Combination Index

This paper presents a new method to perform fault diagnosis for data-correlation based process monitoring. As alternative to the traditional contribution plot method, reconstruction-based contribution of fault detection indices is proposed. The monitored indices are SP E, T 2 and a combined index ϕ. The lack of diagnosability of traditional contributions is analyzed for the case of single sensor faults with large fault magnitudes, whereas for the same case the proposed reconstruction-based contributions guarantee correct diagnosis. Monte Carlo simulation results are provided for the case of modest fault magnitudes by randomly assigning fault sensors and fault magnitudes.

Most current chemotherapy regimens for cancer consist of empirically designed combinations, based on efficacy and lack of overlapping toxicity. In the development of combinations, several aspects are often overlooked: (1) possible metabolic and biological interactions between drugs, (2) scheduling, and (3) different pharmacokinetic profiles. Antimetabolites are used widely in chemotherapy combinations for treatment of various leukemias and solid tumors. Ideally, the combination of two or more agents should be more effective than each agent separately (synergism), although additive and even antagonistic combinations may result in a higher therapeutic efficacy in the clinic. The median-drug effect analysis method is one of the most widely used methods for in vitro evaluation of combinations. Several examples of classical effective antimetabolite-(anti)metabolite combinations are discussed, such as that of methotrexate with 6-mercaptopurine or leucovorin in (childhood) leukemia and 5-fluorouracil (5FU) with leucovorin in colon cancer. More recent combinations include treatment of acute-myeloid leukemia with fludarabine and arabinosylcytosine. Other combinations, currently frequently used in the treatment of solid malignancies, include an antimetabolite with a DNA-damaging agent, such as gemcitabine with cisplatin and 5FU with the cisplatin analog oxaliplatin. The combination of 5FU and the topoisomerase inhibitor irinotecan is based on decreased repair of irinotecan-induced DNA damage. These combinations may increase induction of apoptosis. The latter combinations have dramatically changed the treatment of incurable cancers, such as lung and colon cancer, and have demonstrated that rationally designed drug combinations offer new possibilities to treat solid malignancies. active metabolite of CPT-11; TMQ, trimetrexate; TS, thymidylate synthase; UFT, combination of ftorafur and uracil in a 1

Hybrid-Automatic-Repeat-reQuest (HARQ) has become an indispensable technique in reliable communications systems. However, its performance is inevitably affected by the channel's fading correlation. In this paper, we proposed a novel relay-switching aided HARQ scheme in order to mitigate the detrimental effects of correlated fading without unduly increasing the system's complexity and delay. Our results show that the proposed relay-switching regime operates efficiently in correlated channels, hence significantly reduces the error floor of turbocoded HARQ. Additionally, a HARQ scheme using Segment Selective Repeat (SSR) is incorporated in the relay-switching scheme for achieving further improvements. Quantitatively, the proposed relay-switching aided turbo-coded HARQ scheme using SSR may achieve an approximately 2 dB gain, compared to the conventional amplify-and-forward aided turbo coded HARQ arrangement using Chase Combining.

We investigated the conservation status and ecosystem substitution in six Posidonia oceanica (L.) Delile meadows in 2002 along 300 km of the Ligurian coast (NW Mediterranean Sea). We studied the meadows by scuba transects and we compared the meadows state of health through in situ shoot density counts and computing the Conservation Index (CI), the latter measuring the proportional amount of dead matte relative to live P. oceanica. Both measures evidenced a generalised state of regression for most of the six meadows. We also reported the occurrence, within the meadows, of the other common Mediterranean seagrass Cymodocea nodosa, the Mediterranean green alga Caulerpa prolifera, and the invasive green algae Caulerpa taxifolia and Caulerpa racemosa. We measured the replacement of P. oceanica by these species using the Substitution Index (SI), related to the proportional cover of each substitutes. These were ranked in order of their colonisation potential with respect to P. oceanica. We identified and measured a community ''phase shift'' occurring within the Mediterranean seagrass meadows using a combined index, the Phase-Shift Index (PSI). The analysis of the three environmental indices (CI, SI and PSI) at regional scale allowed to introduce three ''regional'' ordinal scales to classify the conservation status, the degree of substitution and the level of phase shift in P. oceanica meadows.

Biological invasions by non-native or "exotic" plant species are widely recognised as an important component of human-caused global environmental change, often resulting in a sig- nificant loss in the economic value, biological diversity and function of invaded ecosystems. A fundamental challenge posed by biological invasions has been the identification of characteristics associated with the invasion success of exotic species. We

