Development threefold

To comply with existing and future legislation with respect to silver content in processor rinsing water, the approach developed by Agfa is threefold. 

Reciprocating Compressors. Prior to 1895, when Linde developed his air Hquefaction apparatus, none of the chemical processes used industrially required pressures much in excess of I MPa (145 psi) and the need for a continuous supply of air at 20 MPa provided the impetus for the development of reciprocating compressors. The introduction of ammonia, methanol, and urea processes in the early part of the twentieth century, and the need to take advantage of the economy of scale in ammonia plants, led to a threefold increase in the power required for compression from 1920 to 1940. The development of reciprocating compressors was not easy Htfle was known about the effects of cycles of fluctuating pressure on the behavior of the... 

World production of Bra in 1990 was about 438 000 tonnes pa, i.e. about one-hundredth of the scale of the chlorine industry. The main producing countries are (tonnes) USA 177000, Israel 135 000, Russia 60000, UK 28 000, France 18 000 and Japan 15 000. The production capacity of Israel has recently increased almost threefold because of expanded facilities on the Dead Sea. Historically, bromine was shipped in individual 3-kg (net) bottles to minimize damage due to breakage, but during the 1960s bulk transport in monel metal drums (100-kg capacity) or lead-lined tanks (24 or 48 tonnes) was developed and these are now used for transport by road, rail and ship. The price of Bra in tank-car lots was 975/kg in 1990. 

Figure 11.17a to Figure 11.17d show densitograms from the separation of Che-lidonium majus quaternary alkaloids. Various volumes of the extract solution of the same concentration, from 0.2 to 1.6 ml, were introduced to the adsorbent layer. Thus, the following portions of extract of 0.25, 0.5, 1, and 2 mg were chromatographed by the use of threefold development with the multicomponent eluent. The densitograms depict fast loss of resolution with the increase of the introduced sample [114]. 

Figure 11.28 shows densitograms from the separation of Chelidonium majus quaternary alkaloids [114]. It is clearly apparent that multiple development results in better separation of the component bands. Threefold development results in separation or partial separation of eight alkaloid bands (Figure 11.28b), whereas after one run, only four zones — chelirubine, sanguinarine, chelilutine, and chelerithrine... 

FIGURE 11.29 Video scan of alkaloids from Fumaria officinalis herb chromatographed in system silica/PrOH + AcOH + CH2CI2 (4 1 5) (a) plate single developed (b) plate double developed (c) plate threefold developed (d) plate fourfold developed. 

Dopamine agonists are useful as initial therapy, as they can delay the need to start levodopa and can decrease the risk of developing motor fluctuations by two- to threefold during the first 4 to 5 years of treatment. After a few years, dopamine agonists inadequately control the patient s symptoms and levodopa needs to be started. In advanced disease, dopamine agonists can be added to levodopa because they have a longer duration of action, minimize fluctuations in dopamine blood concentrations, decrease off-time, improve wearing-off symptoms, allow a reduction in levodopa dose, and improve ADLs.1-3,16,22,23,26... 

Poor sleep architecture and fragmented sleep secondary to OSA can cause excessive daytime sleepiness (EDS) and neu-rocognitive deficits. These sequelae can affect quality of life and work performance and may be linked to occupational and motor vehicle accidents. OSA is also associated with systemic disease such as hypertension, heart failure, and stroke.21-23 OSA is likely an independent risk factor for the development of hypertension.24 Further, when hypertension is present, it is often resistant to antihypertensive therapy. Fatal and non-fatal cardiovascular events are two- to threefold higher in male patients with severe OSA.25 OSA is associated with or aggravates biomarkers for cardiovascular disease, including C-reactive protein and leptin.26,27 Patients with sleep apnea often are obese and maybe predisposed to weight gain. Hence, obesity may further contribute to cardiovascular disease in this patient population. 

Studies conducted in twins show a threefold increased risk of psoriasis in monozygotic twins versus fraternal twins.7 In addition, based on a study in 3,095 families with psoriasis, the calculated lifetime risk of developing psoriasis if no parent, one parent, or both parents have psoriasis was found to be 0.04, 0.28, and 0.65, respectively. If there was already one affected child in the family, the risks were increased to 0.24, 0.51, and 0.83, respectively.7,9 As many as 71% of patients with psoriasis during childhood have some positive family history.1 Similarly, psoriatic arthritis is heritable, with a prevalence 19 times higher in first-degree relatives of patients with psoriatic arthritis than in the general population.7... 

The plicae circulares, or circular folds, form internal rings around the circumference of the small intestine that are found along the length of the small intestine. They are formed from inward foldings of the mucosal and submucosal layers of the intestinal wall. The plicae circulares are particularly well developed in the duodenum and jejunum and increase the absorptive surface area of the mucosa about threefold. Each plica is covered with millions of smaller projections of mucosa referred to as villi. Two types of epithelial cells cover the villi ... 

Taylor and coworkers also developed similar twofold intramolecular Li-mediated carboadditions [193]. In contrast to the aforementioned sequences, they were able to utilize functionalized triple bonds and to trap the intermediate lithiated species such as 2-352 with other electrophiles besides a proton. Such a 2.2.2 process will be discussed in the following section, which relates to threefold anionic domino processes. 

Another domino cuprate 1,4-addition-initiated threefold anionic domino sequence was developed by Chemla and coworkers (Scheme 2.93) [214]. Michael addition of the a, 3-unsaturated ester 2-387 with PhCu(CN)ZnBr was followed by a carbocyclization to give the zinc species 2-388 which can be intercepted by iodine or an allyl bromide affording substituted pyrrolidines 2-389 and 2-390, respectively. 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

This method represents one of the first attempts towards macromolecular agents.121-123 As many as 60-90 [Gd(DTPA)]2- or [Gd(DOTA)] chelates were first linked to a polylysine chain, then covalently conjugated to a HSA molecule.124 The increase in relaxivity per Gd, as compared with the monomeric chelate, was remarkable (two- to threefold), though far from optimal. However, the development of these albumin conjugates was abandoned at an early stage, since their synthesis is not easily controlled, and there are also toxicity concerns due to the retention of gadolinium observed in the bones and liver.125... 

Miproxifene (TAT-59) is a prodrug of 4-hydroxy-tamoxifen that has been developed for tamoxifen-resistant carcinoma, but relatively little information has been published on this drug. Compared with tamoxifen, miproxifene inhibits estradiol-stimulated proliferation of MCF-7 cells at a threefold lower dose than that of tamoxifen, and of dimethyl-benzanthracene (DMBA)-induced rat mammary tumors at a dose tenfold lower than tamoxifen (Toko et al. 1990). In any event, in preclinical castrated rat models, it shows an endometrial stimulation activity that is similar to that of tamoxifen, which means it has limited potential use in the prevention or treatment of osteoporosis or cardiovascular disease (Shibata et al. 2000). Similarly, considering the preclinical findings of endometrial stimulation reported on GW5638 (Willson et al. 1997), it is likely that this new SERM belonging to the triphenylethylene family will be limited in clinical use to the treatment of advanced tamoxifen-resistant breast cancer once its efficacy is demonstrated in human clinical trials. 

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