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This collaborative three-center study evaluated NCCLS M38-A document testing conditions and other testing conditions for the antifungal susceptibility testing of 35 isolates of Aspergillus nidulans, A. terreus, Bipolaris hawaiiensis, B. spicifera, Cladophialophora bantiana, Dactylaria constricta, Fusarium solani, Paecilomyces lilacinus, Scedosporium prolificans, Trichoderma longibrachiatum, and Wangiella dermatitidis for itraconazole, three new triazoles (voriconazole, posaconazole, and ravuconazole), and amphotericin B. MICs and minimum fungicidal concentrations (MFCs) were determined in each center by using four media (standard RPMI-1640 [RPMI], RPMI with 2% dextrose [RPMI-2%], antibiotic medium 3 [M3], and M3 with 2% dextrose [M3-2%]) and two criteria of MIC determination (complete growth inhibition [MICs-0] and prominent growth inhibition [MICs-2]) at 24, 48 and 72 h. MFCs were defined as the lowest drug concentrations that yielded <3 colonies (approximately 99 to 99.5% killing activity). The reproducibility (within three wells) was higher among MICs-0 (93 to 99%) with either RPMI or M3 media than among all MICs-2 (86 to 95%) for the five agents at 48 to 72 h. The agreement for MFCs was lower (86 to 94%). Based on interlaboratory agreement, the optimal testing conditions were RPMI broth, 48 to 72 h of incubation and 100% growth inhibition (MIC-0); MFCs can be obtained after MIC determination with the above optimal testing parameters. These results warrant consideration for inclusion in the future version of the NCCLS M38 document. However, the role of these in vitro values as predictors of clinical outcome remains to be established in clinical trials.
Although Aspergillus fumigatus is responsible for the majority (85 to 90%) of the different clinical manifestations of mold (filamentous fungi) infections (8), other molds have emerged as important etiologic agents of severe infections, especially in the immunocompromised host (2, 5, 20, 24, 32). With the increased incidence of fungal infections and the growing number of new antifungal agents, the laboratory's role in the selection and monitoring of antifungal therapy has been underscored. As a result of collaborative studies (10, 11), the National Committee for Clinical Laboratory Standards (NCCLS) Subcommittee on Antifungal Susceptibility Tests has developed a reproducible reference procedure for the antifungal susceptibility testing of molds (NCCLS M38-A document [26]). This document describes the following testing conditions: standard RPMI-1640 broth; nongerminated conidial inoculum suspensions of approximately 104 CFU/ml, and incubation at 35°C for 24 h (Rhizopus spp.), 48 h (Aspergillus flavus, A. fumigatus, Fusarium spp.), and 72 h (Pseudallescheria boydii). Because the Subcommittee investigated other conditions for testing Aspergillus spp. against established agents and new triazoles, the conventional MIC criterion (complete or 100% growth inhibition) is recommended for itraconazole and three new triazoles. Data from that study indicated that this criterion more easily and reliably differentiated between susceptible and potentially resistant isolates of Aspergillus spp. than the less stringent criterion (MIC-2 or ⩾50% growth inhibition) described in the older M38 version. The interlaboratory reproducibility of minimum fungicidal concentrations (MFCs) for Aspergillus spp. was also examined in a parallel study (16a). However, none of these studies have included other uncommon pathogenic molds. Because of that, the NCCLS Subcommittee conducted this collaborative study (with three centers) to examine the testing conditions evaluated for Aspergillus spp. for susceptibility testing with itraconazole, new triazoles (posaconazole, ravuconazole, and voriconazole), and amphotericin B (both MICs and MFCs) against a selected set of 35 uncommon mold pathogens.
Study design.Three laboratories participated in the present study, and each laboratory received the same panel of 35 coded (3 isolates each) strains of Aspergillus nidulans, Aspergillus terreus, Bipolaris hawaiiensis, Bipolaris spicifera, Cladophialophora bantiana, Dactylaria constricta, Fusarium solani, Paecilomyces lilacinus, Scedosporium prolificans, Trichoderma longibrachiatum, and Wangiella dermatitidis (Table 1) and two control isolates. MICs for each isolate were obtained in each of the three centers with amphotericin B, itraconazole, posaconazole, ravuconazole, and voriconazole by the broth microdilution method following a standard protocol. This protocol included M38-A and other susceptibility testing conditions to be evaluated: (i) four medium formulations (standard RPMI-1640 [RPMI], RPMI with 2% dextrose [RPMI-2%], antibiotic medium 3 [M3]), and M3 with 2% dextrose [M3-2%]; (ii) three incubation times (24, 48, and 72 h); and (iii) two criteria of MIC determination (100% and ⩾50% growth inhibition). Following MIC determination with the four media, MFCs were determined for each isolate-drug-testing medium combination in the three centers.
Isolates.The set of isolates evaluated is documented in Table 1. These 35 isolates belonged to the culture collections of the University of Texas and the Medical College of Virginia Campus, Virginia Commonwealth University. Each isolate was maintained as a suspension in water at approximately 25°C until testing was performed. The reference isolate A. flavus ATCC 204304 (11, 16) and the quality control strain Candida parapsilosis ATCC 22019 (27) were included as controls each time isolates were tested. For C. parapsilosis ATCC 22019, there are well-established microdilution MIC ranges of the five agents evaluated in this study (4); reference MIC ranges also have been established for the isolate A. flavus ATCC 204304 (11, 16). MIC ranges for these isolates were within established values in the three centers (4, 11, 16, 26).
Broth dilution susceptibility testing.Standard Excel spreadsheets were developed to serve as recording forms and to enter and analyze data. The standard protocol supplied to each laboratory for the broth microdilution method provided detailed instructions concerning the following testing conditions.
A single lot of each of the four liquid medium formulations was provided ready-to-use to all participants by Trek Diagnostic Systems Inc. (Westlake, Ohio). The same lot of each medium was used for the preparation of the drug dilutions. Each batch of standard RPMI and RPMI-2% was supplemented with 0.3 g of l-glutamine per liter and 0.165 M morpholinepropanesulfonic acid buffer (34.54 g/liter) to pH 7.0 ± 0.1 at 35°C and did not contain sodium bicarbonate. Neither batch of M3 and M3-2% was buffered, and the pHs of both media were 7.0 ± 0.1. The five antifungal agents amphotericin B (Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Conn.), itraconazole (Janssen Pharmaceutica, Titusville, N.J.), posaconazole (Schering-Plough Research Institute, Kenilworth, N.J.), ravuconazole (Bristol-Myers Squibb Pharmaceutical Research Institute), and voriconazole (Pfizer Pharmaceuticals, New York, N.Y.) were provided by the manufacturers as assay powders. Additive drug dilutions were prepared as described in the NCCLS M38-A document (26) and previous reports (10, 11, 16) in a central facility (Trek Diagnostic Systems) and shipped frozen to each participant. As previously described (9, 26), stock inoculum suspensions were prepared in sterile saline (provided by Trek Diagnostic Systems) containing 1% Tween 80 from 7-day-old colonies grown on potato dextrose agar slants (provided by Remel, Lenexa, Kans.). The resulting mixture of mostly nongerminated conidia was adjusted spectrophotometrically to optical densities that ranged from 0.09 to 0.3 (Table 1) and were diluted 1:50 in each of the four media, which corresponded to 2 times the density needed for the test of approximately 0.4 × 104 to 5 × 104 CFU/ml. On the day of the test, each microdilution well containing 100 μl of the diluted (2 times) drug concentrations was inoculated with 100 μl of the diluted (2 times) conidial inoculum suspensions (final volume in each well, 200 μl). All microdilution trays were incubated at 35°C and examined after 21 to 26, 46 to 50, and 70 to 74 h of incubation. Two MIC endpoints were determined, the lowest drug concentrations that showed absence of growth or complete growth inhibition (100% inhibition) and the lowest drug concentrations that showed ⩾50% growth inhibition.
MFC determination.The in vitro fungicidal activities (MFCs) were determined for each drug-isolate-medium combination as previously described (13, 14, 16a). After 72 h, 20 μl was subcultured from each well that showed complete inhibition (100% or an optically clear well), from the last positive well (growth similar to that for the growth control well), and from the growth control (drug-free medium) onto Sabouraud dextrose agar plates. The plates were incubated at 35°C until growth was seen in the growth control subculture. The MFC was the lowest drug concentration that showed either no growth or fewer than three colonies (approximately 99 to 99.5% killing activity).
Data analysis.The percentage of inoculum densities that were within the range of 0.4 × 106 to 5 × 106 CFU/ml was calculated, and the geometric means for each species' inoculum sizes were also obtained. Both on-scale and off-scale MIC and MFC values were included in the analysis. MICs and MFCs from the three centers for each drug-isolate-medium-incubation time (the latter for MICs only) combination tested were compared to obtain data regarding reproducibility. As previously analyzed (10, 11, 16, 16a), discrepancies between MIC endpoints of no more than three dilutions (three wells) from the three centers were used for the calculation of the percent values of agreement. A measurement of agreement was then determined as the percentage of endpoints within three dilutions (i.e., 1, 2, and 4 μg/ml) for each combination of drug, isolate, medium, incubation time, and criterion of MIC determination. In addition, each 48- or 72-h MIC was compared to its corresponding MFC to assess the differences between in vitro fungistatic and fungicidal endpoints obtained with each medium for each isolate in each laboratory. Comparisons of proportions were performed by chi-square test for Fisher's exact test as appropriate. A two-tailed P value of <0.05 was considered to be significant.
Reproducibility of spectrophotometric procedure for inoculum preparation.A total of 105 inoculum preparations from the three laboratories were analyzed. The optical density (OD) ranges and actual CFU-per-milliliter ranges for the inoculum size values across the species are shown in Table 1. The CFU-per-milliliter range was within the target range of 0.4 × 106 to 5 × 106 for 9 of the 11 species evaluated (97 of 105 preparations or 92.4%). Substantially lower values (0.07 × 106 to 0.3 × 106 CFU/ml) were reported for 8 of the 18 Bipolaris spp. suspensions (five values for B. hawaiiensis and three for B. spicifera). With the exception of inocula for B. hawaiiensis, the mean inoculum size range was 0.9 × 106 to 1.9 × 106 CFU/ml.
Total MICs and MFCs evaluated.Each isolate had three incubation time readings with the five antifungal agents and by each of the other six testing conditions evaluated (four media and two criteria of MIC determination) in all of the participant centers. A total of 120 readings per isolate in each center, or 360 readings from the three centers, were reported. Since 1,430 readings were scored as 0 (no growth), a total of 11,170 MICs were evaluated for the 35 isolates. In addition, 1,757 MFC values were obtained.
Effect of incubation time on MICs.A total of 3,723 MIC pairs were compared for this evaluation. MICs increased no more than two dilutions between 24 and 48 h or 48 and 72 h for most isolates. A major increase (from 0.06 to 1.0 μg/ml to 1 to 8 μg/ml) in MICs-0 was observed with amphotericin B for B. hawaiiensis and two B. spicifera isolates (24 to 72 h with M3 media) and with posaconazole for T. longibrachiatum (24 to 48 h with RPMI media).
Interlaboratory agreement. (i) Agreement among the four media.The four media supported growth of most of the isolates after 48 h of incubation, and both RPMI broths supported growth for all isolates after 72 h. Insufficient growth precluded MIC determination in two centers for two isolates of C. bantiana (four media) and one isolate of P. lilacinus (M3 media) at 48 h and for one isolate each of these two species at 72 h (M3 media). Although some inocula of Bipolaris spp. were substantially lower, sufficient growth allowed MIC determination at 48 h for all six isolates and for five isolates at 24 h. Table 2 summarizes the percentages of interlaboratory agreement for MICs and MFCs of the five agents obtained with the four media for the 35 isolates; the agreement is stratified by the two criteria of MIC determination. Overall, either RPMI broth or M3 medium demonstrated the best interlaboratory reproducibility for the five agents. Slightly lower interlaboratory agreement was observed among MICs of most of the agents with either M3-2% or RPMI-2% than those with the other two formulations. In general, the agreement was lower among the laboratories for MFC than for MICs; slightly higher values were seen for MFCs obtained following MIC determination with M3 broth (86.6 to 94%) than with RPMI (84.7 to 92%) medium.
(ii) Agreement for the three incubation times.The agreement among the centers was lower (65 to 95%) when 24-h MICs were compared than for those obtained after 48 and 72 h of incubation (86 to 99%) for all the drugs and other testing parameters evaluated (P = 0.001).
