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Sample records for yosetsu aku gensho

  1. An update on molecular genetics of Alkaptonuria (AKU).

    Science.gov (United States)

    Zatkova, Andrea

    2011-12-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria, ochronosis, and ochronotic arthritis. The defect is caused by mutations in the HGD gene, which maps to the human chromosome 3q21-q23. AKU shows a very low prevalence (1:100,000-250,000) in most ethnic groups, but there are countries such as Slovakia and the Dominican Republic in which the incidence of this disorder rises to as much as 1:19,000. In this work, we summarize the genetic aspects of AKU in general and the distribution of all known disease-causing mutations reported so far. We focus on special features of AKU in Slovakia, which is one of the countries with an increased incidence of this rare metabolic disorder.

  2. Pencegahan Penularan HIV/AIDS: Efektivitas Metode KIE “Aku Bangga Aku Tahu (ABAT”

    Directory of Open Access Journals (Sweden)

    Shelly Iskandar

    2016-12-01

    Full Text Available Abstract The epidemic of HIV/AIDS in Indonesia is one of fastest growing among Asian countries. One of the efforts of the government to reduce HIV/AIDS cases is by implementing Information Education and Communication (IEC which is so-called “Aku Bangga Aku Tahu (ABAT”. However, the effectiveness of ABAT and its methods have not been evaluated. The aim of this study is to analyze the effectiveness of IEC of ABAT on knowledge, perception, stigma and HIV/AIDS behavioral prevention among selected high school students. This is a quantitative research, using pre-test, post-test, and control group of Quasi Experimental Design. A number of 221 students were chosen using multistage random sampling, divided into groups of single, multiple and control. The results of this study showed that the IEC of ABAT effectively increased knowledge, perception and preventive behavior, but it had not been able to reduce stigma. IEC of ABAT multiple sessions provided higher impact thanthat of the single session (p < 0.05. It is necessary to improve methods of IEC to encourage the improvement of knowledge, perception, and reduced stigma and HIV/AIDS risk behavior. Keywords: behavior, HIV/AIDS, knowledge, perception, stigma AbstrakLaju peningkatan HIV/AIDS di Indonesia merupakan salah satu yang tercepat di Asia. Sebagai upaya pengendalian HIV/AIDS, pemerintah meluncurkan modul komunikasi informasi dan edukasi Aku Bangga Aku Tahu (KIE ABAT. Efektivitas metode dan KIE ABAT sampai saat ini belum pernah dilakukan evaluasi. Tujuan penelitian ini untuk menganalisis efektivitas KIE ABAT terhadap pengetahuan, persepsi, stigma dan perilaku pencegahan HIV/AIDS pada siswa/siswi SMA. Penelitian ini merupakan penelitian kuantitatif dengan rancangan penelitian Quasi Experiment Design dengan Pre-test Post-test Control Group Design. Sebanyak 221 siswa berpartisipasi dalam penelitian yang dipilih menggunakan multistage random sampling, kemudian dibagi kedalam kelompok single, multiple

  3. Kas Soome on paha maa? / Aku Louhimies ; interv. Margit Tõnson

    Index Scriptorium Estoniae

    Louhimies, Aku

    2006-01-01

    Vestlus soome režissööriga tema festivalidel mitmeid auhindu saanud filmist "Paha maa" : Soome 2005. Režissöör filmib Niguliste kirikus stseene oma neljandasse filmi "Paljas mees". Lisaks fakte "Aku Louhimies - laia ampluaaga filmimees"

  4. Väikeaktsionäril on õigus teada / Aku Sorainen ; interv. Lauri Matsulevitsh

    Index Scriptorium Estoniae

    Sorainen, Aku

    2006-01-01

    Aktsionäri õigustest teabele aktsiaseltsi tegevuse kohta. Intervjuu Investorite Liidu juhatuse liikme ja vandeadvokaadi Aku Soraineniga. Vt ka Äripäev 22.05.2006, lk. 8 ja 23.05.2006 Äripäeva juhtkirja

  5. Kas praktikant on ettevõttes teretulnud? / Valev Mägi, Hedi Hepner, Aku Sorainen ... [jt.

    Index Scriptorium Estoniae

    2009-01-01

    Küsimusele vastavad: Mainori Kõrgkooli üliõpilasesinduse esimees Valev Mägi, Tartu Ülikooli õigusteaduskonna üliõpilane Hedi Hepner, Advokaadibüroo Sorainen juhtiv partner Aku Sorainen, Swedbanki personali planeerimise ja arendamise osakonna juhataja Signe Vaks-Saareoja, Lääne maasekretär Epp Mitt

  6. Novel Aku Mencintaimu Shanyuan Karya Syafruddin Pernyata Dalam Perspektif Perubahan Sosial

    Directory of Open Access Journals (Sweden)

    Derri Ris Riana

    2015-06-01

    Full Text Available Tema perubahan sosial yang ada di dalam sebuah novel sudah banyak dikaji dari berbagai perspektif karena kebermanfaatannya dalam mengetahui sejauh mana perubahan sosial di masyarakat itu terjadi. Akan tetapi, penelitian-penelitian itu hanya memaparkan bentuk-bentuk perubahan sosial dan faktor­‐faktor penyebabnya yang ada di dalam novel. Oleh karena itu, selain untuk mengungkap bentuk­‐bentuk dan faktor­‐faktor penyebab perubahan sosial, tujuan penelitian ini adalah untuk menggali arah perubahan sosial dan upaya menangkal perubahan yang bersifat negatif di dalam novel Aku Mencintaimu Shanyuan. Metode yang digunakan adalah metode deskriptif analisis dengan didukung oleh pendekatan sosiologi sastra. Hasil penelitian menunjukkan bahwa di dalam novel Aku Mencintaimu Shanyuan ini terjadi perubahan sosial di masyarakat Desa Resak, Kabupaten Kutai Barat yang diakibatkan oleh interaksi sosial dengan kebudayaan lain. Akan tetapi, perubahan sosial yang disebabkan oleh faktor eksternal itu masih dalam taraf perubahan pada bagian-bagian sistem, sedangkan sistem masih tetap utuh. Oleh karena itu, arah negatif dari perubahan sosial dapat diatasi dengan melestarikan kearifan lokal dan memperdalam agama yang tampak pada tokoh-tokoh dalam novel Aku Mencintaimu Shanyuan. Abstract: The social change theme in a novel has been analyzed from many perspectives for its advantages in understanding how far social change in the society happens. However, those researchers only explain the social change forms and the causal factors. Therefore, in addition to explaining the social change forms and their underlying factors, this research also aims to describe the social change direction and efforts in preventing negative social change in the novel Aku Mencintaimu Shanyuan. The method used in this research is descriptive analysis supported by sociology theory. The result shows that, in the novel, social change occurs among the society of Resak village, West Kutai

  7. Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene (HGO).

    Science.gov (United States)

    Beltrán-Valero de Bernabé, D; Jimenez, F J; Aquaron, R; Rodríguez de Córdoba, S

    1999-01-01

    We recently showed that alkaptonuria (AKU) is caused by loss-of-function mutations in the homogentisate 1,2 dioxygenase gene (HGO). Herein we describe haplotype and mutational analyses of HGO in seven new AKU pedigrees. These analyses identified two novel single-nucleotide polymorphisms (INV4+31A-->G and INV11+18A-->G) and six novel AKU mutations (INV1-1G-->A, W60G, Y62C, A122D, P230T, and D291E), which further illustrates the remarkable allelic heterogeneity found in AKU. Reexamination of all 29 mutations and polymorphisms thus far described in HGO shows that these nucleotide changes are not randomly distributed; the CCC sequence motif and its inverted complement, GGG, are preferentially mutated. These analyses also demonstrated that the nucleotide substitutions in HGO do not involve CpG dinucleotides, which illustrates important differences between HGO and other genes for the occurrence of mutation at specific short-sequence motifs. Because the CCC sequence motifs comprise a significant proportion (34.5%) of all mutated bases that have been observed in HGO, we conclude that the CCC triplet is a mutational hot spot in HGO. PMID:10205262

  8. Marjinalisasi Perempuan Pertama Melalui Lagu: Suatu Analisis Wacana Kritis Terhadap Lagu “Jadikan Aku Yang Kedua”

    Directory of Open Access Journals (Sweden)

    Endang Setiowati

    2011-10-01

    Full Text Available During 2006 until 2007 there were plenty of songs that are lyrical about adultery or polygamy, in line also with the emergence of the phenomenon of polygamy and infidelity by some famous people ranging from businessmen, preachers, politicians, to academics. One of the most popular songs is a song titled “Jadikan Aku yang Kedua”. Surprisingly, although the title shows that this song legalized polygamy, the majority of listeners who request the song to be played in radio stations are women. The research reveals about the marginalization of women that is implicitly contained in a song lyrics. The research method used is critical discourse analysis with analytical techniques using the model of Norman Fairclough. This study uses substantive theoretical framework such as hegemony, ideology, patriarchy, and feminism and the discourse analysis theory from Michael Foucault. The results showed that the Song is a discourse to marginalize women who occupy the first position, while for the second women or femme fatale, this song is empowering them. Song writer has the power to shape the ideology of consumer (listener toward his patriarchal ideology. He wants to use his power to encourage the women to dare to become a femme fatale.   

  9. Early-onset ocular ochronosis in a girl with alkaptonuria (AKU) and a novel mutation in homogentisate 1,2-dioxygenase (HGD).

    Science.gov (United States)

    Gucev, Z S; Slaveska, N; Laban, N; Danilovski, D; Tasic, V; Pop-Jordanova, N; Zatkova, A

    2011-01-01

    Alkaptonuria (AKU) is a disorder of phenylalanine/tyrosine metabolism due to a defect in the enzyme homogentisate 1,2-dioxygenase (HGD). This recessive disease is caused by mutations in the HGD gene. We report a 14-year-old girl who was referred after presenting black urine. Careful examination revealed ochronosis of the conjunctiva. There was no affection of the cardiac valves. Elevated excretion of homogentisic acid in urine was found. Sequence analysis of the HGD gene from genomic DNA revealed that the patient is a compound heterozygote with a previously described mutation (c.473C>T, p.Pro158Leu), and a novel one (c.821C>T, p.Pro274Leu). Her mother is heterozygous for the novel mutation, while the brother is heterozygous for the previously described mutation. In summary, we describe an alkaptonuric patient with ocular ochronosis and a novel HGD mutation, c.821C>T, p.Pro274Leu.

  10. Sensitivity analysis of weight reduction results of an observational cohort study in overweight and obese children and adolescents in Germany: the EvAKuJ Study

    Directory of Open Access Journals (Sweden)

    Thomas Böhler

    2013-10-01

    Full Text Available In the German EvAKuJ observational cohort study, changes in the body mass index standard deviation score (BMI-SDS of overweight and obese children and adolescents as primary outcome of multimodal (short, inpatient or long, outpatient weight-loss interventions are difficult to interpret. Published intention-to-treat (ITT and per protocol data obtained at the end of the intervention (T1, one year (T2, and two years (T3 after its end were used for sensitivity analysis of treatment success rates. The odds ratio and the number needed to treat (NNT for BMI-SDS reduction of at least −0.2 (successful treatment and at least −0.5 (good treatment success were related to spontaneous BMI-SDS reduction rates in a hypothetical control group (control event rate, CER. At T1, treatment seems to be effective up to a CER of 10% in inpatients and of 5% in outpatients. ITT analysis, compromised by a loss to follow-up of 81 to 90% (inpatients and 57 to 66% (outpatients, indicated that treatment may become less effective at a CER above 1% in inpatients (e.g., successful treatment at T2: NNT=106, at T3: NNT=51, and above 5% in outpatients (successful treatment at T2: NNT=7, at T3: NNT=8; good treatment success at T2 and T3: NNT=25. Positive short-term effects of inpatient treatment of overweight and obese children and adolescents may not be maintained in the long term. Long-term effectiveness of outpatient treatment may depend on age and the degree of overweight.

  11. Welding robot package; Arc yosetsu robot package

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, S. [Yaskawa Electric Corp., Kitakyushu (Japan)

    1998-09-01

    For the conventional high-speed welding robot, the welding current was controlled mainly for reducing the spatters during short circuits and for stabilizing the beads by the periodic short circuits. However, an increase of deposition amount in response to the speed is required for the high-speed welding. Large-current low-spatter welding current region control was added. Units were integrated into a package by which the arc length is kept in short without dispersion of arc length for welding without defects such as undercut and unequal beads. In automobile industry, use of aluminum parts is extended for the light weight. The welding is very difficult, and automation is not so progressing in spite of the poor environment. Buckling of welding wire is easy to occur, and supply of wire is obstructed by the deposition of chipped powders on the torch cable, which stay within the contact chip resulting in the deposition. Dislocation of locus is easy to occur at the corner of rectangular pipe during the welding. By improving these troubles, an aluminum MIG welding robot package has been developed. 13 figs.

  12. 2185-IJBCS-Article-Aduayi-Akue Adote

    African Journals Online (AJOL)

    hp

    différentes parties de l'organisme humain en entraînant des effets chroniques ou aigus sur la santé de l'homme (Were et al., 2008). La pollution par les métaux ... de certaines maladies liées à la contamination aux métaux lourds telles que les affections du foie et des reins, les maladies cardio- vasculaires, les cancers, la ...

  13. Silicon Bipolar Distributed Oscillator Design and Analysis | Aku ...

    African Journals Online (AJOL)

    The design of high frequency silicon bipolar oscillator using common emitter (CE) with distributed output and analysis is carried out. The general condition for oscillation and the resulting analytical expressions for the frequency of oscillators were reviewed. Transmission line design was carried out using Butterworth LC ...

  14. Aksum University (AKU) faculties' needs for support in training and ...

    African Journals Online (AJOL)

    Ethiopian Journal of Business and Economics (The) ... Two Principle Component Analysis factors related to these hypotheses were described as a training factor TFAC1(I need training in data analysis and research report writing ) and a support factor TFAC2 (Internet access is essential and research class would not ...

  15. Akuntansi Nir-Tuhan: Salahkah Aku? (Budaya Barat Menggugat

    Directory of Open Access Journals (Sweden)

    Theresia Woro Damayanti

    2014-12-01

    Full Text Available Penelitian ini akan menguji apakah ketiadaan Allah dalam praktik akuntansi budaya barat merupakan sebuah kesalahan, yang mana budaya barat menggunakan agama Kristen Katolik Roma dan praktek akuntansi yang digunakan dalam penelitian ini adalah PSAK 46 tentang pajak tangguhan. Beberapa peneliti akuntansi menyatakan bahwa akuntansi yang ada mengakomodasi kapitalisme. Selain itu, beberapa peneliti juga mempertanyakan tidak adanya agama dalam akuntansi. Sedangkan agama harus dianggap sebagai perilaku manusia yang mendasari kekuasaan, sehingga budaya yang dapat dilihat sebagai pengaruh penting pada pengembangan kebijakan dan praktik akuntansi. Tidak adanya Allah dalam akuntansi selalu menyalahkan budaya barat sebagai penyebabnya. Artikel ini menunjukkan bahwa budaya barat sangat mendorong warganya untuk membayar pajak. Sementara aturan akuntansi yang diatur dalam PSAK 46 bahkan mengakomodasi perencanaan pajak yang bertujuan untuk meminimalkan pajak yang dibayarkan kepada Negara. Artikel ini memberi kita refleksi: apakah kita masih akan menyalahkan budaya barat sebagai penyebab tidak adanya Allah dalam Praktek Akuntansi? This study will examine whether is nonexistence of God in the accounting practice is western culture’s mistake, which western culture that will be used are the Roman Catholic religion and the accounting practices used in this study is PSAK 46 about deferred tax. Some accounting researchers stated that the existing accounting accommodate capitalism. Moreover, some researchers also questioned the absence of religion in accounting. Whereas religion should be considered as a power underlying human behavior, so that culture can be seen as an important influence on the development of accounting policies and practices. Nonexistence of God in accounting always blaming western culture as the cause. This article shows that the western culture strongly encourages its citizens to pay taxes. While the accounting rules contained in PSAK 46 even accommodate tax planning that aims to minimize taxes paid to the state. This article gives us a reflection: are we still going to blame the western culture as the cause of nonexistence of God in Accounting?

  16. Statistical estimation of absolute gravity values | Aku | Science World ...

    African Journals Online (AJOL)

    Gravity measurements at stations in northwestern Nigeria were assumed to be random variables. Gravity data collected was used to illustrate the gravity network adjustment theories. Residuals of the network were inspected to detect gross errors by standardizing the residuals. Computed standard deviation for unit weight ...

  17. 2410-IJBCS-Article-Aduayi Akue Adoté A

    African Journals Online (AJOL)

    hp

    un impact négatif sur l'environnement. (DP/MERF, 2010). En effet, des études antérieures ont montré la présence de métaux lourds toxiques dans le minerai de phosphates du Sud Togo, ce qui constitue un danger pour l'environnement et la santé humaine. Les organismes vivants s'intoxiquent par l'alimentation, la.

  18. Statistical estimation of absolute gravity values | Aku | Science World ...

    African Journals Online (AJOL)

    Science World Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 2, No 1 (2007) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Download this PDF file. The PDF file you selected should load here ...

  19. Aksum University (AKU) Faculties' needs for Support in Training and ...

    African Journals Online (AJOL)

    User

    Engineering &. Technology. 6. 11.8. 70. 8.6. Natural. &. Comp. Science. 10. 19.6. 85. 11.8. Social Science. & Language. 15. 29.4. 81. 18.5. Health Sciences 5 ... Masters = (16). 31.4%. Doctorate = (5). 9.8%. Sampling Instrument. A pilot instrument was developed based on interviews and administrative presentations on the ...

  20. Fatigue strength of laser welded joint sheet; Laser yosetsu tsugite no hiro kyodo

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, A; Yoshimura, T; Tsuboi, M; Takasago, T; Nishio, T [Toyota Motor Corp., Aichi (Japan)

    1997-10-01

    In this paper, fatigue strength of laser welded butt joint has been investigated. In order to obtain the influence of underfill and pitting, fatigue test was conducted with different sheet thickness and mechanical properties. Fatigue crack initiated at underfill and pitting in the weld metal. Stress concentration factor and hardness of the weld metal were considered to estimate fatigue limit. However, hardness of the weld metal has no significant effect on fatigue strength. As a result, fatigue strength was well estimated by hardness of base metal and stress concentration factor calculated from the shape of underflll and pitting. 7 refs., 9 figs., 5 tabs.

  1. Welding mechanization in shipyard CIM; Zosen ni okeru yosetsu no jidoka robot ka CIM ka

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, T. [Hitachi Zosen Corp., Osaka (Japan)

    1997-12-01

    This paper explains development and examples of application of automated welding devices from a viewpoint of an element technology constituting computer integrated manufacturing (CIM), based on the history of modernization of shipyards that has been achieved to date. In the first step of promoting the modernization, elevating cutting accuracy in the uppermost stream process was thought a starting point of rationalization. What have been achieved therefrom are adoption of the most advanced NC plasma cutting machine, and improvement in the computer aided system for the cutting machines. In addition, a twenty-electrode line welder has been developed, which does not create angle deformation in welding longerons, and can be operated even by unskilled workers. The welder has successfully realized a construction method in which robots can be applied more easily. Further developments have been made on a robot to weld cells, advanced CAD/CAM operation techniques which are linked with data from design, an automatic one-side welding device which can achieve a speed 2.5 times greater than by conventional devices, and an automation device for three-dimensionally bent blocks, whose automation has been regarded difficult. 11 figs., 1 tab.

  2. Mechanized and robotized welding in shipbuilding; Zosen ni okeru yosetsu no jidoka robot ka

    Energy Technology Data Exchange (ETDEWEB)

    Kanda, Y. [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan)

    1997-12-01

    Large-scale ships such as VLCC are built at the Kure No.1 Works of IHI (Ishikawajima-Harima Heavy Industry). This paper introduces current status of mechanized and robotized welding at the works. For the sub-assembly with short weld length and horizontal fillet, simplified automatic welders are used in which mag-welding method using CO2 is adopted. The frequent wound welding of member ends can be automatically conducted using welders developed by IHI. In the large-scale assembly processes, remarkable rationalization and highly accurate assembly of flat plate welding have been promoted. Tankers, container ships, and bulk carriers can be treated at the same time. Teaching times of welding robots can be greatly reduced by a technique called parametric treatment. In the future, it is essential to enhance the accuracy of members by introducing the laser cutting during machining processes. Completely self-type mechanization is required as well as large-output laser welding and sensor technology. 3 refs., 12 figs., 2 tabs.

