Aging Watch, April 8, 2015, Vol. 15, no. 6

Aging Watch is provided in the spirit of information and education. The opinions expressed by the contributors do not necessarily reflect those of the Department or its programs. The Department shall not be liable for any damages that may result from errors or omissions in information distributed in this publication. Aging Watch will be published regularly during the legislative session and monthly in the interim by the Iowa Department on Aging. “Aging Watch.” The Department is providing this update to better inform you about policy affecting older Iowans. In addition to policy updates from the statehouse and the nation’s capitol, you’ll learn about Department programs and changes affecting the landscape. As you’ll learn reading this and future editions, big changes are coming for the Iowa Aging Network. Over the next year the Department will be reducing the number of local Area Agencies on Aging, as required by legislative action. Not surprisingly, this is a major change for everyone.

Floods in the Nishnabotna River Basin, Iowa, HR-140, 1991

Flood-elevation profiles and flood-peak discharges for floods during 1972, 1982, and 1987 in the Nishnabotna River basin are given in the report. The profiles are for the 1972 flood on the West and East Nishnabotna Rivers, the 1982 flood on Indian Creek, and the 1987 flood on the lower West Nishnabotna River. A flood history describes rainfall conditions and reported damages for floods occurring 1947, 1958, 1972, 1982, and 1987. Discharge for the 1982 flood on Indian Creek is 1.1 times larger than the 100-year recurrence interval discharge.

Design of new tools to improve the efficacy of DNA-damaging drugs used in cancer therapy

Résumé Les tumeurs sont diverses et hétérogènes, mais toutes partagent la capacité de proliférer sans contrôle. Une prolifération dérégulée de cellules couplée à une insensibilité à une réponse apoptotique constitue une condition minimale pour que l'évolution d'une tumeur se produise. Un des traitements les plus utilisés pour traité le cancer à l'heure actuelle sont les chimiothérapies, qui sont fréquemment des composés chimiques qui induisent des dommages dans l'ADN. Les agents anticancéreux sont efficaces seulement quand les cellules tumorales sont plus aisément tuées que le tissu normal environnant. L'efficacité de ces agents est en partie déterminée par leur capacité à induire l'apoptose. Nous avons récemment démontré que la protéine RasGAP est un substrat non conventionnel des caspases parce elle peut induire à la fois des signaux anti et pro-apoptotiques, selon l'ampleur de son clivage par les caspases. A un faible niveau d'activité des caspases, RasGAP est clivé, générant deux fragments (le fragment N et le fragment C). Le fragment N semble être un inhibiteur général de l'apoptose en aval de l'activation des caspases. À des niveaux plus élevés d'activité des caspases, la capacité du fragment N de contrecarrer l'apoptose est supprimée quand il est clivé à nouveau par les caspases. Ce dernier clivage produit deux nouveaux fragments, N 1 et N2, qui contrairement au fragment N sensibilisent efficacement des cellules cancéreuses envers des agents chimiothérapeutiques. Dans cette étude nous avons prouvé qu'un peptide, appelé par la suite TAT-RasGAP317-326, qui est dérivé du fragment N2 de RasGAP et est rendu perméable aux cellules, sensibilise spécifiquement des cellules cancéreuses à trois génotoxines différentes utilisées couramment dans des traitements anticancéreux, et cela dans des modèles in vitro et in vivo. Il est important de noté que ce peptide semble ne pas avoir d'effet sur des cellules non cancéreuses. Nous avons également commencé à caractériser les mécanismes moléculaires expliquant les fonctions de sensibilisation de TAT-RasGAP317-326. Nous avons démontré que le facteur de transcription p53 et une protéine sous son activité transcriptionelle, nommée Puma, sont indispensables pour l'activité de TAT-RasGAP317-326. Nous avons également prouvé que TAT-RasGAP317-326 exige la présence d'une protéine appelée G3BP1, une protéine se liant a RasGAP, pour potentialisé les effets d'agents anticancéreux. Les données obtenues dans cette étude montrent qu'il pourrait être possible d'augmenter l'efficacité des chimiothérapies à l'aide d'un composé capable d'augmenter la sensibilité des tumeurs aux génotoxines et ainsi pourrait permettre de traiter de manière plus efficace des patients sous traitement chimiothérapeutiques. Summary Tumors are diverse and heterogeneous, but all share the ability to proliferate without control. Deregulated cell proliferation coupled with suppressed apoptotic sensitivity constitutes a minimal requirement upon which tumor evolution occurs. One of the most commonly used treatments is chemotherapy, which frequently uses chemical compounds that induce DNA damages. Anticancer agents are effective only when tumors cells are more readily killed than the surrounding normal tissue. The efficacy of these agents is partly determined by their ability to induce apoptosis. We have recently demonstrated that the protein RasGAP is an unconventional caspase substrate because it can induce both anti- and pro-apoptotic signals, depending on the extent of its cleavage by caspases. At low levels of caspase activity, RasGAP is cleaved, generating an N-terminal fragment (fragment N) and a C-terminal fragment (fragment C). Fragment N appears to be a general Mocker of apoptosis downstream of caspase activation. At higher levels of caspase activity, the ability of fragment N to counteract apoptosis is suppressed when it is further cleaved. This latter cleavage event generates two fragments, N1 and N2, which in contrast to fragment N potently sensitizes cancer cells toward DNA-damaging agents induced apoptosis. In the present study we show that a cell permeable peptide derived from the N2 fragment of RasGAP, thereafter called TAT-RasGAP317-326, specifically sensitizes cancer cells to three different genotoxins commonly used in chemotherapy in vitro and in vivo models. Importantly this peptide seems not to have any effect on non cancer cells. We have also started to characterize the molecular mechanisms underlying the sensitizing functions of TAT-RasGAP317-326. We have demonstrated that the p53 transcription factor and a protein under its transcriptional activity, called Puma, are required for the activity of TATRasGAP317-326. We have also showed that TAT-RasGAP317-326 requires the presence of a protein called G3BP1, which have been shown to interact with RasGAP, to increase the effect of the DNA-damaging drug cisplatin. The data obtained in this study showed that it is possible to increase the efficacy of current used chemotherapies with a compound able to increase the efficacy of genotoxins which could be beneficial for patients subjected to chemotherapy.