The present study analyses the effect of two plant phenolic compounds, namely chlorogenic acid and ferulic acid, and a plant alkaloid, berberine, alone and also in combination with two commercial oral hypoglycemic drugs (OHD), namely metformin and 2,4-thiazolodinedione (THZ), on the uptake of 2-deoxyglucose (2DG) by L6 myotubes. 2-DG uptake is determined using an enzymatic assay. All the three natural products enhance the uptake of 2DG in time- and dose-dependent manner. A combination of different concentrations of chlorogenic acid and metformin or THZ, has a synergistic effect in the uptake of 2DG with a maximum of 5.0- and 5.3-times respectively, with reference to the base value (without the drugs or the natural products). Ferulic acid in combination with metformin or THZ has also shown a synergistic effect and the 2DG uptake increases by 4.98- and 5.11-fold when compared to the control respectively. Whereas, berberine, in combination with either metformin or THZ, has shown an additive effect with maximum 2DG uptake of 4.1- and 4.7-times from the base value, respectively. The synergistic interaction has been explained with the use of combination index and isobologram. Expression of GLUT4 and PPAR-γ gene were elevated in chlorogenic acid and berberine treated cells, whereas expression of GLUT4 and PI3K transcripts were significantly enhanced in ferulic acid treated cells. The studies indicate that chlorogenic acid enhances glucose uptake by increasing GLUT4 expression via PI3K independent pathway whereas ferulic acid increases glucose uptake by PI3K dependent pathway. The current findings suggest that the phytochemicals can replace the commercial drugs in part, which could lead to a reduction in toxicity and side effects of the later.

Most CBIR systems use low-level visual features for representation and retrieval of images. Generally such methods suffer from the problems of high-dimensionality leading to more computational time and inefficient indexing and retrieval performance. This paper focuses on a low-dimensional color and shape based indexing technique for achieving efficient and effective retrieval performance. We propose a combined index using color and shape features. A new shape similarity measure is proposed which is shown to be more effective. Images are indexed by dominant color regions and similar images form an image cluster stored in a hash structure. Each region within an image is further indexed by a region-based shape index. The shape index is invariant to translation, rotation and scaling. A JAVA based query engine supporting query-byexample is built to retrieve images by color and shape. The retrieval performance is studied and compared with a region-based shape indexing scheme.

Purpose The histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) enhances taxolinduced antitumor eVects against some human cancer cells. The aim of this study is to investigate whether SAHA can enhance taxol-induced cell death against human breast cancer cells and to illustrate the mechanism in detail. Methods A panel of eight human breast cancer cell lines and an immortalized human breast epithelial cell line were used to determine the inhibitory eVects of SAHA, taxol, or their combination by MTT assay. The eVects of SAHA with or without taxol on cell cycle distributions, apoptosis, and protein expressions were also examined. The inhibitory eVects on tumor growth were characterized in vivo in BALB/c nude mice bearing a breast cancer xenograft model. Results Taxol-resistant and multi-resistant breast cancer cells were as sensitive to SAHA as taxol-sensitive breast cancer cells. A dose-dependent synergistic growth inhibition was found in all the tested breast cancer cell lines treated with the SAHA/taxol combinations. The synergetic eVect was also observed in the in vivo xenograft tumor model. The cell cycle analysis and apoptosis assay showed that the synergistic eVects resulted from enhanced G2/M arrest and apoptosis. Conclusions SAHA increased the anti-tumor eVects of taxol in breast cancer in vitro and in vivo. The combination of SAHA and taxol may have therapeutic potential in the treatment of breast cancer.

This paper demonstrates the respective roles that combined index-and gain-coupling play in the overall link performance of distributed feedback (DFB) lasers. Their impacts on both static and dynamic properties such as slope efficiency, resonance frequency, damping rate, and chirp are investigated. Simulation results are compared with experimental data with good agreement. Transmission-oriented optimization is then demonstrated based on a targeted specification. The design tradeoffs are revealed, and it is shown that a modest combination of index-and gain-coupling enables optimum transmission at 10 Gbit/s.

This paper presents two-stream processing of audio to index the audio content for Spoken Web search. The first stream indexes the meta-data associated with a particular audio document. The meta-data is usually very sparse, but accurate. This therefore results in a high-precision, low-recall index. The second stream uses a novel language-independent speech recognition to generate text to be indexed. Owing to the multiple languages and the noise in user generated content on the Spoken Web, the speech recognition accuracy of such systems is not high, thus they result in a low-precision, high-recall index. The paper attempts to use these two complementary streams to generate a combined index to increase the precision-recall performance in audio content search. The problem of audio content search is motivated by the real world implication of the Web in developing regions, where due to literacy and affordability issues, people use Spoken Web which consists of interconnected VoiceSites, which have content in audio. The experiments are based on more than 20,000 audio documents spanning over seven live VoiceSites and four different languages. The results suggest significant improvement over a meta-data-only or a speech-recognitiononly system, thus justifying the two-stream processing approach. Audio content search is a growing problem area and this paper wishes to be a first step to solving this at a large scale, across languages, in a Web context.

Methods were developed to allow quality assessment of academic research in linguistics in allsub-disciplines. Data were obtained from samples of respondents from Flanders, the Netherlands,as well as a world-wide sample, evaluated journals, publishers, and scholars. Journals andpublishers were ranked by several methods. First, we weighted the number of times journals orpublishers were ranked as 'outstanding', 'good', or 'occasionally/not at all good'. To reduce theinfluence of unduly positive or negative biases of respondents, the most extreme ratings weretrimmed. A second weight reflects the (international) visibility of journals and publishers. Here,journals or publishers nominated by respondents from various countries or samples received agreater weight than journals or publishers nominated by respondents from one country or onesample only. Thirdly, a combined index reflects both quality and international visibility. Its use isillustrated on the output of scholars in linguistics. Limitations and potentials for application ofbibliometric methods in output assessments are discussed.

Fibromyalgia (FM) is a complex syndrome that affects many aspects of the patients life and it is very difficult to evaluate in clinical practice. A recent study has developed the Combined Index of Severity of Fibromyalgia (ICAF), an instrument that evaluates diverse aspects of FM ...