  3. Eetilisemat Eestit ehitav advokaat naudib masu / Aku Sorainen ; intervjueerinud Tuuli Koch

    Index Scriptorium Estoniae

    Sorainen, Aku

    2009-01-01

    15 aastat Eestis elanud advokaat ja Malta aukonsul vastab küsimustele, mis puudutavad töötmist Eestis, ärikultuuri, poliitilist kultuuri, eliiti. Ta leiab, et Eesti on lähenemas Põhjamaade eetilisele ja väärtusi toetavale ärikultuurile

  4. Ärikultuur 15 aastat tagasi / Urve Vilk ; kommenteerinud Aku Sorainen

    Index Scriptorium Estoniae

    Vilk, Urve

    2011-01-01

    Krediidipanga juhatuse esimehe Andrus Kluge hinnangul oli ärikeskkond Eestis 15 aastat tagasi mitteformaalsem, naiivsem ja spontaansem kui praegu, kõik tegelesid kõigega. Margus Alviste hinnangul on 15 aastaga muutunud tavad ja kombed, rohkem on variserlikkust, eestlaste ettevõtlikkus on vähenenud

  5. "Utuslah Aku": Eksposisi Yunus Pasal 3-4 Tentang Pengutusan Nabi Yunus Berdasarkan Perspektif Allah Menyesal

    Directory of Open Access Journals (Sweden)

    Peniel C.D. Maiaweng

    2012-10-01

    Full Text Available mereka yang seharusnya dipanggilTuhan untuk pergi ke Niniwe (1:1-2, tetapi melarikan diri ke Tarsis (1:4-14, dan saat ini sedang berdoa dalam perut ikan besar dengankebingungannya (Yun. 2:1-9, akan kembali kepada panggilannya, yaituberbalik arah menuju ke Niniwe (3:1-2, untuk melaksanakanpelayanannya (3:4-9, karena Allah yang memanggil, walaupun Iadisebut Allah yang menyesal, tetapi Ia adalah Allah yang menyerukananugerah, Allah menerima pertobatan, dan diakui dalam pemberitaanPerjanjian Lama. Sebagai Allah yang menyesal, Ia adalah Allah yangterbuka terhadap orang-orang yang belum diselamatkan; Ia adalah Allahyang berdaulat untuk melakukan yang terbaik bagi manusia; Ia adalahAllah yang Mahatahu yang mengantisipasi segala perubahan sikap hidupmanusia di masa yang akan datang; Ia adalah Allah yang konsistenterhadap firman yang telah dinyatakan-Nya; dan Ia adalah Allah yangkonsisten terhadap sifat-sifat-Nya, sebagai Allah yang penyayang danpengasih serta panjang sabar dan berlimpah kasihs setia (4:2.

  6. Fiscal 2000 achievement report on development of high-efficiency high-reliability welding technology through improvement on welding techniques; 2000 nendo yosetsu gijutsu no kodoka ni yoru kokoritsu koshinraisei yosetsu gijutsu no kaihatsu seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-04-01

    Efforts are made to develop a welding design support system capable of increasing reliability and enhancing welding efficiency. Activities are conducted in the six fields of (1) the development of welding process simulation models, (2) development of welded section structure simulation models, (3) development of simulation models for predicting welding caused deformation, (4) integration of the models, (5) analysis of the welding phenomenon, and (6) the elucidation of the defect generation mechanism. In field (1), efforts are made to develop an arc plasma model, a molten pool convective heat transportation model, and a welding process model. In the effort to develop an arc plasma model, studies are made about a stationary axisymmetric arc in its steady state and about a constitutive equation and computation algorithm for developing a model in which a tungsten electrode (cathode) and an arc plasma welding pool (anode) are integrated. Furthermore, the simulation outcomes are experimentally verified. Satisfactory models are obtained as far as qualitative properties are concerned. (NEDO)

  7. Application of laser cladding to the aeroengine component. Koku engine buhin eno laser nikumori yosetsu no tekiyo

    Energy Technology Data Exchange (ETDEWEB)

    Morita, A [Ishikawajima-Harima Heavy Industries, Co. Ltd., Tokyo (Japan)

    1991-08-01

    Keeping the pace with recent development and application of laser cladding, hard-facing is used more frequently on turbine blades made of superalloys used in aeroengines. This paper explains the basic principles and features of laser hard-facing technique, welding parameters, and examples of practical use. Examples of practical use include application to turbine blades used in ALF502R-5 turbo fan engines for commuter aircraft and high-pressure turbine blades used in RB211 turbo fan engines for large passenger aircraft. In the former engine, improvement of abrasion resistance was intended at the shroud section where blades are in contact with each other, for which inconel was used as the base material and CO-group alloy as the welding material. The welding used a powder supply system with a laser generator oscillating CO{sub 2} at 5 kW and employing a beam collecting mirror plus scanner to attain a beam covering wider width. Faces with higher performance were obtained than by the conventional TIG welding, and the finishing time was decreased largely. 2 refs., 9 figs., 3 tabs.

  8. Analysis of flame propagation phenomenon in simplified stratified charge conditions; Tanjunkasareta sojo kyukiba ni okeru kaen denpa gensho no kansatsu

    Energy Technology Data Exchange (ETDEWEB)

    Moriyoshi, Y; Morikawa, H [Chiba University, Chiba (Japan); Kamimoto, T [Tokyo Institute of Technology, Tokyo (Japan)

    1997-10-01

    Since the local inhomogeneity of mixture concentration inside the cylinder affects the combustion characteristics, a basic research on combustion phenomenon in stratified charge conditions is required. The authors have made experiments with a constant-volume chamber, which can simulate an idealized stratified charge field by using a removable partition, to obtain the combustion characteristics. Also, numerical calculations are made using some combustion models. As a result, the important feature that the combustion speed is faster in stratified condition than in homogeneous condition can be predicted by the two-step reaction model. 4 refs., 8 figs.

  9. Time contour expression of limited range phenomena on stack chart; Jugo chart jo deno kyokuchi gensho jikan contour

    Energy Technology Data Exchange (ETDEWEB)

    Kametani, T

    1997-05-27

    Time contour expression of limited range phenomena on stack chart is examined for further improvement on the result of the ultimate interpretation in the seismic reflection survey. The policy is made clear from the beginning that local phenomena are to be discussed, and data prior CMP stacking is interpreted in detail. For this purpose, it is effective to make use of the time contour expression in the midpoint-offset plane simultaneously with the CMP and COP panels. For the review of data prior to CMP stacking, it is convenient to use the CMP (CDP) stacking chart in which the data is arranged methodically. In this chart, all the channels which are crude data prior to stacking are plotted on midpoint-offset coordinates, which plane is called the MOD (Midpoint Offset Domain) panel. Various panels can be chosen unrestrictedly, and their mutual relations can be easily grasped. When data points are given a time axis, they can be expressed in a time contour. Studies are conducted about the underground structure, multiple reflection paths divided by it, and characteristics of detour reflection attributable to faults. 4 refs., 9 figs.

  10. Application fo tunneling and atomic force detection to machines and scientific instruments. Tunnel gensho ya genshikan no mechatronics eno oyo

    Energy Technology Data Exchange (ETDEWEB)

    Kawakatsu, H. (The University of Tokyo, Tokyo (Japan). Institute of Industrial Science)

    1991-11-01

    It is now about ten years since the scanning tunnel microscope (STM) and the atomic force microscope (AFM) were invented. These microscopes are used very importantly today as a surface analyzer capable of atomic order analysis for their very high resolution. The STM and AFM obtain images of atomic orders by means of mechanical scanning of the probes. This means that the microscopes can control positioning, force detection and displacement in regions of sub-nanometer orders. Examples of researches may include detection of acceleration, length measurement, positioning, force detection, nano-tripology, processing and gravitational wave detection. As described above, this paper notes the researches derived from the operational principles of the STM and AFM, rather than the researches on the observation objects. The great diversity of the researches taken up and the greatness in the number of researches in the STM and AFM gather how superbly germinative these were. 34 refs.

  11. Ketika Aku dan Kamu Menjadi Kita: Dialog Misi Penginjilan Kristen dengan Dakwah Islam Menggunakan Pendekatan Teologi Interkultural dalam Konteks Indonesia

    Directory of Open Access Journals (Sweden)

    Daniel Syafaat Siahaan

    2017-04-01

    Full Text Available Evangelism and da'wah are two obligations or responsibilities of people, Christians and muslims. I wonder how long these two religions involved in a "cold war" or even a real war, because of arrogant fundamentalist notion. Arrogant because with full consciousness has monopolized the truth, and act like they own the only true God. God has been reduced to their own and considers others deify the wrong god. As a result, the shape of evangelism is not far from the impression of christianization, and the form of da'wah not far from the impression of islamization. Whereas, we find the plural phenomenon in Indonesia. In fact, with the philosophy of Bhinneka Tunggal Ika, Indonesian society should be able to appreciate and preserve otherness in harmony better. But reality says different. Christianization and islamization, plural occurs. Intention to write this article, arose from this concern. How evangelism and da'wah should be done in the context of the plurality of Indonesia, so in the end, You and I become Us.

  12. Visualization and image analysis of dynamic stall phenomenon for a Darrieus wind turbine; Darrieus fusha ni okeru doteki shissoku gensho no kashika to gazo kaisekini kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, N.; Shibuya, S.; Takano, T. [Niigata University, Niigata (Japan)

    1999-10-25

    The flow field around a Darrieus wind turbine is studied by flow visualization and PIV measurement in a rotating frame of reference to understand the unsteady nature of dynamic stall appearing at low tip-speed ratios. The qualitative nature of the dynamic stall observed by the flow visualization using dye injection technique is quantitatively reproduced in the instantaneous velocity distributions around the blade measured by PIV technique. These results indicate that two pairs of stall vortices are generated in one cycle of the turbine rotation and they grow in size as the tip-speed ratio decreases. The mechanism of the dynamic stall is found to be due to the flow separation over the suction side of the blade followed by the generation of in-flow motion from the pressure side to the suction side of the blade through the trailing edge. (author)

  13. Simulation on breakage of heterogeneous materials caused by detonative loading; Bakugo shogeki ni yoru fukinshitsu zairyo no hakai gensho no simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sassa, K; Watanabe, T; Ashida, Y [Kyoto University, Kyoto (Japan). Faculty of Engineering

    1996-05-01

    Investigations were conducted by simulation of breakage of inhomogeneous materials (rock) attributable to detonative loading, which simulation used the Days-2 Code. During the simulation, one-free-face blastings were used for testing a homogeneous structure, horizontal 2-layer structure, and horizontal 3-layer structure. Property values were assigned to the rocks on the assumption that they were sedimentary rocks such as sandstone or mudstone or hard rocks such as granite. As the result, it was found that a detonative loading resulted in shear failure in a sphere near the focus that was followed by radially developed cracks due to tension breakage, that more area is damaged in a soft rock than in a hard rock, that cracks due to breakage are produced by the overlapping of waves directly from the focus and those reflected from the free face in case of one-free-face blastings, that such cracks propagated along the soft rock layer in case there is a soft rock layer in a hard rock, but that breakage does not extend beyond the soft rock layer. 6 refs., 6 figs., 1 tab.

  14. Effects of mechanical stimulating treatment on self-organization phenomena of materials; Kikaiteki reiki shori. Zairyo no jiko soshikia gensho ni oyobosu sono koka

    Energy Technology Data Exchange (ETDEWEB)

    Hida, M. [Okayama University, Okayama (Japan). Faculty of Mechanical Engineering

    1999-03-31

    The atoms and atom clusters around dislocation cores in crystals or surface layer deformed by mechanical energy are locally excited so as to give rise some chemical reactions and to self-organize their products into a kind of Spatial-Temporal Pattern Formation as a dissipative structure. A famous coupling phenomenon between mechanical and chemical process in solid materials must have been mechanical alloing. This report explains that various mechano-chemical treatments are powerfull method for entraining the solid system into non-equilibrium states and interesting phenomena stimulated by the mechanical self-catalysis reaction causing self-organization. (author)

  15. Characteristic analysis of turbulent heat diffusion in a multi-compartment structure; Takukakuka kukan kozo ni okeru ranryunetsu kakusan gensho no kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Hu, C; Fukuchi, N [Kyushu University, Fukuoka (Japan). Faculty of Engineering

    1997-10-01

    An analysis was made on turbulent heat diffusion in a multi-compartment structure necessary for designing calorific power and environment for functional systems used in marine vessels and off-shore structures. In a multi-compartment structure, the diffusion phenomenon is complex because of movement of air flow in turbulence and buoyancy resulted from non-isothermal condition. The phenomenon is largely affected by space shapes and walls, and the conditions in heat diffusion field is governed also by shapes of opening connecting the compartments. An analysis was made by using the SIMPLE method on turbulent heat diffusion in a multi-compartment space with high Raleigh number in which natural convection is dominant. If the opening is small, the Coanda effect appears, in which air flow passing through the opening rises along the wall, wherein a high-temperature layer is formed near the ceiling, making the heat diffusion inactive. If the opening is large, a jetting flow from the opening and a large circulating flow are created, which cause active advection mixture, making temperature gradient smaller in the upper layer. Heat transfer intensity in an opening on a partition wall decays in proportion with 1/4th power of the opening ratio. 7 refs., 11 figs.

  16. Fiscal 2000 survey report. Basic research on dissimilar metal welding technology; 2000 nendo izai yosetsu gijutsu no kiso kenkyu chosa hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    Basic data for the above subject were collected through technical research on the melt welding of dissimilar metals and through conducting experiments under microgravity concerning the phenomenon of melt welding. The technical research covered reports published in the past 25 years on the welding or bonding of dissimilar materials. For each of the combinations of dissimilar materials of steel, nonferrous metal, and ceramics for producing a transitional joint, investigations were conducted as to whether dissimilar metal welding or bonding was currently feasible under each of the welding or bonding methods, and problems were extracted and remedies were gathered. No melt welding technology was found, however, capable of directly welding dissimilar materials for a transitional joint in which intermetallic compounds were to be formed. In a melt welding experiment conducted under microgravity, investigations were conducted into the effect of surface tension and gravity on convection inside a molten pool and into the bonding of dissimilar materials for which Al/Cu and Al/Mg were involved. It was then shown that microgravity is effective in mitigating stirring and segregation in a molten pool. (NEDO)

  17. Investigation of migration of organic silicone into stone and its prevention; Silicone kei dansei secchakuzai no seibun ga sekizaichu ni shinto suru gensho no kyumei to shinto taisaku

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, M.; Sasaki, M. [Kajima Construction Co. Ltd., Tokyo (Japan)

    1998-07-30

    Quantitative analyses of silicone migration into marble from elastic silicon adhesive were carried out by EPMA and LMA, and the amount of migrated silicone was calculated in terms of silicone concentration. By EPMA, silicone distribution into the area centering around the boundary between elastic adhesive and marble was clarified, and the migrating condition of silicone from elastic adhesive to marble was made clear. In the case of LMA, silicone concentration in micro-area in marble was measured to use the measured result for the succeeding analyses. As a result of the analysis, the trend of the change of silicone migration with the passage of time could be expressed by treating the silicone migration as diffusion phenomenon, and the depth of silicone migration could be quantified. It was confirmed that the cover primer applied at the back of marble to inhibit migration could prevent contamination of marble caused by silicone migration. The analytical method of this study seemed to be applicable to other stone materials or other adhesive and sealing materials. 14 refs., 12 figs., 2 tabs.

  18. Study of the heat island phenomenon in large cities and the measures to prevent it; Daitoshi ni okeru heat island gensho to sono taisaku ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Kawasaki, T.; Ishitani, H.; Matsuhashi, T. [The University of Tokyo, Tokyo (Japan). Faculty of Engineering

    1997-01-30

    The paper made an analysis of the heat island phenomenon in the Kanto area using 3-D numerical analysis models and a study on the effectiveness of the measures to prevent it. The models are composed of advection/diffusion models of heat/steam in the wind-velocity field and atmospheric air, heat diffusion models in the underground and undersea, and heat balance models on the ground surface and sea surface. In the calculation, a simulation was conducted of the case of taking the following three measures: the case where the exhaust heat was reduced 30% in the assumed typical day of summer; the case where the heat volume of buildings/trunk roads was reduced; the case where the evaporation efficiency of buildings/trunk roads was raised. The result of the study was as follows: The reduction effect of the exhaust heat is totally large, but precisely observing, some meshes contrarily showed rises in temperature in the suburbs. Also in the case of reducing the heat volume, the same phenomenon occurred, but the effect was large in the center of a city. It was found that the effect was unexpectedly large in the case of increasing the evaporation efficiency. 7 refs., 14 figs., 2 tabs.

  19. Welding in Singapore; Singapore no yosetsu jijo. Sekai no 40% no seizo kichi (2010 nen) (Tonan Asia no doko) donoyonishite ibunka no kabe wo koeruka

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, S. [Singapore Welding Society, (Singapore)

    1997-07-01

    From the position participating as a president of the Singapore Welding Society invited from Japan, the author of this paper introduces the welding situation in that country with emphasis placed on technical exchanges. South East Asia consists of a number of countries in which different kinds of races are present with different cultures. The region is now accomplishing a transfiguration into the manufacturing base of the world. Singapore exists as its core, and is carrying out lubricating functions for industrial growth of the region. It is an important matter how technical transfer will be made from industrialized nations such as Europe, America and Japan into Singapore to meet the above functions. Being different from Japan where a homogeneous society is viewed more importantly, welders, for example, change their place of employment from one to another despite the fact that welders are qualified for their skills by companies independently. Therefore, people concerned with welding in oil refineries, the government agencies and academic societies have developed extensive committee activities for unification of standards for welding skill examinations and for preparation of common implementation law bills. They have spent two years only for preparing the drafts. As a result, a network covering different kinds of business was successfully realized to exchange human resources and information and perform skill management. 4 figs.

  20. Fatigue behavior of boxing welded joint under biaxial cyclic loads; 2juku kurikaeshi kajuka ni okeru kakumawashi yosetsu keishu no hiro kyodo

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, I.; Takada, A.; Akiyama, S.; Ushijima, M.; Maenaka, H. [Ministry of Transportation, Tokyo (Japan)

    1998-12-31

    Various forces such as gravity, wave induced force, inertial force etc. compositely act on a ship body from various directions. Therefore, while discussing strength or life of structural elements of ship body, it is necessary to understand the effects of the composite force condition. In this study, fatigue tests of boxing welded joint under rectangular biaxial cyclic loads are performed, the following results are obtained. Even under he biaxial cyclic loads, it is the same as the uniaxial test, the cracks occurred at the boxing weld toes propagate almost in the straight y-direction, but no oblique propagation of the cracks caused by the lad in the y-direction occurs. That the crack at initial stage of the crack progress is improved in y-direction can be illustrated by the facts that the residual stress in x-direction near the toes reaches to the yield stress, and the stress concentration in the welded toes is bigger in x-direction than that in y-direction. But as for prediction of the progress route, a further study including amplitude ratio of the biaxial loads, effects of width of test specimen is necessary. 4 refs., 12 figs., 4 tabs.

  1. Study on unified fatigue strength assessment method for welded structure. Hot spot stress evaluating method for various combinations of plate thickness and weld leg length; Yosetsu kozo no toitsutekina hiro kyodo hyokaho ni kansuru kenkyu. Itaatsu to yosetsu ashinaga no kumiawase ni taisuru hot spot oryoku sanshutsu ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nihei, K.; Inamura, F.; Koe, S. [Kawasaki Heavy Industries, Ltd., Kobe (Japan)

    1996-12-31

    There has been tried to apply unified assessment method using hot spot stress, which is effective to evaluate fatigue strength of fillet welded structures for ships and marine structures. This method can be applied to complicated structures and is independent of welding processes. In this study, first, stress analysis has been conducted for two-dimensional fillet welded joint models with various combinations of plate thickness and weld leg length of general fillet structures by means of boundary element method. Then, critical position, which is not affected by local stress concentration due to bead, was determined from the detailed stress distribution in the vicinity of weld toe. As a result, a general equation has been proposed to estimate the hot spot stress by one-point representative method. Second, the fatigue tests of typical fillet welded joints have been conducted by applying this method. Consequently, it was demonstrated that the unified fatigue strength can be evaluated by the S-N data based on hot spot stress range determined from the proposed equation, independent of structural stress concentration. 22 refs., 14 figs.

  2. Study on unified fatigue strength assessment method for welded structure. Hot spot stress evaluating method for various combinations of plate thickness and weld leg length; Yosetsu kozo no toitsutekina hiro kyodo hyokaho ni kansuru kenkyu. Itaatsu to yosetsu ashinaga no kumiawase ni taisuru hot spot oryoku sanshutsu ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nihei, K; Inamura, F; Koe, S [Kawasaki Heavy Industries, Ltd., Kobe (Japan)

    1997-12-31

    There has been tried to apply unified assessment method using hot spot stress, which is effective to evaluate fatigue strength of fillet welded structures for ships and marine structures. This method can be applied to complicated structures and is independent of welding processes. In this study, first, stress analysis has been conducted for two-dimensional fillet welded joint models with various combinations of plate thickness and weld leg length of general fillet structures by means of boundary element method. Then, critical position, which is not affected by local stress concentration due to bead, was determined from the detailed stress distribution in the vicinity of weld toe. As a result, a general equation has been proposed to estimate the hot spot stress by one-point representative method. Second, the fatigue tests of typical fillet welded joints have been conducted by applying this method. Consequently, it was demonstrated that the unified fatigue strength can be evaluated by the S-N data based on hot spot stress range determined from the proposed equation, independent of structural stress concentration. 22 refs., 14 figs.

