The Ontario Ministry of the Environment (MOE) conducted a survey in 2006 on emerging organic contaminants (EOCs) which included pharmaceuticals, hormones and bisphenol A (BPA). The survey collected ...258 samples over a 16month period from selected source waters and 17 drinking water systems (DWSs), and analyzed them for 48 EOCs using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and isotope dilution mass spectrometry (IDMS) for the highest precision and accuracy of analytical data possible. 27 of the 48 target EOCs were detected in source water, finished drinking water, or both. DWSs using river and lake source water accounted for>90% detections. Of the 27 EOCs found, we also reported the first detection of two antibiotics roxithromycin and enrofloxacin in environmental samples. The most frequently detected compounds (≥10%) in finished drinking water were carbamazepine (CBZ), gemfibrozil (GFB), ibuprofen (IBU), and BPA; with their concentrations accurately determined by using IDMS and calculated to be 4 to 10 times lower than those measured in the source water. Comparison of plant specific data allowed us to determine removal efficiency (RE) of these four most frequently detected compounds in Ontario DWSs. The RE of CBZ was determined to be from 71 to 93% for DWSs using granulated activated carbon (GAC); and was 75% for DWSs using GAC followed by ultraviolet irradiation (UV). The observed RE of GFB was between 44 and 55% in DWSs using GAC and increased to 82% when GAC was followed by UV. The use of GAC or GAC followed by UV provided an RE improvement of BPA from 80 to 99%. These detected concentration levels are well below the predicted no effect concentration or total allowable concentration reported in the literature. Additional targeted, site specific comparative research is required to fully assess the effectiveness of Ontario DWSs to remove particular compounds of concern.
► Occurrence and typical range of 45 selected pharmaceuticals and hormones and bisphenol A in aquatic environment of Ontario, Canada were determined in a 16-month survey. ► IDMS analysis ensured monitoring data are with high precision and accuracy. ► Reported the first detection of two antibiotics roxithromycin and enrofloxacin in aquatic environmental samples. ► Compared removal efficiency of carbamazepine, gemfibrozil, ibuprofen, and BPA in DWSs using granulated activated carbon and ultraviolet treatment processes.
A frequency-domain approach is used to study the effects of a velocity-dependent force caused by the rubbing between the reamer margins and the hole wall. The solution method determines tool ...stability and hole form. The velocity-dependent force, colloquially known as process damping, has been used in turning and milling, where it has been shown to stabilize the system at low spindle speeds. The addition of the process-damping model in the reamer model stabilizes self-excited chatter near the first fundamental tool bending frequency, but destabilizes low-frequency vibration. The method yields combinations of cutting speed and depth of cut that bind stable cutting regions. The boundaries for reaming with no process damping closely resemble the shape of milling stability diagrams, but the small radial depth of cut is unrealistic. The addition of process damping changes the shape of the stability regions and also increases the stable depth of cut. Notably, eigenvalue solutions are found with increased process damping that lead to low-frequency whirling modes, which resemble those found in practice. A simulation using a numerical Euler integration technique will be used to match the analytical model. The simulation will allow for future research using nonlinear models, uneven tooth spacing, and arbitrary initial hole profile data.
We consider a class of pure jump Markov processes in
whose jump kernels are comparable to those of symmetric stable processes. We prove a support theorem, a lower bound on the occupation times of ...sets, and show that we can approximate resolvents using smooth functions.
Legal context
In 2008, the validity of more than 25 patents was considered by the Patents County Court, Patents Court, Court of Appeal, and House of Lords. Unsurprisingly, given such activity, the ...law is constantly evolving and being refined; in the past 5 years, an unprecedented six patent cases have been considered by the House of Lords, four of which were concerned with validity. This article considers whether recent case law developments have led to the courts becoming more 'patentee-friendly', both by considering the case law itself and by an analysis of the outcome of patent cases over the past 5 years
Key points
There have been major developments in the law of novelty, inventive step, and sufficiency. In respect of novelty, the requirements of disclosure and enablement have been distinguished, meaning that attacks on novelty must be tightly focused and rely on prior art which 'plants a flag' on the invention disclosed by the patent. When considering inventive step, it is now clear that the issue of obviousness is to be assessed on the basis of what is claimed, rather than what is disclosed in the patent specification. Furthermore, if a revocation action is based on an 'obvious to try' argument, the court is required to decide, on the facts, what level of success the skilled person would need to foresee in order to render the patent in question invalid for obviousness. In some circumstances, the fact that a skilled person would consider the alleged invention 'obvious to try with a reasonable expectation of a beneficial result' (the old test) may no longer be sufficient to revoke the patent. Finally, the scope of 'Biogen insufficiency' has been circumscribed, and the doctrine is inapplicable to straightforward patent claims.
Practical significance
The above developments are all to the advantage of patentees. Over time, this ought to mean that a greater proportion of patents which are contested in the English courts will be upheld as valid.
Using a combination of NMR and fluorescence measurements, we have investigated the structure and dynamics of the complexes formed between calcium-loaded calmodulin (CaM) and the potent breast cancer ...inhibitor idoxifene, a derivative of tamoxifen. High-affinity binding (
nM) saturates with a
complex. The complex is an ensemble where each idoxifene molecule is predominantly in the vicinity of one of the two hydrophobic patches of CaM but, in contrast with the lower-affinity antagonists TFP, J-8, and W-7, does not substantially occupy the hydrophobic pocket. At least four idoxifene orientations per domain of CaM are necessary to satisfy the intermolecular nuclear Overhauser effect (NOE) restraints, and this requires that the idoxifene molecules switch rapidly between positions. The CaM molecule is predominantly in the form where the N and C-terminal domains are in close proximity, allowing for the idoxifene molecules to contact both domains simultaneously. Hence, the
complex illustrates how high-affinity binding occurs without the loss of extensive positional dynamics.
The binding of the antagonists N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (J-8) and trifluoperazine (TFP) to intact calcium-saturated bovine calmodulin (CaM) and also of J-8 to the C-terminal ...domain (tr2c) has been investigated. Using a combination of NMR methods, including NOESY data, mobility measurements, and chemical shift and line-shape analysis, we show that the primary interaction between J-8 and tr2c is between the naphthalene ring of the antagonist and the hydrophobic pocket of the protein, similar to the binding of the hydrophobic side-chain residues of calmodulin target peptides. Comparison of the mobility of the drug, the intensity and pattern of intermolecular NOESY cross-peaks, and chemical shift changes shows that there is no significant change in the binding mode in J-8. CaM compared to J-8.tr2c, with one molecule binding to each domain. In particular, we find that the mobility of the aliphatic amino "tail" of J-8 remains highly mobile in both systems. This contrasts with the notion that the tail may bridge between the two domains to give a "globular" form of CaM. We also show that TFP induces very similar shift changes to J-8 and that the stoichiometry of the major binding event in all three cases is one drug molecule per domain. It also appears that secondary binding sites for the drug molecules are present in all three systems.
Manufacture or repair revisited Whitehead, Brian; Kempner, Richard
Journal of intellectual property law & practice,
08/2011, Letnik:
6, Številka:
8
Journal Article
Recenzirano
The Court of Appeal for England and Wales has overturned Floyd J's judgment in Schütz v Werit. While it is still the case that there is no free-standing right to repair in patent law, the 'whole of ...the inventive concept' test (ie asking whether, when the part in question is removed, what is left embodies the whole of the inventive concept of the claim) is no longer applicable to patent infringement. Instead, the correct approach is simply to ask whether the defendant has made a product falling within the scope of the patent claims.
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