This article argues that counterintuitively, the unrelenting multivictim terrorist attacks on Israel between 1996 and 2004 did not bring about a linear escalation in the intensity of media coverage nor in the demoralization of the public, as seen in the changes in daily routine and in the radicalization of political attitudes. By the use of a combined index based on the length of television's disaster marathons, their viewing rates, and the extent of changes in the daily lives and the political attitudes of Israelis (drawing on secondary analysis of various sources), the authors distinguish between two periods in terms of the impact of terror. In the first period, from1996 to the end of 2002, they observed a relatively strong effect in all the indicators mentioned above. From the beginning of 2003, in spite of the continuing high frequency of the attacks, the authors see a process of routinization apparent in all our indicators, on the part of the media and of the public.

This paper presents a new method to perform fault diagnosis for data-correlation based process monitoring. As alternative to the traditional contribution plot method, reconstruction-based contribution of fault detection indices is proposed. The monitored indices are SP E, T 2 and a combined index ϕ. The lack of diagnosability of traditional contributions is analyzed for the case of single sensor faults with large fault magnitudes, whereas for the same case the proposed reconstruction-based contributions guarantee correct diagnosis. Monte Carlo simulation results are provided for the case of modest fault magnitudes by randomly assigning fault sensors and fault magnitudes.

To improve effectiveness of protected areas, selection of priority areas should include consideration of three main components, namely special conservation elements, focal species and representation. We present a three-track approach related to these components for vertebrate conservation planning in Castilla-La Mancha, central Spain. As special conservation elements, we identified Priority Areas for Conservation of species using five criteria: species richness, geographic rarity, species vulnerability, a Combined Index of these three criteria, and a Standardised Biodiversity Index (SBI) that integrate the three criteria and four studied taxa. The Natura 2000 Network was used to include conservation areas for focal species. We evaluated the representation of every landscape type in the existing conservation areas. To delineate the spatial configuration for vertebrate conservation, we combined the identified Priority Areas for Conservation, existing conservation areas and connectivity areas by cost–distance analysis. The Combined Index was the most efficient criterion analyzed to identify Priority Areas for Conservation. The Natura 2000 Network showed a high percentage of coincidence with identified Priority Areas for Conservation, whereas the natural protected areas network had a low percentage of coincidence. Six agricultural landscapes were inadequately represented in the current conservation network. According to our multi-track approach, ∼29% of study area was required to capture 100% of vertebrate species and all landscape types. Our results show that the existing conservation areas are insufficient to guarantee the conservation of biodiversity in the study region. Additional areas with outstanding features of diversity, connectivity areas, and establishment of targets for off-reserve conservation are of fundamental importance for strengthening biodiversity conservation.► We use an approach that integrate special elements, focal species and representation. ► We identified Priority Areas for Conservation of species using five criteria of diversity. ► Our Combined Index is an effective and robust measure of biodiversity. ► Natura 2000 represents insufficiently the traditional agricultural landscapes. ► Our approach achieves representation of every landscape and vertebrate diversity.

It has been suggested that dietary interventions may improve the eectiveness of cancer chemotherapy. We have examined the combined in vitro cytotoxicity of paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid (OA, in human breast carcinoma MDA-MB-231 cells. The eect of fatty acids on paclitaxel chemosensitivity was determined by comparing IC 50 and IC 70 (50 and 70% inhibitory concentrations, respectively) obtained when the cells were exposed to IC 50 and IC 70 levels of paclitaxel alone and fatty acids were supplemented either before or during the exposure to paclitaxel. The 3-4,5-dimethylthiazol-2yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine cell growth inhibition. GLA by itself showed antiproliferative eects, and a possible GLA±paclitaxel interaction at the cellular level was assessed by the isobologram and the combination-index (CI) methods. Isobole analysis at the isoeect levels of 50 and 70% revealed that drug interaction was predominantly synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell cultures. Interaction assessment using the median-eect principle and the combination-index (CI) method showed that exposure of MDA-MB-231 cells to an equimolar combination of concurrent GLA plus paclitaxel for 24 h resulted in a moderate synergism at all eect levels, consistent with the results of the isobologram analysis. When exposure to GLA (24 h) was followed sequentially by paclitaxel (24 h) only an additive eect was observed. The GLA-mediated increase in paclitaxel chemosensitivity was only partially abolished by Vitamin E, a lipid peroxidation inhibitor, suggesting a limited in¯uence of the oxidative status of GLA in achieving potentiation of paclitaxel toxicity. When OA (a non-peroxidisable fatty acid) was combined with paclitaxel, an enhancement of chemosensitivity was found when OA was used concurrently with paclitaxel, although less markedly than with GLA. Pretreatment of MDA-MB-231 cells with OA for 24 h prior to a 24 h paclitaxel exposure produced greater enhancement of paclitaxel sensitivity at high OA concentrations than the concurrent exposure to OA and paclitaxel. The OA-induced sensitisation to paclitaxel was not due to the cytoxicity of the fatty acid itself. When these observations were extended to three additional breast carcinoma cell lines (SK-Br3, T47D and MCF-7), simultaneous exposure to GLA and paclitaxel also resulted in synergism. GLA preincubation followed by paclitaxel resulted in additivity for all cell lines. Simultaneous exposure to paclitaxel and OA enhanced paclitaxel cytotoxicity in T47D and MCF-7 cells, but not in SK-Br3 cells, whereas preincubation with OA failed to increase paclitaxel eectiveness in all three cell lines. For comparison, the eects of other fatty acids on paclitaxel chemosensitivity were examined: GLA was the most potent at enhancing paclitaxel cytotoxicity, followed by alpha-linolenic acid (ALA; 18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not increase paclitaxel toxicity. These ®ndings provide experimental support for the use of fatty acids as modulators of tumour cell chemosensitivity in paclitaxel-based therapy. #