  3. “Saya Mau Bu!” or “Aku Mau Bu!”? from the Teachers and Students’ Point of View

    Directory of Open Access Journals (Sweden)

    Ienneke Indra Dewi

    2009-05-01

    Full Text Available Article describes a research which purpose was to find out whether there was a shift in the use of “aku” and “saya” from the children and teenagers’ points of view as well as their teachers’s. The shift of those expressions was based on the factors of concept, family education,, and the influence of media i.e. television. The objects of this research were 140 elementary and high school students as well as their teachers. Questionnaires were distributed to them. The results showed that there was a shift from the expression “saya” to “aku” in the students and teachers’ perception. However, when tested using statistics, the differences in the shift and in the perception between students and teachers concerning this matter were not significant. 

  4. Recycling method of rubbish glass, wasted slate and oyster shell; Gan Ca haizai wo riyosuru kenzaiyo glass kuzu oyobi senshoseki kuzu no recycle

    Energy Technology Data Exchange (ETDEWEB)

    Okawa, A.; Omi, M. [Tohoku University, Sendai (Japan). Institute for Advanced Materials Processing

    1996-03-29

    Examination was made about the method of recycling rubbish glass and Gensho-stone slate, left after the use of construction materials, and oyster shells. In the experiment, quartz powder having the highest softening temperature was used instead of rubbish glass powder, and H3PO4 was used as the additive agent. The Gensho-stone slate was ground in a ball mill into power smaller than 100 mesh. The main constituent of the oyster shell, CaCO3, was subjected to thermolysis for conversion into CaO; and calcium phosphate was used as animal bone powder. The above-said materials as the starting materials were subjected to pressure-forming, and heating was done in the air at 1173K for 7.2ks for the production of sintered pellets. The sintered bodies were left in the air for 30 days and examined for geometrical changes, and it was found that the Gensho-stone slate was the best specimen, with the oyster shell occupying the second place, and that the sintered bodies of bone powder and SiO2 absorbed moisture indicating they were short of serviceability. As for the use of sintered bodies, Gensho stone may be used as material for landscape building while CaO may be used as a Ca ion source in the sea for cultivating seashells. 5 refs., 5 figs., 3 tabs.

  5. High Frequency of Alkaptonuria in Slovakia: Evidence for the Appearance of Multiple Mutations in HGO Involving Different Mutational Hot Spots

    Science.gov (United States)

    Zatková, Andrea; de Bernabé, Daniel Beltrán Valero; Poláková, Helena; Zvarík, Marek; Feráková, Eva; Bošák, Vladimir; Ferák, Vladimír; Kádasi, L'udovít; de Córdoba , Santiago Rodríguez

    2000-01-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by the deficiency of homogentisate 1,2 dioxygenase (HGO) activity. AKU shows a very low prevalence (1:100,000–250,000) in most ethnic groups. One notable exception is in Slovakia, where the incidence of AKU rises to 1:19,000. This high incidence is difficult to explain by a classical founder effect, because as many as 10 different AKU mutations have been identified in this relatively small country. We have determined the allelic associations of 11 HGO intragenic polymorphisms for 44 AKU chromosomes from 20 Slovak pedigrees. These data were compared to the HGO haplotype data available in our laboratory for >80 AKU chromosomes from different European and non-European countries. The results show that common European AKU chromosomes have had only a marginal contribution to the Slovak AKU gene pool. Six of the ten Slovak AKU mutations, including the prevalent G152fs, G161R, G270R, and P370fs mutations, most likely originated in Slovakia. Data available for 17 Slovak AKU pedigrees indicate that most of the AKU chromosomes have their origins in a single very small region in the Carpathian mountains, in the northwestern part of the country. Since all six Slovak AKU mutations are associated with HGO mutational hot spots, we suggest that an increased mutation rate at the HGO gene is responsible for the clustering of AKU mutations in such a small geographical region. PMID:11017803

  6. Identification of forty cases with alkaptonuria in one village in Jordan.

    Science.gov (United States)

    Al-Sbou, Mohammed; Mwafi, Nesrin; Lubad, Mohammad Abu

    2012-12-01

    Alkaptonuria (AKU) is one of the four initially identified inborn errors of metabolism. The prevalence of AKU is unknown in Jordan. Therefore, a research project was started in April 2009 at the Faculty of Medicine/Mutah University in southern Jordan. The aims of the project were to identify people with AKU, to screen all family members with history of AKU, and to increase the awareness about the disease among health care professionals and the community in southern Jordan. Targeted family screening method was used to identify patients with AKU. In this paper, we present preliminary results of screening 17 families with history of AKU in a single village in southern region of Jordan. Forty cases with AKU were identified in this village (age range, 1-60 years). Early cases with AKU were diagnosed through out this study, two-third of patients (n = 28) were under the age of thirty. Interestingly, nine cases with AKU were identified in one family. Our experience suggests that for the identification of cases with AKU where consanguinity is common, the focus for screening should be extended to all family members. The prevalence of AKU among Jordanian is likely to be greater than the prevalence rates worldwide due to high rates of consanguineous marriages. Further studies and effective screening programs are needed to detect undiagnosed cases of AKU, to provide genetic counseling, and ultimately to prevent the occurrence of new cases of AKU in Jordan.

  7. Economic strategy of Arab to cope with EC unification; Establishment of blocks for economic unification. EC togo o niranda Arab keizai senryaku; Keizai togo e no block ka gensho

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Hideki (The Inst. of energy Economics, Tokyo (Japan))

    1990-01-01

    The agreement of the Arab Coopration Council (ACC) mentions the final aim of achieving the common market type economic unification by promoting economic cooperation within the area. All the ACC member nations are facing economical difficulties, and are in need of outside financial help. ACC was followed by the Arab Maghreb Union (AMU). The AMU is giving priority to the economic cooperation and cooperative projects within the area seeking tangible advantages, and its distinguishing characters and aims are analyzed. The accumulated debt problem of the AMU member nations is as serious as that of the ACC. The births of the ACC and AMU mean that the Arab world became a tripolar structure together with the Gulf Cooperation Council (GCC) established in 1981. The desire for the estblishment of Arab common market is common for the ACC, AMU and GCC. Problems confronting the GCC, ACC and AMU are described. 11 refs., 2 figs., 11 tabs.

  8. Decreasing fuel cost weight in electric utility business. ; Urged peak measures and management constitution improvement. Denki jigyo no nenryohi weight wa gensho. ; Isogareru peak taisaku to keiei taishitsu kaizen

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    The electric power industry has made stable and economic power supply possible by advancing diversification in power sources and shifting the petroleum supply sources to southern countries and China. The cost constitution of the electric utility business in the fiscal year 1992 was such that the ratio of fuel cost is 15.9% against the total cost amount of 13 trillion 399.3 billion yen. As opposed, the fuel cost percent in the fiscal 1980 was 37.7%. This means that the effect of the fuel cost on the total cost has become smaller even if the fuel cost varies as a result of external factors including fluctuation in foreign exchange rates. Peaks in the power demand have been recorded in day time in high summer when air conditioning demand increases, which have been growing year after year. Expenses to maintain facilities and functions to deal with this demand increase have been increasing. The owned capital ratio in the electric power business was 15.7% in the fiscal 1992, which is by far lower than the average of whole industry of 28%. Execution of measures against the power peaks and improvement of the management constitution are the problems posed on the electric power industry. 4 figs., 1 tab.

  9. FY1995 development of a clean CVD process by evaluation and control of gas phase nucleation phenomena; 1995 nendo kisokaku seisei gensho no hyoka to seigyo ni yoru clean CVD process no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The purpose of this study is to develop a high-rate and clean chemical vapor deposition (CVD) process as a breakthrough technique to overcome the problems that particles generated in the gas phase during CVD process for preparation of functional thin films cause reduced product yield and deterioration of the films. In the CVD process proposed here, reactant gas and generated particles are electrically charged to control the motion of them with an electric field. In this study, gas-phase nucleation phenomena are evaluated both theoretically and experimentally. A high-rate, ionized CVD method is first developed, in which reactant gas and generated particles are charged with negative ions generated from a radioisotope source and the UV/photoelectron method, and the motion of the charged gas and particles is controlled with an electric field. Charging and transport processes of fine particles are then investigated experimentally and theoretically to develop a clean CVD method in which generated particles are removed with the electric forces. As a result, quantitative evaluation of the charging and transport process was made possible. We also developed devices for measuring the size distribution and concentration of fine particles in low pressure gas such as those found in plasma CVD processes. In addition, numerical simulation and experiments in this study for a TEOS/O{sub 3} CVD process to prepare thin films could determine reaction rates which have not been known so far and give information on selecting good operation conditions for the process. (NEDO)

  10. 3Wave propagation in rock samples under medium and low temperature conditions. Characteristics of methane hydrate-BSR phenomena; Chu teion ryoiki ni okeru ganseki shiryo no hado denpa tokusei. 1. Methane hydrate BSR gensho no kosatsu suitei

    Energy Technology Data Exchange (ETDEWEB)

    Rokugawa, S; Kato, Y; Matsushima, J; Sano, A [The University of Tokyo, Tokyo (Japan). Faculty of Engineering

    1997-10-22

    In relation to sea-bottom pseudo reflection face and methane hydrate in seismic exploration records, fundamental experimental studies have been made. In order to get a handhold to elucidate phenomena accompanying methane hydrate, the studies have investigated wave propagation behavior of rock samples and sandy sediments under medium and low temperature conditions. The experiments have used a constant-temperature cooling water circulating equipment to control temperatures of each sample. The samples were placed in a cooler box with the vibration transmitter and receiver fixedly installed, and changes of the waves against temperature change were measured. Sand-stones and two kinds of tuffs were used as rock samples for the measurement. Artificial sand sample soaked in water was used as a substitute for a methane hydrate layer. As a result of the experiments, the relation between the hydrate layer and the gas layer was comprehended. In addition, the blanking phenomenon was thought occurring as a result of the nearly whole substance presenting the speed of ice due to freezing of the sediments, rather than by what is described in the ground homogeneousness theory. 5 refs., 9 figs.

  11. Proceedings of the Spring Meeting of the Society of Naval Architects of Japan (1996). Part 2. Structure, materials, welding, construction, and design; Nihon zosen gakkai (1996 nen) shunki koen ronbun maezuri. 2. Kozo, zairyo, yosetsu, kosaku, sekkei

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    This is a proceedings of the Spring Meeting of the Society of Naval Architects of Japan made public on May 15 and 16, 1996. In the basic research, the following are included: Basic studies on computer aided concurrent engineering for hull structure design and piping design; Fundamental study on the new method to estimate vibration level on a ship; Flat plate approximation in the three-dimensional slamming; Development of new finite element by source method, etc. As to fracture and cracks, Equivalent CTOD concept based on the local approach and its application to fracture performance evaluation of welded joints; Fracture mechanical modeling of brittle crack propagation and arrest of steel; An evaluation method for ductile crack propagation in pre-strained plates; Multiple fatigue cracks propagating in a stiffened panel, etc. Relating to fatigue strength, Fatigue life estimation of welded joints of an aluminum alloy under superimposed random load waves; Study on unified fatigue strength assessment method for welded structure, etc.

  12. Proceedings of the Spring Meeting of the Society of Naval Architects of Japan (1996). Part 2. Structure, materials, welding, construction, and design; Nihon zosen gakkai (1996 nen) shunki koen ronbun maezuri. 2. Kozo, zairyo, yosetsu, kosaku, sekkei

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    This is a proceedings of the Spring Meeting of the Society of Naval Architects of Japan made public on May 15 and 16, 1996. In the basic research, the following are included: Basic studies on computer aided concurrent engineering for hull structure design and piping design; Fundamental study on the new method to estimate vibration level on a ship; Flat plate approximation in the three-dimensional slamming; Development of new finite element by source method, etc. As to fracture and cracks, Equivalent CTOD concept based on the local approach and its application to fracture performance evaluation of welded joints; Fracture mechanical modeling of brittle crack propagation and arrest of steel; An evaluation method for ductile crack propagation in pre-strained plates; Multiple fatigue cracks propagating in a stiffened panel, etc. Relating to fatigue strength, Fatigue life estimation of welded joints of an aluminum alloy under superimposed random load waves; Study on unified fatigue strength assessment method for welded structure, etc.

  13. Fatigue strength of field welded joints in I-section girders of thick flange plates with cope hole details; Sukarappu wo yusuru atsuita I gata danmen keta genba yosetsu tsugitebu no hiro kyodo

    Energy Technology Data Exchange (ETDEWEB)

    Minami, K.; Miki, C.; Tateishi, K. [Tokyo Institute of Technology, Tokyo (Japan)

    1997-10-15

    Field welding an I-section girder forms details having scallop at the web, whereas the presence of the scallop causes shear deformation and localized stress concentration. Therefore the details in joints with low fatigue strength are ranked as class G in the fatigue design guideline published by JSSC. With special notice on the effect of shear, the present study has varied the phase by using multiple number of jacks; so loaded that the direction of the shear force will change; assumed field welding of a bridge constructed with a few number of main girders; and verified fatigue strength at thick flange plates. In addition, in order to improve the fatigue strength, elucidation was given on the effect of grinder finish at boxing welds. From these results, items to be considered were made clear when structural details are designed and fabricated, in which I-section girders having scallop are welded in fields. Furthermore, it was considered that stress in web plate jointing welding bead becomes relatively higher than local stress in boxing, which was indicated as a point requiring precaution. 8 refs., 20 figs., 2 tabs.

  14. Chondroptosis in Alkaptonuric Cartilage

    Science.gov (United States)

    Millucci, Lia; Giorgetti, Giovanna; Viti, Cecilia; Ghezzi, Lorenzo; Gambassi, Silvia; Braconi, Daniela; Marzocchi, Barbara; Paffetti, Alessandro; Lupetti, Pietro; Bernardini, Giulia; Orlandini, Maurizio

    2015-01-01

    Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of treatment is palliative and little is known about AKU physiopathology. Chondroptosis, a peculiar type of cell death in cartilage, has been so far reported to occur in osteoarthritis, a rheumatic disease that shares some features with AKU. In the present work, we wanted to assess if chondroptosis might also occur in AKU. Electron microscopy was used to detect the morphological changes of chondrocytes in damaged cartilage distinguishing apoptosis from its variant termed chondroptosis. We adopted histological observation together with Scanning Electron Microscopy and Transmission Electron Microscopy to evaluate morphological cell changes in AKU chondrocytes. Lipid peroxidation in AKU cartilage was detected by fluorescence microscopy. Using the above‐mentioned techniques, we performed a morphological analysis and assessed that AKU chondrocytes undergo phenotypic changes and lipid oxidation, resulting in a progressive loss of articular cartilage structure and function, showing typical features of chondroptosis. To the best of our knowledge, AKU is the second chronic pathology, following osteoarthritis, where chondroptosis has been documented. Our results indicate that Golgi complex plays an important role in the apoptotic process of AKU chondrocytes and suggest a contribution of chondroptosis in AKU pathogenesis. These findings also confirm a similarity between osteoarthritis and AKU. J. Cell. Physiol. 230: 1148–1157, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25336110

  15. Petroleum activity in ice covered waters - development and operation phase. Focus of eventual consequential explanation; Petroleumsvirksomhet i isfylte farvann - utbyggings- og driftsfase. Maalfokusering for eventuell konsekvensutredning. Arbeidsdokument fra AKU/AEAM-seminar, Stavanger 4. - 6. desember 1995

    Energy Technology Data Exchange (ETDEWEB)

    Thomassen, J; Andresen, K H; Moe, K A

    1996-06-01

    This report from a seminar relates to the petroleum activities in the Barentshavet north. The focal point was to put on petroleum activities in ice covered waters covering the drilling and operation phase, to identify discharges from various technical solutions, and to classify possible research requirements when mapping the impacts of such components. In addition to this approach, the seminar also focused on other factors regarding drilling and production activities in ice covered waters. 3 refs., 13 figs., 25 tabs.

  16. Alkaptonuria is a novel human secondary amyloidogenic disease.

    Science.gov (United States)

    Millucci, Lia; Spreafico, Adriano; Tinti, Laura; Braconi, Daniela; Ghezzi, Lorenzo; Paccagnini, Eugenio; Bernardini, Giulia; Amato, Loredana; Laschi, Marcella; Selvi, Enrico; Galeazzi, Mauro; Mannoni, Alessandro; Benucci, Maurizio; Lupetti, Pietro; Chellini, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2012-11-01

    Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Angiogenesis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Bernardini, Giulia; Marzocchi, Barbara; Braconi, Daniela; Geminiani, Michela; Gambassi, Silvia; Laschi, Marcella; Frediani, Bruno; Galvagni, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2016-11-01

    Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Here, we investigated the presence of neoangiogenesis in AKU synovium and healthy controls. Synovium from AKU patients, who had undergone total joint replacement or arthroscopy, or from healthy patients without any history of rheumatic diseases, who underwent surgical operation following sport trauma was subjected to hematoxylin and eosin staining. Histologic grades were assigned for clinical disease activity and synovitis based on cellular content of the synovium. By immunofluorescence microscopy, using different endothelial cell markers, we observed large vascularization in AKU but not in healthy synovium. Moreover, Western blotting and quantification analyses confirmed strong expression of endothelial cell markers in AKU synovial tissues. Importantly, AKU synovium vascular endothelium expressed high levels of β-dystroglycan, a protein previously involved in the regulation of angiogenesis in osteoarthritic synovium. This is the first report providing experimental evidences that new blood vessels are formed in AKU synovial tissues, opening new perspectives for AKU therapy.

  18. Redox proteomics gives insights into the role of oxidative stress in alkaptonuria.

    Science.gov (United States)

    Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Santucci, Annalisa

    2013-12-01

    Alkaptonuria (AKU) is an ultra-rare metabolic disorder of the catabolic pathway of tyrosine and phenylalanine that has been poorly characterized at molecular level. As a genetic disease, AKU is present at birth, but its most severe manifestations are delayed due to the deposition of a dark-brown pigment (ochronosis) in connective tissues. The reasons for such a delayed manifestation have not been clarified yet, though several lines of evidence suggest that the metabolite accumulated in AKU sufferers (homogentisic acid) is prone to auto-oxidation and induction of oxidative stress. The clarification of the pathophysiological molecular mechanisms of AKU would allow a better understanding of the disease, help find a cure for AKU and provide a model for more common rheumatic diseases. With this aim, we have shown how proteomics and redox proteomics might successfully overcome the difficulties of studying a rare disease such as AKU and the limitations of the hitherto adopted approaches.

  19. Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

    Science.gov (United States)

    Thorpe, Stephen D; Gambassi, Silvia; Thompson, Clare L; Chandrakumar, Charmilie; Santucci, Annalisa; Knight, Martin M

    2017-09-01

    Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

  20. Detection of strain behavior during phase-transformation in welds by the laser speckle method. Report 3. Application of the laser speckle method to strain masurement in the welding process; Reza supekkuru ho ni yoru yosetsubu no sohentai tojo no hizumi kenshutsu. 3. Reza supekkuru ni yoru hizumi sokuteiho no yosetsu eno tekiyo

    Energy Technology Data Exchange (ETDEWEB)

    Muramatsu, Y.; Kuroda, S. [National Research Inst. for Metals, Tsukuba, Ibaraki (Japan); Gross, H-G. [Rostock Univ., Rostock (Germany)

    1996-11-05

    It corresponds to an information relating to defect formation due to residual stress and its accompanying defect formation to find out the period of phase-transformation and expansion volume on the transformation forming at welding. In order to estimate texture of the heat affected zone, there is an SH-CCT diagram, which is important on weld metallurgy. However, this is formed by giving a thermal recycling to a small size specimen under stress-free, which has some problems to estimate the transformation starting period in actual welding. And, the expansion volume containing the transformation cannot be found out directly by this. In this study, as the first step adaptable to this problem with laser speckle method measurable with non-contact and high precision, a linear heating with TIG to a SUS304 stainless steel thin plate without transformation was executed at first, the strain behavior accompanied with it was confirmed. Secondly, using a thin plate of 9% Ni steel showing any transformation at comparatively low temperature, probability of a phase transformation detection was investigated on a way of cooling by executing resemble linear heating. As a result, the laser speckle method was confirmed to be adaptable to this problem. 14 refs., 17 figs., 1 tab.

  1. Theoretical study on instability mechanism of jet-induced sloshing. Model development using Orr-Sommerfeld equation generalized for non-parallel flow; Funryu reiki sloshing gensho no hassei kiko ni kansuru rironteki kenkyu. Hiheiko nagare ni ippankashita Orr-Sommerfeld hoteishiki wo mochiita model ka

    Energy Technology Data Exchange (ETDEWEB)

    Eguchi, Y. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1998-07-25

    A theoretical model was developed to study the mechanism of free surface sloshing in a vessel induced by a steady vertical jet flow. In the model, jet deflection is calculated with eigen values of the generalized Orr-Sommerfeld equation which is applicable to slightly non-parallel jet. Instability criteria employed in the model are (1) resonace condition between sloshing and jet frequencies and (2) {pi} phase relation between jet displacement at an inlet and global jet deflection. Numerical results of the mathematical model have shown good agreement with experimental ones, which justifies that the inherent instability of free jet itself and edge tone feedback are the main causes of the self-excited sloshing. 9 refs., 10 figs.