(iii). Agreement for the two criteria of MIC determination.Overall, the interlaboratory agreement was higher for MICs-0 (93 to 99%) than for MICs-2 (86 to 95%) for four of the five agents with the four media (Table 2). The exceptions were posaconazole MICs, for which the agreement was more dependent on medium and MIC determination criterion; a better agreement was seen with both RPMI for MIC-2 endpoints (89 to 92%) than for MICs-0 (87 to 89%). On the other hand, agreement values were lower with M3 broths for MICs-2 (88 to 92%) than for MICs-0 (92 to 95%). Although the majority (84 to 98%) of MICs-0 were the same or no more than two dilutions higher than MICs-2, differences were seen with all media among posaconazole MICs for T. longibrachiatum and one B. spicifera (MICs-2 of 0.5 to 1.0 μg/ml versus MICs-0 of 4 to >8 μg/ml) and with ravuconazole and voriconazole for two S. prolificans isolates (MICs-2 of 1 to 4 μg/ml versus MICs-0 of ⩾8 μg/ml). A similar trend was observed with voriconazole in RPMI broth for one isolate of B. spicifera (MICs-2 of 0.5 to 2 μg/ml versus MICs-0 of 4 to >8 μg/ml) and F. solani (MICs-2 of 2 to 4 μg/ml versus MICs-0 of 4 to >8 μg/ml). Other major discrepancies between the two criteria of MIC determination were due to the weaker agreement observed among the laboratories for MICs-2.
Interlaboratory agreement for azole and amphotericin B MICs.For amphotericin B and itraconazole, the agreement was good to excellent (94 to 99%) for MICs-0 with RPMI and M3 media. The agreement decreased 1 to 9% with RPMI-2% and M3-2% (Table 2). Greater interlaboratory agreement (93 to 99%) was observed for voriconazole and ravuconazole MICs-0 at both 48 and 72 h than for posaconazole (87 to 95%).
Optimal testing conditions for MIC determination.Although good to excellent agreement (>90%) was found for the four agents with some of the various combinations of media, MIC determination criteria, and incubation times, the testing conditions that better encompassed the five agents were the following: (i) the 100% growth inhibition criterion (MIC-0) with (ii) the standard RPMI broth, and (iii) after 48 to 72 h of incubation. Although reproducibility was higher for posaconazole MICs with M3 broths than with RPMI media, both M3 media did not support growth of all isolates. RPMI was also superior in distinguishing different patterns of fungistatic and fungicidal activity for some agent and species combinations, especially for amphotericin B.
Antifungal activities (MICs and MFCs) of the five agents.Table 3 depicts 48-h MICs-0 as well as MFC results of the five agents obtained with RPMI for each of the species. MICs for C. bantiana and D. constricta are 72-h values, because growth for the former species and the agreement for MICs among the centers for the latter species were better at that incubation time. Although the range of amphotericin B MICs was narrow for 6 of the 11 species, wider ranges (0.06 to 4 μg/ml) were observed for Bipolaris spp. and F. solani; MICs for Bipolaris spp. were bimodal. Also, high amphotericin B MICs (>2 μg/ml) were obtained in the three centers for S. prolificans and P. lilacinus. Most triazole MICs were clustered within a relatively low, narrow range, but lack of or low in vitro antifungal activity was observed for F. solani, S. prolificans, and T. longibrachiatum while the activity was good for the other species. MICs-0 of voriconazole and posaconazole for S. prolificans had a bimodal susceptibility pattern (MICs-0 of 0.5 to 1.0 μg/ml for one isolate and of ⩾8 μg/ml for the other two isolates); this pattern was not observed for MICs-2. For Bipolaris spp., the bimodal pattern was species specific with ravuconazole and voriconazole (MICs-0 of <1.0 μg/ml for B. hawaiiensis and MICs-0 of 2 to >8 μg/ml for B. spicifera after 48 and 72 h of incubation), while low and high MICs-0 were obtained for both species with the other three agents. The wide itraconazole MIC ranges for P. lilacinus reflect the poor agreement among the three centers for this species by all testing conditions.
In contrast to MICs with RPMI, amphotericin B MICs obtained with M3 media were uniformly higher and the range was wide only for Bipolaris spp. (Table 4). Although the bimodal pattern with M3 for amphotericin B for Bipolaris spp. was similar to that with RPMI, MICs were high for five isolates with M3 but for only one isolate with RPMI. The activity of triazoles with M3 media was similar to that observed with RPMI for most of the species, but a bimodal activity was observed with ravuconazole for S. prolificans (Table 4).
MFCs of amphotericin B were either the same or no more than two dilutions higher than MICs for 32 of the 35 isolates when testing with RPMI (Table 3). Amphotericin MFCs were >3 dilutions higher than MICs-0 for one isolate each of B. hawaiiensis, B. spicifera, and A. terreus (0.06 to 1.0 μg/ml versus 1 to >8 μg/ml). MFCs of 1 to ⩾8 μg/ml for Bipolaris spp. only reflected poor interlaboratory agreement for two isolates. Among the triazoles, ravuconazole MFCs in RPMI were substantially higher than MICs (0.5 to 1.0 versus 4 to ⩾8 μg/ml) for one isolate of B. hawaiiensis and two isolates of A. terreus. The same applied to the other two new triazoles for two isolates of A. terreus and for posaconazole with one isolate of B. spicifera. With M3, MFC values tended to be higher and differences between fungistatic and fungicidal activities tended to be less distinctive, especially for posaconazole and ravuconazole (Table 4).
Our study describes the first collaborative evaluation of testing parameters for testing of susceptibility (fungicidal and fungistatic) of nine species of uncommon dematiaceous and moniliaceous molds to amphotericin B, itraconazole, and three new triazoles (posaconazole, ravuconazole, and voriconazole). Our set of isolates included species that are recognized as resistant or less susceptible to the agents evaluated, e.g., S. prolificans and A. terreus (7, 20, 33). An agent with fungicidal activity may have a therapeutic advantage over an inhibitory agent. However, only one collaborative study has been conducted to detect optimal testing parameters for MFC determination for three Aspergillus spp. (16a). Because of that, we examined the effects of the various parameters on both MIC and MFC values regarding the potential detection of different patterns of susceptibility. We also examined the differences between MIC and MFC endpoints for the same purpose.
As for any antimicrobial procedure, the issue of reliability of the different testing parameters should be addressed. Our study has confirmed the reliability of the spectrophotometric procedure for preparing inoculum suspensions of common molds (10, 11, 16) and expanded its use for other, less common species (Table 1). With the exception of Bipolaris spp. inocula, excellent reproducibility was demonstrated for the other preparations from the three laboratories. The conidia of Bipolaris spp. and the macroconidia of Fusarium spp. are larger (6 to 12 by 16 to 35 μm) than conidia of the other species evaluated (2 to 5 by 2 to 13 μm). However, most Fusarium spp. also produce much smaller microconidia. Because inoculum suspensions of both Bipolaris spp. were below the desired CFU/ml range, these suspensions may require a 10% lower dilution factor than that used for the other species, or the density of these suspensions should be adjusted by using conventional cell counting with a hemacytometer (conidial size is irrelevant). Reliable conidial suspensions can be prepared by both methods (29), but inoculum quantification is highly recommended for confirmation of actual inoculum size (CFU/ml) by either method.
We examined the combined effect of incubation time and MIC determination criterion on MICs as well as their reliability. As previously described (16), MIC increases (⩾2 dilutions) between incubation times occurred more frequently for MICs-0 than for MICs-2. In this study, only posaconazole MICs-0 increased >3 dilutions for T. longibrachiatum and the different susceptibilities among isolates to the new triazoles were more obvious with MICs-0. However, the clinical significance of discrepant MICs by both criteria should be determined in clinical trials or animal studies. Although it has been reported (3) that the incubation time had no substantial effect on azole and amphotericin B MICs, the combined effects of incubation time and inoculum have increased azole MICs for A. fumigatus, A. flavus (18), and Fusarium spp. (30). As previously reported (16), 24-h MICs yielded the weaker interlaboratoy agreement in our study and, with the exception of Aspergillus isolates, lack of growth precluded 24-h MIC determination for some isolates of most other species. Furthermore, it was the 48-h incubation, in addition to the conventional MIC criterion, that allowed eight laboratories to better distinguish itraconazole-resistant isolates from susceptible isolates of A. fumigatus (16); these testing parameters have been introduced in the new version of the NCCLS M38 document.
The standard RPMI broth and the M3 medium consistently yielded ⩾90% agreement among the laboratories for MICs of the five antifungal agents. Also, interlaboratory agreement of triazole MICs was improved (94 to 99%) over that obtained in the Aspergillus spp. study (90 to 100%) (16). RPMI-2% did not increase the growth rate or density of any of the species tested at 24 h as has been documented for yeasts (27), and use of this formulation lowered MIC reproducibility (3 to 8%) (Table 2). Similar results have been reported previously for Aspergillus spp. (16). The present study has examined the effect of two formulations of M3 on MICs and MFCs. However, in addition to the lot variability reported for M3 (22), its value as a predictor of amphotericin B resistance in candidemia has been questioned (28). In our study, both M3 media precluded MIC determination of all C. bantiana and P. lilacinus isolates even after 72 h. Arikan et al. (3) reported that buffered (phosphate) M3-2% had a tendency to yield lower MICs of amphotericin B, itraconazole and voriconazole than those obtained with RPMI. In our study, triazole MICs with both M3 and RPMI were essentially the same, but amphotericin B fungicidal and fungistatic concentrations were substantially higher than those with RPMI (Tables 3 and 4). Because of that, the different susceptibilities of our isolates to amphotericin B were better detected with MICs-0 determined using the RPMI broth. The discrepant results between this and Arikan et al.'s study (3) could be due to either the low reliability of M3 or their use of buffered medium. Due to the low M3 reliability, our data suggest that optimal testing conditions for MIC determination of these five agents for the species evaluated are the combination of standard RPMI broth, 48-h incubation for most species, and the conventional MIC criterion or 100% inhibition. For C. bantiana and D. constricta, 72 h appears to be the most reliable incubation time. MFCs (<3 colonies or approximately 99 to 99.5% killing activity) can be determined following MIC determination with those parameters.
Overall, our MIC and MFC data generated by the optimal testing conditions are comparable to those obtained in other studies for the five agents (1, 6, 7, 12, 13, 15, 16, 16a, 17, 19, 21, 24, 25, 31, 33). Our amphotericin B MIC and MFC values were high, or ranges were wide, for Bipolaris spp., F. solani, P. lilacinus, and S. prolificans. In addition, amphotericin B had fungicidal activity beyond safely achievable serum concentrations (MFC of ⩾4 μg/ml) for one isolate of Bipolaris spp. and A. terreus, while MICs (⩽1 μg/ml) were within safely achievable serum levels. Both RPMI broths yielded two distinct fungicidal levels among isolates of A. terreus, S. prolificans, and B. hawaiiensis. The low in vitro fungicidal activity of amphotericin B has been demonstrated for the former two species but not for Bipolaris spp. (14, 15, 33). However, evaluations of in vitro fungicidal activities have focused on more common molds. With the exception of MFCs for some isolates of the new triazoles (A. terreus) and ravuconazole (B. hawaiiensis, S. prolificans, and Bipolaris spp.), other triazole fungicidal levels were no more than two dilutions higher than corresponding MICs. In the Aspergillus spp. study, MFCs were also consistently higher (1 to 4 dilutions) than corresponding MICs for A. terreus isolates with RPMI media. The potential discriminatory value of amphotericin B and voriconazole MFCs for this latter species has been demonstrated (14, 33).
In conclusion, because standard RPMI is a chemically defined medium and reproducibility was good to excellent, RPMI appears to be a suitable testing medium for determination of MICs of the agents and species evaluated. Their fungicidal activities (<3 colonies) can be evaluated following determination of MICs-0 (100% growth inhibition) with standard RPMI broth after 48 h of incubation. However, for C. bantiana and D. constricta, 72 h appears to be the best incubation time for MIC determination. Our data also suggest that these MIC parameters have a superior discriminatory power in recognizing different patterns of in vitro antifungal susceptibility, as was demonstrated for Aspergillus spp. (16). Although these data indicate that MFCs could be more useful than MICs for some of the species evaluated, further evaluations with isolates that have well-documented in vivo data must confirm their clinical value. The use of M3 is limited until the problem of lot variation is investigated and resolved. Results of this NCCLS collaborative study warrant their introduction in a more advanced version of the NCCLS M38 document.
This work was partially supported by grants from Pfizer Inc., Schering-Plough Research Institute, and Bristol-Myers Squibb.
- Received 14 May 2002.
- Returned for modification 17 June 2002.
- Accepted 30 June 2002.
- Copyright © 2002 American Society for Microbiology


