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)     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

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.     

Apoptosis and delayed neuronal damage after carbon monoxide poisoning in the rat

Delayed neurological damage after CO hypoxia was studied in rats to determine whether programmed cell death (PCD), in addition to necrosis, is involved in neuronal death. In rats exposed to either air or CO (2500 ppm), microdialysis in brain cortex and hippocampus was performed to determine the extent of glutamate release and hydroxyl radical generation during the exposures. Groups of control and CO-exposed rats also were tested in a radial maze to assess the effects of the CO exposures on learning and memory. At 3, 7, and 21 days after CO exposure brains were perfusion-fixed and hematoxylin-eosin (H&E) was used to assess injury and to select regions for further examination. DNA fragmentation was sought by examining cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) reaction. We found significant increases in glutamate release and .OH generation during and immediately after CO hypoxia. CO-exposed rats showed learning and memory deficits after exposure associated with heterogeneous cell loss in cortex, globus pallidus, and cerebellum. The frontal cortex was affected most seriously; the damage was slight at Day 3, increased at Day 7, and persistent at Day 21 after CO exposure. TUNEL staining was positive at all three time points, and TUNEL-labeled cells were distributed similarly to eosinophilic cells. The number of cells stained by TUNEL was less than by H&E and amounted to 2 to 5% of all cell nuclei in regions of injury. Ultrastructural features of both neuronal necrosis and apoptosis also were observed readily by electron microscopy. These findings indicate that both necrosis and apoptosis (PCD) contribute to CO poisoning-induced brain cell death.     

Surveillance of developmental disabilities with an emphasis on special studies

The developing central nervous system seems to be particularly vulnerable to chemical insults. A model for developmental disabilities surveillance is presented that provides a reasonable framework for monitoring the prevalence of various developmental abnormalities in human populations. Effective monitoring will not only increase the likelihood of detecting the adverse effects of new physical or chemical agents in the environment but will provide a readily available case series for specially directed case-control studies. A specific example is provided of a large case-control study of cerebral palsy and intrapartum magnesium exposure among very low birth weight children, which is being conducted within the framework of a developmental disabilities surveillance program.