  2. Fatigue life estimation of welded joints of an aluminium alloy under superimposed random load waves (follow-up report). Effects of high frequency components; Jujo random kajuka ni okeru aluminium gokin yosetsu tsugite no hiro jumyo suitei (zokuho). Koshuha seibun no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, I.; Maenaka, H.; Takada, A. [Ship Research Inst., Tokyo (Japan)

    1996-12-31

    In order to examine fatigue behavior of boxing welded joints of anticorrosion aluminum A 5083 P-O alloy, the residual stress measurements, static loading tests, elastic finite element analyses, constant amplitude fatigue tests, and random fatigue tests were conducted. For a load wave in the random loading fatigue tests, a direct current component, a zero-mean narrow band random process, and a high frequency component were combined and superimposed, to examine the effect of the high frequency component and the effect of the stress cycle count method and the mean stress correction on the life estimation. For the fatigue analysis, a reference stress, such as that considering the structural stress concentration, was proved effective in reducing the amount of scattering in the fatigue test results and in improving the life estimation accuracy. Accordingly, for the actual scale measurements, it is insufficient only to measure the stress at points far from the crack initiation place. It is required to analyze the fatigue by measuring the reference stress same as the basic data acquisition tests in the laboratory. 4 refs., 21 figs., 4 tabs.

  3. FY 1998 annual summary report on development of techniques for keeping water environments in good conditions by utilizing phenomena involving immobilization of microorganisms on soft structures of carbon fibers (abbreviated to carbon/water environment project); 1998 nendo tanso sen'i nansoshiki eno biseibutsu kochaku gensho wo riyoshita mizukankyo seibi gijutsu no kaihatsu seika hokokusho. Ryakusho tanso mizukankyo project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    This project is aimed at creation of the new industry of keeping water environments in good conditions in wide amphitrichous areas by establishing the technical systems for applying the phenomena in which microorganisms are massively immobilized on a carbon fiber bundle suspended in water to, e.g., purification of sewage systems, rivers and ponds, and providing sites for algae to grow, and by commercializing these systems. The following 3 themes have been established. The first theme is to develop the techniques for braiding/weaving carbon fibers. The second theme is to analyze characteristics of the immobilized microorganism groups. The third theme is to establish the principles of utilization. The FY 1997 R&D efforts were directed to production of a total of 57 types of braided/woven carbon fibers, development of sizing agents, and analysis of microorganism groups. In FY 1998, the carbon fibers treated with new sizing agents have been developed, and the braided/woven carbon fibers are being tested in water purification systems and algae sites. It is found that the microorganism groups exhibit synergistic effects between the pumping function and carbon/gel materials. The simulation models are being developed for system designs. The systems which apparently show the effects of this method have been classified by analyzing the field test results. (NEDO)

  4. Fatigue life estimation of welded joints of an aluminium alloy under superimposed random load waves (follow-up report). Effects of high frequency components; Jujo random kajuka ni okeru aluminium gokin yosetsu tsugite no hiro jumyo suitei (zokuho). Koshuha seibun no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, I; Maenaka, H; Takada, A [Ship Research Inst., Tokyo (Japan)

    1997-12-31

    In order to examine fatigue behavior of boxing welded joints of anticorrosion aluminum A 5083 P-O alloy, the residual stress measurements, static loading tests, elastic finite element analyses, constant amplitude fatigue tests, and random fatigue tests were conducted. For a load wave in the random loading fatigue tests, a direct current component, a zero-mean narrow band random process, and a high frequency component were combined and superimposed, to examine the effect of the high frequency component and the effect of the stress cycle count method and the mean stress correction on the life estimation. For the fatigue analysis, a reference stress, such as that considering the structural stress concentration, was proved effective in reducing the amount of scattering in the fatigue test results and in improving the life estimation accuracy. Accordingly, for the actual scale measurements, it is insufficient only to measure the stress at points far from the crack initiation place. It is required to analyze the fatigue by measuring the reference stress same as the basic data acquisition tests in the laboratory. 4 refs., 21 figs., 4 tabs.

  5. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.

    Science.gov (United States)

    Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

    2013-09-01

    Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

  6. Diagnosis of secondary amyloidosis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Lupetti, Pietro; Perfetto, Federico; Orlandini, Maurizio; Santucci, Annalisa

    2014-09-26

    Alkaptonuria (AKU) is an inborn error of catabolism due to a deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a severe arthropathy, cardiovascular and kidney disease but other organs are affected, too. We found secondary amyloidosis as a life-threatening complication in AKU, thus opening new perspectives for its treatment. We proved that methotrexate and anti-oxidants have an excellent efficacy to inhibit the production of amyloid in AKU model chondrocytes. Owing to the progressive and intractable condition, it seems important to detect amyloid deposits at an early phase in AKU and the choice of specimens for a correct diagnosis is crucial. Ten AKU subjects were examined for amyloidosis; abdominal fat pad aspirates, labial salivary gland, cartilage and synovia specimens were analysed by CR, Th-T, IF, TEM. Amyloid was detected in only one abdominal fat pad specimen. However, all subjects demonstrated amyloid deposition in salivary glands and in other organ biopsies, indicating salivary gland as the ideal specimen for early amyloid detection in AKU. This is, at the best of our knowledge, the first report providing correct indications on the diagnosis of amyloidosis in AKU, thus offering the possibility of treatment of such co-morbidity to AKU patients. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_185.

  7. Mutational analysis of the HGO gene in Finnish alkaptonuria patients

    Science.gov (United States)

    de Bernabe, D. B.-V.; Peterson, P.; Luopajarvi, K.; Matintalo, P.; Alho, A.; Konttinen, Y.; Krohn, K.; de Cordoba, S. R.; Ranki, A.

    1999-01-01

    Alkaptonuria (AKU), the prototypic inborn error of metabolism, has recently been shown to be caused by loss of function mutations in the homogentisate-1,2-dioxygenase gene (HGO). So far 17 mutations have been characterised in AKU patients of different ethnic origin. We describe three novel mutations (R58fs, R330S, and H371R) and one common AKU mutation (M368V), detected by mutational and polymorphism analysis of the HGO gene in five Finnish AKU pedigrees. The three novel AKU mutations are most likely specific for the Finnish population and have originated recently.


Keywords: alkaptonuria; homogentisate-1,2-dioxygenase; Finland PMID:10594001

  8. Amyloidosis in alkaptonuria.

    Science.gov (United States)

    Millucci, Lia; Braconi, Daniela; Bernardini, Giulia; Lupetti, Pietro; Rovensky, Josef; Ranganath, Lakshminaryan; Santucci, Annalisa

    2015-09-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces an HGA-melanin ochronotic pigment, of hitherto unknown composition. Besides the accumulation of HGA, the potential role and presence of unidentified proteins has been hypothesized as additional causal factors involved in ochronotic pigment deposition. Evidence has been provided on the presence of serum amyloid A (SAA) in several AKU tissues, which allowed classifying AKU as a novel secondary amyloidosis. In this paper, we will briefly review all direct and indirect lines of evidence related to the presence of amyloidosis in AKU. We also report the first data on abnormal SAA serum levels in a cohort of AKU patients.

  9. Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

    Science.gov (United States)

    Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

    2017-11-01

    Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

  10. A quantitative assessment of alkaptonuria: testing the reliability of two disease severity scoring systems.

    Science.gov (United States)

    Cox, Trevor F; Ranganath, Lakshminarayan

    2011-12-01

    Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied clinical manifestations mainly by a process of conversion of HGA to a polymeric melanin-like pigment known as ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, successful demonstration of its efficacy in modifying the natural history of AKU requires an effective quantitative assessment tool. We have described two potential tools that could be used to quantitate disease burden in AKU. One tool describes scoring the clinical features that includes clinical assessments, investigations and questionnaires in 15 patients with AKU. The second tool describes a scoring system that only includes items obtained from questionnaires used in 44 people with AKU. Statistical analyses were carried out on the two patient datasets to assess the AKU tools; these included the calculation of Chronbach's alpha, multidimensional scaling and simple linear regression analysis. The conclusion was that there was good evidence that the tools could be adopted as AKU assessment tools, but perhaps with further refinement before being used in the practical setting of a clinical trial.

  11. Oxidative stress and mechanisms of ochronosis in alkaptonuria.

    Science.gov (United States)

    Braconi, Daniela; Millucci, Lia; Bernardini, Giulia; Santucci, Annalisa

    2015-11-01

    Alkaptonuria (AKU) is a rare metabolic disease due to a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD), involved in Phe and Tyr catabolism. Due to such a deficiency, AKU patients undergo accumulation of the metabolite homogentisic acid (HGA), which is prone to oxidation/polymerization reactions causing the production of a melanin-like pigment. Once the pigment is deposited onto connective tissues (mainly in joints, spine, and cardiac valves), a classical bluish-brown discoloration is imparted, leading to a phenomenon known as "ochronosis", the hallmark of AKU. A clarification of the molecular mechanisms for the production and deposition of the ochronotic pigment in AKU started only recently with a range of in vitro and ex vivo human models used for the study of HGA-induced effects. Thanks to redox-proteomic analyses, it was found that HGA could induce significant oxidation of a number of serum and chondrocyte proteins. Further investigations allowed highlighting how HGA-induced proteome alteration, lipid peroxidation, thiol depletion, and amyloid production could contribute to oxidative stress generation and protein oxidation in AKU. This review briefly summarizes the most recent findings on HGA-induced oxidative stress in AKU, helping in the clarification of the molecular mechanisms of ochronosis and potentially providing the basis for its pharmacological treatment. Future work should be undertaken in order to validate in vivo the results so far obtained in in vitro AKU models. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Alkaptonuria, more than just a mere disease

    Directory of Open Access Journals (Sweden)

    Abdul Qayyum Rana

    2015-01-01

    Full Text Available Alkaptonuria (AKU is considered a rare autosomal recessive condition that results in an accumulation of homogentisic acid in body tissues and causes long-term clinical, neurological and psychological complications. We present a comprehensive evaluation of an atypical 46-year-old Caucasian male who developed all clinical diagnostic symptoms of AKU (ochronotic pigmentations, dark urine and clinical arthritis of major joints including spine by 25 years of age, well before the typical age mentioned in many reviews. First signs of ochronotic ear pigmentations unexpectedly started appearing as early as 12 years of age. A long "disease-free" period typical in classical AKU patient was also absent. This case report highlights the importance of considering psychological issues in AKU patients. The patient showed symptoms of dysthymia reporting social isolation, diminished interest in pleasurable activities, feeling of worthlessness and irritability as major psychological issues. Early ochronotic pigmentation, advanced spinal myelopathy and arthropathy of major joints suggests aggressive course of the disease. Our patient underwent bilateral shoulder replacement due to AKU-induced arthropathy resulting in restoration of some range of motions. AKU is not fully understood and we recommend treating it as a multidimensional disease with simultaneous physiological, neurological and psychological effects. Early diagnosis, understanding of disease prognosis and emphasis on psychological health is needed to improve the quality of life of AKU patients.

  13. GPM, DPR Level 2A Ku Precipitation V03

    Data.gov (United States)

    National Aeronautics and Space Administration — The 2AKu algorithm provides precipitation estimates from the Ku radar of the Dual-Frequency Precipitation Radar on the core GPM spacecraft. The product contains one...

  14. Search Results | Page 42 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 411 - 420 of 9601 ... Journal articles. HIGHER EDUCATION INSTITUTIONS GENDER RELATIONS SEXUAL BEHAVIOUR ... utilization (AKU) of patent and research exemptions in academic institutions and industry in Botswana ... Training report on environmental education and waste management, Koh Sralao village.

  15. Search Results | Page 39 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 381 - 390 of 9576 ... Journal articles. HIGHER EDUCATION INSTITUTIONS GENDER RELATIONS SEXUAL BEHAVIOUR ... utilization (AKU) of patent and research exemptions in academic institutions and industry in Botswana ... Training report on environmental education and waste management, Koh Sralao village.

  16. Genetics of alkaptonuria – an overview

    Directory of Open Access Journals (Sweden)

    Zatkova Andrea

    2015-12-01

    Full Text Available Alkaptonuria (AKU is the first described inborn error of metabolism and a classical example of rare autosomal recessive disease. AKU patients carry homozygous or compound heterozygous mutations of the gene coding for enzyme homogentisate dioxygenase (HGD involved in metabolism of tyrosine. The metabolic block in AKU causes accumulation of homogentisic acid (HGA that, with advancing age of the patient, leads to severe and painful ochronotic arthropathy. HGD gene was mapped to chromosome 3q13.3 and is composed of 14 exons. In about 400 patients, 142 pathogenic variants were reported that are listed in HGD mutations database (http://hgddatabase.cvtisr.sk/. In this review, we summarise different aspects of AKU genetics and impact of the HGD variants on enzyme function.

  17. Kontoris kolme kitsega / Silvia Pärmann

    Index Scriptorium Estoniae

    Pärmann, Silvia

    2014-01-01

    Tallinnas Hobujaama tänaval asuva firma NG Investeeringud kontori interjöör, sisearhitekt Kaire Kemp-Tišler (ArtAku Sisearhitektuuribüroo). Ruumides eksponeeritakse Enn Kunila kunstikogusse kuuluvaid töid

  18. Fiscal 1999 achievement report on regional consortium research and development project. Regional consortium research and development in its 3rd year (Development of technology for treating aquatic environments using microorganisms fixed carbon fibers--Abbreviation: Carbon/aquatic environment project); 1999 nendo tanso sen'i nansoshiki eno biseibutsu kochaku gensho wo riyoshita mizukankyo seibi gijutsu no kaihatsu (ryakusho: tanso mizukankyo project) seika hokokusho. 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    A carbon fiber has been developed, which is easy to fabricate and allows microorganisms to anchor on. For its application to purify water, the fiber should be formed into an umbrella-type fringe and used in water featuring BOD (biological oxygen demand): 5-600ppm and chlorophyll-a: 80{mu}g/L or less and flowing at an appropriate speed. Communities of microbes speedily anchor themselves in large quantities on the carbon fiber fringe, and they are difficult to remove and highly active. Inside the anchored groups, there exist, in addition to aerobic microbial phases, anaerobic microbial phases occupying 40%. In an appropriate flow the microbial communities on the fringe perform a kind of pumping motion and exhibits a great mass transfer velocity. Carboniphilic bacteria exert a great influence during the initial stage of the anchoring process. Various woven carbon fiber products are used as artificial waterweeds and provide spawning grounds which are favored by fishes. The carbon fiber products may have some attractive trait which invites them. The characteristics of the anchored microbial communities are determined by synergism between the physical/chemical peculiarities of the carbon fiber and the nature of carbon favorable toward living organisms. Principles to follow in the use of carbon fiber products are mentioned. (NEDO)

  19. Report of the results of the fiscal 1997 regional consortium R and D project. Regional consortium field / Development of technology to treat aquatic environment by using microorganisms fixed on carbon fabrics (abbreviation: carbon/aquatic environment project) (first fiscal year); 1997 nendo chiiki consortium kenkyu kaihatsu jigyo. Chiiki consortium bun`ya / tanso sen`i nansoshiki eno biseibutsu kochaku gensho wo riyoshita mizukankyo seibi gijutsu no kaihatsu (ryakusho: tanso mizu kankyo project) daiichi nendo seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    Out of the development of technology to arrange the aquatic environment using phenomena of microorganism fixation on carbon fiber soft textures, the paper stated the fiscal 1997 result. On carbon fibers in a state of swaying in water, microorganisms in water fix in an amazingly large quantity. A catalog was compiled of 58 kinds of carbon fabrics trially woven and knitted. When carbon fiber is used as activated sludge carrier, activity of microorganism lasts more than one year. Only a little amount of surplus sludge is generated. The fixed microorganisms are more active in case of carbon fiber than in case of nylon and polyester fibers. Fiber texture models of carbon fiber fixing activated sludge groups were proposed. By pump operation, the water flow inside/outside microorganism groups is being accelerated. Several new strains of bacillus carboniphilus were isolated/identified from soil and marsh. To grasp relationships of characteristics among three elements such as the state of aquatic environment, fiber, and microorganism group, the experiment was prepared. Preliminary work is conducted to derive a simple equation for facility design, and experimental directions to obtain design conditions were proposed. 6 refs., 166 figs., 47 tabs.

  20. Improvement of sensitizatiuon in weld metals of austenitic stainless steels by laser surface melting treatment. Report 3. Study on low temperature sensitization in weldments of austenitic stainless steels ans its improvement by laser surface melting treatment; Reza hyomen yoyu shori ni yoru sutenresu ko yosetsu kinzoku no enbinka kaizen. 3. Osutenaito kei sutenresu ko yosetsubu no teion enbinka to reza hyomen yoyu shori ni yoru sono kaizen

    Energy Technology Data Exchange (ETDEWEB)

    Nishimoto, K. [Osaka Univ., Osaka (Japan). Faculty of Engineering; Mori, H. [Osaka Univ., Osaka (Japan). Graduate School; Yamamura, T. [Mitsubishi Heavy Industries Ltd., Tokyo (Japan)

    1997-05-05

    Laser surface melting treatment used for the improvement of intergranular corrosion resistance of sensitized austenitic stainless steel weld metal was studied. As a result, it was revealed that as compared to untreated material, sensitization was improved widely and intergranular corrosion resistance was improved to a level of base metal when laser surface melting treatment of sensitized weld metal was carried out. Further, sensitization effect at a condition of laser traveling velocity of 0.00167m/s was slightly insufficient compared to that of laser traveling velocity above 0.00833m/s. This phenomena was caused due to the existence of {delta} ferrite that accelerates the precipitation of Cr carbides inside the laser treatment portion and together with this, the Cr carbides are precipitated in {delta}/{gamma} grain boundary due to the effect of laser heat cycle with insufficient cooling velocity and this has caused desensitization. 16 refs., 13 figs., 3 tabs.

  1. Franchising as a potential growth strategy for a small enterprise

    OpenAIRE

    Lavonen, Riikka

    2010-01-01

    This thesis is to examine franchising as a possible growth strategy for a clothing store called Aku & Ada. The company is new; it has been open for only eight months now. Already during the business plan writing process was franchising brought up as a possibility for the company. The purpose for this thesis is to find out whether franchising could be an option for Aku & Ada to expand their business operations. The theoretical part has been separated into two different categories. The fist...

  2. Cartilage biomarkers in the osteoarthropathy of alkaptonuria reveal low turnover and accelerated ageing.

    Science.gov (United States)

    Taylor, Adam M; Hsueh, Ming-Feng; Ranganath, Lakshminarayan R; Gallagher, James A; Dillon, Jane P; Huebner, Janet L; Catterall, Jon B; Kraus, Virginia B

    2017-01-01

    Alkaptonuria (AKU) is a rare autosomal recessive disease resulting from a single enzyme deficiency in tyrosine metabolism. As a result, homogentisic acid cannot be metabolized, causing systemic increases. Over time, homogentisic acid polymerizes and deposits in collagenous tissues, leading to ochronosis. Typically, this occurs in joint cartilages, leading to an early onset, rapidly progressing osteoarthropathy. The aim of this study was to examine tissue turnover in cartilage affected by ochronosis and its role in disease initiation and progression. With informed patient consent, hip and knee cartilages were obtained at surgery for arthropathy due to AKU (n = 6; 2 knees/4 hips) and OA (n = 12; 5 knees/7 hips); healthy non-arthritic (non-OA n = 6; 1 knee/5 hips) cartilages were obtained as waste from trauma surgery. We measured cartilage concentrations (normalized to dry weight) of racemized aspartate, GAG, COMP and deamidated COMP (D-COMP). Unpaired AKU, OA and non-OA samples were compared by non-parametric Mann-Whitney U test. Despite more extractable total protein being obtained from AKU cartilage than from OA or non-OA cartilage, there was significantly less extractable GAG, COMP and D-COMP in AKU samples compared with OA and non-OA comparators. Racemized Asx (aspartate and asparagine) was significantly enriched in AKU cartilage compared with in OA cartilage. These novel data represent the first examination of cartilage matrix components in a sample of patients with AKU, representing almost 10% of the known UK alkaptonuric population. Compared with OA and non-OA, AKU cartilage demonstrates a very low turnover state and has low levels of extractable matrix proteins. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Natural history of alkaptonuria revisited: analyses based on scoring systems.