Lésions du ligament croisé antérieur de l'enfant [Anterior cruciate ligament injuries in children].

An increasing number of anterior cruciate ligament injuries are now seen in children and girls seem to be equally affected. Such neglected or untreated lesions could be the cause of early degenerative changes. Recently, many authors support the trend toward early surgical management in skeletally immature patients with complex meniscal tear or recurrent knee instability after proper rehabilitation. Improvement in pediatric knowledge and surgical techniques tend to support a tendency for more surgical treatment in children. The type of management is choosing according to history and physical examination. Magnetic resonance imaging is a useful tool not only for diagnosis but also for surgical treatment planning. We usually recommend anterior cruciate ligament reconstruction in children with knee instability or with further damages to the joint.

Proteomics of methylene blue photo-treated plasma before and after removal of the dye by an absorbent filter.

Methylene blue (MB) and light are used for virus inactivation of plasma for transfusion. However, the presence of MB has been the subject of concern, and efforts have been made to efficiently remove the dye after photo-treatment. For this study, plasma was collected by apheresis from 10 donors (group A), then treated using the MacoPharma THERAFLEX procedure (MB; 1 microM, and light exposure; 180 J/cm(2)) (group B), and finally filtered in order to remove the dye (group C). Proteins were analyzed by two-dimensional electrophoresis, and peptides showing modifications were characterized by mass spectrometry. Clottable and antigenic fibrinogen levels, as well as fibrin polymerization time were measured. Analyses of the gels focused on a region corresponding to pI between 4.5 and 6.5, and M(r) from 7000 to 58 000. In this area, 387 +/- 47 spots matched, and four of these spots presented significant modifications. They corresponded to changes of the gamma-chain of fibrinogen, of transthyretin, and of apolipoprotein A-I, respectively. A decrease of clottable fibrinogen and a prolongation of fibrin polymerization time were observed in groups B and C. Removal of MB by filtration was not responsible for additional protein alterations. The effect of over-treatment of plasma by very high concentrations of MB (50 microM) in association with prolonged light exposure (3 h) was also analyzed, and showed complex alterations of most of the plasma proteins, including fibrinogen gamma-chain, transthyretin, and apolipoprotein A-I. Our data indicates that MB treatment at high concentration and prolonged illumination severely injure plasma proteins. By contrast, at the MB concentration used to inactivate viruses, damages are apparently very restricted.

