be compromised when alternative crossing options are available (e.g., through holes in exclusion structures. Our rigorous evaluation of reptile roadway mitigation demonstrated that when exclusion structures fail, the effectiveness of population connectivity structures is compromised. Our project emphasizes the need to design mitigation measures with the biology and behavior of the target species in mind, to implement mitigation designs in a rigorous fashion, and quantitatively

Public health risk of antimicrobial resistance transfer from companion animals.

Science.gov (United States)

Pomba, Constança; Rantala, Merja; Greko, Christina; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Mateus, Ana; Moreno, Miguel A; Pyörälä, Satu; Ružauskas, Modestas; Sanders, Pascal; Teale, Christopher; Threlfall, E John; Kunsagi, Zoltan; Torren-Edo, Jordi; Jukes, Helen; Törneke, Karolina

2017-04-01

Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For

Studies on irradiation resisting paints for concrete structures in nuclear power plant, 4

International Nuclear Information System (INIS)

Kita, Daizo; Sumino, Masahiro; Goto, Tomoaki.

1978-01-01

It is necessary for irradiation resisting paints to adhere tightly to concrete in order to exhibit superior effects. Adhesion of paints to concrete is greatly affected by moisture content and the form of moisture in concrete. Further, adhesion will probably be affected by differences in concrete surface conditions between floors, walls and ceilings. Therefore, experiments were conducted with concrete to make clear allowable moisture conditions and the influence of these concrete surfaces. The following results were obtained. (1) Adhesion of paint becomes stronger as pF-value increases, that is, as moisture content falls. (2) The allowable pF-values and moisture contents were respectively 5.5 over and 4.5% under at floor, 4.4 over and 4.9% under at wall, and 4.3 over and 5% under at ceiling. (3) Fractures of paint films under these allowable conditions occurred in paint-concrete composites, and the fractured concrete thickness than was 0.5-0.8 mm and measured adhesion strength was 33 kg/cm 2 . (auth.)

Sitagliptin down-regulates retinol-binding protein 4 and reduces insulin resistance in gestational diabetes mellitus: a randomized and double-blind trial.

Science.gov (United States)

Sun, Xia; Zhang, Zhendong; Ning, Hui; Sun, Hong; Ji, Xianghong

2017-06-01

Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks. Glucose and insulin profiles, as well as serum RBP-4 level, were measured at both baseline and end of the study. After 16 weeks of treatment, participants in the STL group exhibited significantly improved levels of fasting plasma glucose and serum insulin, homeostasis model of assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR), compared with those in the placebo group. Serum levels of RBP-4 were also markedly decreased in the sitagliptin treatment group, and more importantly it was positively correlated with improved insulin resistance parameters. Our study supports a potentially promising role of sitagliptin in improving insulin resistance by decreasing RBP-4 in GDM-affected women.

Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice

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Baoan Chen

2009-03-01

Full Text Available Baoan Chen1,* Jian Cheng1,* Yanan Wu1, Feng Gao1, Wenlin Xu2, et al 1Department of Hematology;2Department of Hematology, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, PR China *These authors have contributed equally to this workAbstract: In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet and magnetic nanoparticle of Fe3O4 (MNP-Fe3O4 combined with daunorubicin (DNR in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 × 107 cells/each respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice were assigned randomly into five groups which were treated with normal saline; DNR; NP-Fe3O4 combined with DNR; 5-BrTet combined with DNR; 5-BrTet and MNP-Fe3O4 combined with DNR, respectively. The incidence of formation, growth characteristics, weight, and volume of tumors were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of Bcl-2, and BAX were detected by Western blot. Bcl-2, BAX, and caspase-3 genes were also detected. For K562/A02 cells xenograft tumors, 5-BrTet and MNP-Fe3O4 combined with DNR significantly suppressed growth of tumor. A histopathologic examination of tumors clearly showed necrosis of the tumors. Application of 5-BrTet and MNP-Fe3O4 inhibited the expression of Bcl-2 protein and upregulated the expression of BAX and caspase-3 proteins in K562/A02 cells xenograft tumor. It is concluded that 5-BrTet and MNP-Fe3O4 combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model.Keywords: 5-bromotetrandrine, magnetic nanoparticle of Fe3O4, multidrug-resistance, xenograft model