    Science.gov (United States)

    Ranganath, Lakshminarayan R; Cox, Trevor F

    2011-12-01

    Increased circulating homogentisic acid in body fluids occurs in alkaptonuria (AKU) due to lack of enzyme homogentisate dioxygenase leading in turn to conversion of HGA to a pigmented melanin-like polymer, known as ochronosis. The tissue damage in AKU is due to ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, deploying nitisinone effectively requires its administration at the most optimal time in the natural history. AKU has a long apparent latent period before overt ochronosis develops. The rate of change of ochronosis and its consequences over time following its recognition has not been fully described in any quantitative manner. Two potential tools are described that were used to quantitate disease burden in AKU. One tool describes scoring the clinical features that includes clinical assessments, investigations and questionnaires in 15 patients with AKU. The second tool describes a scoring system that only includes items obtained from questionnaires in 44 people with AKU. Analysis of the data reveals distinct phases of the disease, a pre-ochronotic phase and an ochronotic phase. The ochronotic phase appears to demonstrate an earlier slower progression followed by a rapidly progressive phase. The rate of change of the disease will have implications for monitoring the course of the disease as well as decide on the most appropriate time that treatment should be started for it to be effective either in prevention or arrest of the disease.

  4. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

    Directory of Open Access Journals (Sweden)

    Lia Millucci

    2014-01-01

    Full Text Available Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.

  5. Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence.

    Science.gov (United States)

    Sakthivel, Srinivasan; Zatkova, Andrea; Nemethova, Martina; Surovy, Milan; Kadasi, Ludevit; Saravanan, Madurai P

    2014-05-01

    Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin. © 2014 John Wiley & Sons Ltd/University College London.

  6. Identification of alkaptonuria in the general population: a United Kingdom experience describing the challenges, possible solutions and persistent barriers.

    Science.gov (United States)

    Ranganath, L; Taylor, A M; Shenkin, A; Fraser, W D; Jarvis, J; Gallagher, J A; Sireau, N

    2011-06-01

    Progress in research into rare diseases is challenging. This paper discusses strategies to identify individuals with the rare genetic disease alkaptonuria (AKU) within the general population. Strategies used included a questionnaire survey of general practitioners, a dedicated website and patient network contact, targeted family screening and medical conference targeting. Primary care physicians of the UK were targeted by a postal survey that involved mailing 11,151 UK GPs; the response rate was 18.2%. We have identified 75 patients in the UK with AKU by the following means: postal survey (23), targeted family screening (11), patient networks and the website (41). Targeting medical conferences (AKU, rare diseases, rheumatology, clinical biochemistry, orthopaedics, general practitioners) did not lead to new identification in the UK but helped identify overseas cases. We are now aware of 626 patients worldwide including newly identified non-UK people with AKU in the following areas: Slovakia (208), the rest of Europe (including Turkey) (79), North America (including USA and Canada) (110), and the rest of the world (154). A mechanism for identifying individuals with AKU in the general population-not just in the UK but worldwide-has been established. Knowledge of patients with AKU, both in the UK and outside, is often confined to establishing their location in a particular GP practice or association with a particular medical professional. Mere identification, however, does not always lead to full engagement for epidemiological research purposes or targeting treatment since further barriers exist.

  7. Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

    Science.gov (United States)

    Ghezzi, Lorenzo; Giorgetti, Giovanna; Viti, Cecilia; Geminiani, Michela; Soldani, Patrizia; Lupetti, Pietro; Benvenuti, Chiara; Perfetto, Federico; Spreafico, Adriano; Santucci, Annalisa

    2014-01-01

    Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart. PMID:24876668

  8. A new light on Alkaptonuria: A Fourier-transform infrared microscopy (FTIRM) and low energy X-ray fluorescence (LEXRF) microscopy correlative study on a rare disease.

    Science.gov (United States)

    Mitri, Elisa; Millucci, Lia; Merolle, Lucia; Bernardini, Giulia; Vaccari, Lisa; Gianoncelli, Alessandra; Santucci, Annalisa

    2017-05-01

    Alkaptonuria (AKU) is an ultra-rare disease associated to the lack of an enzyme involved in tyrosine catabolism. This deficiency results in the accumulation of homogentisic acid (HGA) in the form of ochronotic pigment in joint cartilage, leading to a severe arthropathy. Secondary amyloidosis has been also unequivocally assessed as a comorbidity of AKU arthropathy. Composition of ochronotic pigment and how it is structurally related to amyloid is still unknown. We exploited Synchrotron Radiation Infrared and X-Ray Fluorescence microscopies in combination with conventional bio-assays and analytical tools to characterize chemical composition and morphology of AKU cartilage. We evinced that AKU cartilage is characterized by proteoglycans depletion, increased Sodium levels, accumulation of lipids in the peri-lacunar regions and amyloid formation. We also highlighted an increase of aromatic compounds and oxygen-containing species, depletion in overall Magnesium content (although localized in the peri-lacunar region) and the presence of calcium carbonate fragments in proximity of cartilage lacunae. We highlighted common features between AKU and arthropathy, but also specific signatures of the disease, like presence of amyloids and peculiar calcifications. Our analyses provide a unified picture of AKU cartilage, shedding a new light on the disease and opening new perspectives. Ochronotic pigment is a hallmark of AKU and responsible of tissue degeneration. Conventional bio-assays have not yet clarified its composition and its structural relationship with amyloids. The present work proposes new strategies for filling the aforementioned gap that encompass the integration of new analytical approaches with standardized analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria.

    Science.gov (United States)

    Arnoux, Jean-Baptiste; Le Quan Sang, Kim-Hanh; Brassier, Anais; Grisel, Coraline; Servais, Aude; Wippf, Julien; Dubois, Sandrine; Sireau, Nicolas; Job-Deslandre, Chantal; Ranganath, Lakshminarayan; de Lonlay, Pascale

    2015-09-01

    Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It results in an accumulation of homogentisate which oxidizes spontaneously to benzoquinone acetate, a highly oxidant compound, which polymerises to a melanin-like structure, in a process called ochronosis. Asymptomatic during childhood, this accumulation will lead from the second decade of life to a progressive and severe spondylo-arthopathy, associated with multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly understood, but recent advances lead us to reconsider the treatment strategy in AKU patients. Besides the supporting therapies (pain killers, anti-inflammatory drugs, physiotherapy, joints replacements and others), specific therapies have been considered (anti-oxidant, low protein diet, nitisinone), but clinical studies have failed to prove efficiency on the rheumatological lesions of the disease. Here we propose a treatment strategy for children and adults with AKU, based on a review of the latest findings on AKU and lessons from other aminoacipathies, especially tyrosinemias.

  10. Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria in an in vitro human cell model.

    Science.gov (United States)

    Tinti, Laura; Spreafico, Adriano; Braconi, Daniela; Millucci, Lia; Bernardini, Giulia; Chellini, Federico; Cavallo, Giovanni; Selvi, Enrico; Galeazzi, Mauro; Marcolongo, Roberto; Gallagher, James A; Santucci, Annalisa

    2010-10-01

    Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid (HGA) and its oxidized derivatives in polymerized form in connective tissues especially in joints. Currently, AKU lacks an appropriate therapy. Hence, we propose a new treatment for AKU using the antioxidant N-acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side-effects of ASC. We established an in vitro cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33 mM). We used this experimental model to undertake pre-clinical testing of potential antioxidative therapies for AKU, evaluating apoptosis, viability, proliferation, and metabolism of chondrocytes exposed to HGA and treated with NAC and ASC administered alone or in combination addition of both. NAC decreased apoptosis induced in chondrocytes by HGA, increased chondrocyte growth reduced by HGA, and partially restored proteoglycan release inhibited by HGA. A significantly improvement in efficacy was found with combined addition of the two antioxidants in comparison with NAC and ASC alone. Our novel in vitro AKU model allowed us to demonstrate the efficacy of the co-administration of NAC and ASC to counteract the negative effects of HGA for the treatment of ochronotic arthropathy. (c) 2010 Wiley-Liss, Inc.

  11. Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria.

    Science.gov (United States)

    Laschi, Marcella; Tinti, Laura; Braconi, Daniela; Millucci, Lia; Ghezzi, Lorenzo; Amato, Loredana; Selvi, Enrico; Spreafico, Adriano; Bernardini, Giulia; Santucci, Annalisa

    2012-09-01

    Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy. Copyright © 2011 Wiley Periodicals, Inc.

  12. Towards excellence in cardiac surgery: experience from a developing country.

    Science.gov (United States)

    Saifuddin, Aamir; Shahabuddin, Syed; Perveen, Shazia; Furnaz, Shumaila; Sharif, Hasanat

    2015-08-01

    The objective of this study is an attempt to measure the performance in terms of comparing results with a large internationally recognized database used as a benchmark. Cross-sectional (prospectively collected data analysed and compared retrospectively). Aga Khan University Hospital, Karachi, Pakistan. From January 2006 to December 2010, information of the 2198 CABGs performed at Aga Khan University Hospital (AKU) was collected prospectively. This included patient characteristics and specific intra- and post-operative outcomes and compared with findings from the American Society of Thoracic Surgeons' National Cardiac Database (STS-NCD). There were more male patients in the AKU cohort and more diabetics. In AKU, more cases involved three or more grafts (85 vs. 78%), and in both groups, an internal mammary artery graft was used over 90% of the time. The overall 30-day mortality was 2.7% at AKU, compared with 1.5% in the STS-NCD data. AKU had a lower incidence of permanent stroke (0.5 vs. 1.2%), prolonged ventilation (10.5 vs. 11.0%), deep sternal wound infection (0.2 vs. 0.4%) and reoperation (4.0 vs. 4.7%). It had more cases of renal failure (5.4 vs. 3.6%). Readmission rates within 30 days were also less in AKU (3.9 vs. 9.1%). The outcomes of this study compare very favourably with the benchmark (STS). This demonstrates that high level of quality care can be achieved in this part of the world. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  13. Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on ‘black bone disease' in Italy

    Science.gov (United States)

    Nemethova, Martina; Radvanszky, Jan; Kadasi, Ludevit; Ascher, David B; Pires, Douglas E V; Blundell, Tom L; Porfirio, Berardino; Mannoni, Alessandro; Santucci, Annalisa; Milucci, Lia; Sestini, Silvia; Biolcati, Gianfranco; Sorge, Fiammetta; Aurizi, Caterina; Aquaron, Robert; Alsbou, Mohammed; Marques Lourenço, Charles; Ramadevi, Kanakasabapathi; Ranganath, Lakshminarayan R; Gallagher, James A; van Kan, Christa; Hall, Anthony K; Olsson, Birgitta; Sireau, Nicolas; Ayoob, Hana; Timmis, Oliver G; Le Quan Sang, Kim-Hanh; Genovese, Federica; Imrich, Richard; Rovensky, Jozef; Srinivasaraghavan, Rangan; Bharadwaj, Shruthi K; Spiegel, Ronen; Zatkova, Andrea

    2016-01-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650–85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy. PMID:25804398

  14. Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

    Science.gov (United States)

    Beltrán-Valero de Bernabé, D; Granadino, B; Chiarelli, I; Porfirio, B; Mayatepek, E; Aquaron, R; Moore, M M; Festen, J J; Sanmartí, R; Peñalva, M A; de Córdoba, S R

    1998-01-01

    Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles. PMID:9529363

  15. Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

    Science.gov (United States)

    Nemethova, Martina; Radvanszky, Jan; Kadasi, Ludevit; Ascher, David B; Pires, Douglas E V; Blundell, Tom L; Porfirio, Berardino; Mannoni, Alessandro; Santucci, Annalisa; Milucci, Lia; Sestini, Silvia; Biolcati, Gianfranco; Sorge, Fiammetta; Aurizi, Caterina; Aquaron, Robert; Alsbou, Mohammed; Lourenço, Charles Marques; Ramadevi, Kanakasabapathi; Ranganath, Lakshminarayan R; Gallagher, James A; van Kan, Christa; Hall, Anthony K; Olsson, Birgitta; Sireau, Nicolas; Ayoob, Hana; Timmis, Oliver G; Sang, Kim-Hanh Le Quan; Genovese, Federica; Imrich, Richard; Rovensky, Jozef; Srinivasaraghavan, Rangan; Bharadwaj, Shruthi K; Spiegel, Ronen; Zatkova, Andrea

    2016-01-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.

  16. FY 1999 Report on the results of technological development of machine tools for rationalization of energy utilization. Development of a lathe with high precision and conservation of energy using natural phenomenon (Thermal countermeasure using self compulsory cooling and thermal insensitive structure - results of the first year); 1999 nendo energy shiyo gorika kosaku kikai nado gijutsu kaihatsu seika hokokusho. Shizen gensho wo takumi ni oyoshita sho energy koseido senban no kaihatsu (self kyosei reikyaku to netsufukan gijutsu wo mochiita netsuhenkei yokusei taisaku - dai 1 nendo)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    A lathe, which is a central tool in a factory of automobiles or home electric appliances, tends to suffer decreased machining precision resulting from thermal deformation. This project is aimed at development of the energy-saving, high-precision lathe technologies using self compulsory cooling and thermal insensitive technologies as the countermeasures against the thermal deformation. The self compulsory cooling is a method of cooling by evaporation of water with an evaporative, water-absorptive cloth being bonded to a machine tool surface around the major axis. The thermal insensitive technologies include the three-dimensionally zero-center design technologies which help design a lathe in such a way to set the processing point (tool working point) at the base of thermal deformation in the X, Y and Z axis directions; material combination technologies to control thermal deformation; and coloring technologies to control thermal deformation. The development target is the high-precision lathe fabrication technologies, which realize a temporal precision change of 1 to 2 {mu}m or less per work dimension of 100mm. The activities cover 5 areas, including development of elementary technologies for each item and construction/evaluation of the full-size test unit. (NEDO)

  17. Spontaneous Achilles tendon rupture in alkaptonuria

    Directory of Open Access Journals (Sweden)

    Omar A. Alajoulin

    2015-12-01

    Full Text Available Alkaptonuria (AKU is a rare inborn metabolic disease characterized by accumulation of homogentisic acid (HGA. Excretion of HGA in urine causes darkening of urine and its deposition in connective tissues causes dark pigmentation (ochronosis, early degeneration of articular cartilage, weakening of the tendons, and subsequent rupture. In this case report, we present a rare case of a patient presented with unilateral spontaneous rupture of Achilles tendon due to AKU. The patient developed most of the orthopedic manifestations of the disease earlier than typical presentations. Alkaptonuria patients should avoid strenuous exercises and foot straining especially in patients developing early orthopedic manifestations.

  18. Spontaneous Achilles tendon rupture in alkaptonuria.

    Science.gov (United States)

    Alajoulin, Omar A; Alsbou, Mohammed S; Ja'afreh, Somayya O; Kalbouneh, Heba M

    2015-12-01

    Alkaptonuria (AKU) is a rare inborn metabolic disease characterized by accumulation of homogentisic acid (HGA). Excretion of HGA in urine causes darkening of urine and its deposition in connective tissues causes dark pigmentation (ochronosis), early degeneration of articular cartilage, weakening of the tendons, and subsequent rupture. In this case report, we present a rare case of a patient presented with unilateral spontaneous rupture of Achilles tendon due to AKU. The patient developed most of the orthopedic manifestations of the disease earlier than typical presentations. Alkaptonuria patients should avoid strenuous exercises and foot straining especially in patients developing early orthopedic manifestations.

  19. Kaurismäki Soome parim

    Index Scriptorium Estoniae

    2007-01-01

    Soome filmiauhinna Jussi võitis A. Kaurismäki "Äärelinna tuled" ("Laitakaupungin valot"), viis Jussit sai Aku Louhimiehe film "Jäine linn" ("Valkoinen kaupunki") ja kaks Jussit Eesti osalusega "Igavese armastuse sõdalane - Jade Warrior"

  20. Pangad koorivad kaks nahka / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2008-01-01

    Ilmunud ka: Delovõje Vedomosti 21. mai lk. 10. Kohustusliku pensionisamba kliendid maksavad pankadele topelt teenustasusid, sest mitu panka investeerivad pensionifondide vara iseenda teistesse fondidesse. Vt. samas: Kolme suurema panga investeeringud oma fondidesse; Kuidas kujuneb topelttasu; Hansa ja SEB klientide arvult pikalt ees. Kommenteerivad Mihkel Oja ja Aku Sorainen. Vastuseks vt. ka Sven Kunsingi art. 21. mai lk. 26

  1. Kõltsu mõis = Kõltsu Manor

    Index Scriptorium Estoniae

    2011-01-01

    Kõltsu mõisa peahoone restaureerimisest ja sisearhitektuursest lahendusest. Sisearhitektid Ea Andla ja Kaire Kemp-Tišler (SAB ArtAku). Arhitekt Jüri Irik. Vitraažidega lükandseina tegi Valev Sein. Kaminaahju sepistas Heigo Jelle

  2. Treatment of femoral neck fracture by Moore Prosthesis in Cotonou ...

    African Journals Online (AJOL)

    Treatment of femoral neck fracture by Moore Prosthesis in Cotonou. AHM Akue, M Lawson, S Madougou, R Zannou, J Padonou. Abstract. Keywords: Benin; hip; Moore prosthesis; results. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  3. Elamise kunst ja unistuste julgus juubeli-PÖFFil / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2006-01-01

    10nda Pimedate Ööde Filmifestivali võidufilmid : "TumeSininePeaaeguMust", režissöör Daniel Sanchez Arevalo : Hispaania 2006, "Taksitermia", režissöör György Palfi : Ungari-Austria-Prantsusmaa 2006. Lisaks Joachim Lafosse'i filmist "Eravaldus" ja Aku Louhimiehe filmist "Lahtikistud mees"

  4. Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress.

    Science.gov (United States)

    Braconi, Daniela; Bernardini, Giulia; Paffetti, Alessandro; Millucci, Lia; Geminiani, Michela; Laschi, Marcella; Frediani, Bruno; Marzocchi, Barbara; Santucci, Annalisa

    2016-12-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Acute fatal metabolic complications in alkaptonuria.

    Science.gov (United States)

    Davison, A S; Milan, A M; Gallagher, J A; Ranganath, L R

    2016-03-01

    Alkaptonuria (AKU) is a rare inherited metabolic disorder of tyrosine metabolism that results from a defect in an enzyme called homogentisate 1,2-dioxygenase. The result of this is that homogentisic acid (HGA) accumulates in the body. HGA is central to the pathophysiology of this disease and the consequences observed; these include spondyloarthropathy, rupture of ligaments/muscle/tendons, valvular heart disease including aortic stenosis and renal stones. While AKU is considered to be a chronic progressive disorder, it is clear from published case reports that fatal acute metabolic complications can also occur. These include oxidative haemolysis and methaemoglobinaemia. The exact mechanisms underlying the latter are not clear, but it is proposed that disordered metabolism within the red blood cell is responsible for favouring a pro-oxidant environment that leads to the life threatening complications observed. Herein the role of red blood cell in maintaining the redox state of the body is reviewed in the context of AKU. In addition previously reported therapeutic strategies are discussed, specifically with respect to why reported treatments had little therapeutic effect. The potential use of nitisinone for the management of patients suffering from the acute metabolic decompensation in AKU is proposed as an alternative strategy.

  6. Two novel mutations in the homogentisate-1,2-dioxygenase gene identified in Chinese Han Child with Alkaptonuria.

    Science.gov (United States)

    Li, Hongying; Zhang, Kaihui; Xu, Qun; Ma, Lixia; Lv, Xin; Sun, Ruopeng

    2015-03-01

    Alkaptonuria (AKU) is an autosomal recessive disorder of tyrosine metabolism, which is caused by a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) with subsequent accumulation of homogentisic acid. Presently, more than 100 HGD mutations have been identified as the cause of the inborn error of metabolism across different populations worldwide. However, the HGD mutation is very rarely reported in Asia, especially China. In this study, we present mutational analyses of HGD gene in one Chinese Han child with AKU, which had been identified by gas chromatography-mass spectrometry detection of organic acids in urine samples. PCR and DNA sequencing of the entire coding region as well as exon-intron boundaries of HGD have been performed. Two novel mutations were identified in the HGD gene in this AKU case, a frameshift mutation of c.115delG in exon 3 and the splicing mutation of IVS5+3 A>C, a donor splice site of the exon 5 and exon-intron junction. The identification of these mutations in this study further expands the spectrum of known HGD gene mutations and contributes to prenatal molecular diagnosis of AKU.

  7. Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria.

    Science.gov (United States)

    Vilboux, Thierry; Kayser, Michael; Introne, Wendy; Suwannarat, Pim; Bernardini, Isa; Fischer, Roxanne; O'Brien, Kevin; Kleta, Robert; Huizing, Marjan; Gahl, William A

    2009-12-01

    Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder, characterized by accumulation of homogentisic acid, leading to darkened urine, pigmentation of connective tissue (ochronosis), joint and spine arthritis, and destruction of cardiac valves. AKU is due to mutations in the homogentisate dioxygenase gene (HGD) that converts homogentisic acid to maleylacetoacetic acid in the tyrosine catabolic pathway. Here we report a comprehensive mutation analysis of 93 patients enrolled in our study, as well as an extensive update of all previously published HGD mutations associated with AKU. Within our patient cohort, we identified 52 HGD variants, of which 22 were novel. This yields a total of 91 identified HGD variations associated with AKU to date, including 62 missense, 13 splice site, 10 frameshift, 5 nonsense, and 1 no-stop mutation. Most HGD variants reside in exons 3, 6, 8, and 13. We assessed the potential effect of all missense variations on protein function, using five bioinformatic tools specifically designed for interpretation of missense variants (SIFT, POLYPHEN, PANTHER, PMUT, and SNAP). We also analyzed the potential effect of splice-site variants using two different tools (BDGP and NetGene2). This study provides valuable resources for molecular analysis of alkaptonuria and expands our knowledge of the molecular basis of this disease.