To examine ␤-cell function in glucose-tolerant offspring of type 2 diabetic families, 41 insulin-resistant (hyperinsulinemiceuglycemic clamp, P F .001) first-degree relatives and 32 controls underwent oral (OGTT) and intravenous (IVGTT) glucose tolerance tests and a constant intravenous glucose infusion (4.0 or 4.5 mg/kg/min) with blood sampling every minute for insulin determinations. Insulin concentration time-series were analyzed with complementary mathematical models (deconvolution and autocorrelation analysis, approximate entropy [ApEn], and coefficient of variation [CV] for a 6-point moving average, together with a combined index for regularity and stationarity [RaS] based on the last 2 measures). During the OGTT, the area under the curve (AUC) for plasma glucose was moderately (11%) but significantly (P F .01) elevated in the relatives despite a trend for increased serum insulin (AUC, P ‫؍‬ .14). The acute-phase serum insulin response (IVGTT) did not differ between groups (2,055 ؎ 330 v 1,766 ؎ 229 pmol/L · 10 min, P ‫؍‬ .84) but was inappropriately low (individually, P F .05 v control group) for the degree of insulin resistance in 16 relatives. Deconvolution analysis of the insulin time-series did not uncover differences in either the intersecretory pulse interval (5.8 ؎ 0.2 v 5.7 ؎ 0.2 min/pulse) or the fractional secretory burst amplitude (133% ؎ 10% v 116% ؎ 7% over basal) between the 2 groups. Similarly, significant autocorrelation coefficients were observed in a comparable number of relatives and control subjects (P ‫؍‬ .74). In contrast, the RaS index was significantly higher (ie, insulin time-series was more irregular and nonstationary) in the relatives (0.221 ؎ 0.194) than in the controls (؊0.318 ؎ 0.176, P F .05), primarily attributed to the pattern of insulin secretion in relatives with a strong genetic burden. In conclusion, nonstationary and disorderly insulin secretion patterns during glucose stimulation and a low acute-phase serum insulin response associated with significant insulin resistance suggest early ␤-cell regulatory dysfunction in individuals genetically predisposed to type 2 diabetes mellitus prior to any evident alterations in insulin secretory burst frequency or mass.

Conventional quantities (stream length, number of streams, bifurcation ratio, density of streams per unit drainage area, elevation difference, slope, and perimeter and area of drainage basins) were extracted for approximately 322 drainage basins from a DEM of the Oak Ridges Moraine area, southern Ontario. These values were mapped and analyzed using statistical and multifractal approaches and GIS to characterize the stream networks and drainage basin systems. Useful measures for characterizing drainage basins in the area included, slope, stream densities, ratio of perimeter and area, and ratio of stream lengths. The distinct patterns identified on the basis of these parameters and on the combined indexes generated by using multivariate statistical analysis were compared with other datasets (geology, bedrock topography, and drift thickness). The associations illustrate the relationship between stream patterns and geological and geomorphological factors. The stream networks in the area as a whole have statistical space-filling properties or are free of geological constraints; however, the variance of individual drainage basins can be characterized by a combined principal component consisting of several quantities. Geological and hydrological interpretations suggest that geological structures, bedrock topography, drift thickness, lithology and slope of drainage basins are the main geological and geomorphological factors influencing the evolution of streams in the area. The results obtained on the basis of stream and drainage basin analysis may provide information for an improved understanding of hydrological characteristics in the area. As an example, the drainage basins along the Niagara Escarpment and on the south side of the Oak Ridges Moraine show distinct patterns with relatively high stream densities and steeper slopes, which may be one of the reasons why these basins have relatively high baseflow compared to basins elsewhere. In addition, high baseflow may have partly induced a relatively high stream density.

Small scale tree domestication, tree breeding and genetic conservation activities face different challenges compared to large and highly developed programs. There are various economical and logistical constraints as listed below, particularly in developing countries. In general, there is not sufficient financial support or land to develop rigorous and largescale tree breeding programs for many forest tree species The scale (and cost) of the improvement program should be customized to the (financial and planting) capacities of the end users, or the cultivation range of the species. Most countries have to deal with multiple species Some countries have forest land with steep slopes and low fertility land. Progeny testing is costly and physically challenging. In most instances, conventional tree breeding is not appropriate. Conservation of genetic resources of minor species may require different strategy compared to widely used forest tree species To address problems outlined above, an international meeting was held on October 9-13, 2006, in Belek, Antalya, Turkey. The topics included the following: Low-cost domestication, breeding and testing strategies Economic analysis of small scale forest tree breeding and gene conservations strategies in reducing the cost? Use of molecular markers and biotechnology in designing and implementing cost efficient breeding and gene conservation programs The role of in-vitro / vegetative propagation in design and implementation of cost efficient breeding programs, the role of clonal testing and selection Low-cost gene conservation strategies Tree selection, domestication and improvement for agroforestry. This booklet contains the program and the abstracts of the presentations at the meeting. The full versions of the presentations will be available soon at the congress website, and will remain there for about six months (until June 30 th 2007).