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New App Models National Building Energy Use
Looking around the typical home or office, many homeowners and employees will find a staggering amount of technology on display: the refrigerator that keeps our food fresh; the thermostat that controls room temperature; the array of electronics to enable (and sometimes impede) our productivity; the lights that make tasks visible at night.
"As this large technology base continues to grow, the number of ways that a building can use energy grows with it, meaning that the best opportunities for saving energy in buildings are always changing," said Jared Langevin, research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab). "What's more, the pace of change is relatively quick—ask a homeowner from the year 2000 what they think of smart thermostats or where they buy their LED light bulbs, and they'd have little clue of what you were talking about."
Into this technology development maelstrom enters Scout, a software program developed by the U.S. Department of Energy Building Technologies Office (BTO) in partnership with Berkeley Lab and the National Renewable Energy Laboratory (NREL). Scout estimates the national impacts of emerging energy-efficient technologies and systems on building energy use and operating costs, drawing from a consistent energy use baseline, standard energy conservation measure (ECM) definitions, and realistic simulations of stock turnover and ECM competition dynamics. With support from BTO, Scout is now available as a web-based application for sharing Scout's capabilities with the broader energy analysis community.
"The Scout web app (scout.energy.gov) will be of interest to users who want to know how new energy-saving technologies or approaches fit into the larger U.S. market for energy efficiency—both at present and decades into the future," said Chioke Harris, an NREL research engineer collaborating with Langevin on the project. Looking for simple definitions of technologies and their national impacts to compare with similar technologies? Visit the ECM Summaries page. Curious about the total impacts of a technology portfolio and which end uses or technologies contribute most to those impacts? The Analysis Results page presents those insights. Just want to know about the status-quo outlook for U.S. building energy use? The Baseline Energy Calculator provides that information.
The web app can help all kinds of folks better understand how energy use in buildings might change with the adoption of energy-efficient technologies, as well as the potential cost savings from those technologies. Companies that own or manage large building portfolios can learn about the financial performance of various technologies using metrics that can help them with the business justification for investing in energy efficiency. Energy policy organizations and nonprofits can look at those same technologies through the lenses of their energy and cost savings potential for a specific region or across the United States. Researchers interested in developing next-generation energy-efficient building technologies can use the baseline energy use projections and ECM definitions to better understand where they can have the greatest impact. Users intrigued by the app can take the leap and download the Scout analysis engine to get results custom tailored to their unique interests.
"Looking ahead, Scout's flexibility to folding in new input data, technology areas, and valuation metrics will be essential in keeping the program viable as the building energy use landscape continues to change," said Langevin. In just the last few months, for example, Scout's baseline data were updated reflect the latest Energy Information Administration national energy use projectionsand new analysis capabilities were piloted that will allow users to value energy efficiency differently by time of day and season, reflecting an increasing focus on buildings as a source of grid services. All of these updates were pushed to the Scout GitHub repository and were carefully documented with an eye towards transparency.
"We expect that scout.energy.gov will bring new tests of Scout's flexibility, opening the program to exciting use cases and avenues of investigation that have yet to be explored," Langevin said. In the meantime, interested readers are encouraged to get started with their own Scout analyses and to keep an eye out for new Scout releases.