  8. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    Science.gov (United States)

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-05

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. INTRODUCTION The Benue trough is a linear northeast- southwest ...

    African Journals Online (AJOL)

    Modal analysis framework grains suggest a subarkosic sandstone. ... sandstones using the framework mineral composition .... angular to subrounded, are not morphologically ..... 6: The Effect of Source Rock on Composition of the Eze-Aku Sandstone using Suttner et al. ..... on Water Quality and Planktonic Production in an.

  10. Kontorihoone : Järvevana tee 9g, Tallinn = Office Building : 9g Järvevana Str., Tallinn / Raivo Puusepp

    Index Scriptorium Estoniae

    Puusepp, Raivo

    2003-01-01

    Merko Ehituse 6-korruseline suletud kabinetsüsteemis büroohoone. Arhitekt Raivo Puusepp, kaasa töötasid Maike Heido ja Peeter Loo. Sisekujundaja Kaire Kemp (ArtAku). Konstruktiivne lahendus: Neoprojekt. Projekt 2001, valmis 2003. I korruse plaan, sise- ja 2 välisvaadet

  11. Kõltsu mõisa peahoone = Kõltsu manor house / Jüri Irik, Kaire Kemp-Tišler ; intervjueerinud Margit Mutso

    Index Scriptorium Estoniae

    Irik, Jüri, 1961-

    2011-01-01

    Kõltsu mõisa peahoone restaureerimisest. Arhitekt Jüri Irik (AB Ehala & Irik). Sisearhitektid Kaire Kemp-Tišler, Ea Andla (SAB ArtAku). Maastikuarhitektid Ülle Grišakov, Triin Järve. Vitraažide autor Valev Sein. Sepiste autor Heigo Jelle

  12. A comparative analysis of watershed and edge based segmentation ...

    African Journals Online (AJOL)

    MJP

    2015-03-17

    Mar 17, 2015 ... This is an Open Access article distributed under the terms of the creative commons Attribution 4.0 licence. (http://creativecommons.org/licenses/by/4.0) which ... Ajala F.A1*, Fenwa O.D1, Aku. M.A2. 1Department of Computer Science and Engineering, Ladoke Akintola University of Technology, Ogbomoso,.

  13. Petroleum potential of campano-maastrichtian shales of Anambra ...

    African Journals Online (AJOL)

    The samples were analyzed for the total carbon content (TOC), extract yield, organic matter types and organic maturity level. As screening criteria, all the sample set were subjected to TOC measurement (LECO). The TOC values range from 0.81-1.40% (AKU2) and from 0.82-1.81% (AMA.1) most of the samples meet up with ...

  14. Valgussähvatused saalipimedusest / Katrin Rajasaare

    Index Scriptorium Estoniae

    Rajasaare, Katrin

    2002-01-01

    6. Pimedate Ööde Festivali filmidest : "Puur" ("La Cage"), režissöör Alain Raoust : Prantsusmaa 2002, "Kuuvalgel" ("Kuutamolla"), režissöör Aku Louhimies : Soome 2001, "Kaunis Martha" ("Bella Martha"), režissöör Sandra Nettelbeck : Saksamaa 2001

  15. Maternal-Newborn and Surgical Nurses’ Perceptions of Professional Autonomy During the Development of Shared Governance

    Science.gov (United States)

    1993-01-01

    dependent, and deferent beings--hardly characteristics associated with autonomy. Despite the emergence of the feminist movement, these stereotypes...recently, most women have not had occupational roles. Even though Erikson’s model does not stand well from a feminist perspective, many women define...patient clnc.perinetal clinic. AKU. IVF) g. suep"" Nurse Regisry h. Other (MA. Oiech Planning, Ed. Coord.. Adm. Mgmt. Shift Manager. IV Therapy

  16. Pöff : Võistlevad Euroopa ja Aasia / Andris Feldmanis

    Index Scriptorium Estoniae

    Feldmanis, Andris, 1982-

    2006-01-01

    10nda Pimedate Ööde Filmifestivali filmidest lõpetamise eel : "TumeSininePeaaeguMust", režissöör Daniel Sanchez Arevalo : Hispaania 2006, "Taksitermia", režissöör György Palfi : Ungari-Austria-Prantsusmaa 2006, Joachim Lafosse'i filmist "Eravaldus" ja Aku Louhimiehe filmist "Lahtikistud mees". Lisatud "Mehed metsas" Eesti "Meeletu" ja Leedu "Sina olen mina"

  17. Recent advances in management of alkaptonuria (invited review; best practice article).

    Science.gov (United States)

    Ranganath, Lakshminarayan R; Jarvis, Jonathan C; Gallagher, James A

    2013-05-01

    Alkaptonuria (AKU) is an autosomal recessive condition arising as a result of a genetic deficiency of the enzyme homogentisate 1,2 dioxygenase and characterised by accumulation of homogentisic acid (HGA). Oxidative conversion of HGA leads to production of a melanin-like polymer in a process termed ochronosis. The binding of ochronotic pigment to the connective tissues of the body leads to multisystem disorder dominated by premature severe spondylo-arthropathy. Other systemic features include stones (renal, prostatic, salivary, gall bladder), renal damage/failure, osteopenia/fractures, ruptures of tendons/muscle/ligaments, respiratory compromise, hearing loss and aortic valve disease. Detection of these features requires systematic investigation. Treatment in AKU patients is palliative and unsatisfactory. Ascorbic acid, low protein diet and physiotherapy have been tried but do not alter the underlying metabolic defect. Regular surveillance to detect and treat complications early is important. Palliative pain management is a crucial issue in AKU. Timely spinal surgery and arthroplasty are the major treatment approaches at present. A potential disease modifying drug, nitisinone, inhibits 4-hydroxy-phenyl-pyruvate-dioxygenase and decreases formation of HGA and could prevent or slow the progression of disease in AKU. If nitisinone therapy is able to complement the biochemical 'cure' with improved outcomes, it will completely alter the way we approach the management of this disease. Greater efforts to improve recognition and registration of the disease will be worthwhile. Improved laboratory diagnostics to monitor the tyrosine metabolic pathway that includes plasma metabolites including tyrosine to monitor efficacy, toxicity and safety postnitisinone will also be required.

  18. Ochronosis in a murine model of alkaptonuria is synonymous to that in the human condition

    Science.gov (United States)

    Taylor, A.M.; Preston, A.J.; Paulk, N.K.; Sutherland, H.; Keenan, C.M.; Wilson, P.J.M.; Wlodarski, B.; Grompe, M.; Ranganath, L.R.; Gallagher, J.A.; Jarvis, J.C.

    2012-01-01

    Objective Alkaptonuria (AKU) is a rare genetic disease which results in severe early onset osteoarthropathy. It has recently been shown that the subchondral interface is of key significance in disease pathogenesis. Human surgical tissues are often beyond this initial stage and there is no published murine model of pathogenesis, to study the natural history of the disease. The murine genotype exists but it has been reported not to demonstrate ochronotic osteoarthropathy consistent with the human disease. Recent anecdotal evidence of macroscopic renal ochronosis in a mouse model of tyrosinaemia led us to perform histological analysis of tissues of these mice that are known to be affected in human AKU. Design The homogentisate 1,2-dioxygenase Hgd+/−Fah−/− mouse can model either hereditary tyrosinaemia type I (HT1) or AKU depending on selection conditions. Mice having undergone Hgd reversion were sacrificed at various time points, and their tissues taken for histological analysis. Sections were stained with haematoxylin eosin (H&E) and Schmorl’s reagent. Results Early time point observations at 8 months showed no sign of macroscopic ochronosis of tissues. Macroscopic examination at 13 months revealed ochronosis of the kidneys. Microscopic analysis of the kidneys revealed large pigmented nodules displaying distinct ochre colouration. Close microscopic examination of the distal femur and proximal fibula at the subchondral junctions revealed the presence of numerous pigmented chondrocytes. Conclusions Here we present the first data showing ochronosis of tissues in a murine model of AKU. These preliminary histological observations provide a stimulus for further studies into the natural history of the disease to provide a greater understanding of this class of arthropathy. PMID:22542924

  19. Kaire Kemp-Tishler: "Igatsen luua midagi kole-ilusat" / Gitte Hint

    Index Scriptorium Estoniae

    Hint, Gitte

    2003-01-01

    Kaire Kemp-Tishler (sünd. 1964) kodu sisekujunduse projekteerimisest, tasakaalust sisearhitektuuris, oma kodust. Kaire Kemp-Tishlerist, tema tehtud tööde loetelu. 1998. aastast teeb K. Kemp-Tishler koostööd Ea Andlaga, kellega koos asutas 2001. a. OÜ sisearhitektuuribüroo ArtAku. Ill.: K. Kemp-Tishleri värv. portree

  20. Severe Osteoarthritis of the Knee as an Early Symptom of Alkaptonuria: A Case Report

    Directory of Open Access Journals (Sweden)

    Alois Franz

    2016-02-01

    Full Text Available Introduction: Alkaptonuria (AKU is a very rare disease and occurs due to the deficiency of the enzyme homogentisate1, 2-dioxygenase (HGD which results in ochronosis, a term used to describe the dark pigmentation of the tissues. Alkaptonuria affects mostly the knee joint followed by the hip as major weight bearing joints, where the life quality of such patients is severely affected. Case Presentation: We present a case of Caucasian male who was suffering from severe osteoarthritis of the knee. Initially he underwent an arthroscopic partial meniscectomy in a nearby hospital. Fourteen months later we performed a total knee replacement using the Journey II CR prosthesis. We found a dark pigmentation of the inside of the knee (synovial tissue and cartilage. A positive urine test and a pathological specimen examination revealed the diagnosis of AKU. The patient had no complications after the surgery and underwent a standard rehabilitation program. Conclusions: Osteoarthritis could be the first manifestation of patients with AKU and the onset of the joint disease could be late and rapid.

  1. Toward a generalized computational workflow for exploiting transient pockets as new targets for small molecule stabilizers: Application to the homogentisate 1,2-dioxygenase mutants at the base of rare disease Alkaptonuria.

    Science.gov (United States)

    Bernini, Andrea; Galderisi, Silvia; Spiga, Ottavia; Bernardini, Giulia; Niccolai, Neri; Manetti, Fabrizio; Santucci, Annalisa

    2017-10-01

    Alkaptonuria (AKU) is an inborn error of metabolism where mutation of homogentisate 1,2-dioxygenase (HGD) gene leads to a deleterious or misfolded product with subsequent loss of enzymatic degradation of homogentisic acid (HGA) whose accumulation in tissues causes ochronosis and degeneration. There is no licensed therapy for AKU. Many missense mutations have been individuated as responsible for quaternary structure disruption of the native hexameric HGD. A new approach to the treatment of AKU is here proposed aiming to totally or partially rescue enzyme activity by targeting of HGD with pharmacological chaperones, i.e. small molecules helping structural stability. Co-factor pockets from oligomeric proteins have already been successfully exploited as targets for such a strategy, but no similar sites are present at HGD surface; hence, transient pockets are here proposed as a target for pharmacological chaperones. Transient pockets are detected along the molecular dynamics trajectory of the protein and filtered down to a set of suitable sites for structural stabilization by mean of biochemical and pharmacological criteria. The result is a computational workflow relevant to other inborn errors of metabolism requiring rescue of oligomeric, misfolded enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Alkaptonuria: a very rare metabolic disorder.

    Science.gov (United States)

    Aquaron, Robert

    2013-10-01

    Alkaptonuria (AKU) is a very rare autosomal recessive disorder of tyrosine metabolism in the liver due to deficiency of homogentisate 1,2 dioxygenase (HGD) activity, resulting in the accumulation of homogentisic acid (HGA). Circulating HGA pass into various tissues through-out the body, mainly in cartilage and connective tissues, where its oxidation products polymerize and deposit as a melanin-like pigment. Gram quantities of HGA are excreted in the urine. AKU is a progressive disease and the three main features, according the chronology of appearance, are: darkening of the urine at birth, then ochronosis (blue-dark pigmentation of the connective tissue) clinically visible at around 30 yrs in the ear and eye, and finally a severe ochronotic arthropathy at around 50 yrs with spine and large joints involvements. Cardiovascular and renal complications have been described in numerous case report studies. A treatment now is available in the form of a drug nitisinone, which decreases the production of HGA. The enzymatic defect in AKU is caused by the homozygous or compound heterozygous mutations within the HGD gene. This disease has a very low prevalence (1:100,000-250,000) in most of the ethnic groups, except Slovakia and Dominican Republic, where the incidence has shown increase up to 1:19,000. This review highlights classical and recent findings on this very rare disease.

  3. Alkaptonuria: An example of a "fundamental disease"--A rare disease with important lessons for more common disorders.

    Science.gov (United States)

    Gallagher, James A; Dillon, Jane P; Sireau, Nicolas; Timmis, Oliver; Ranganath, Lakshminarayan R

    2016-04-01

    "Fundamental diseases" is a term introduced by the charity Findacure to describe rare genetic disorders that are gateways to understanding common conditions and human physiology. The concept that rare diseases have important lessons for biomedical science has been recognised by some of the great figures in the history of medical research, including Harvey, Bateson and Garrod. Here we describe some of the recently discovered lessons from the study of the iconic genetic disease alkaptonuria (AKU), which have shed new light on understanding the pathogenesis of osteoarthritis. In AKU, ochronotic pigment is deposited in cartilage when collagen fibrils become susceptible to attack by homogentisic acid (HGA). When HGA binds to collagen, cartilage matrix becomes stiffened, resulting in the aberrant transmission of loading to underlying subchondral bone. Aberrant loading leads to the formation of pathophysiological structures including trabecular excrescences and high density mineralised protrusions (HDMPs). These structures initially identified in AKU have subsequently been found in more common osteoarthritis and appear to play a role in joint destruction in both diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

    Science.gov (United States)

    Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

    2016-02-01

    Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Knowledge, attitudes and practices around health research: the perspective of physicians-in-training in Pakistan

    Directory of Open Access Journals (Sweden)

    Khan Sadaf

    2009-07-01

    Full Text Available Abstract Background Health research training is an essential component of medical education and a vital exercise to help develop physician research skills. This study was carried out to assess the level of knowledge, attitudes and practices towards research amongst a group of Post Graduate Medical Trainees (PGMTs' at Aga Khan University (AKU, Pakistan. Methods A cross sectional health research survey was carried out on all PGMTs' at AKU Pakistan. AKU is a tertiary care health facility which offers residency in 28 specialties and fellowship in 16 programs. Knowledge, attitudes and practices related to health research were assessed using a pretested, structured and validated questionnaire. Health research related practices of the residents were examined using questions graded on Likert scale. Results Mean percentage score ± SD on the knowledge scale was 36.9% ± 20.2 and 47.19% ± 25.18 on the attitude scale. Of 104(55.6% who had previously participated in research 28(26.9% had been involved in basic science research only, 62(59.6% in clinical research and 14(13.5% had participated in both clinical and basic science research projects. 88(47.1% planned to pursue a future research career. Those who planned to pursue a future research career had more positive health research attitudes p Conclusion PGMTs' demonstrate inadequate knowledge, while they have moderate attitudes towards health research. Residency training and research facilities at the institution need to undergo major transformation in order to encourage meaningful research by resident trainees.

  6. Alkaptonuria in France: past experience and lessons for the future.

    Science.gov (United States)

    Aquaron, Robert Raphael

    2011-12-01

    Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA) or alkaptonuria, ochronosis then ochronotic arthropathy. This inborn error of metabolism is caused by mutations in the HGD gene. In this work we report observations of 96 AKU French patients from 81 families collected in the literature since 1882 and from our personal contribution since 1986, giving an incidence of the disease of around 1:680,000 (96/64.10(6)). As expected for an autosomal recessive disorder the main findings of this study were: a slight predominance of males (51/93, 54,8%) over females (42/93, 45,2%), a strong predominance of sibships with one affected individual (68/81, 84,0%) over sibships with two (11/81, 13.6%) and three(2/81, 2.4%) affected individuals. AKU families are scaterred among the French territory suggesting that most cases occured in non-consanguineous unions. Consanguinity was only found in five families. Other peculiarities of this study were (a) ten of these families have both parents from a foreign geographical origin: Poland(3), Italy(3), Portugal(2), Ukraine(1) and India(1) and four families with only one foreign parent (Algeria, Armenia, Serbia, UK), (b) HGD mutations were found in 23 families, (c) four of theses 96 patients were seen by us respectively 28, 29, 39 and 45 years after their report in the literature and (d) seven patients present cardiac and/or renal complications.

  7. Attitudes of medical students towards incentives offered by pharmaceutical companies -- perspective from a developing nation -- a cross-sectional study.

    Science.gov (United States)

    Siddiqui, Usman Tariq; Shakoor, Amarah; Kiani, Sarah; Ali, Farwa; Sharif, Maryam; Kumar, Arun; Raza, Qasim; Khan, Naseer; Alamzaib, Sardar Mohammed; Farid-ul-Husnain, Syed

    2014-05-05

    A training physician has his first interaction with a pharmaceutical representative during medical school. Medical students are often provided with small gifts such as pens, calendars and books, as well as free lunches as part of drug promotion offers. Ethical impact of these transactions as perceived by young medical students has not been investigated in Pakistan before. This study aimed to assess the association of socio-demographic variables with the attitudes of medical students towards pharmaceutical companies and their incentives. As part of a cross-sectional survey, a validated questionnaire previously used for assessing attitude of medical students towards pharmaceutical industry, was modified, pre-tested and distributed among consenting clinical year students at DUHS and AKU. Questions included acceptability of pharmaceutically sponsored gifts, events and tuition fee, and their impact on future prescription. Responses were graded as agree, disagree or neutral which were then scored according to the AMSA guidelines of ethical conduct. Out of a total of 353 targeted students 303 responded, corresponding to a response rate of 85.8%. Responses indicated that 42.7% students believed in no interaction with drug companies during medical school. However, 81% of students favored pharmaceutical sponsorship of student-body events/seminars at medical colleges. More than one-third of the students were comfortable receiving gifts from drug companies. Overall, the results of this study offer an interesting comparison between the students of a private medical school (AKU) and a public medical school (DUHS); AKU students exhibited a greater degree of mistrust towards drug information provided by pharmaceutical companies compared to DUHS students (p = 0.040). Furthermore, when asked if there was a need to incorporate guidelines in the undergraduate curriculum with regard to interaction with drug companies, 84.2% students at AKU agreed, compared to 54.9% at DUHS. Medical

  8. Attitudes of medical students towards incentives offered by pharmaceutical companies- perspective from a developing nation- a cross sectional study

    Science.gov (United States)

    2014-01-01

    Background A training physician has his first interaction with a pharmaceutical representative during medical school. Medical students are often provided with small gifts such as pens, calendars and books, as well as free lunches as part of drug promotion offers. Ethical impact of these transactions as perceived by young medical students has not been investigated in Pakistan before. This study aimed to assess the association of socio-demographic variables with the attitudes of medical students towards pharmaceutical companies and their incentives. Methods As part of a cross-sectional survey, a validated questionnaire previously used for assessing attitude of medical students towards pharmaceutical industry, was modified, pre-tested and distributed among consenting clinical year students at DUHS and AKU. Questions included acceptability of pharmaceutically sponsored gifts, events and tuition fee, and their impact on future prescription. Responses were graded as agree, disagree or neutral which were then scored according to the AMSA guidelines of ethical conduct. Results Out of a total of 353 targeted students 303 responded, corresponding to a response rate of 85.8%. Responses indicated that 42.7% students believed in no interaction with drug companies during medical school. However, 81% of students favored pharmaceutical sponsorship of student-body events/seminars at medical colleges. More than one-third of the students were comfortable receiving gifts from drug companies. Overall, the results of this study offer an interesting comparison between the students of a private medical school (AKU) and a public medical school (DUHS); AKU students exhibited a greater degree of mistrust towards drug information provided by pharmaceutical companies compared to DUHS students (p = 0.040). Furthermore, when asked if there was a need to incorporate guidelines in the undergraduate curriculum with regard to interaction with drug companies, 84.2% students at AKU agreed

  9. On the regularity of mild solutions to complete higher order differential equations on Banach spaces

    Directory of Open Access Journals (Sweden)

    Nezam Iraniparast

    2015-09-01

    Full Text Available For the complete higher order differential equation u(n(t=Σk=0n-1Aku(k(t+f(t, t∈ R (* on a Banach space E, we give a new definition of mild solutions of (*. We then characterize the regular admissibility of a translation invariant subspace al M of BUC(R, E with respect to (* in terms of solvability of the operator equation Σj=0n-1AjXal Dj-Xal Dn = C. As application, almost periodicity of mild solutions of (* is proved.

  10. Strontium measurement results from the Federal Republic of Germany and from Switzerland after the Chernobyl reactor accident

    International Nuclear Information System (INIS)

    Neu, A.; Goll, L.; Voelkle, H.; Winter, M.