the impact based on the novelty of the idea, revenues generated/costs saved, dissemination within and outside the organization, extent of commercialization and patentability, was used to categorize the innovations into high impact (HI) and low impact (LI) groups. The analysis of the two groups was qualitative and was based on the detailed case studies prepared through extensive interviews of people involved in the projects. Inferences from the comparative analysis are explained under six sub-themes that emerged as important in differentiating between low and high impact innovations, namely: individual versus team action; the top management support; the role of the immediate supervisor; rewards, recognition and incentives; focus on core versus non core areas; and documenting and patenting practices. An important factor that enhances the impact of innovations is that organizations should have a deliberate innovation strategy and corresponding organizational structures and processes. Coupled with the innovation strategy, organizations should also develop and implement a value appropriation strategy.

Purpose Microtubule-stabilizing agents are an important class of anticancer compounds. Peloruside A and laulimalide bind to a different site on the microtubule to taxoid site drugs such as paclitaxel (Taxol®), docetaxel (Taxotere®), ixabepilone (Ixempra®), the epothilones, and discodermolide. The purpose of this study was to examine the synergistic interactions of these drugs when given in combination in relation to the differences in their binding sites on the microtubule. Methods Human ovarian carcinoma cells (1A9 cells) and murine T cells were treated with different combinations of microtubule-stabilizing or destabilizing agents. The compounds were given individually and in combination, and the antiproliferative activity was assessed to calculate a combination index (CI) from the equation: CI = D 1/Dx 1 + D 2/Dx 2 in which D 1 and D 2 are the concentrations of drug 1 and drug 2 that when given together give the same response as drug 1 and 2 alone (Dx 1 and Dx 2). Thus, a CI value of less than 1.0 indicates a synergistic effect between the two drugs in which the response to the two drugs given together is greater than the additive response of the two drugs if given on their own. Results As anticipated from previous in vitro studies, peloruside A and laulimalide did not synergize with each other. They also failed to synergize with the microtubule-destabilizing agents vinblastine and 2-methoxyestradiol. Peloruside A and laulimalide did, however, synergize with the epothilones, as had been previously shown, but not with docetaxel or discodermolide. Conclusions Combining two microtubule-targeting agents with different binding sites does not guarantee a synergistic interaction in cells, and additional factors are likely to be involved. This study highlights the importance of preclinical testing of actual combinations of drugs before proceeding into clinical trials.

With an approach to enhance the efficacy of chemotherapy agents against breast cancer treatment, here, we investigated the anti-cancer effects of grape seed extract (GSE) and doxorubicin (Dox), either alone or in combination, in estrogen receptor-positive MCF-7 and receptor-negative MDA-MB468 human breast carcinoma cells. GSE (25–200 µg/ml) treatment of cells resulted in 16–72% growth inhibition and 9–33% cell death, in a dose- and a time-dependent manner. In other studies, Dox (10–100 nM) treatment showed 23–96% growth inhibition and 10–55% cell death. Based on these results, several combinations of GSE (25–100 µg/ml) with Dox (10–75 nM) were next assessed for their synergistic, additive and/or antagonistic efficacy towards cell growth inhibition and death. In both MCF-7 and MDA-MB468 cells, a combination of 100 µg/ml GSE with 25–75 nM Dox treatment for 48 h showed a strong synergistic effect [combination index (CI) < 0.5] in cell growth inhibition, but mostly an additive effect (CI ∼ 1) in cell death. In cell-cycle progression studies, GSE plus Dox combination resulted in a moderate increase in G1 arrest in MCF-7 cells compared to each agent alone. GSE plus Dox combination showed a very strong and significant G1 arrest in MDA-MB468 cells when compared with Dox alone, however, it was less than that observed with GSE alone. In quantitative apoptosis studies, GSE and Dox alone and in combination showed comparable apoptotic death of MCF-7 cells, however, a combination of the two was inhibitory to Dox induced apoptosis in MDA-MB468 cells. This was further confirmed in another estrogen receptor-negative MDA-MB231 cell line, in which GSE and Dox combination strongly inhibited cell growth but did not show any increase in apoptotic cell death caused by Dox. Together, these results suggest a strong possibility of synergistic efficacy of GSE and Dox combination for breast cancer treatment, independent of estrogen receptor status of the cancer cell.

Cross-system adaptation and system combination methods, such as ROVER and confusion network combination, are known to lower the word error rate of speech recognition systems. They require the training of systems that are reasonably close in performance but at the same time produce output that differs in its errors. This provides complementary information which leads to performance improvements. In this paper we demonstrate the gains we have seen with cross-system adaptation and system combination on the English EPPS and RT0-05S lecture meeting task. We obtained the necessary varying systems by using different acoustic front-ends and phoneme sets on which our models are based. In a set of contrastive experiments we show the influence that the exchange of the components has on adaptation and system combination.