Granulocyte macrophage colony stimulating factor improves mucosal repair in a mouse model of acute colitis (P278)

Background and Aims: Granulocyte-macrophage colonystimulating factor (GM-CSF), a cytokine modulating the number and function of innate immune cells, has been shown to provide symptomatic benefit in some patients with Crohn's disease (CD). Since, it becomes widely appreciated that a timely and spatially regulated action of innate immune cells is critical for tissue regeneration, we tested whether GM-CSF therapy may favours intestinal mucosal repair in the acute mouse model of dextran sulfate sodium (DSS)-induced colitis. Methods: Mice treated with GM-CSF or saline were exposed for 7 days to DSS to induce colitis. On day 5, 7 and 10, mice were subjected to colonoscopy or sacrificed for evaluation of inflammatory reaction and mucosal healing. Results: GM-CSF therapy prevented body weight loss, diarrhea, dampened inflammatory reactions and ameliorated mucosal damages. Mucosal repair improvement in GM-CSF-treated mice was observed from day 7 on both by colonoscopy (ulceration score 1.2}0.3 (GM-CSF-treated) vs 3.1}0.5 (untreated), p = 0.01) and histological analysis (percentage of reepithelialized ulcers 55%}4% (GM-CSF-treated) vs 18%}13% (untreated), p = 0.01). GM-CSF therapy can still improve the colitis when hematopoietic, but not non-hematopoietic cells, are responsive to GM-CSF, as shown in WT→GM-CSFRKO chimeras. Lastly, we observed that GM-CSF-induced promotion of wound healing is associated with a modification of the cellular composition of DSS-induced colonic inflammatory infiltrate, characterized by the reduction of neutrophil numbers and early accumulation of CD11b+Gr1lo myeloid cells. Conclusion: Our study shows that GM-CSF therapy accelerates the complex program leading to tissue repair during acute colitis and suggests that GM-CSF promotion of mucosal repair might contribute to the symptomatic benefits of GM-CSF therapy observed in some CD patients.

RDM1, a novel RNA recognition motif (RRM)-containing protein involved in the cell response to cisplatin in vertebrates.

A variety of cellular proteins has the ability to recognize DNA lesions induced by the anti-cancer drug cisplatin, with diverse consequences on their repair and on the therapeutic effectiveness of this drug. We report a novel gene involved in the cell response to cisplatin in vertebrates. The RDM1 gene (for RAD52 Motif 1) was identified while searching databases for sequences showing similarities to RAD52, a protein involved in homologous recombination and DNA double-strand break repair. Ablation of RDM1 in the chicken B cell line DT40 led to a more than 3-fold increase in sensitivity to cisplatin. However, RDM1-/- cells were not hypersensitive to DNA damages caused by ionizing radiation, UV irradiation, or the alkylating agent methylmethane sulfonate. The RDM1 protein displays a nucleic acid binding domain of the RNA recognition motif (RRM) type. By using gel-shift assays and electron microscopy, we show that purified, recombinant chicken RDM1 protein interacts with single-stranded DNA as well as double-stranded DNA, on which it assembles filament-like structures. Notably, RDM1 recognizes DNA distortions induced by cisplatin-DNA adducts in vitro. Finally, human RDM1 transcripts are abundant in the testis, suggesting a possible role during spermatogenesis.

Ilmastonmuutoksen vaikutussähköverkkoliiketoimintaan

Tässä diplomityössä tutkittiin ilmastonmuutoksen vaikutusta sähköverkkoliiketoimintaan. Ilmastonmuutosennusteet laadittiin RCAOilmastomallin antamien laskelmien perusteella. Ilmastomuuttujien ennusteet tehtiin ajanjaksolle 2016 - 2045 ja ennusteiden vertailujaksona käytettiin ajanjaksoa 1960 - 1990. Ennusteet laadittiin sadannalle, lämpötilalle, kuuraantumiselle, huurteelle, ukkoselle, routaantumiselle ja tuulisuudelle. Ilmastomuuttujien vaikutukset arvioitiin sekä tekniseltä että taloudelliselta kannalta. Ilmastonmuutoksen myötä on odotettavissa, että ilmastomuuttujien aiheuttamat rasitukset verkkoliiketoimintaa kohtaan tulevat olemaan niistä saatuja hyötyjä suuremmat. Vikamäärien kasvu on merkittävin ja haastavin ilmastonmuutoksen aiheuttama haitta. Ukkonen, lumikuormat ja tuuli tulevat aiheuttamaan nykyistä enemmän vikoja erityisesti keskijänniteverkoissa avojohdoille ellei verkkoja kehitetä vikavarmemmiksi. Lämpötilan nousun seurauksena lämmitystarve laskee ja jäähdytystarve nousee. Tämä näkyy merkittävimmin voimakkaasti lämpötilariippuvaisten käyttäjäryhmien sähkönkulutuksessa ja huippukuormissa.

