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Smectite clays suspended in a platinum deposition solution are here shown to increase the specific surface area of electrodeposited Pt on gold and porous carbon paper supports, and to enhance the specific activity of Pt towards methanol oxidation under steady-state conditions. Organomodified natural bentonite shows a more pronounced effect with respect to natural montmorillonite and synthetic laponite. The effect of clay, as evidenced by microscopy and X-ray diffraction, is to decrease the average size of the Pt crystallites and simultaneously the degree of their mutual coalescence. This effect is associated with suppression of Pt secondary nucleation observed in deposition current transients, and the electrocatalytic activity is suggested to be affected by the intergrain boundaries.

Particles of Fe2Al5 (60–211 μm diameter) were leached at 10, 30 and 50 °C in 3 M NaOH containing varying amounts of sodium chromate in the range 0.005–0.05 M. The kinetics of leaching was fitted to solid-state kinetic models. The model best fitting the data was the Avrami–Erofeev model −ln(1 − α)1/1.5 = kt. Apparent activation energies were in the range 60–63 kJ mol−1. The BET surface areas of the promoted materials were high, with values in the range 57–91 m2 g−1. Catalysts were tested for the water–gas-shift (WGS) reaction at 350 °C and it was found that the chromium content of the catalysts had a significant effect on the WGS activity, which went through a maximum for a catalyst containing around 2 wt% chromium.

Bendamustine has demonstrated substantial efficacy in the treatment of hematologic malignancies and continues to distinguish itself from other alkylating agents with regard to its activity in tumor cells. The mechanistic and clinical differences associated with bendamustine may be directly related to its unique structural features. Although the precise mechanisms of action are still poorly understood, bendamustine is associated with extensive and durable DNA damage. The increased potency of bendamustine may be due to secondary mechanisms such as inhibition of mitotic checkpoints, inefficient DNA repair, and initiation of p53-dependent DNA-damage stress response, all of which lead to mitotic catastrophe and apoptosis. It has also been hypothesized that the presence of a benzimidazole ring in addition to the nitrogen mustard group may influence the way bendamustine interacts with DNA and/or confer antimetabolite properties. Further elucidation of the mechanisms of action for bendamustine and the signaling pathways involved in the response to bendamustine-induced DNA damage is essential to maximize its therapeutic potential, identify biomarkers for response, and understand the potential for synergy with other agents involved in DNA damage and inhibition of DNA repair. This review will discuss the current understanding and hypotheses regarding bendamustine mechanisms of action and suggest future investigations that would shed light on the many unanswered questions.

This paper presents a comprehensive study of the resistance of solder joints to failure when subjected to strain rates that simulate the conditions of drop-impact on a portable electronic product. Two test methods are used in this study: the board level drop/shock test (BLDT) and the component level ball impact shear test (BIST). The performance of (i) 12 material combinations consisting of six solder alloys and two pad finishes; and (ii) 11 manufacturing variations covering three vendors, two finishes, three immersion gold thicknesses and three thermal aged conditions, were investigated using these two test methods, and analysis of correlations between the methods was performed. Quantitative correlation and sensitivity coefficients for the failure modes and the measured characteristic parameters – number of drops to failure for BLDT and peak load, total fracture energy, and energy-to-peak load for BIST – were evaluated. The lack of universal correlations between the two test methods has ruled out the use of BIST for evaluating solder joint materials, but BIST is recommended as a test method for quality assurance in view of the strong correlation between the measured parameters and the failure mode. The total fracture energy parameter is preferred over the peak load and energy-to-peak load due to its higher sensitivity and reduced susceptibility to measurement error.

Drop impact reliability has become an important criterion when assessing the reliability of portable electronics. Finite element software such as ABAQUS is used to simulate solder joints during drop-impact tests and determine the drop-impact reliability of the product. This modelling requires the rate-dependent constitutive properties of the solder in the range of strain rates between 0.1 s− 1 to 300 s− 1. Unfortunately, the constitutive properties of most solder materials in this range of strain rates have not been characterized. This paper presents the mechanical properties of four solder alloys — 63Sn37Pb, Sn1.0Ag0.1, Sn3.5Ag, and Sn3.0Ag0.5Cu at strain rates between 0.005 s− 1 and 300 s− 1. The lead-free solder alloys tested exhibited greater strain rate sensitivity compared to 63Sn37Pb. In addition, both the lead-free solders with high Ag content (≥ 3%) exhibited much higher flow stresses compared to 63Sn37Pb. The higher flow stress could explain the lower reliability of these joints in drop tests as a result of shifting of the failure site from the ductile solder to the brittle intermetallic compound [Wong EH, Rajoo R, Mai Y-W, Seah SKW, Tsai KT, Yap LM. Proc. 55th Elec. Comp. & Tech. Conf. 2005;1202–9]. Based on the data obtained, Sn1.0Ag0.1 seems to be the most suitable lead-free alloy to replace eutectic tin-lead in products where drop-impact performance is required.