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Aptics lending software solution handles accounts for deposits, revolving credits, unsecured loans, and loans with collateral for clients or on one's behalf. Account administration can be tailored to the needs of the business. The process flows, parameter settings, and service definitions automate processes and provide the opportunity to set up the account types and flows, unique to each client. The flexibility and degree of automation are further increased with integration with, for instance, suppliers of credit rating information, printers, proprietary systems, etc.
Flexible and adaptable to your needs
Deposits, revolving credits, unsecured loans, and loans with collaterals, all can be handled in one single platform. Through parameters, you set up the system to suit your needs, i.e., limits, minimum and maximum amounts, credit limits, number of free withdrawals, and interest calculation, etc.
Extensive reporting abilities
Transaction statistics, credit risks, balances, fees, commissions, and other measurable variables can be presented and reported both to the client and internally. Reports can be printed directly, routed to a specific printer, or made available to the client on the web interface.
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The notification procedure may include direct debit, SMS reminders, phone actions, etc. It is also possible to use integration solutions with a credit rating agency to improve the efficiency of phone number retrieval, address checks, and credit checks.
Promentor Finans
"Aptic are notable for receptiveness and professionalism, and they have natural flexibility as the software solution is built that way. It's a complete solution that supports the whole chain of our operation."


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Talend (NASDAQ: TLND), leader in cloud and big data integration solutions, announced it is working with Capgemini to integrate Talend's on-demand training courses into the company's University Learning Management System. This provides Capgemini's 13,000 Insights & Data consultants with unlimited technical training on Talend's cutting-edge big data and cloud technologies, to further support clients in achieving their desired business outcomes.
Forrester Research, Inc. notes, "digital technology has fundamentally changed two things: the dynamics of the markets in which you operate and the speed that you need to remain competitive."[1] Keeping up with the latest developments in big data and cloud technologies can be a challenge given the rapid pace at which these two markets move. Capgemini elected to work with Talend on the development of its new learning program to leverage Talend's deep expertise in both megamarkets, and its arsenal of courses that provide hands-on practice using big data and cloud technologies to implement real-world business scenarios.
"Big data is a disruptive force in today's marketplace that is spurring companies to rethink existing business processes and transform the way they operate. This includes helping up-skill their workforce to meet emerging customer needs and fluctuating industry requirements," said Mike Pickett, VP of Business Development and Partner Ecosystems, Talend. "We're excited that Capgemini has chosen to work with Talend and incorporate our training into its comprehensive curriculum to teach its talented consultants more about our cutting-edge cloud and big data solutions."
Training is key to remaining competitive in a world of rapid change. Capgemini continues to equip its global team of consultants with the latest knowledge and hands-on expertise on emerging big data and cloud solutions. The company decided to integrate Talend's cloud-hosted technical curriculum with its existing employee training program. The new combined curriculum offers employees courses ranging from big data basics to advanced topics such as Apache Spark streaming, machine learning, and data governance, that are essential for companies to further their digital transformation goals and remain compliant with evolving data regulations. The integrated solution allows Capgemini to incorporate Talend courses into its own customized learning paths, to address changing business needs.
"Effectively transforming an organization for the digital economy requires more than just an understanding of our client's business and their competitive landscape; it also entails having a broad understanding of the tools and technologies that will help our clients best achieve their desired business outcomes," said Steve Jones, VP of Big Data at Capgemini. "Leveraging Talend's training courses allows us to not only train our consultants on cutting-edge big data and cloud technologies, but also allows them to deliver high quality data integration solutions that help our customers get closer to the point of execution"
Further information on how Capgemini is utilizing Talend solutions can be found here. A listing of the big data and cloud technology training courses Talend offers can be found at https://www.talend.com/services/training/. For details on Capgemini's Insights & Data services visit https://www.capgemini.com/insights-data.
Like this story? Tweet this: @Capgemini institutes consultant training system based on @Talend to advance clients' digital transformation initiatives http://bit.ly/2kerC3S
[1] "The Digital Business Imperative" by Ted Schadler and Nigel Fenwick, Forrester Research, Inc., February 15, 2017.


