2014 Registered Flex Fuel Vehicles

Iowa Code section 452A.33(3) requires a report regarding flexible fuel vehicles registered in Iowa. The report includes the number of flexible fuel vehicles according to year of manufacture; the number of passenger vehicles according to year of manufacture; and the number of light pickup trucks according to the year of manufacture.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

AIM: To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). METHODS AND RESULTS: Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES  vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). CONCLUSION: A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175.

The effects resulting from the introduction of an oxime group in place of the distal aromatic ring of the diphenyl moiety of LT175, previously reported as a PPARα/γ dual agonist, have been investigated. This modification allowed the identification of new bioisosteric ligands with fairly good activity on PPARα and fine-tuned moderate activity on PPARγ. For the most interesting compound (S)-3, docking studies in PPARα and PPARγ provided a molecular explanation for its different behavior as full and partial agonist of the two receptor isotypes, respectively. A further investigation of this compound was carried out performing gene expression studies on HepaRG cells. The results obtained allowed to hypothesize a possible mechanism through which this ligand could be useful in the treatment of metabolic disorders. The higher induction of the expression of some genes, compared to selective agonists, seems to confirm the importance of a dual PPARα/γ activity which probably involves a synergistic effect on both receptor subtypes.

Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

Pathogenesis in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA) is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/-) mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65), was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/-) mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-)/Gnat1(-/-) mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-)/Bax(-/-) mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/-) mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-)/Bax(-/-) mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice.This is the first report, to our knowledge, that a single genetic mutation can trigger two independent apoptotic pathways in rod and cone photoreceptors in Rpe65-dependent LCA disease. These results highlight the necessity to investigate and understand the specific death signaling pathways committed in rods and cones to develop effective therapeutic approaches to treat RP diseases.

Evaluation of the Need for Longitudinal Median Joints in Bridge Decks on Dual Structures, TR-661, 2015

The primary objective of this project was to determine the effect of bridge width on deck cracking in bridges. Other parameters, such as bridge skew, girder spacing and type, abutment type, pier type, and number of bridge spans, were also studied. To achieve the above objectives, one bridge was selected for live-load and long-term testing. The data obtained from both field tests were used to calibrate a three-dimensional (3D) finite element model (FEM). Three different types of loading—live loading, thermal loading, and shrinkage loading—were applied. The predicted crack pattern from the FEM was compared to the crack pattern from bridge inspection results. A parametric study was conducted using the calibrated FEM. The general conclusions/recommendations are as follows: -- Longitudinal and diagonal cracking in the deck near the abutment on an integral abutment bridge is due to the temperature differences between the abutment and the deck. Although not likely to induce cracking, shrinkage of the deck concrete may further exacerbate cracks developed from thermal effects. -- Based upon a limited review of bridges in the Iowa DOT inventory, it appears that, regardless of bridge width, longitudinal and diagonal cracks are prevalent in integral abutment bridges but not in bridges with stub abutments. -- The parametric study results show that bridge width and skew have minimal effect on the strain in the deck bridge resulting from restrained thermal expansion. -- Pier type, girder type, girder spacing, and number of spans also appear to have no influence on the level of restrained thermal expansion strain in the deck near the abutment.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.

In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption.

We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyrosine kinase inhibitor [TKI])-trastuzumab combination and lapatinib alone (dual HER2/EGFR TKI) and explored their possible mechanisms of action. The effects on tumor growth and animal survival of the three therapies were assessed in nude mice xenografted with the human pancreatic carcinoma cell lines Capan-1 and BxPC-3. After therapy, EGFR and HER2 expression and AKT phosphorylation in tumor cells were analyzed by Western blot analysis. EGFR/HER2 heterodimerization was quantified in BxPC-3 cells by time-resolved FRET. In K-ras-mutated Capan-1 xenografts, the 2mAbs therapy gave significantly higher inhibition of tumor growth than the erlotinib/trastuzumab combination, whereas in BxPC-3 (wild-type K-ras) xenografts, the erlotinib/trastuzumab combination showed similar growth inhibition but fewer tumor-free mice. Lapatinib showed no antitumor effect in both types of xenografts. The efficacy of the 2mAbs therapy was partly Fc-independent because F(ab')(2) fragments of the two mAbs significantly inhibited BxPC-3 growth, although with a time-limited therapeutic effect. The 2mAbs therapy was associated with a reduction of EGFR and HER2 expression and AKT phosphorylation. BxPC-3 cells preincubated with the two mAbs showed 50% less EGFR/HER2 heterodimers than controls. In pancreatic carcinoma xenografts, the 2mAbs therapy is more effective than treatments involving dual EGFR/HER2 TKIs. The mechanism of action may involve decreased AKT phosphorylation and/or disruption of EGFR/HER2 heterodimerization.

Aminoterminal amphipathic α-helix AH1 of hepatitis C virus nonstructural protein 4B possesses a dual role in RNA replication and virus production.

Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV) replication complex formation. In concert with other nonstructural proteins, it induces a specific membrane rearrangement, designated as membranous web, which serves as a scaffold for the HCV replicase. The N-terminal part of NS4B comprises a predicted and a structurally resolved amphipathic α-helix, designated as AH1 and AH2, respectively. Here, we report a detailed structure-function analysis of NS4B AH1. Circular dichroism and nuclear magnetic resonance structural analyses revealed that AH1 folds into an amphipathic α-helix extending from NS4B amino acid 4 to 32, with positively charged residues flanking the helix. These residues are conserved among hepaciviruses. Mutagenesis and selection of pseudorevertants revealed an important role of these residues in RNA replication by affecting the biogenesis of double-membrane vesicles making up the membranous web. Moreover, alanine substitution of conserved acidic residues on the hydrophilic side of the helix reduced infectivity without significantly affecting RNA replication, indicating that AH1 is also involved in virus production. Selective membrane permeabilization and immunofluorescence microscopy analyses of a functional replicon harboring an epitope tag between NS4B AH1 and AH2 revealed a dual membrane topology of the N-terminal part of NS4B during HCV RNA replication. Luminal translocation was unaffected by the mutations introduced into AH1, but was abrogated by mutations introduced into AH2. In conclusion, our study reports the three-dimensional structure of AH1 from HCV NS4B, and highlights the importance of positively charged amino acid residues flanking this amphipathic α-helix in membranous web formation and RNA replication. In addition, we demonstrate that AH1 possesses a dual role in RNA replication and virus production, potentially governed by different topologies of the N-terminal part of NS4B.

The Adoption of Technologies, Policies, and Systems for Improving Fleet Fuel Performance, 2007

The dramatic rise in fuel prices and growing environmental concerns are pressing freight transportation companies to pursue new systems and methods to improve fuel efficiency and reduce their environmental impact. While select major carriers appear to be leading efforts to adopt technologies that support a dramatic improvement in fuel performance, there appears to be little understanding as to the breadth and depth of efforts being taken by the broader motor carrier community, consisting of over 20,000 companies of all sizes. The purpose of this study was to investigate the level of adoption of technologies and policies to support improved fuel efficiency among motor carrier fleets.

FY'15 Biodiesel Fuel Revolving Fund Expenditures Report

Pursuant to Iowa Code section 307.20, the biodiesel fuel revolving fund (Fund) was created and is to be used to purchase biodiesel fuel for use in the Department of Transportation’s vehicles. The act directed that the Fund receive money from the sale of EPAct credits banked by the DOT on the effective date of the act, monies appropriated by the General Assembly, and any other monies obtained or accepted by the DOT for deposit in the Fund. This report is of the expenditures made from the Fund during FY 2015.

2016 Registered Flex Fuel Vehicles

Iowa Code section 452A.33(3) requires a report regarding flexible fuel vehicles registered in Iowa. The report includes the number of flexible fuel vehicles according to year of manufacture; the number of passenger vehicles according to year of manufacture; and the number of light pickup trucks according to the year of manufacture.

Purpura de Henoch-Schönlein: une prise en charge entre pédiatre et néphrologue pédiatre [Henoch-Schönlein Purpura a dual follow up between pediatrician and pediatric nephrologist].

Henoch-Schönlein purpura is a well known paediatric disease characterized by the classic triad: purpura, arthritis and abdominal pain. Short term prognosis is excellent and is mostly dependant on abdominal complications. Long term morbidity depends essentially on the severity of renal involvement which occurs in 35% of cases. Microhematuria and light proteinuria are the only signs in 80% of cases. The remaining 20% presents with nephrotic or nephritic syndrome and acute renal insufficiency. Among patients with Henoch-Schönlein nephritis the risk of developing renal insufficiency varies between 11-30% of cases. Currently, the follow up guidelines are multiple and the optimal treatment of nephritis is controversial; this is what this article proposes to discuss.

Dual-purpose wheat grain and animal production under different grazing periods

The objective of this work was to evaluate the influence of different grazing periods on beef animal production and on wheat forage and grain yield. The experiment was carried out in Pato Branco, PR, Brazil. Six grazing periods were evaluated (0, 21, 42, 63, 84, and 105 days) on dual-purpose wheat cultivar BRS Tarumã. Purunã steers, with average live weight of 162 kg and ten months of age, were kept under continuous grazing using a variable stocking rate, in order to maintain the established sward height of 25 cm. Greater increases in total animal gain (TAG) occurred with longer grazing periods. However, there was little increase after 63 days (490 kg ha-1), and TAG decreased from 552 to 448 kg ha-1 between 84 and 105 days. Grain yield decreased from 2,830 to 610 kg ha-1 when the grazing period increased from 0 to 105 days, but there was little change after 63 days (750 kg ha-1). Cultivar BRS Tarumã shows excellent animal production potential, and the decision on how long wheat pastures should be grazed must be based on relative prices of grain and livestock.