The p16INK4A/CDKN2A (p16) gene on chromosome 9p21 is inactivated in >90% of invasive pancreatic cancers. In 40% of pancreatic cancers the p16 gene is inactivated by homozygous deletion, in 40% by an intragenic mutation coupled with loss of the second allele, and in 10-15% by hypermethylation of the p16 gene promoter. Immunohistochemical labeling for the p16 gene product parallels gene status, but does not provide information of the mechanism of p16 gene inactivation. The methylthioadenosine phosphorylase gene (MTAP) gene also resides on chromosome 9p21, approximately 100 kb telomeric to the p16 gene. The MTAP gene is frequently contained within p16 homozygous deletions, producing concordant loss of both p16 and MTAP gene expression. Concordant loss of both p16 and MTAP protein expression can therefore be used as a surrogate marker for p16 homozygous deletion. Here we immunolabeled a series of pancreatic intraepithelial neoplasia (PanIN) lesions of various histologic grades for the p16 and MTAP gene products using a high-throughput PanIN tissue microarray (TMA) format. We demonstrate concordant loss of p16 and MTAP protein expression in 6/73 (8%) PanINs, including five high-grade lesions and one low-grade lesion. Immunolabeling for both p16 and MTAP protein expression provides a tool to evaluate tissues with intact morphology for p16 gene homozygous deletions. The concordant loss of expression of both genes in PanIN lesions demonstrates that homozygous deletions of the p16 tumor suppressor gene can occur in noninvasive precursor lesions.

R-etodolac, a nonsteroidal anti-inflammatory drug, inhibits the progression of CWRSA6 androgen-independent and LuCaP-35 androgen-dependent prostate cancer xenograft growth through downregulation of cyclin D1 expression via the PPARgamma pathway. PPARgamma protein degradation, observed post-R-etodolac treatment, resulted from phospho-MAP kinase (p44/42) induction by R-etodolac negatively regulating PPARgamma function. Negative regulation of PPARgamma was overcome by a combination regimen of R-etodolac with the HER-kinase axis inhibitor, rhuMab 2C4, which demonstrated an additive antitumor effect. We further show that the inhibition of HER-kinase activity by rhuMab 2C4 is sufficient to inhibit PPARgamma protein degradation. This study introduces a novel concept of an in vivo crosstalk between the HER-kinase axis and PPARgamma pathways, ultimately leading to negative regulation of PPARgamma activity and tumor growth inhibition.

s ( t 1 h s c l B t Chemotherapy is the cornerstone of current treatment strategies for many hematologic malignancies, including most indolent B-cell alignancies such as chronic lymphocytic leukemia CLL), follicular lymphoma (FL), as well as diffuse arge B-cell lymphoma (DLBCL), and mantle cell lymhoma (MCL). However, for most of these diseases, urrent therapies are rarely curative. The majority of atients will eventually relapse and require effective alvage therapies. Although great progress has been ade in the past 30 years with the introduction of ore effective chemotherapy regimens and the adition of biologic and targeted agents, there remains n unmet need for more effective and less toxic egimens that can provide durable long-term remisions and are effective in the relapsed and refractory etting. Standard front-line regimens used to treat FL, DLCL, CLL, and MCL predominantly consist of alkylating gents (eg, cyclophosphamide and chlorambucil), puine analogues (eg, fludarabine), anthracyclines (eg, oxorubicin), and vinca alkaloids (eg, vincristine), ost often in combination. Standard chemotherapy egimens include cyclophosphamide, doxorubicin, incristine, and prednisone (CHOP); cyclophosph

The response to humidity of porous ceramics with composition BaMO3, with M=Ti, Zr, Hf or Sn, was studied. Samples were obtained by cold isostatic pressing and sintering of fine powders prepared by wet chemical synthesis. Sensitivity and response time have been obtained by electrical impedance measurements realised in different conditions of relative humidity (R.H.) at 25 � C. An increase of both capacitance and conductivity with humidity was observed in all samples with open porosity. Sensitivity increased with R.H. and decreased with frequency, indicating a major contribution from the surface of crystals exposed to water vapour, particularly in BaTiO3 where 4000% change in permittivity was registered over the range 20–80% R.H. Time response was in the typical range of capacitive humidity sensors, with fast (10–100 s) equilibration time for intermediate values of R.H. # 2001 Elsevier Science Ltd. All rights reserved.