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The Wychwood Brewery Session is now in regular monthly form.
The session is "trad and trad-based tunes and songs", is collaborative encouraging people to play together, and welcomes players of all ability, confidence and experience. All the details are here (but please note that there a few edits required to reflect the now regular format - I'll get round to that ASAP): http://www.bamptonfolkclub.org.uk/the-wychwood-brewery-session/
The Wychwood Brewery Tap is easy enough to find, but SatNav will likely take you to the back door of the Brewery which isn't ideal. The Wychwood Brewery Tap is accessed from The Crofts, off Corn Street. Parking is often a bit tight, if that's the case then you can park on Corn Street and there is a little lane through to the Crofts to the side of the Corn Street Dental Practice.


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Progress continues on new food store in Huntington Center
Work continues on turning the former Beechwood Market into a natural foods store in Huntington Center.
As of last week, the inside of the 6,500-square-foot retail space had been essentially gutted. New refrigerator and freezer units have been placed across the back of the store and a walk-in cooler added on the side.
The old floor has been removed and a new tile floor will soon be put in. There also will be new lighting, shelving and check-out counters, and the entire inside will be painted.
The new store, to be named the Common Bond Market, will sell fresh produce, packaged foods, prepared foods to go, and nutritional supplements. It will have a deli, bulk-bin areas, kitchen and offices.
The landlord is building a new entrance foyer and brick facade in the front, and has added dormers to the roof.
In late August last year, Beechwood Market closed unexpectedly after more than a half century in Shelton.
Will open in the spring
Joshua Elliott, who will oversee the store, said he hopes the Common Bond Market can open its doors in late March or April. "We want to open as soon as possible in the spring," he said.
Elliott said some of the interior work is dependent on the exterior work being done, and weather has been an issue.
He likes the new look being given to the structure's outside by the landlord. "It makes the building stand out more," Elliott said. "It makes the building look more alive when you drive by."
The goal is to make the building's front "more aesthetically pleasing" so it blends in well with Huntington Center, he said.
Three owners are involved
The Common Bond Market will be owned and operated by three people with connections to Thyme & Season, a similar establishment in business since 1997 in Hamden.
Elliott is partnering with his mother, Mary Ellen Stearman, and her fiancé, Mark Woollard, on the new business in Shelton.
Stearman owns Thyme & Season and was one of the founders of the FoodWorks natural foods markets, with stores in suburban towns east of New Haven as well as one in Monroe. She is no longer involved with FoodWorks.
The new market's name comes from Elliott's vision of food as something that brings people together, such as when families or friends share meals. "I see food as a cohesive bond between people," he said.
Elliott said creating a new space has been a learning process for the store owners. "We knew it would take a while," he said. "We have a giant to-do list."
Forming relationships
Elliott said the new store expects to build strong relationships with its customers and employees, similar to what has happened in Hamden.
"We are on a first-name basis with our customers," he said of Thyme & Season.
Like the Hamden store, the Common Bond Market will sponsor lectures and tastings. The new market will work with local vendors and companies. "We can help these businesses and producers," Elliott said.
He expects to begin interviewing for employment positions in February or March, and some people already are dropping off resumes at Thyme & Season in Hamden. The Shelton store could initially hire from 20 to 25 people, both full and part time.
The public reaction to the new store coming to Huntington Center has been encouraging, said Elliott, a recent Quinnipiac University Law School graduate. "People are excited," he said.
Learn more about the store and the construction process at the store's website, www.thecommonbondmarket.com.


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Undergraduate Degree, Institut Teknologi Bandung, 1989
Doctoral Degree, Durham University, U.K., 1995
Post Doctoral (visiting researcher), University of Twente, Netherlands, 2003-2004
Nanophotonics (theory and modelling)
1. G.W. Putra Data, A.A. Iskandar and M.O.Tjia, Numerical study of anomalous TE-polarized light scattering by metallic nanowires using realistic data, J. of Nonlin. Opt. Phys. and Mat. 23(1) (2014), 1450005.
2. B.S. Nugroho, A.A. Iskandar, V.A. Malyshev and J. Knoester, Bistable optical response of a nanoparticle heterodimer: Mechanism, phase diagram, and switching time, J. Chem. Phys. 139 (2013) 014303.
3. R.N.S. Suryadharma, A.A. Iskandar and M.O.Tjia, Overlapping TE and TM Band Gaps in Square Lattice Photonic Crystal of Hollow Dielectric Rods, J. of Nonlin. Opt. Phys. and Mat. 21(1) (2012), 1250008.
4. H. Alatas, A.A. Iskandar and M.O. Tjia, Structure Dependent Variations of Group Velocity, Energy Loss and Confinement in a Regular Grated Waveguide, J. of Nonlin. Opt. Phys. and Mat. 21(1) (2012), 1250009.
5. A. Putra, A.A. Iskandar and M.O. Tjia, Performance Enhancement of Single Defect Microcavity and Related Localization of Evanescent Bloch Waves, Phys. Rev. B84 (2011) 075159.
6. H. Alatas, H.J.W.M. Hoekstra, A.A. Iskandar and M.O. Tjia, Group-Index and Resonant Field Enhancement in Symmetric Double-Sided Grated Waveguide, J. Opt. Soc. Am. A28 (2011) 1197.
7. H. Alatas, A.A. Iskandar, H.J.W.M. Hoekstra and M.O. Tjia, Performance changes of a grated waveguide at resonance wavelengths next to its band-edges due to modified edge sections, J. Opt. Soc. Am. B27 (2010) 2743.
8. I. Karnadi, A.A. Iskandar, M.O. Tjia, Analysis of Ag-Superlens Performances using Spatial Convolution Formulation, J. Opt. Soc. Am. A27 (2010) 268.
9. H. Alatas, A.A. Iskandar, M.O. Tjia, Tailoring spatial soliton characteristics and its dynamical behaviors in nonlinear reflection gratings, J. Opt. Soc. Am. B27 (2010) 238.
10. H. Alatas, A.A. Kandi, A.A. Iskandar, M.O. Tjia, New Class of Bright Spatial Solitons obtained by Hirota's Method from Generalized Coupled Mode Equations of Nonlinear Optical Bragg Grating, J. of Nonlin. Opt. Phys. and Mat. 17 (2008) 225.
11. Muldarisnur, A. Soehianie, A.A. Iskandar and M.O. Tjia, Analysis of Asymmetric Bragg Coupler Based Optical Add-Drop Multiplexer Operating on certain Phase Matching Conditions, Journ. of Appl. Phys. 103 (2008) 123110.
1. Principal Investigator, Surface Plasmon Resonance in Electromagnetic Wave Scattering on Nano Structure, funded by the Decentralization Research Grant of the Ministry of Education and Culture.
2. Principal Investigator, Substrate Effects on Surface Plasmon Resonance of Metallic Nanoparticles, funded by the Research and Innovation Grant of Institut Teknologi Bandung.
1. Principal Investigator, Dynamic Optical Response of a Metal Nano Particle – Semiconductor Quantum Dot Hybrid System, funded by the Research and Innovation Grant of Institut Teknologi Bandung.
1. Principal Investigator, Hybrid Metal-Dielectric Photonic Crystal Systems, funded by the Decentralization Research Grant of the Ministry of Education and Culture.
2. Principal Investigator, Complete Photonic Bandgap in 2D Photonic Crystals, funded by the Research and Innovation Grant of Institut Teknologi Bandung.
3. Visiting Scientist at the Condensed Matter Theory Group of Zernike Institute for Advanced Materials at the University of Groningen, the Netherlands, for joint supervision (with Prof. Dr. Jasper Knoester) of Mr. Bintoro S. Nugroho.
1. Principal Investigator, Analysis of Optical Properties of Hybrid Semiconductor – Metal Nano Particle, funded by the Asahi Glass Foundation.
1. Research Team Member, Development of Quantitative Evaluation Method for Subwavelength Imaging using Silver-Superlens (Principal Investigator : A. Soehianie), funded by the Capacity Enhancement Research Grant Institut Teknologi Bandung.
2. Visiting Scientist at the Integrated Optical Micro System Group of MESA+ Research Institute at the University of Twente, the Netherlands, conducting a joint research under the auspies of SPIN KNAW Postdoc of Dr. Husin Alatas on a research topic of Density of optical states modeling of highly resonant Photonic Crystal based cavities, funded by the Royal Dutch Academy of Arts and Sciences (KNAW).
1. Principal Investigator, Study and Modeling of Nano Photonic Devices based on Photonic Crystals and Surface Plasmon Waveguide, funded by the Competence Research grant from the Ministry of National Education of Indonesia.