Tasasähkön hyödyntämismahdollisuudet sähkönjakelussa

Tässä työssä on tutkittu tasasähkönsiirron tuomia mahdollisuuksia sähkönjakelussa, kun pienjännitedirektiivin pienjännitemäärittelyn soveltamista laajennetaan koskemaan vaihtojännitteen lisäksi myös tasajännitettä. Aiemmin tasasähköjärjestelmiä on käytetty ainoastaan sähköistymisen alkuaikoina 1900-luvun alussa. Viime vuosikymmeninä on sähkönjakelussa käytetty pelkästään vaihtosähköverkkoja, koska tehoelektronisten laitteiden korkea hintataso ja tekniset ominaisuudet ovat mahdollistaneet tasasähkön käytön vain suurjännitteellä. Suomalaisten sähkönkäyttö on lisääntynyt muutamalla prosenttiyksiköllä vuosittain ja kasvun taantumista ei ole odotettavissa lähiaikoina. Samaan aikaan yhteiskunta muuttuu jatkuvasti yhä riippuvaisemmaksi sähköstä ja odotukset toteutuvasta sähkönlaadusta ovat jatkuvasti korkeammat. Sähkönlaadun näkökulmasta ilmasto on tuonut aiempia suurempia haasteita sähkön toimitusvarmuudelle, kun myrskyjen aiheuttamat tuhot ovat olleet yhä entisiä suurempia. Toimitusvarmuuden parantamiseksi ovat muutamat vuosikymmenen alun rajut myrskyt johtaneet pohdintaan tulevien haasteiden hoitamiseksi ja edelleen uuden 3-portaiseen 20/1/0,4 kV vaihtosähköjärjestelmän kehittämiseen. Tasasähkönsiirron avulla halutaan tuoda käyttöön niitä hyötyjä, joita järjestelmän vaihdolla on saavutettavissa. Täysimääräisellä tasajännitteen hyödyntämisellä voidaan saavuttaa mm. aiempaa edullisempia investointivaihtoehtoja,parempi sähkönlaatu, parempi hajautetun tuotannon liitettävyys verkkoon ja erilaisten asiakaskohtaisten laitteiden helppo integroitavuus osaksi jakelujärjestelmää. Tämän työn puitteissa on pohdittu sekä teknisiä ratkaisuja että järjestelmän teknistaloudellista käyttöaluetta. Lisäksi on pyritty hahmottamaan eri tekijöiden vaikutuksia sähkönjakeluun.

Vastuu toimitusvahingoista polttonesteen toimituksissa, case oy Shell ab

Tutkimustyön tavoitteena oli selvittää polttonesteiden toimituksiin osallistuvien tahojen, eli myyjän, itsenäisen rahdinkuljettajan ja ostajan vastuun jakautuminen.. Lähtökohtaisesti myyjällä on viivästystilanteissa sekä kuluttaja-, että yritysasiakkaita kohtaan kontrollivastuu välittömistä ja tuottamusperusteinen vastuu välillisistä vahingoista, mutta korvausvelvollisuudesta voidaan vapautua tietyt tunnusmerkit täyttävän esteen perusteella. Virhevastuukin perustuu samanlaiselle kaksinkertaiselle vahinkolajikohtaiselle vastuuperuste-erottelulle, mutta myyjän on aina korvattava kuluttajalle aiheutuneet välittömät vahingot aiheuttamisvastuun perusteella. Lisäksi hän voi joutua hyvittämään kaikki mahdolliset menetyksen annetun erityisen sitoumuksen nojalla. Maksuviivästystilanteissa ostajan molempia vahinkolajeja koskeva vastuuperuste sijoittuu puhtaan aiheuttamis- ja kontrollivastuun väliin. Lainmukaisen myötävaikutusvelvollisuuden laiminlyönnin aiheuttamat vahingot korvataan noudattamalla myyjän viivästysvastuusäännöksiä, mutta tavaran vastaanottamisen tai noutamisen osalta vastuun toteutuminen edellytetään vielä sitä, että kaupankohteen pois toimittamisella on ollut myyjäpuolelle erityistä merkitystä. Kuluttaja-asiakkaalla ei kuitenkaan ole edellä mainittua vastuuta. Rahdinkuljettajalla on tavara- ja viivästysvahingoista ankara vastuu tietyn force majeure poikkeuksin. Tavallisesti korvausvelvollisuus rajoittuu tavaravahinkojen osalta 20 euroon painokiloa kohti ja viivästysvahingot on korvattava rahtia vastaavaan rahamäärään saakka. Kyseinen taho voi myös vapautua vastuusta kokonaan laissa mainittujen vastuuvapausperusteiden nojalla, mutta tahallinen tai törkeän huolimaton toiminta aiheuttaa täyden vahingonkorvausvastuun.