Experimental design. In vitro radiation response was determined for 4 cell lines and 26 fresh tumor explants in an agar-based assay. Cells were exposed to increasing doses of RT with or without cisplatin (CDDP), carmustine (BCNU), buthionine sulfoximine (BSO), or paclitaxel (Tax). Cell suspensions were cultured for 5 days, with [ 3 H]thymidine added on day 3 and proliferation was measured. Results were reported as the fraction of proliferation compared to control (FC). For each combination of irradiation and drug, synergy was tested using the Chou analysis, where a combination index (CI) <1 indicated synergistic interaction. In simple correlation analysis, an R value of >0.7 indicated cross-resistance.

... Fish collection was done using a Smith-Root R battery powered backpack electrofisher to ... Also, the number of toler-ant and intolerant species and abundance was deter ... For macroinvertebrate data, the Ephemeroptera, Plecoptera, and Trichoptera (EPT) in-dex (Plafkin et al ...

Small scale tree domestication, tree breeding and genetic conservation activities face different challenges compared to large and highly developed programs. There are various economical and logistical constraints as listed below, particularly in developing countries. In general, there is not sufficient financial support or land to develop rigorous and largescale tree breeding programs for many forest tree species The scale (and cost) of the improvement program should be customized to the (financial and planting) capacities of the end users, or the cultivation range of the species. Most countries have to deal with multiple species Some countries have forest land with steep slopes and low fertility land. Progeny testing is costly and physically challenging. In most instances, conventional tree breeding is not appropriate. Conservation of genetic resources of minor species may require different strategy compared to widely used forest tree species To address problems outlined above, an international meeting was held on October 9-13, 2006, in Belek, Antalya, Turkey. The topics included the following: Low-cost domestication, breeding and testing strategies Economic analysis of small scale forest tree breeding and gene conservations strategies in reducing the cost? Use of molecular markers and biotechnology in designing and implementing cost efficient breeding and gene conservation programs The role of in-vitro / vegetative propagation in design and implementation of cost efficient breeding programs, the role of clonal testing and selection Low-cost gene conservation strategies Tree selection, domestication and improvement for agroforestry. This booklet contains the program and the abstracts of the presentations at the meeting. The full versions of the presentations will be available soon at the congress website, and will remain there for about six months (until June 30 th 2007).

Purpose Oxaliplatin eVect in the treatment of colorectal cancer is improved upon combination with thymidylate synthase (TS) inhibitors. Pemetrexed is polyglutamated by the folylpolyglutamate synthase (FPGS) and blocks folate metabolism and DNA synthesis by inhibiting TS, dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). The present study evaluates the pharmacological interaction between oxaliplatin and pemetrexed in colorectal cancer cells. Methods Human HT29, WiDr, SW620 and LS174T cells were treated with oxaliplatin and pemetrexed. Drug interaction was studied using the combination index method, while cell cycle was investigated with Xow cytometry. The eVects of drugs on Akt phosphorylation and apoptosis were studied with ELISA and Xuorescence microscopy, respectively. RT-PCR analysis was performed to assess whether drugs modulated the expression of pemetrexed targets and of genes involved in DNA repair (ERCC1 and ERCC2). Finally, platinum-DNA adduct levels were detected by ultra-sensitive multi-collector inductively coupled plasma mass spectrometry (ICP-MS). Results A dose-dependent inhibition of cell growth was observed after drug exposure, while a synergistic interaction was detected preferentially with sequential combinations. Oxaliplatin enhanced cellular population in the S-phase. Drug combinations increased apoptotic indices with respect to single agents, and both drugs inhibited Akt phosphorylation. RT-PCR analysis showed a correlation between the FPGS/(TS £ DHFR £ GARFT) ratio and pemetrexed sensitivity, as well as a downregulation of ERCC1, ERCC2, TS, DHFR and GARFT after drug exposure. In addition, pretreatment with pemetrexed resulted in an increase of oxaliplatin-DNA adducts. Conclusion These data demonstrate that oxaliplatin and pemetrexed synergistically interact against colon cancer cells, through modulation of cell cycle, inhibition of Akt phosphorylation, induction of apoptosis and modulation of gene expression.

It has been suggested that the combination of cancer chemotherapy with antiviral therapy is helpful for the containment of lymphomas in HIV-infected patients. Since we have recently shown that the nucleic acid binding chemotherapeutic agent bleomycin in itself has antiviral properties, we looked to see if there was any possible synergy with current anti-HIV agents. Combinations of zidovudine, indinavir or ritonavir with bleomycin, synergistically inhibited HIV-1 AT replication in stimulated peripheral blood lymphocytes (combination index at 50% virus inhibition was 0.427, 0.604 and 0.535, respectively) and this synergism was not accompanied by any synergistic effects on cytotoxicity. We conclude from these data that further studies to investigate the clinical efficacy of combinations of antiviral and cancer chemotherapeutic agents are warranted in relation to viral load improvement.