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text:
Talent-project docking fair for returned talents held
- Details
- Category: On The Campus
- Published: Tuesday, 21 June 2016 16:24
On the morning of June 14, the talent-project docking fair for the "Ningbo Summit of 1000 Returned Talents" was held by the picturesque Siming Lake, attracting over 400 attendees, including representatives from prominent domestic investment agencies, high-end talents and talent teams in the robot and intelligence economy field from home and abroad, members of the overseas high-end talent fraternity of Ningbo, and representatives from related local enterprises.
In recent years, Ningbo Municipal Party Committee and Ningbo Municipal Government have acceleratted its pace in building the "deep-blue intelligent valley" and an ideal ecology for talents by focusing on the talent work in technological innovation and transformation. So far, 97 high-end talent teams and 333 returned talents have been listed in the "3315 Plan", including 75 selected in the national "1000 Talents Plan" and 198 in the provincial "1000 Talents Plan". With an annual increase of over 1600 talents, there are now over 8000 high-end returned talents in Ningbo.
To fuel the intelligence economy in Ningbo, the summit invited the global talents to come and settle down in Ningbo for entrepreneurship and innovation. At the docking fair, the joint research institute for Ningbo Western Returned Scholars Association, serve base for returned talents, and the "1000 Talents Plan" was inaugurated, serving as another important platform for Ningbo's globe-oriented talent introduction.
Meanwhile, the on-site negotiation, roadshow and docking were carried out for over 50 talent projects featuring robot elements and technological intelligence, including the smart health examination system, the big-data home service products, and the new products for multi-dimensional warning and production efficiency improvement.


text:
Content Count3
Last visited
Days Won1
Everything posted by fsociety
Automatic system updates?
fsociety replied to paddymac's topic in Dev Centralhttps://pypi.python.org/pypi/jw.emerge_update If you didn't know, there is quite the fancy python script hidden in pip/Pypy for updates. I'm in the midst of writing a python script that can detect what is going and update accordingly. I'll post it when I've completed it. Hopefully soon.
About nvidia-drivers 358.09
fsociety replied to Sandro's question in Installation HelpI haven't actually seen any actual use cases of this feature yet. I know this is going to help with the framebuffer in the future without having to use v86d but I'm not sure how to implement this myself or if the kernel can utilise it at this point.
fsociety replied to haxmeister's topic in General DiscussionMoved to Funtoo from Arch after many years. Did try Gentoo six months back but it was a dependency nightmare compared to Funtoo. I love how Funtoo just works and seems to be a little more intuitive with packages and current versions. Anyway here is a pic of my desktop. Running bspwm on a 32" Samsung Ultra Wide Screen curved monitor. Top screen shot is a nice empty one and the bottom is a wonderfully fake busy ;)
x11-drivers/nvidia-drivers-355.11-r2 wont compile
fsociety replied to ainsley31415926's topic in Funtoo InfrastructureUnmask 358.16-r1 and you won't have an issue. They maybe beta but its better than using that fix I personally think. Just add =x11-drivers/nvidia-drivers-358.16-r1 to your /etc/portage/package.unmask file and emerge it.


text:
Pinta tu propio azulejo de Triana
#con_Paula y #con_Eva
Comparte tu creatividad con autenticos artesanos de Triana en sus estudios y disfruta creando tu propio azulejo guiado por nuestra artesana Paula
Conoce de primera mano la legendaria cultura alfarera de Triana que data de los tiempos romanos, evolucionó en la epoca musulmana y se desarrollo en la edad media y edad moderna. Una inmersion cultural en la Triana artesana. Un taller original y divertido apto para todas las edades. Ven y pruebalo, todo el mundo tiene un artista dentro!
Amazing Triana with Eva, amazing Tiles workshop!We were 2 families with 2 kids each, travelling to Seville in July. We really want to enjoy some original, authentic and creative activity with our kids but not sure which one... so we found Eva´s website and asked her for our needs and likes. She was really lovely trying to accommodate us in all, even taking note of our kid´s ages- from 5 to 10 y.o.-. So our final choice was a DYI workshop suitabable for kids and adults who are interested in handicraft and in a bit of history. We did not know, how important and connected was the pottery with Triana and Sevilla! Awe! We loved the way Eva tell us in an interactive way about Tiles, Triana and we could watch it on the way to the craft studio. The workshop was very instructive and funny, even for kids!!! The artisan told us more about the evolution of the tiles while Eva translated. We were there painting our own tile! The activity let us appreciate even more how much time and how difficult was and is being an artisan! Afterwords, we were strolling through Seville enjoying their meaningfull balconies, facades and tiles. Visiting Alcazar with all its amazing tiles from Triana was awesome. It was a highlight of our trip! We highly recommend Triana, Tiles workshop and Eva to everyone! Victoria S. USA
- Horario: Lunes-Miercoles-Viernes 10am/12pm
- Duración: 2 horas.
- Precio para grupos privados: Desde 55€/persona.Pregunta por los suplementos por grupos privados de dos y un viajero
- Tamaño del grupo: Minimo 1 persona / Máximo 12 personas.
- Para quién? Todas las edadades
- Punto de encuentro: en la puerta principal del Mercado de Triana
- Idiomas: English, Deutsch y Español.
Cuéntame tus preferencias y personalizo actividades ó/y rutas a tu medida.
+34 626 00 78 68


