Twin screw granulation – review of current progress

Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of research has evolved over the short time since this process was introduced but generally with little comparison of results. A certain degree of confidence has been developed through these studies related to how process variables and many attributes of machinery configuration will affect granulation but some major challenges still lay ahead related to scalability, variations in the processing regimes related to degree of channel fill and the impact of wetting and granulation of complex powder formulations. This review examines the current literature for wet granulation processes studied in twin screw extrusion machinery, summarizing the influences of operational and system parameters affecting granule properties as well as strives to provide some practical observations to newly interested users of the technique.     

Protecting local access telecommunications networks: Toward a minimum-cost solution

The problem of designing fibre-optic networks for local-access telecommunications generates (at least) three non-trivial subproblems. In the first of these subproblems one must determine how many fibre-optic cables (fibres) are required at either end of a street. In the next subproblem a minimum-cost network must be designed to support the fibres. The network must also provide distinct paths from either end of the street to the central exchange(s). Finally, the fibre-optic cables must be placed in protective covers. These covers are available in a number of different sizes, allowing some flexibility when covering each section of the network. In this paper we describe a dynamic programming (DP) formulation for finding a minimum-cost (protective) covering for the network (the third of the subproblems). This problem is a generalised set covering problem with side constraints and is further complicated by the introduction of fixed and variable welding costs. The DP formulation selects covers along each arc (in the network), but cannot exactly model the fixed costs and so does not guarantee optimality. We also describe an integer programming (IP) formulation for assessing the quality of the DP solutions. The cost of the networks constructed by the IP model is less than those designed using the DP model, but the saving is not significant for the problems examined (less than 0.1%). This indicates that the DP model will generally give very good solutions. Furthermore, as the problem dimensions grow, DP gives significantly better solution times than IP.     

Platinum Binuclear Complexes as Phosphorescent Dopants for Monochromatic and White Organic Light‐Emitting Diodes

Efficient blue‐, green‐, and red‐light‐emitting organic diodes are fabricated using binuclear platinum complexes as phosphorescent dopants. The series of complexes used here have pyrazolate bridging ligands and the general formula C^∧NPt(μ‐pz)₂PtC^∧N (where C^∧N = 2‐(4′,6′‐difluorophenyl)pyridinato‐N,C^2′, pz = pyrazole ( 1 ), 3‐methyl‐5‐tert‐butylpyrazole ( 2 ), and 3,5‐bis(tert‐butyl)pyrazole ( 3 )). The Pt–Pt distance in the complexes, which decreases in the order 1 > 2 > 3 , solely determines the electroluminescence color of the organic light‐emitting diodes (OLEDs). Blue OLEDs fabricated using 8 % 1 doped into a 3,5‐bis(N‐carbazolyl)benzene (mCP) host have a quantum efficiency of 4.3 % at 120 Cd m^–2, a brightness of 3900 Cd m^–2 at 12 V, and Commission Internationale de L'Eclairage (CIE) coordinates of (0.11, 0.24). Green and red OLEDs fabricated with 2 and 3 , respectively, also give high quantum efficiencies (～ 6.7 %), with CIE coordinates of (0.31, 0.63) and (0.59, 0.46), respectively. The current‐density–voltage characteristics of devices made using dopants 2 and 3 indicate that hole trapping is enhanced by short Pt–Pt distances (< 3.1 Å). Blue electrophosphorescence is achieved by taking advantage of the binuclear molecular geometry in order to suppress dopant intermolecular interactions. No evidence of low‐energy emission from aggregate states is observed in OLEDs made with 50 % 1 doped into mCP. OLEDs made using 100 % 1 as an emissive layer display red luminescence, which is believed to originate from distorted complexes with compressed Pt–Pt separations located in defect sites within the neat film. White OLEDs are fabricated using 1 and 3 in three different device architectures, either with one or two dopants in dual emissive layers or both dopants in a single emissive layer. All the white OLEDs have high quantum efficiency (～ 5 %) and brightness (～ 600 Cd m^–2 at 10 V).     

Effects of SiN passivation and high-electric field on AlGaN-GaN HFET degradation

The authors report on the effects of silicon nitride (SiN) surface passivation and high-electric field stress (hot electron stress) on the degradation of undoped AlGaN-GaN power HFETs. Stressed devices demonstrated a decrease in the drain current and maximum transconductance and an increase in the parasitic drain series resistance, gate leakage, and subthreshold current. The unpassivated devices showed more significant degradation than SiN passivated devices. Gate lag phenomenon was observed from unpassivated devices and removed by SiN passivation. However, SiN passivated devices also showed gate lag phenomena after high-electric field stress, which suggests possible changes in surface trap profiles occurred during high-electric field stress test.     

Life is pleasant--and memory helps to keep it that way!

People's recollections of the past are often positively biased. This bias has 2 causes. The 1st cause lies in people's perceptions of events. The authors review the results of several studies and present several new comparative analyses of these studies, all of which indicate that people perceive events in their lives to more often be pleasant than unpleasant. A 2nd cause is the fading affect bias: The affect associated with unpleasant events fades faster than the affect associated with pleasant events. The authors review the results of several studies documenting this bias and present evidence indicating that dysphoria (mild depression) disrupts such bias. Taken together, this evidence suggests that autobiographical memory represents an important exception to the theoretical claim that bad is stronger than good. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene

The acid sphingomyelinase (ASM) gene, which has been implicated in ceramide-mediated cell signaling and atherogenesis, gives rise to both lysosomal SMase (L-SMase), which is reportedly cation-independent, and secretory SMase (S-SMase), which is fully or partially dependent on Zn2+ for enzymatic activity. Herein we present evidence for a model to explain how a single mRNA gives rise to two forms of SMase with different cellular trafficking and apparent differences in Zn2+ dependence. First, we show that both S-SMase and L-SMase, which contain several highly conserved zinc-binding motifs, are directly activated by zinc. In addition, SMase assayed from a lysosome-rich fraction of Chinese hamster ovary cells was found to be partially zinc-dependent, suggesting that intact lysosomes from these cells contain subsaturating levels of Zn2+. Analysis of Asn-linked oligosaccharides and of N-terminal amino acid sequence indicated that S-SMase arises by trafficking through the Golgi secretory pathway, not by cellular release of L-SMase during trafficking to lysosomes or after delivery to lysosomes. Most importantly, when Zn2+-dependent S-SMase was incubated with SMase-negative cells, the enzyme was internalized, trafficked to lysosomes, and became zinc-independent. We conclude that L-SMase is exposed to cellular Zn2+ during trafficking to lysosomes, in lysosomes, and/or during cell homogenization. In contrast, the pathway targeting S-SMase to secretion appears to be relatively sequestered from cellular pools of Zn2+; thus S-SMase requires exogeneous Zn2+ for full activity. This model provides important information for understanding the enzymology and regulation of L- and S-SMase and for exploring possible roles of ASM gene products in cell signaling and atherogenesis.     

Current practice in software quality and the impact of certification schemes

The paper presents the findings of a survey that investigated the level of quality management practice within some 150 UK companies from a sample of 500. It provides a snapshot of practice at the time of the survey, and assesses the impact of government quality initiatives particularly, the TickIT scheme at that time. The survey methodology is described, together with the results and conclusions. The sample has been graded by size of company, which the authors consider to have a significant effect upon the adoption of quality practices. The survey highlights the need to encourage small companies to adopt quality practices and to assist them with the short-term costs incurred.