Low temperature aqueous synthesis (LTAS) has been applied to the preparation of La or Nb-doped (Ba,Sr)TiO 3 powders. Doping elements have been mixed to precursors, in order to directly obtain crystalline powders with modified composition. Similar powders, doped by conventional wet ball-milling process, have been also prepared for comparison. Ceramic samples have been obtained by isothermal sintering in air at different temperatures. Microstructural characterisation showed the presence of a secondary phase, identified as a Ti-rich barium titanate compound. Impedance spectroscopy (IS) has been used to study the PTCR behaviour of such materials. IS results are analysed, taking into account effect of the secondary phase, to discuss bulk and grain boundary characteristics.

Solid state reactions in the Y2O3-Fe2O3 system were studied by means of different types of diffusion couples. Simultaneous growth of the YFeO3 and Y3Fe5O12 ternary phases was observed on Y2O3-Fe2O3 couples, whereas only the YFeO3 phase grows on Y2O3-Y3Fe5O12 and Y2O3-gas-Fe2O3 couples. The growth rates were determined by layer thickness measurements on couples reacted at 1220, 1300 and 1352°C in air and at 1403°C in oxygen for times ranging from 8 to 256 h. The growth kinetics is parabolic in all cases. Based on a model for growth of multiple layers, the intrinsic parabolic growth constants were calculated from the apparent experimental rate constants. In the case of Y3Fe5O12 growth, the intrinsic rate constants were compared with those predicted by Wagner's theory. The probable mechanism is the equidirectional coupled diffusion of O2− and Y3+ ions. Gas phase transport of iron, in the form of Fe(OH)2, becomes important above 1300°C.

Zirconium titanate (ZT–ZrTiO4) is a well-known ferroelectric material commonly used as a dielectric in microwave devices due to its high permittivity at microwave frequencies. Reactive precursors of ZT in form of nanopowders have been prepared in a very simple way by hydrolysis of an aqueous solution of TiCl4 and ZrOCl2 using ammonia. ZT single-phase powder has been obtained by high temperature reaction during calcination at 1200 � C. a-PbO2-type structure was stabilised by air quenching to room temperature. Sinterability was investigated by constant heating-rate and isothermal sintering. High-density ceramics were obtained by firing performed at different temperatures and prototypes of substrates for microwave devices were prepared. # 2001 Elsevier Science Ltd. All rights reserved.

Bendamustine is a bifunctional mechlorethamine derivative that shares similarities to other alkylators; however, the presence of a benzimidazole ring may confer "nucleoside-like" properties and may allow the stabilization of the molecule leading to longer lasting DNA damage. Though bendamustine has demonstrated promising response rates in preclinical and clinical studies, particularly in follicular lymphoma, chronic lymphocytic leukemia, diffuse B-cell lymphoma, and mantle cell lymphoma, the unique and exact mechanism of action of this agent remains unclear. Several studies have been initiated to address this question, and it is hoped that emerging data will provide the basis for more effective utilization of this interesting drug. Several recent clinical trials have reported impressive results with bendamustine in lymphoid malignancies, and appropriate clinical use of this agent and the rationale behind its use are of growing importance. This review discussed emerging data and aimed to provide clinical updates and scientific rationales that are relevant to practicing clinicians who provide care to patients with lymphoid malignancies, and/or who are interested in understanding the evolving role of bendamustine in this setting.

To define the toxicity and effectiveness of concomitant Chemotherapy (CTH) and HFX in Non Small Cell Lung Cancer (NSCLC), a phase 1/II study was conducted with Cisplatin 4 mg/day (16 mg/mq/week) given during two daily fractions irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in a 6 weeks time. Thirty-six eligible patients (PTS) (81% males, 58% squamous, 25% adeno, 17% NSC—carcinomas, 53% stage III B) were treated in 5 different lospitals. Protocol treatment was completed in 56% ofthe PTS; in 81% the total radiation was > 66 Gy; in 69% Cisplatino total dose was > 64 mg/mq. Acute toxicity was (EORTC scale): 17% esophagitis grade (gr) 3, 31% gr 2–upper GI 3% gr 3, II % gr 2–hematologic 11% gr 2–3. There wasa subacute lung toxicity death. Median survival time was 14 months (range 6–21); 25 PTS (69%) died, 4 (11%) are alive with disease and 7 (19%) alive and well. Concurrent CHT and HPX for NSCLC appears to be feasible, but short-term seem not to be better than in standard treatments.