text:
The IoT (Internet of Things), connected cars, autonomous driving, and such are all the rage these days. And as the topic du jour, there's a lot of uninformed analysis and speculation being thrown around - even by big banking analysts who you'd normally expect to know what they're talking about.
So there is a big need to set the record straight.
But before I drag some big names in banking and electronics through the mud, I should probably explain why I'm qualified to say they're not qualified. Which brings me back to my day job.
I'm a pretty humble guy most of the time. A few weeks ago I lapped Buttonwillow (a roughly 2 minute track) almost 20 seconds slower than my buddy who was competing in Spec 3 (same car). So, I'm not fast. At all. And there are definitely people out there who are smarter than me. But you want to talk about cars and connectivity and electronics/smartphones/wearables? I feel like I'm decently qualified in that area.
I'm the competitive intelligence lead in the corporate strategy team at a major electronics manufacturer. You have a roughly 50% chance of having a phone made by my company in your pocket.
Phone dump - everything out of my backpack that I DIDN'T take on my last business trip.
Before this gig, I was in an internal consulting group at a major automaker. I worked across the company - in R&D (battery, alt fuel, connectivity, etc), marketing, product planning, strategy.
I still do automotive consulting work, as well as some automotive work at my present company.
The Autoextremist is fond of saying that you can't ever understand the vast complexity of the auto industry if you've never been part of it. I've been an enthusiast for most of my life, and it wasn't until I got my job in the industry that I realized how true that statement is.
This is a key point I'll return to. I'm not trying to make any fellow Jalops feel bad, but if you've never been inside it is incredibly difficult to really grasp the complexity, risk aversion, scale, and timing of the industry. Which also means a Harvard education and investment banking background don't help, either.
Doing your own work DOES help, however - teaches you how things get engineered, how things work, and why it's not worth saving $0.05 on a slightly cheaper part sometimes. Pic from my head gasket job...
So all of this is just a long way of saying I do have some idea what I'm talking about with both cars and this new connectivity business, and these Wall Street types have no more idea than your kindergartner does of how to do the valve adjustment on the solid lifters on the S54 in your swapped E30 race car. (yes, even your kindergartner, who knows the difference between a crankshaft and a camshaft).
Speaking of kindergartners, this is how I feed the addiction when I'm at the day job...
If you're reading this, you probably read this story from a few days ago, rebutting an article claiming autonomous cars will kill 9 billion jobs and usher in the apocalypse.
You should expect a lot more of this type of analysis (the original, not the Jalopnik story. Ballaban could have gone after them even more and it still wouldn't have been everything they deserve). It sells papers (well, not really papers, but you get the idea). If only they knew headlines don't sell papes (yes, that's right - Newsies sell papes).
You probably missed it, but days after the Apple Car rumor first hit, both Bank of America and Morgan Stanley analysts published papers on Apple's prospects in the car business. They were on opposite sides of the issue, but both MILES from having a clue.
The Bank of America analysts cited four reasons Apple wouldn't build a car (I have the research note, but can't find it online). Some of them were completely idiotic, including "they could look elsewhere for growth." So these brilliant analysts have concluded that Tim Cook does not in fact have a gun to his head, forcing him to enter the auto market, and that because they can look elsewhere they will look elsewhere.
But other reasons they cited sound downright convincing. The one I'm referring to in particular said something along the lines of, "Apple uses contract manufacturing rather than manufacturing themselves [i.e. Foxconn], and since that doesn't exist for auto manufacturing, they won't do it."
Which totally sounds reasonable - unless you've heard of Magna or AM General (you know, those guys who built Doug's Hummer. Yep, they build stuff for other people). In which case these guys look like they've got such weak homework skills you wonder how they got past second grade.
In fact, they were SO ignorant they didn't read the article in the WSJ the week before, which cited Apple talks with automotive contract manufacturer Magna as evidence Apple was getting into the business.
Then on the other side you have Morgan Stanley, who said OF COURSE Apple is getting into the car business. In just 8 short years Apple already has like 25% share of the $400 million global smartphone market. And if Apple could likewise get 25% of the $1.6 TRILLION global automotive market, that would be as much as the WHOLE smartphone market. So that's a total no-brainer, right?
Now, I haven't chased this number down exactly, but I'm pretty sure the last time any automaker had 25% global market share their cars were also still legitimately competing with horses as a valid transportation option, even in New York and London. (I will admit that after both German and Japanese manufacturing were destroyed during WWII, GM may have been close. But Morgan Stanley's note didn't mention WWIII. Of course, even if it did, the way OEMs have diversified their manufacturing means even that strategy wouldn't work so well these days).
This is fanciful to the degree of idiocy.
Now, you may be saying the same thing they did when they threw out this crazy number. They said the auto industry is ripe for a shakeup. They're old. They don't innovate.
And here I'll revisit the Autoextremist's point. This thinking shows an utter ignorance of the industry at such a base level it's laughable.
I'm going to use the iPhone as an example. We got the iPhone in 2007. Depending on where you live, we also got the new E90 BMW 3-Series around the same time (2005 in Europe, 2006 in the US).
We've had 7 new iPhones since then, and will get an 8th later this year.
Now class, how many new 3-Series did we get in the same time period? One, in 2011. So Apple made 5 new iPhones in the same time BMW come out with one new 3-Series.
Of a necessity, automotive product cycles are much longer than that of consumer electronics. You already knew that, so I'm not going to get into the many reasons for it (engineering, validation, liability, manufacturing, etc), but it's not one of those things that needs to change. It is an unavoidable reality Apple will have to adopt.
So calling the automakers out for a lack of innovation because YOU don't understand that the auto industry has a different product cycle from the electronics industry is easy and can make you sound smart, but is actually just ignorant. (Hmm, I keep using that "ignorant" word).
It also means (like our Bank of America friends) that they're not paying any attention to the industry - they're just jumping in on this topic because they heard the word "Apple." They obviously haven't paid any attention to anything the actual automakers have been doing lately, which is quite a lot.
But I hear some of you saying Apple really IS innovative. And I'll tell you why - even if you really believe that - it doesn't matter.
In the electronics industry patents provide protection for as many as 16-17 product cycles (since, you know, patents last 17 years and at best take a year or two to make it into consumers' hands). At best, patents only provide protection for 2-3 automotive product cycles. Makes it much harder to maintain your competitive advantage in the long run, no?
And if you look at how evenly distributed global automotive market share is, it really rings true.
And what about all the things Apple has no clue about? What does Apple know about lightweight materials? Engineering engines, motors, safety structures? Ride and handling, NVH, aerodynamics? On balance, they don't really have that much on the positive side of the balance sheet in this car space.
But it's what they do have that matters. There are some subtleties in the language used here that are very important.
If you're a geek, you may remember in June 2013 at their World Wide Developer's Conference (WWDC) Apple announced "iOS in the car." They went away, and I assume worked on it for the next whole year. But they never announced anything. Fast forward to June 2014 and Apple announced CarPlay at WWDC 2014.
I'll let that just sink in for a minute.
This was a huge failure by Apple. But even more astoundingly, it was completely missed by the media.
The key here is that Apple thought they could get what they wanted from the automakers, but they were completely unprepared to have every single automaker turn them down because they were completely ignorant of the industry's liability and attendant risk aversion behavior and attitude toward driver distraction.
What do you think "iOS in the Car" means? I think it's fair to assume that means iOS, running in the car. Running the whole infotainment system (maybe more). But at the very least it meant Apple's software running the show on the automaker's infotainment system.
So what's the big deal?
The deal is that CarPlay is Apple backtracking on that grand plan. And pretending that was the plan all along.
What is CarPlay? CarPlay plays your iPhone's display as an app on top of the automaker's infotainment system.
Some of you may wonder why the implementation matters, but others may see where this is going.
It wasn't all about liability. It was really about control. Liability is a huge factor, but as cars get smarter and start driving themselves, liability goes down. The real opportunity as cars start driving themselves is that people can start doing other things with their newfound free time while they ride instead of drive. (This also is why longtime holdouts like BMW are finally putting touchscreens in their cars. Once the car can drive itself, touchscreen distraction is no longer an issue).
If Apple is in control, Apple can sell you content from iTunes to watch or listen to. Apple gets the HBO Go delivery fee. Etc, etc.
But Apple didn't get any takers. Automakers declined to put iOS in the car because they want to capture the value of that content themselves rather than just handing it over to Apple.
And once it became clear to Apple that they were effectively going to get sidelined (if not completely shut out of the car eventually), they decided to pull a Tesla and enter the market themselves.
And how will they do that? What do they know about actually building a car? We've already established that IP (patents - Intellectual Property) doesn't last long in automotive terms. Combine that with poaching talent and reverse engineering, and you get going in no time.
Just ask Tesla...


text:
Does Alli work?
Well, according to this editorial in the Lancet:
According to the big brains over at the Lancet:
- The average weight loss with alli is only 2.5 kg / 5 lbs per year.
- The cost of OTC alli is 6 times higher than the equivalent dose of prescription Orlistat.
- Both OTC alli and prescription Orlistat have the unfortunate side effect of steatorrhoea
And, for those of you that don't know what steatorrhoea is:
- Steatorrhea is the presence of excess fat in feces.
As a result:
- Stools may also float due to excess gas
- Stools may have an oily appearance
- Stools may be especially foul smelling
- You may experience an increased number of bowel movements
- You may experience an urgent need to have a bowel movement
- You may experience an inability to control your bowel movements
And, as a result:
- You may experience an oily anal leakage or some level of fecal incontinence.
And, just to remind you:
The average weight loss with alli is only 2.5 kg / 5 lbs per year.
Good Luck!
If you like what you see here, click here for updates
Related Posts
- HIIT Training: The Cure for Obesity
- 1 in 3 People Infected with Obesity Virus
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The Lancet – doi:10.1016/S0140-6736(09)60115-X


text:
Photograph as originally submitted to
this page
in the Historical Marker Database
. Click on photo to resize in browser. Scroll down to see metadata.
Photographer: Douglass Halvorsen
Taken: April 20, 2018
Free Emigrant Road Marker
Submitted: April 23, 2018, by Douglass Halvorsen of Klamath Falls, Oregon.
Database Locator Identification Number: p424557
File Size: 3.306 Megabytes
To see the metadata that may be embedded in this photo, sign in and then return to this page.
Copyright © 2005–2020, Some rights reserved.