The effect of oxygen delignification on fiber properties in kraft pulp production - a review

Fiber damages comprise fiber deformations, characterized as fiber curl, kink, dislocations and strength losses as well as some yet unidentified factors. This recently discovered phenomenon is especially evident in mill scale kraftpulps. Laboratory produced pulps tend to have less damages and superior strength properties compared to those produced in pulp mills. Generally fiber damages pose a problem in the production of reinforcement pulp because they tend to decrease the ability of fibers to transmit load. Previous studies on fiber damage have shown that most of the fiber damages occur during brown stock processing starting from cooking and discharging. This literature review gives an overall picture on fiber damages occurring during softwood kraft pulp production with an emphasis on the oxygen delignification stage. In addition the oxygen delignification stage itself is described in more detailed extent in order to understand the mechanisms behind the delignification and fiber damaging effect. The literature available on this subject is unfortunately quite contradictory and implicates a lotof different terms. Only a few studies have been published which help to understand the nature of fiber damages. For that reason the knowledge presented in this work is not only based on previous studies but also on research scientist and mill staff interviews.

SIMULATION OF AMB SUPPORTED ROTOR DURING DROP ON RETAINER BEARINGS

The active magnetic bearings present a new technology which has many advantages compared to traditional bearing designs. Active magnetic bearings, however, require retainer bearings order to prevent damages in the event of a component, power or a control loop failure. In the dropdown situation, when the rotor drops from the magnetic bearings to the retainer bearings, the design parameters of the retainer bearings have a significant influence on the behaviour of the rotor. In this study, the dynamics of an active magnetic bearings supported electric motor during rotor drop on retainer bearings is studied using a multibody simulation approach. Various design parameters of retainer bearings are studied using a simulation model while results are compared with those found in literature. The retainer bearings are modelled using a detailed ball bearing model, which accounts damping and stiffness properties, oil film and friction between races and rolling elements. The model of the ball bearings includes inertia description of rollingelements. The model of the magnetic bearing system contains unbalances of the rotor and stiffness and damping properties of support. In this study, a computationally efficient contact model between the rotor and the retainer bearings is proposed. In addition, this work introduces information for the design of physicalprototype and its retainer bearings.

Sujetos responsables por los daños derivados del uso de un producto peligroso. Comentario a la STS, 1a, 21.11.2008 (MP:José Antonio Seijas Quintana), RJ 2009\144

La STS, 1a, 21.11.2008, objeto de este comentario, plantea a un tiempo la responsabilidad del consumidor, vendedor, fabricante y Administración pública por los daños materiales causados por la explosión de un producto altamente inflamable que había sido vendido a un particular para la desinfección de su vivienda.

El derecho penal ante el fenómeno sectario

El fenómeno de las sectas destructivas pone de manifiesto los riesgos de un abusivo recurso a la vía punitiva, por lo que el Derecho penal debe hacer frente a diversas dificultades para adentrarse en el terreno de las actividades que puedan desarrollarse en el seno de estas agrupaciones. Así, tras analizar la relevancia jurídico penal de las actividades de las sectas destructivas, aludiendo tanto a las conductas relativas a menores de edad e incapaces, como a las conductas delictivas contra adultos, se propone la forma de superar las dificultades para una adecuada identificación y persecución de los responsables.