    1987-10-01

    The Working Group Environmental Monitoring (AKU) of Fachverband fuer Strahlenschutz e.V. (Radiation Protection Association) performed an inquiry about the time after the Chernobyl reactor accident concerning the results of strontium-90 measurements carried out for the territories of the Federal Republic of Germany and Switzerland. The data suppliers listed in the report furnished to AKU results of Sr-90 measurements made on approximately 1000 samples in total. The individual measuring results have been entered into separate tables in a uniform representation. The tables also include the results of Sr-89-measurements as well as the Cs-137/Sr-90 ratios as far as they were available. The results of measurements presented here taken together prove that contamination with Sr-90 of the environmental media including food as a result of the Chernobyl fallout were only low in the Federal Republic of Germany and in Switzerland compared with the contamination due to the nuclides I-/131 and Cs-137. The same applies to the amount of Sr-90 transferred into the soil as compared with the level of existing contamination due to nuclear weapons fallout which has accumulated since the 60ies. (orig.) [de

  11. Interferences of homogentisic acid (HGA) on routine clinical chemistry assays in serum and urine and the implications for biochemical monitoring of patients with alkaptonuria.

    Science.gov (United States)

    Curtis, S L; Roberts, N B; Ranganath, L R

    2014-05-01

    We have assessed the effect of elevated concentrations of homogentisic acid (HGA) as in alkaptonuria (AKU), on a range of routine chemistry tests in serum and urine. HGA was added to pooled serum and a range of assays was analysed with Roche Modular chemistries. Effects on urine were assessed by diluting normal urine with urine from a patient with AKU, adding HGA to urine and after lowering output of urinary HGA with nitisinone treatment. Serum enzymatic creatinine showed 30% negative interference with 100μmol/L HGA and >50% at 400μmol/L. Serum urate 100 to 480μmol/L was reduced up to 20% at 100 and to 50% with 400μmol/L HGA. Serum cholesterol between 3 and 11mmol/L was reduced by 0.5mmol/L with 400μmol/L HGA. Urine enzymatic creatinine and urate with >2mmol/L HGA showed concentration dependent negative interference up to 80%. A positive interference in urine total protein by benzethonium turbidometric assay was observed, with 10mmol/L HGA equivalent to 1g/L protein. Jaffe creatinine, Na, K, Cl, Mg, Ca, phosphate, ALT, GGT, ALP activities and urea in serum and or urine were not affected by increases in HGA. To avoid interferences by HGA in alkaptonuria concentration of HGA should be established before samples are assayed with peroxidase assays and benzethonium urine protein. Copyright © 2013 The Canadian Society of Clinical Chemists. All rights reserved.

  12. First report of HGD mutations in a Chinese with alkaptonuria.

    Science.gov (United States)

    Yang, Yong-jia; Guo, Ji-hong; Chen, Wei-jian; Zhao, Rui; Tang, Jin-song; Meng, Xiao-hua; Zhao, Liu; Tu, Ming; He, Xin-yu; Wu, Ling-qian; Zhu, Yi-min

    2013-04-15

    Alkaptonuria (AKU) is one of the first prototypic inborn errors in metabolism and the first human disease found to be transmitted via Mendelian autosomal recessive inheritance. It is caused by HGD mutations, which leads to a deficiency in homogentisate 1,2-dioxygenase (HGD) activity. To date, several HGD mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the HGD mutation is very rarely reported. For the Chinese population, no literature on HGD mutation screening is available to date. In this paper, we describe two novel HGD mutations in a Chinese AKU family, the splicing mutation of IVS7+1G>C, a donor splice site of exon 7, and a missense mutation of F329C in exon 12. The predicted new splicing site of the mutated exon 7 sequence demonstrated a 303bp extension after the mutation site. The F329C mutation most probably disturbed the stability of the conformation of the two loops critical to the Fe(2+) active site of the HGD enzyme. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Verivärskeid elamusi igale maitsele / Marianne Kõrver

    Index Scriptorium Estoniae

    Kõrver, Marianne, 1980-

    2007-01-01

    Ülevaade 10. PÖFFi võistlusprogrammist. PÖFFi filme: "Meeletu" (rezh. Elmo Nüganen), "TumeSininePeaaeguMust" (rezh. Daniel Sanchez Arevalo), "Taksitermia" (rezh. György Palfi), "Eravaldus" (rezh. Joachim Lafosse), "Lahtikistud mees" (rezh. Aku Louhimies), "Rõhkkonnad" (rezh. Nuri Bilge Ceylan), "Reekviem" (rezh. Hans-Christian Schmid), "Väikesed punased lilled" (rezh. Zhang Yuan), "Sündroomid ja sajand" (režissöör Apichatpong Weerasethakul), "Mängides ohvrit" (rezh. Kirill Serebrennikov), "Et taevasse pääseda, tuleb kõigepealt surra" (rezh. Djamshed Usmonov), "Pojad" (rezh. Erik Strand Richter), "Maximo Oliverose õitseaeg" (rezh. Auraeus Solito), "Kelner" (rezh. Alex van Warmerdam), "Tagasinõudja" (rezh. Slawomir Fabick), "Mehed tööl" (rezh. Mani Haghighi), "4,6 miljardit aastat armastust" (rezh. Takashi Miike), "Sina oled mina" (rezh. Kristijonas Vildziunas)

  14. The Army Study Program.

    Science.gov (United States)

    1983-05-31

    a- - - - - m .aKU i~ n I n i n K K iK G. (J- zow w w w m m cc co n CD a) w u u w w w v IA a :aP aj I 4p . V 4 p IV V A 4 4 v I . V a t1 1 4 acca n...xi W Uc -K. U4 0-0)0- 0- 4 -01 4 02 - n U ) U x14 4, 04:1)6 hi u 0) ki V3 1 z- P7 a. ** hi * U,0 .04 K hi 0 Z) hiJ 0. U W 9 4 W 0. U a Cc z A. 4A 0

  15. Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

    Science.gov (United States)

    Hogendorf, Anna; Pietrzak, Iwona; Antosik, Karolina; Borowiec, Maciej; Młynarski, Wojciech

    2016-01-01

    We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes. © Polish Society for Pediatric Endocrinology and Diabetology.

  16. Renal and prostate stones composition in alkaptonuria: a case report.

    Science.gov (United States)

    Wolff, Fleur; Biaou, Ibrahim; Koopmansch, Caroline; Vanden Bossche, Marc; Pozdzik, Agnieszka; Roumeguère, Thierry; Cotton, Frédéric

    2015-12-01

    Alkaptonuria is a genetic disorder characterized by an accumulation of homogentisic acid due to an enzymatic defect of homogentisate 1,2 dioxygenase. The homogentisic acid is excreted exclusively by both glomerular filtration and tubular secretion leading to the renal parenchyma being exposed to high concentrations of homogentisic acid. The alkaptonuric patients are at higher risk of renal stones (and of prostate stones for males), usually in the later stages of the disease. We describe the case of a 51-year-old man whose renal and prostate stones were analyzed by X-ray diffraction and infrared spectroscopy, respectively. We review the cases of alkaptonuria (AKU) patients reported in the literature for whom the composition of kidney or prostate stones was assessed with physical or chemical techniques. In this paper, we also discuss the advantages and drawbacks of the different methodologies.

  17. Üks PÖFF, tuhat maailma / Mathura

    Index Scriptorium Estoniae

    Mathura, pseud., 1973-

    2006-01-01

    Autorit enim köitnud filmidest PÖFFil: "Paani labürint" (režissöör Guillermo del Toro, Mehhiko-Hispaania, 2006), "Lillede org" (režissöör Pan Nalin, India-Prantsusmaa-Saksamaa-Jaapan, 2006), "Opera Jawa" (režissöör Garin Nugroho, Indoneesia-Austria, 2006), "Tsotsi" (režissöör Gavin Hood, LAV-Inglismaa, 2005), "Põuaperiood" (režissöör Mahamat-Saleh Haroun, Tšaad-Prantsusmaa-Belgia-Austria, 2006), "Meeletu" (režissöör Elmo Nüganen, Eesti, 2006), "Lahtikistud mees" (režissöör Aku Louhimies, Soome, 2006)

  18. Water pollution in relation to mineral exploration: a case study from Alayi-Ovim area of southeastern Nigeria.

    Science.gov (United States)

    Ibe, Kalu K; Akaolisa, Casmir C Zanders

    2012-05-01

    Water samples from rivers, streams, springs, and shallow wells in Alayi-Ovim area of southeast Nigeria have been analyzed for Pb, Ca, Mg, Fe, Mg, PO(4), NO(3), CO(3), SO(4), Cl, and pH. The analyses were carried out using atomic absorption spectrometer and Hach Direct Reading Equipment. Results of the analyses from the area conform to the WHO (1995) standards for drinking water. However, the results show relative enrichment of Ca, pH, Mg, CO(3), and Cl. Low values were obtained for Fe, SO(4), and NO(3). While the Cl and Pb enrichment in the area north of Alayi-Ovim axis is attributed to proximity to the lead-zinc and chloride-rich formations of the Turonian Eze-Aku and the Albian Asu River; the Ca, Mg, SO(4), and CO(3) enrichment in Southern part of Alayi-Ovim is due to the limestone-bearing Late Maastrichtian Nsukka Formation. Furthermore, the very low values of less than 5 ppm for these characters in water in the central region correlate well with the relatively clean Maastrichtian quartz arenite Ajali Sandstone Formation. The Pb-Zn and Cl incursions into the water system from the Older Albian Asu River/Turonian Eze-Aku Formations in the northern part of Alayi-Ovim area and the leaching of Mg, and Ca into the water system in the Maastrichtian limestone area in the south thus constitute geochemical indices for chemical pollution and mineral exploration for brine and dolomitic limestone in the area.

  19. Osteoarticular cells tolerate short-term exposure to nitisinone-implications in alkaptonuria.

    Science.gov (United States)

    Mistry, J B; Jackson, D J; Bukhari, M; Taylor, A M

    2016-02-01

    Alkaptonuria (AKU) is a rare genetic disease resulting in severe, rapidly progressing, early onset multi-joint osteoarthropathy. A potential therapy, nitisinone, is being trialled that reduces the causative agent; homogentisic acid (HGA) and in a murine model has shown to prevent ochronosis. Little is currently known about the effect nitisinone has on osteoarticular cells; these cells suffer most from the presence of HGA and its polymeric derivatives. This led us to investigate nitisinone's effect on chondrocytes and osteoblast-like cells in an in vitro model. Human C20/A4 immortalized chondrocytes, and osteosarcoma cells MG63 cultured in DMEM, as previously described. Confluent cells were then plated into 24-well plates at 4 × 10(4) cells per well in varying concentrations of nitisinone. Cells were cultured for 7 days with medium changes every third day. Trypan blue assay was used to determine viability and the effect of nitisinone concentration on cells. Statistical analysis was performed using analysis of variance, and differences between groups were determined by Newman-Keuls post-test. Analysis of C20/A4 chondrocyte and MG63 osteoblast-like cell viability when cultured in different concentrations of nitisinone demonstrates that there is no statistically significant difference in cell viability compared to control cultures. There is currently no literature surrounding the use of nitisinone in human in vitro models, or its effect on chondrocytes or osteoblast like cells. Our results show that nitisinone does not appear detrimental to cell viability of chondrocytes or osteoblast-like cells, which adds to the evidence that this therapy could be useful in treating AKU.

  20. First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria.

    Science.gov (United States)

    Zouheir Habbal, Mohammad; Bou-Assi, Tarek; Zhu, Jun; Owen, Renius; Chehab, Farid F

    2014-01-01

    Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD). Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5-16 Mb), one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband's phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin.

  1. First report of a deletion encompassing an entire exon in the homogentisate 1,2-dioxygenase gene causing alkaptonuria.

    Directory of Open Access Journals (Sweden)

    Mohammad Zouheir Habbal

    Full Text Available Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD. Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5-16 Mb, one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband's phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin.

  2. Perlawanan Terhadap Penjajahan dalam Puisi-Puisi Indonesia dan Korea

    Directory of Open Access Journals (Sweden)

    Yusri Fajar

    2015-12-01

    Full Text Available Penjajahan di muka bumi, seperti yang dialami Indonesia dan Korea telah mengakibatkan kerugian materiil dan non materiil. Akibat-a­kibat dari kolonialisme ini mendapat respon puitik dari para penyair Indonesia dan Korea yang tidak hanya menulis puisi namun juga bersentuhan dengan gerakan perlawanan untuk menggapai kemerdekaan. Artikel ini membahas resistensi terhadap penjajahan sebagaimana tercermin dalam puisi-puisi para penyair Indonesia dan Korea. Untuk meneliti puisi-puisi tersebut konsep sastra bandingan digunakan dan dielaborasi bersama dengan teori kolonialisme. Sumber data penelitian ini adalah antologi puisi Korea yang berjudul Puisi buat Rakyat Indonesia (terjemahan Chung Yong Rim tahun 2013 dan antologi puisi Indonesia Aku ini Binatang Jalang karya Chairil Anwar cetakan tahun 2015. Hasil penelitian menunjukkan bahwa pengalaman ketika dijajah Jepang membuat para penyair kedua negara ini melahirkan puisi-puisi yang secara tematis menggambarkan berbagai akibat kolonialisme dan semangat antipenjajahan yang lahir sebagai bentuk perlawanan. Abstract: Colonization as experienced by Indonesia and Korea brought about impacts on infrastructure and people of both countries. Those effects triggered Indonesian and Korean poets to give poetical response. These poets not only wrote poems but also involved in the movement in gaining independence. This article discusses the resistance toward colonization as represented in the poems by Indonesian and Korean Poets. The concept of comparative literature and colonialism are employed in this research. Sources of the data in this research are taken from the anthology of Korean poems entitled Puisi buat Rakyat Indonesia (translated into Indonesian by Chung Yong Rim in 2013 and anthology of Indonesian poems by Chairil Anwar entitled Aku ini Binatang Jalang published in 2015. The result of the research shows that colonization in Indonesia and Korea inspired the poets from these two colonized countries to

  3. STUDI KASUS KONSEP DIRI SISWA SEKOLAH DASAR

    Directory of Open Access Journals (Sweden)

    Anita Putri Budiarsih

    2016-09-01

    analisis data, serta 6Penyiapan laporan. Pengumpulan data dilakukan menggunakan teknik wawancara dan observasi. Data dianalisis melalui tahap reduksi data, penyajian data dan penarikan kesimpulan. Hasil penelitian ini yaitu tiga konsep diri siswa yang terdiri dari:(aAku bisa nyopir dan akan jadi sopir, (bAku adalah anak andalan keluarga yang harus membantu mencari nafkah, dan (cAku tidak pintar matematika. Selain itu, hasil lain dari penelitian ini adalah faktor yang mempengaruhi konsep diri siswa terdiri dari faktor yang berasal dari dalam diri siswa, yang diwujudkan melalui pembandingan dirinya dengan  orang lain, dan faktor yang berasal dari luar diri yang berupa proses identifikasi perilaku sang kakek oleh siswa. Serta diketahui pula perilaku belajar yang muncul akibat konsep diri siswa yang meliputi membolos dan pasif ketika di kelas.

  4. Tyrosinase, could it be a missing link in ochronosis in alkaptonuria?

    Science.gov (United States)

    Taylor, Adam M; Kammath, Vishnu; Bleakley, Aaron

    2016-06-01

    The hypothesis that is proposed is that tyrosinase, an enzyme widely found within the human body is implicated in the ochronosis that occurs in alkaptonuria; an autosomal recessive condition first used by Archibald Garrod to describe the theory of "Inborn Errors of Metabolism." The disease results from the absence of a single enzyme in the liver that breaks down homogentisic acid; this molecule becomes systemically elevated in sufferers. The condition is characterised by a clinical triad of symptoms; homogentisic aciduria from birth, ochronosis (darkening) of collagenous tissues (from ∼30years of age) and ochronotic osteoarthropathy in weight bearing joints due to long term ochronosis in them (from ∼40years of age). Tyrosinase, a polyphenol oxidase has been shown in many species to contribute to the darkening of tissues in many organisms; including humans in the production of melanin. Tyrosinase under the right conditions shows alterations in its substrate specificity and may contribute to the darkening seen in AKU where it moves away from polymerising tyrosine but also homogentisic acid, the causative molecule in alkaptonuria, that is present in excess. Copyright © 2016. Published by Elsevier Ltd.

  5. Neurological Assessment and Nerve Conduction Study Findings in 22 Patients with Alkaptonuria from Jordan.

    Science.gov (United States)

    Alrawashdeh, Omar; Alsbou, Mohammad; Alzoubi, Hamed; Al-Shagahin, Hani

    2016-11-02

    Alkaptonuria is a rare metabolic disease characterised by accumulative deposition of homogentisic acid in the connective tissue of the body. This results in early degeneration of tendons, cartilages, heart valves, and other tissues. The main objective of the study is to examine the possibility of the nervous system involvement in patients with alkaptonuria The sample consists of two groups; 22 patients with AKU and 20 controls. A neurological assessment has been carried out including detailed medical history, neurological examination, and a nerve conduction study of the nerves of the dominant hand. The prevalence of any abnormality was compared between the two groups using chi square test. The mean values of the nerve conduction study were compared between the two groups using student t-test. There was a higher prevalence of low back pain, hearing problems and tinnitus, numbness and neuropathic pain in alkaptonuria patients. There was no significant difference between the two groups in other conditions such as seizures, headache, and syncope. The values of the nerve conduction study did not show significant difference between the two groups. Neurologically related symptoms in alkaptonuria mostly represent complications of the connective tissue degeneration rather than direct involvement of the nervous system. This has been supported further by the normal findings of the neurophysiology study in patients with alkaptonuria.

  6. Neurological assessment and nerve conduction study findings in 22 patients with alkaptonuria from Jordan

    Directory of Open Access Journals (Sweden)

    Omar Alrawashdeh

    2017-01-01

    Full Text Available Alkaptonuria is a rare metabolic disease characterised by accumulative deposition of homogentisic acid in the connective tissue of the body. This results in early degeneration of tendons, cartilages, heart valves, and other tissues. The main objective of the study is to examine the possibility of the nervous system involvement in patients with alkaptonuria The sample consists of two groups; 22 patients with AKU and 20 controls. A neurological assessment has been carried out including detailed medical history, neurological examination, and a nerve conduction study of the nerves of the dominant hand. The prevalence of any abnormality was compared between the two groups using chi square test. The mean values of the nerve conduction study were compared between the two groups using student t-test. There was a higher prevalence of low back pain, hearing problems and tinnitus, numbness and neuropathic pain in alkaptonuria patients. There was no significant difference between the two groups in other conditions such as seizures, headache, and syncope. The values of the nerve conduction study did not show significant difference between the two groups. Neurologically related symptoms in alkaptonuria mostly represent complications of the connective tissue degeneration rather than direct involvement of the nervous system. This has been supported further by the normal findings of the neurophysiology study in patients with alkaptonuria.

  7. Representasi Homoseksualitas dalam Film Indonesia Kontemporer

    Directory of Open Access Journals (Sweden)

    Maimunah Maimunah

    2007-06-01

    Full Text Available This paper examines the emergence of non-normative sexual orientations in contemporary Indonesian films. Unlike the representation of sexuality in New Order Indonesian films, which centred on the female reproductive role and presented the nation as constructed of heterosexual families rather than individual citizens, a number of 200(s Indonesian films can be seen as negotiations of new understandings of sexual diversity and individual subjectivity. These films represent a challenge to monolithic and essentialist constructions of sexuality in Indonesia, and portray characters and situations in ways that seem to fulfil the five selection criteria which Griffin and Benshoff (2006 apply to the definition of 'queer' cinema. As such, they are indicative of a paradigm shift in Indonesian cinema, which needs to be studied in association with broader patterns of social and political change. The paper describes three categories in the representation of sexual minorities in contemporary Indonesian films. The first category is represented by films such as Arisanl and , Gie, which portray characters and situations deal with male homosexual subjectivity or homoeroticism. The second category concerns films of this type that portray female characters, such as Detik Terakhirand TentangDia. In the third category are films which depict waria (male to female transgender characters and transsexuals, represented by Panggil Aku Puspa and Realita Cinta dan Rock n Roll. The paper examines these films in the light of Boellstorff's (2005 study of gay and lesbi communities and subjectivities in Indonesia, as a way of situating them in a larger cultural picture. It suggests that the makers of these films are attempting to change the perception of their audiences about non-normative sexualities, and investigates the strategic devices used by the film makers to subvert censorship codes and social taboos in a country where homosexual behaviour is accommodated, but homosexual

  8. Coupled behaviour of bentonite buffer results of PUSKURI project

    International Nuclear Information System (INIS)

    Olin, M.; Rasilainen, K.; Itaelae, A.