text:
Revolutionary War Weekend
Where: George Washington's Mount Vernon
3200 Mount Vernon Memorial Highway, Mount Vernon, Virginia 22121
When: Saturday, May 6, 2017 | 9:00 am – 5:00 pm
Details: Step back in time during Mount Vernon's Revolutionary War Weekend. This two-day event will be one of the largest Revolutionary War re-enactments of the year! See more than 700 Continentals, Redcoats, Hessians…
Cost: Free
Click here for more information.


text: I was sitting on the patio watching the fireworks display and suddenly out of nowhere i saw an amber sphere appear a few hundred feet above the height of the highest fireworks going off. it appeared 3 times above the fireworks just after they went off as if to be concerned about them. first it was travelling north to south, then westerly and finally south westerly. it would appear directly above the fireworks and then travel on a horizontal plane extremely fast for about 2-3 seconds then disappear. nothing man made can move that fast. again it was seen 3 times travelling in different directions. i was not seeing things and it was not part of the fireworks display.


text:
Page 1 - Cancelling, Noise, Chrome, Edition
K40 Antennas&accessories 4-PIN Noise Cancelling Chrome Edition Cb Radio Microphone
Musical Instruments - The K40 Antennasaccessories 4PIN Noise made by K40 Antennas & Accessories is a nice product for your CB radio. K40 Antennasaccessories 4PIN Noise is an example of good quality item you can get out there. If you're looking to acquire a radio, you've come to the right spot. We provide you special discounted rates just for this item with protected financial transaction. The part number for this CB part is K4B321140MICCH. One of the several features for this product is the extra-long 9' super flexible microphone cord. Additional features include things like black wire mesh grille.
Cancelling, Noise, Chrome, Edition


text:
Gardening is one of the most fun hobbies out there. Not only you get to have a good time, you can make your home look nicer and have healthy fruits and veggies to eat if you garden. So, here are some tips to make gardening easier for you:
Dye Rain Gauge
It can be hard to read the measurements of a rain gauge when the water is so clear after a rainy say. Here's an easy workaround to this problem: dye. Add a drop of food dye, watercolor or some other coloring that will dissolve in water. Once the rain lets, you will be able to read the dial easy.
Your gloves, knee pads, hygrometer in Singapore and rain gauges should all be neatly organized in one place. Not only will doing so make gardening easy and simple, it will also save you storage space. After all, keeping these things in different places can take up space for other things.
Fill Large Pots
If you are planting seeds in large flower pots, it can be a pain when the time comes to transplant these. It's difficult to pull potted plants out of large containers. However, you might have no choice as some plants do not grow in small pots. Therefore, the solution is to fill the bottom part of a deep pot with something non-degradable, like packing peanuts or stuff it with bubble wrap to make it easier to pull plants out later.
Buy Online
When you buy gardening equipment like hygrometer, soil pH tester, or rain gauge that you need to take measurements, buy them online. Individual items are far cheaper online than in retail stores or specialty shops. You can find these items for cheap on sites like Amazon and eBay. However, be careful to read all customer reviews in advance. Also, Google the product and the brands to make sure that it is actually good to use. Don't fall for cheap items.
Use Mulch
You can avoid having to use harmful pesticides or weedicide by using spreading some much around the area where the plant is growing. Mulch is wetter than soil, so seeds of weeds will go bad without growing. Pests like ants and snails will also go away.
Pick Early
We all love the look of growing vegetables and fruits in the garden. However, as nice as they look, you will have to pick them on time to avoid them going to waste because of animals, pests or ripening.
If you follow the above tips, your gardening time will be fun and far more convenient than before.


text:
Dear Grammar and Spelling,
I'm writing to tell you that I've had about enough of your self-importance. From here on out, I no longer give a flying pigeon about you. You can put glaring red squiggles beneath my writing in Microsoft Word all you like. I no longer care. I'll spell pillow with ten L's if I want to, and I'll typo to, too, and two as many times as I like.
Who gives a crap if occasionally mi vocabulario espanol wriggles its way into my writing on occasion? I most certainly do not. My sentences can be bilingual if they like, whenever they like, however they like.
If I ever see that awful blue squiggle line, I may freak out in an entirely violent and uncalled for way. What does that even mean, anyway? It's bad enough you've forever desecrated the color red as the messenger of my so-called errors. Now you're going to drag blue into it, as well?
Furthermore, I dislike your obstinate attitude. If I say ignore an "error," then just ignore it! Would it kill you to allow me to do what I like? I don't know if you know this, but humans don't use proper grammar at all times. Especially in dire circumstances. We're not worried about your versus you're and gonna versus going to when we're excited or worried. You shouldn't be, either.
That's all I have to say to you. Good day.


text:
mte567ca | Graduate
Curriculum Const & Assmt: Secondary History/social Science
- Overview
- Topics
- Costs
This graduate-level course is 6 This course is available to take individually or To enroll, speak with an Enrollment Representative.
Course details:
topic title goes here
Parent, Teacher, and Community Collaboration and Professional Development
- Explore strategies to utilize community resources in the social studies classroom.
- Explore the range of social, health, education, and language-related service agencies and other resources that are available at school or off-campus.
- Examine how family and personal experiences shape teaching and learning perceptions in the social studies or history classroom.
- Determine strategies for increasing the level of parental involvement in education.
- Analyze professional resources and continued development opportunities available to social studies teachers.
History, Trends, and Content Knowledge in History and Social Studies Education
- Examine your stateâs teacher licensure examinations for history and social science education.
- Examine trends in the history of social studies instruction in public schools.
- Identify current trends and issues in the teaching of social studies.
- Examine state and national standards for secondary history and social studies.
Standards and Assessments
- Review state and national social studies standards and assessments.
- Analyze the implications of the National Council for the Social Studies (NCSS) themes for instruction.
- Identify various strategies for assessing social studies learning objectives for all learners.
- Analyze formative and summative social studies assessments and rubrics.
- Develop rubrics to evaluate and assess student performance.
Instructional Approaches and Strategies
- Review approaches to unit and lesson planning in teaching social studies.
- Propose innovative instructional strategies and materials used to teach social studies to adolescents.
- Analyze ways in which differentiating instruction occurs in the social studies classroom.
- Identify ways in which classroom management techniques can enhance the social studies classroom.
- Develop an instructional unit for social studies.
Media and Technology
- Analyze the legal and ethical issues regarding the use of technology in the classroom.
- Incorporate the use of technology in social studies instruction.
- Identify major online websites for the teaching of social studies.
- Identify media sources for teaching social studies.
- Research options for students who do not have access to technology in their homes and classrooms.
Reading and Writing Strategies
- Describe methods to incorporate reading and writing strategies into social studies lessons.
- Examine strategies for building student comprehension and vocabulary skills in social studies.
- Integrate reading and writing strategies into a social studies lesson.
- Examine how primary source literature can shape teaching and learning perceptions in the social studies or history classroom.
- Examine how secondary source literature can shape teaching and learning perceptions in the social studies or history classroom.
Please ask about these special rates:
Teacher Rate: For some courses, special tuition rates are available for current, certified P-12 teachers and administrators. Please speak with an Enrollment Representative today for more details.
Military Rate: For some courses, special tuition rates are available for active duty military members and their spouses. Please speak with an Enrollment Representative today for more details.
The University of Phoenix reserves the right to modify courses.
While widely available, not all programs are available in all locations or in both online and on-campus formats. Please check with a University Enrollment Representative.
Transferability of credit is at the discretion of the receiving institution. It is the student's responsibility to confirm whether or not credits earned at University of Phoenix will be accepted by another institution of the student's choice.