With an approach to enhance the efficacy of chemotherapy agents against breast cancer treatment, here, we investigated the anti-cancer effects of grape seed extract (GSE) and doxorubicin (Dox), either alone or in combination, in estrogen receptor-positive MCF-7 and receptor-negative MDA-MB468 human breast carcinoma cells. GSE (25–200 µg/ml) treatment of cells resulted in 16–72% growth inhibition and 9–33% cell death, in a dose- and a time-dependent manner. In other studies, Dox (10–100 nM) treatment showed 23–96% growth inhibition and 10–55% cell death. Based on these results, several combinations of GSE (25–100 µg/ml) with Dox (10–75 nM) were next assessed for their synergistic, additive and/or antagonistic efficacy towards cell growth inhibition and death. In both MCF-7 and MDA-MB468 cells, a combination of 100 µg/ml GSE with 25–75 nM Dox treatment for 48 h showed a strong synergistic effect [combination index (CI) < 0.5] in cell growth inhibition, but mostly an additive effect (CI ∼ 1) in cell death. In cell-cycle progression studies, GSE plus Dox combination resulted in a moderate increase in G1 arrest in MCF-7 cells compared to each agent alone. GSE plus Dox combination showed a very strong and significant G1 arrest in MDA-MB468 cells when compared with Dox alone, however, it was less than that observed with GSE alone. In quantitative apoptosis studies, GSE and Dox alone and in combination showed comparable apoptotic death of MCF-7 cells, however, a combination of the two was inhibitory to Dox induced apoptosis in MDA-MB468 cells. This was further confirmed in another estrogen receptor-negative MDA-MB231 cell line, in which GSE and Dox combination strongly inhibited cell growth but did not show any increase in apoptotic cell death caused by Dox. Together, these results suggest a strong possibility of synergistic efficacy of GSE and Dox combination for breast cancer treatment, independent of estrogen receptor status of the cancer cell.

This paper proposes a joint feature-based model indexing and geometric constraint based alignment pipeline for efficient and accurate recognition of 3D objects from a large model database. Traditional approaches either first prune the model database using indexing without geometric alignment or directly perform recognition based alignment. The indexing based pruning methods without geometric constraints can miss the correct models under imperfections such as noise, clutter and obscurations. Alignment based verification methods have to linearly verify each model in the database and hence do not scale up. The proposed techniques use spin images as semi-local shape descriptors and locality-sensitive hashing (LSH) to index into a joint spin image database for all the models. The indexed models represented in the pruned set are further pruned using progressively complex geometric constraints. A simple geometric configuration of multiple spin images, for instance a doublet, is first used to check for geometric consistency. Subsequently, full Euclidean geometric constraints are applied using RANSAC-based techniques on the pruned spin images and the models to verify specific object identity. As a result, the combined indexing and geometric alignment based pipeline is able to focus on matching the most promising models, and generate far less pose hypotheses while maintaining the same level of performance as the sequential alignment based recognition. Furthermore, compared to geometric indexing techniques like geometric hashing, the construction time and storage complexity for the proposed technique remains linear in the number of features rather than higher order polynomial. Experiments on a 56 3D model database show promising results.

Oncolytic herpes viruses are attenuated, replication-competent viruses that selectively infect, replicate within, and lyse cancer cells and are highly efficacious in the treatment of a wide variety of experimental cancers. The current study seeks to define the pharmacologic interactions between chemotherapeutic drugs and the oncolytic herpes viral strain NV1066 in the treatment of pancreatic cancer cell lines. The human pancreatic cancer cell lines Hs 700T, PANC-1, and MIA PaCa-2 were treated in vitro with NV1066 at multiplicities of infection (MOI; ratio of the number of viral particles per tumor cell) ranging from 0.01 to 1.0 with or without 5-fluorouracil (5-FU) or gemcitabine. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Viral replication was measured using a standard plaque assay. Six days after combination therapy, 76% of Hs 700T cells were killed compared with 43% with NV1066 infection alone (MOI = 0.1) or 0% with 5-FU alone (2 βmol/L) (P

Simvastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) is known to stimulate apoptotic cell death and induce cell cycle arrest through inhibition of proteasome. The purpose of this study is to investigate whether simvastatin would be synergistic with irinotecan against human non-small cell lung cancer (NSCLC) cells. Antitumor effect was measured by growth inhibition of cells and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cytotoxic interaction between irinotecan and simvastatin was assessed using the combination index. Effects on cell cycle distribution and apoptosis were determined by flow cytometry and DNA fragmentation. Proteasome activity was measured by ELISA quantification of 20S proteasome. NF-κB activation was determined using TransAM™ NF-κB p65 Transcription Factor Assay Kit. IκB-α was measured by immunoblot. A combination of irinotecan with simvastatin showed significantly enhanced cell growth inhibition compared with irinotecan alone, which resulted in a synergistic cytotoxicity. Irinotecan and simvastatin combination treatment of A549 and H460 cells increased G1 phase arrest, which was associated with up-regulation of p21WAF1/CIP and p53 compared with irinotecan alone. In addition, simvastatin combination treatment increased irinotecan-related apoptosis as determined by fluorescence microscopy and flow cytometric analysis. We also found that combination therapy showed superior proteasome inhibitory activity leading to effectively suppress NF-κB transcription factor activation. Consistently, this effect was associated with up-regulation of IκB-α. These findings suggest that simvastatin enhances irinotecan-induced apoptosis in human NSCLC cells through inhibition of proteasome activity.