    2011-08-01

    In the report main results form a KYT2010 programme's project Coupled behaviour of bentonite buffer (PUSKURI) are presented. In THC modelling, Aku Itaelae made and published his Master of Science Thesis. Itaelae was able to successfully model the LOT-experiment. Additionally, he also listed problems and development proposals for THC-modelling of bentonite buffer. VTT and Numerola created in collaboration a model coupling saturation, diffusion and cation exchange; the model was implemented and tested in Numerrin, COMSOL and TOUGHREACT. Petri Jussila's PhD THM-model was implemented into COMSOL to facilitate further development. At GTK, the mineralogical characterisation of bentonite was planned. The previous THM model (Jussila's model) including only small deformations was successfully generalized to finite deformations in way at least formally preserving the original formalism. It appears that the theory allows also a possibility to include finite plastic deformations in the theory. In order to measure the relevant mechanical properties of compacted bentonite, two different experiments, namely hydrostatic compression experiment and one-dimensional compression experiment were designed. In the hydrostatic compression experiment, a cylindrical sample of compacted bentonite covered with liquid rubber coating is placed in the sample chamber equipped with a piston. The same device was also used in one-dimensional compression experiment. X-ray microtomographic techniques were used in order to study the basic mechanisms of water transport in bentonite. The preliminary results indicate that in the present experimental set-up, water transport is dominated by a dispersive mechanism such as diffusion of vapour in gas phase or diffusion of water in solid phase. (orig.)

  9. JERAMI SEBAGAI BAHAN BAKU PANEL AKUSTIK PELAPIS DINDING

    Directory of Open Access Journals (Sweden)

    Christina E. Mediastika

    2008-01-01

    Full Text Available The demand of walling panels with acoustic qualification has surprisingly increased, due to the needs for home theaters and mini recording studios in the increase of environmental noise. Therefore, good supply of acoustic panels, especially those with lower price are necessary. A series of study to explore possibility in using paddy-straw as main material to construct cheap and high quality panels has been developed. Prior to this study, an earlier small research showed there was a great potency in using paddy-straw as panels, especially ones drawn from paddy in type IR. The earlier study recommends further research to examine strength of compression and tensile of the constructed panels to go for building materials, which is presented in this paper. Acoustic qualification of the panels is subject for further reserach. Abstract in Bahasa Indonesia: Kebutuhan akan panel pelapis dinding yang bersifat akustik terus meningkat seiring meningkatnya kebisingan dan kebutuhan terhadap ruang studio pribadi. Ketersediaan panel pelapis dinding dengan harga yang lebih terjangkau seperti yang terbuat dari bahan limbah sangatlah dibutuhkan. Pada penelitian awal telah diselidiki kemungkinan penggunaan jerami yang merupakan limbah sebagai bahan baku pembuatan panel akustik. Penelitian tersebut menunjukkan bahwa jerami sangat potensial digunakan sebagai bahan aku panel, terutama jerami padi berjenis IR. Selanjutnya panel jerami ini perlu mendapatkan perlakukan uji desak dan lentur untuk memastikan kemampuannya menahan berat sendiri dan kekuatannya saat proses penggunaan, sebelum akhirnya mengalami pengujian berkaitan dengan kualitas akustik. Kekuatan desak dan lentur panel dimaksud, tersaji dalam tulisan ini. Kata kunci: panel jerami, uji desak, uji lentur.

  10. IMPLEMENTASI PENDIDIKAN KARAKTER DI SMP NEGERI 8 DAN SMP NEGERI 9 PURWOKERTO

    Directory of Open Access Journals (Sweden)

    Tutuk Ningsih

    2016-10-01

    Full Text Available Penelitian ini bertujuan untuk menemukan dan mendeskripsikan; (1 implementasi pendidikan karakter (IPK di SMP Negeri 8 dan SMP Negeri 9 Purwokerto; (2 peran kepala sekolah, guru, dan siswa dalam IPK; dan (3 aktualisasi nilai-nilai karakter dalam IPK. Metode yang digunakan dalam penelitian ini merupakan metode kualitatif dengan pendekatan kualitatif-naturalistik.Teknik pengumpulan data yang digunakan adalah pengamatan partisipan, wawancara mendalam, dan dokumentasi. Analisis data menggunakan model interaktif Miles dan Huberman. Berdasarkan hasil penelitian ditarik kesimpulan berikut ini. (1 Implementasi pendidikan karakter yang lakukan melalui pola kegiatan terpadu antara kegiatan intrakurikuler dan ektrakurikuler. (2 Implementasi pendidikan karakter yang dilakukan oleh kepala sekolah, guru, dan siswa mempunyai peranan yang positif dalam pembentukan kultur sekolah yang berkarakter. Peran kepala sekolah, guru, dan siswa dalam IPK diwujudkan dalam: (a peran kepala sekolah sebagai motivator, pemberi contoh keteladanan, pelindung, penggerak kegiatan, perancang kegiatan, pendorong, dan pembimbing; (b peran guru sebagai pendidik, pengasih, dan pengasuh; dan (c peran siswa sebagai subjek didik dan pelaksana kegiatan di sekolah. (3 Aktualisasi nilai-nilai karakter dalam IPK cenderung mengacu pada prinsip ABITA (Aku Bangga Indonesia Tanah Airku berbasis kebangsaan dan religius yang meliputi 18 nilai karakter, yaitu: (a nilai religius, (b kejujuran, (c demokratis, (d tanggungjawab, (e disiplin, (f peduli lingkungan, (g peduli sosial, (h kerja keras, (i mandiri, (j cinta tanah air, (k semangat kebangsaan, (l rasa ingin tahu, (m gemar membaca, (n menghargai prestasi, (o cinta damai, (p bersahabat/komunikatif, (q toleran, dan (r kreatif. (4 Terdapat persamaan dan perbedaan dalam IPK di kedua SMP tersebut, persamaannya adalah mengacu pada nilai-nilai yang ada pada prinsip ABITA, perbedaannya kalau di SMP Negeri 8 melaksanakan 12 nilai karakter dan kegiatan

  11. Simultaneous detection of diagnostic biomarkers of alkaptonuria, ornithine carbamoyltransferase deficiency, and neuroblastoma disease by high-performance liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Hsu, Wei-Yi; Chen, Ching-Ming; Tsai, Fuu-Jen; Lai, Chien-Chen

    2013-05-01

    Urinary homovanillic acid (HVA)/vanillylmandelic acid (VMA), orotic acid (OA), and homogentisic acid (HGA) are diagnostic biomarkers of neuroblastoma, ornithine carbamoyl transferase deficiency (OCTD), and alkaptonuria (AKU), respectively. In this study, a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous quantification of HVA, VMA, OA, and HGA in urine. After sample preparation, which involved only the dilution procedure, samples were quantified by LC-MS/MS. Full-scan MS/MS mode enabled the urinary markers to be quantified with a high degree of specificity and sensitivity. Rather than using a separate enzymatic method to normalize the concentration of creatinine in urine, we quantified the level of creatinine in urine in one LC-MS run. The limits of detection were 10 μg/l for HGA, 25 μg/l for HVA/VMA, and 50 μg/l for OA with a single-to-noise ratio of 3; the limits of quantification were 50 μg/l for HVA and HGA, 100 μg/l for VMA, and 250 μg/l for OA. The linear dynamic range for quantification of the analytes covered 2 to 3 orders of magnitude, depending on the analyte. The relative standard deviation of the developed LC-MS/MS method was less than 4% for the intra-day validation and 10% for the inter-day validation. The results show that our LC-MS/MS technique is a highly sensitive and rapid method for screening for biomarkers that are diagnostic of three metabolic diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Coupled behaviour of bentonite buffer results of PUSKURI project; Bentoniittipuskurin kytketty kaeyttaeytyminen PUSKURI-hankkeen tuloksia

    Energy Technology Data Exchange (ETDEWEB)

    Olin, M.; Rasilainen, K.; Itaelae, A. [and others

    2011-08-15

    In the report main results form a KYT2010 programme's project Coupled behaviour of bentonite buffer (PUSKURI) are presented. In THC modelling, Aku Itaelae made and published his Master of Science Thesis. Itaelae was able to successfully model the LOT-experiment. Additionally, he also listed problems and development proposals for THC-modelling of bentonite buffer. VTT and Numerola created in collaboration a model coupling saturation, diffusion and cation exchange; the model was implemented and tested in Numerrin, COMSOL and TOUGHREACT. Petri Jussila's PhD THM-model was implemented into COMSOL to facilitate further development. At GTK, the mineralogical characterisation of bentonite was planned. The previous THM model (Jussila's model) including only small deformations was successfully generalized to finite deformations in way at least formally preserving the original formalism. It appears that the theory allows also a possibility to include finite plastic deformations in the theory. In order to measure the relevant mechanical properties of compacted bentonite, two different experiments, namely hydrostatic compression experiment and one-dimensional compression experiment were designed. In the hydrostatic compression experiment, a cylindrical sample of compacted bentonite covered with liquid rubber coating is placed in the sample chamber equipped with a piston. The same device was also used in one-dimensional compression experiment. X-ray microtomographic techniques were used in order to study the basic mechanisms of water transport in bentonite. The preliminary results indicate that in the present experimental set-up, water transport is dominated by a dispersive mechanism such as diffusion of vapour in gas phase or diffusion of water in solid phase. (orig.)

  13. Pseudogene accumulation in the evolutionary histories of Salmonella enterica serovars Paratyphi A and Typhi

    Directory of Open Access Journals (Sweden)

    White Brian

    2009-01-01

    Full Text Available Abstract Background Of the > 2000 serovars of Salmonella enterica subspecies I, most cause self-limiting gastrointestinal disease in a wide range of mammalian hosts. However, S. enterica serovars Typhi and Paratyphi A are restricted to the human host and cause the similar systemic diseases typhoid and paratyphoid fever. Genome sequence similarity between Paratyphi A and Typhi has been attributed to convergent evolution via relatively recent recombination of a quarter of their genomes. The accumulation of pseudogenes is a key feature of these and other host-adapted pathogens, and overlapping pseudogene complements are evident in Paratyphi A and Typhi. Results We report the 4.5 Mbp genome of a clinical isolate of Paratyphi A, strain AKU_12601, completely sequenced using capillary techniques and subsequently checked using Illumina/Solexa resequencing. Comparison with the published genome of Paratyphi A ATCC9150 revealed the two are collinear and highly similar, with 188 single nucleotide polymorphisms and 39 insertions/deletions. A comparative analysis of pseudogene complements of these and two finished Typhi genomes (CT18, Ty2 identified several pseudogenes that had been overlooked in prior genome annotations of one or both serovars, and identified 66 pseudogenes shared between serovars. By determining whether each shared and serovar-specific pseudogene had been recombined between Paratyphi A and Typhi, we found evidence that most pseudogenes have accumulated after the recombination between serovars. We also divided pseudogenes into relative-time groups: ancestral pseudogenes inherited from a common ancestor, pseudogenes recombined between serovars which likely arose between initial divergence and later recombination, serovar-specific pseudogenes arising after recombination but prior to the last evolutionary bottlenecks in each population, and more recent strain-specific pseudogenes. Conclusion Recombination and pseudogene-formation have been

  14. Improvement of the environmental quality through speed-affecting measures on major roads in municipalities. Final report and appendix; Verbesserung der Umweltqualitaet in Kommunen durch geschwindigkeitsbeeinflussende Massnahmen auf Hauptverkehrsstrassen. Abschlussbericht und Anlagenband

    Energy Technology Data Exchange (ETDEWEB)

    Hunger, Ditmar; Fiedler, Frank; Hunger, Matthias; Becker, Udo J.; Richter, Falk [Planungsbuero Dr.-Ing. Ditmar Hunger, Stadt - Verkehr - Umwelt, SUV, Dresden/Berlin (Germany)

    2007-02-15

    The research project analyses the influence of exceeded speeds on main urban roads in terms of environmental quality. In the analysis, aspects of emissions of harmful substances, noise, the quality of living and residential surrounding, urban separation effects as well as road safety aspects concerning pedestrians and cyclists were examined. Speed surveillance and accordant ticketing in case of violation are common in German cities. A survey carried out in several cities revealed that environmental aspects play hardly a role when considering control measures. Such measures are mainly viewed as 'traffic safety measures'. The most important result was that sanctioned monitoring (with fines) is indispensable for better compliance with the permissible maximum speed. Sanctions and their effect on speed behaviour were examined in the sample cities Rostock, Berlin and Dresden. In situations with a reasonably steady traffic flow speeds between 30 and 50 km/h were found to be most consistent with environmental protection objectives. Attaining this level requires a combination of conceptual planning measures and statutory regulatory measures, as well as the comprehensive involvement of all interested parties in the planning processes, the use of active and passive enforcement efforts, short-term interventions to modify streets or their cross-sections, and targetted public relations efforts. Within the study, an 'Analytical plan to evaluate complex environmental effects' (AKU) was developed. This plan serves as a tool for evaluation and decision making for certain measures and for the analysis of traffic effects on residents. In this plan, conclusions concerning various environmental aspects and the effect on residents are considered and assessed by a simplified approach. Furthermore, action priorities with a conceptual planning bias were derived. With regard to regulative judicial measures the study identified that speeding violations have to be monitored

  15. GPM SLH: Convective Latent Heating Estimated with GPM Dual-frequency Precipitation Radar Data

    Science.gov (United States)

    Takayabu, Y. N.; Hamada, A.; Yokoyama, C.; Ikuta, Y.; Shige, S.; Yamaji, M.; Kubota, T.

    2017-12-01

    Three dimensional diabatic heating distribution plays essential roles to determine large-scale circulation, as well as to generate mesoscale circulation associated with tropical convection (e.g. Hartmann et al., 1984; Houze et al. 1982). For mid-latitude systems also, diabatic heating contributes to generate PVs resulting in, for example, explosive intensifications of mid-lattitude storms (Boettcher and Wernli, 2011). Previously, with TRMM PR data, we developed a Spectral Latent Heating algorithm (SLH; Shige et al. 2004, etc.) for 36N-36S region. It was based on the spectral LH tables produced from a simulation utilizing the Goddard Cloud Ensemble Model forced with the TOGA-COARE data. With GPM DPR, the observation region is extended to 65N-65S. Here, we introduce a new version of SLH algorithm which is applicable also to the mid-latitude precipitation. A new global GPM SLH ver.5 product is released as one of NASA/JAXA GPM standard products on July 11, 2017. For GPM SLH mid-latitude algorithm, we employ the Japan Meteorological Agency (JMA)'s high resolution (horizontally 2km) Local Forecast Model (LFM) to construct the LUTs. With collaborations of JMA's forecast group, forecast data for 8 extratropical cyclone cases are collected and utilized. For mid-latitude precipitation, we have to deal with large temperature gradients and complex relationship between the freezing level and cloud base levels. LUTs are constructed for LH, Q1-QR, and Q2 (Yanai et al. 1973), for six different precipitation types: Convective and shallow stratiform LUTs are made against precipitation top heights. For deep stratiform and other precipitation, LUTs are made against maximum precipitation to handle the unknown cloud-bases. Finally, three-dimensional convective latent heating is retrieved, utilizing the LUTs and precipitation profile data from GPM 2AKu. We can confirm that retrieved LH looks very similar to simulated LH, for a consistency check. We also confirm a good continuities of

  16. Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

    Directory of Open Access Journals (Sweden)

    Antoine Marmignon

    2014-08-01

    Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium

  17. Tanda-Tanda Puitik Sajak “Pertanyaan Srikandi” Karya Wiyatmi

    Directory of Open Access Journals (Sweden)

    Puji Santosa

    2016-06-01

    Full Text Available Abstrak: Tujuan penelitian ini mengungkapkan dan mendeskripsikan tanda-­‐tanda puitik sajak “Pertanyaan Srikandi” karya Wiyatmi dengan pendekatan semiotik. Masalah penelitian adalah bagaimana tanda-­‐tanda puitik pada tataran sintaktik, semantik, dan pragmatik terekspresikan dalam sajak “Pertanyaan Srikandi”? Metode yang digunakan adalah metode kualitatif interpretatif dengan ditopang analisis konten. Hasil penelitian membuktikan bahwa tanda-­‐tanda puitik sajak “Pertanyaan Srikandi” pada tataran: (1 sintaktik semiotik menunjukkan bentuk sajak bebas; (2 semantik semiotik menunjukkan adanya testimoni Srikandi yang berisi pernyataan jati diri semasa kini sebagai perempuan androgini atau semasa generasi Sri Kresna sebagai kenya wandu yang berusaha menggugat akan kesetaraan gender; dan (3 pragmatik semiotik membuktikan adanya bentuk ujaran tunggal, komunikasi searah dengan saluran komunikasi teks tertulis, sudut pandang aku terlibat, dan menonjolkan fungsi bahasa aspek referensial situasional yang berisi pesan gugatan seorang perempuan dalam menghadapi tebalnya tembok patriarkat. Kata-­‐Kata Kunci: tanda-­‐tanda puitik, semiotik, sintaksis, semantik, pragmatik Abstract: This study aims to reveal and describe the poetic signs of "Pertanyaan Srikandi" by Wiyatmi with semiotic approach. The research problem is how the poetic signs at the syntactic, semantic, and pragmatic levels are expressed in the poem "Pertanyaan Srikandi". The study used qualitative method supported with the content analysis. The result shows that: (1 at syntactic level, the poetic signs of "Pertanyaan Srikandi" show the form of free verse; (2 at semantic level, the signs show Srikandi’s testimony containing statements during her current identity as an androgynous woman or during the generation of Sri Krishna as kenya wandu ‘androgyny’ seeking a gender equality; and (3 at pragmatic level, they prove the existence of singular speech form

  18. Identification of Water Quality Significant Parameter with Two Transformation/Standardization Methods on Principal Component Analysis and Scilab Software

    Directory of Open Access Journals (Sweden)

    Jovan Putranda

    2016-09-01

    Full Text Available Water quality monitoring is prone to encounter error on its recording or measuring process. The monitoring on river water quality not only aims to recognize the water quality dynamic, but also to evaluate the data to create river management policy and water pollution in order to maintain the continuity of human health or sanitation requirement, and biodiversity preservation. Evaluation on water quality monitoring needs to be started by identifying the important water quality parameter. This research objected to identify the significant parameters by using two transformation or standardization methods on water quality data, which are the river Water Quality Index, WQI (Indeks Kualitas Air, Sungai, IKAs transformation or standardization method and transformation or standardization method with mean 0 and variance 1; so that the variability of water quality parameters could be aggregated with one another. Both of the methods were applied on the water quality monitoring data which its validity and reliability have been tested. The PCA, Principal Component Analysis (Analisa Komponen Utama, AKU, with the help of Scilab software, has been used to process the secondary data on water quality parameters of Gadjah Wong river in 2004-2013, with its validity and reliability has been tested. The Scilab result was cross examined with the result from the Excel-based Biplot Add In software. The research result showed that only 18 from total 35 water quality parameters that have passable data quality. The two transformation or standardization data methods gave different significant parameter type and amount result. On the transformation or standardization mean 0 variances 1, there were water quality significant parameter dynamic to mean concentration of each water quality parameters, which are TDS, SO4, EC, TSS, NO3N, COD, BOD5, Grease Oil and NH3N. On the river WQI transformation or standardization, the water quality significant parameter showed the level of

  19. ULUSLARARASILAŞMANIN MARKALAŞMADAKİ İTİCİ GÜCÜ: İNCİ AKÜ ÜZERİNE BİR ÇALIŞMA

    Directory of Open Access Journals (Sweden)

    Ayben ÇELİK

    2015-03-01

    Full Text Available Uluslararasılaşma günümüz işletmeleri için kaçınılmaz bir olgudur. Globalleşmenin yarattığı küresel rekabet, işletmelerin üretim ve pazarlama faaliyetlerini dünya ölçeğinde planlama zorunluluğunu doğurmuştur. İşletmeler de çeşitli modellerle uluslararasılaşmalarını gerçekleştirmektedirler. Uluslararasılaşma sürecinde, markalaşmayı başarabildikleri ölçüde pazarda kalıcı olma ve yüksek kazanç elde etme olasılıkları artmaktadır. Bu çalışma ile yabancı menşeli şirketlerle sermayeye dayalı kurulan stratejik ortaklıkların “uluslararasılaşmaya” kazandırdığı ivme ve uluslararasılaşmanın “markalaşma sürecinde” yarattığı itici gücün ortaya konması amaçlanmaktadır. Araştırmada, Turquality desteğinden yararlanan İnci Akü’nün, uluslararasılaşma ve markalaşma süreçlerindeki evreleri ve global ortaklarının bu süreçteki etkisi örnek olay yöntemiyle analiz edilmektedir. Araştırma sonucunda, işletmelerin iç ve dış dinamikler doğrultusunda, klasik uluslararasılaşma süreçlerinin dışında, stratejik yabancı ortaklıklar ile karşı tarafın şebeke ağına dahil olarak uluslararasılaşmalarını hızlandırabildiği ortaya çıkmıştır. Bu ortaklık girişimleri hem yönetim ve üretim bilgisinin transferini hem de sahip olunan ağdan yararlanma şansını yerli ortağa tanıdığından dış pazarlara entegrasyonu kolaylaştırmaktadır. Uluslararasılaşma da beraberinde markalaşma ihtiyacını doğurmakta ve süreç üzerinde hızlandırıcı rol oynamaktadır.