The calibration database implemented for the Chandra X-ray Observatory is the most detailed and extensive CalDB of its kind to date. Built according to the NASA High Energy Astrophysics Science Archive Research Center (HEASARC) CalDB prescription, the Chandra CalDB provides indexed, selectable calibration data for detector responses, mirror effective areas, grating efficiencies, instrument geometries, default source aim points, CCD characteristics, and quantum efficiencies, among many others. The combined index comprises approximately 500 entries. A standard FTOOLS parametric interface allows users and tools to access the index. Unique dataset selection requires certain input calibration parameters such as mission, instrument, detector, UTC date and time, and certain ranged parameter values. The goals of the HEASARC CalDB design are (1) to separate software upgrades from calibration upgrades, (2) to allow multi-mission use of analysis software (for missions with a compliant CalDB) and to facilitate the use of multiple software packages for the same data. While we have been able to meet the multivariate needs of Chandra with the current CalDB implementation from HEASARC, certain requirements and desirable enhancements have been identified that raise the prospect of a developmental rewrite of the CalDB system. The explicit goal is to meet Chandra's specific needs better, but such upgrades may also provide significant advantages to CalDB planning for future missions. In particular we believe we will introduce important features aiding in the development of mission-independent analysis software. We report our current plans and progress.

Bisphosphonates (BPs), the synthetic analogues of pyrophosphate, are widely used in the treatment of metabolic bone diseases. BPs exhibit a preferential accumulation in malignant pleural mesothelioma (MPM) and, furthermore, nitrogen-containing BPs (n-BPs) show significant inhibition of MPM cell proliferation. We synthesised dinuclear platinum(II) complexes containing a n-BP moiety as bridging ligand and am(m)ines as terminal ligands (Pt-n-BP)s, with the aim of obtaining bifunctional mesothelioma-targeted drugs. We compared the antiproliferative effect of the single drugs (i.e. Pt-model and n-BPs) with that of the preformed Pt-n-BP complexes by means of the combination index (CI) in order to assess the synergistic/additive/antagonistic effect of the two constituents in the resulting conjugates. The combination of the two individual drugs was almost additive, while the preformed Pt-n-BP produced an antagonistic effect. Furthermore, (Pt-n-BP)s neither inhibited the mevalonate pathway (as n-BPs normally do) nor increased the Pt uptake. The minimal biological results of these conjugates could be traced back to a slow and inappropriate hydrolysis, that does not split the adduct into active components.

The anti-HSV-1 activity of meliacine (MA), a peptide isolated from leaves of Meliu azedurach L., alone and in combination with acyclovir (ACV), was assayed against thymidine kinase-deficient (TK-) virus yields in vitro. MA alone proved to inhibit significantly TK-viral replication, whereas ACV was more potent than MA as an inhibitor of TK+ replication. TK-and TK+ synergistic inhibition by the combination of both agents was observed at concentrations that did not alter cell viability. The interaction between MA and ACV was quantitatively determined by calculating the combination index and plotting the data by the isobologram method. Besides, MA and ACV were able to suppress synergistically the antigen expression on HSV-I infected cells processed by an immunotluorescence assay. These in vitro findings suggest that combinations of MA and ACV at appropriate doses may provide an increased efficacy in inhibiting both TK-and TK + HSV-1 multiplication. 0 1997 Elsevier Science B.V.

Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved in cell division. Tubulin is subject to specific enzymatic posttranslational modifications including cyclic tyrosine removal and addition at the COOH terminus of the alpha-subunit. Tubulin is normally extensively tyrosinated in cycling cells. However, we have previously shown that detyrosinated tubulin accumulates in cancer cells during tumor progression in nude mice. Tubulin detyrosination, resulting from suppression of tubulin tyrosine ligase and the resulting unbalanced activity of tubulin-carboxypeptidase, apparently represents a strong selective advantage for cancer cells. We have now analyzed the occurrence and significance of tubulin detyrosination in human breast tumors. We studied a total of 134 breast cancer tumors from patients with or without known complications over a follow-up period of 31 +/- 10 months. The mean age of the patients at the time of diagnosis was 57 years. Fo...

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4 + MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC 95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

Conventional quantities (stream length, number of streams, bifurcation ratio, density of streams per unit drainage area, elevation difference, slope, and perimeter and area of drainage basins) were extracted for approximately 322 drainage basins from a DEM of the Oak Ridges Moraine area, southern Ontario. These values were mapped and analyzed using statistical and multifractal approaches and GIS to characterize the stream networks and drainage basin systems. Useful measures for characterizing drainage basins in the area included, slope, stream densities, ratio of perimeter and area, and ratio of stream lengths. The distinct patterns identified on the basis of these parameters and on the combined indexes generated by using multivariate statistical analysis were compared with other datasets (geology, bedrock topography, and drift thickness). The associations illustrate the relationship between stream patterns and geological and geomorphological factors. The stream networks in the area as a whole have statistical space-filling properties or are free of geological constraints; however, the variance of individual drainage basins can be characterized by a combined principal component consisting of several quantities. Geological and hydrological interpretations suggest that geological structures, bedrock topography, drift thickness, lithology and slope of drainage basins are the main geological and geomorphological factors influencing the evolution of streams in the area. The results obtained on the basis of stream and drainage basin analysis may provide information for an improved understanding of hydrological characteristics in the area. As an example, the drainage basins along the Niagara Escarpment and on the south side of the Oak Ridges Moraine show distinct patterns with relatively high stream densities and steeper slopes, which may be one of the reasons why these basins have relatively high baseflow compared to basins elsewhere. In addition, high baseflow may have partly induced a relatively high stream density. #