Indoor Localization Using Uncooperative Wi-Fi Access Points.

Indoor localization using fine time measurement (FTM) round-trip time (RTT) with respect to cooperating Wi-Fi access points (APs) has been shown to work well and provide 1-2 m accuracy in both 2D and 3D applications. This approach depends on APs implementing the IEEE 802.11-2016 (also known as IEEE 802.11mc) Wi-Fi standard ("two-sided" RTT). Unfortunately, the penetration of this Wi-Fi protocol has been slower than anticipated, perhaps because APs tend not to be upgraded as often as other kinds of electronics, in particular in large institutions-where they would be most useful. Recently, Google released Android 12, which also supports an alternative "one-sided" RTT method that will work with legacy APs as well. This method cannot subtract out the "turn-around" time of the signal, and so, produces distance estimates that have much larger offsets than those seen with two-sided RTT-and the results are somewhat less accurate. At the same time, this method makes possible distance measurements for many APs that previously could not be used. This increased accessibility can compensate for the decreased accuracy of individual measurements. We demonstrate here indoor localization using one-sided RTT with respect to legacy APs that do not support IEEE 802.11-2016. The accuracy achieved is 3-4 m in cluttered environments with few line-of-sight readings (and using only 20 MHz bandwidths). This is not as good as for two-sided RTT, where 1-2 m accuracy has been achieved (using 80 MHz bandwidths), but adequate for many applications A wider Wi-Fi channel bandwidth would increase the accuracy further. As before, Bayesian grid update is the preferred method for determining position and positional accuracy, but the observation model now is different from that for two-sided RTT. As with two-sided RTT, the probability of an RTT measurement below the true distance is very low, but, in the other direction, the range of measurements for a given distance can be much wider (up to well over twice the actual distance). We describe methods for formulating useful observation models. As with two-sided RTT, the offset or bias in distance measurements has to be subtracted from the reported measurements. One difference is that here, the offsets are large (typically in the 2400-2700 m range) because of the "turn-around time" of roughly 16 µs (i.e., about two orders of magnitude larger than the time of flight one is attempting to measure). We describe methods for estimating these offsets and for minimizing the effort required to do so when setting up an installation with many APs.

Observation Model for Indoor Positioning.

The IEEE 802.11mc WiFi standard provides a protocol for a cellphone to measure its distance from WiFi access points (APs). The position of the cellphone can then be estimated from the reported distances using known positions of the APs. There are several "multilateration" methods that work in relatively open environments. The problem is harder in a typical residence where signals pass through walls and floors. There, Bayesian cell update has shown particular promise. The Bayesian grid update method requires an "observation model" which gives the conditional probability of observing a reported distance given a known actual distance. The parameters of an observation model may be fitted using scattergrams of reported distances versus actual distance. We show here that the problem of fitting an observation model can be reduced from two dimensions to one. We further show that, perhaps surprisingly, a "double exponential" observation model fits real data well. Generating the test data involves knowing not only the positions of the APs but also that of the cellphone. Manual determination of positions can limit the scale of test data collection. We show here that "boot strapping," using results of a Bayesian grid update method as a proxy for the actual position, can provide an accurate observation model, and a good observation model can nearly double the accuracy of indoor positioning. Finally, indoors, reported distance measurements are biased to be mostly longer than the actual distances. An attempt is made here to detect this bias and compensate for it.

Doubling the Accuracy of Indoor Positioning: Frequency Diversity.

Determination of indoor position based on fine time measurement (FTM) of the round trip time (RTT) of a signal between an initiator (smartphone) and a responder (Wi-Fi access point) enables a number of applications. However, the accuracy currently attainable-standard deviations of 1-2 m in distance measurement under favorable circumstances-limits the range of possible applications. An emergency worker, for example, may not be able to unequivocally determine on which floor someone in need of help is in a multi-story building. The error in position depends on several factors, including the bandwidth of the RF signal, delay of the signal due to the high relative permittivity of construction materials, and the geometry-dependent "noise gain" of position determination. Errors in distance measurements have unusal properties that are exposed here. Improvements in accuracy depend on understanding all of these error sources. This paper introduces "frequency diversity," a method for doubling the accuracy of indoor position determination using weighted averages of measurements with uncorrelated errors obtained in different channels. The properties of this method are verified experimentally with a range of responders. Finally, different ways of using the distance measurements to determine indoor position are discussed and the Bayesian grid update method shown to be more useful than others, given the non-Gaussian nature of the measurement errors.

Joint positive control testing in guinea pig skin sensitization tests. A harmonized approach.

A scheme for the performance of positive control studies within a coordinated group of laboratories was proposed (joint positive control testing). The procedure has been described, as well as the first results of the validation phase of this joint positive control testing project. Adoption of this proposal within the participating six laboratories would lead to a reduction in the number of guinea pigs required for reliability and sensitivity checks from current approximate 12 studies per year down to 2 studies, i.e., 150-300 fewer animals per year. Another benefit would be the use of a harmonized, and therefore more comparable, method to perform guinea pig tests and interpret the data. In the validation phase of joint reading of the positive control studies, the congruency of reading could clearly be demonstrated. From the experience gained up to now, it was possible to draw the conclusion that a coordinated interlaboratory approach for positive control testing was fully acceptable and an improvement with regard to animal welfare.

Skin sensitisation testing--new perspectives and recommendations.

Various methodological aspects of skin sensitisation testing have been explored, particularly in the context of animal welfare considerations and reliability and sensitivity of test methods. Recommendations are made for the conduct of current and proposed OECD skin sensitisation tests with respect to appropriate test configurations for the purposes of hazard identification and labelling, and the requirement for positive controls. Specifically, the following aspects of guinea pig sensitisation test methods have been addressed: (1) the number of test and control animals required; (2) the option of using joint positive controls between independent laboratories; (3) the choice of positive control chemicals; (4) the optimal conduct and interpretation of rechallenge; and (5) the requirement for pretreatment with sodium lauryl sulfate. In addition, the use of the murine local lymph node assay (LLNA) has been considered. A number of conclusions have been drawn and recommendations made as follows: In many instances, particularly with the conduct of the guinea pig maximisation test, it is acceptable to halve the number of test and control animals used. An optional scheme for the conduct of joint positive control studies within a co-ordinated group of laboratories is appropriate. Only one positive control chemical (alpha-hexyl cinnamic aldehyde) is necessary for the routine assessment of assay sensitivity. The proper conduct and interpretation of rechallenge can provide valuable information and confirmation of results in guinea pig sensitisation tests. Sodium lauryl sulfate should no longer be used as a pretreatment in the guinea pig maximisation test. The LLNA is a viable and complete alternative to traditional guinea pig test methods for the purposes of skin sensitisation hazard identification. These recommendations provide the opportunity for both animal welfare benefits and improved hazard identification.

Skin sensitization testing in potency and risk assessment.

The purpose of this article is to review, and make recommendations for, the use of relevant skin sensitization test methods, for the purposes of determination of relative potency and the threshold dose necessary for the induction of skin sensitization, and for risk assessment. In addressing the first area, the utility of three guinea pig tests (the guinea pig maximization test, the occluded patch test, and the open epicutaneous test) of the local lymph node assay (LLNA) and of human volunteer testing for the assessment of relative potency and identification of thresholds for sensitization were considered. The following conclusions were drawn. (1) Although attempts have been made to modify the guinea pig maximization test for the purposes of deriving dose-response relationships, this method is usually unsuitable for determination of relative sensitizing potency. (2) Guinea pig methods that do not require the use of adjuvant and which employ a relevant route of exposure (the occluded patch test and the open epicutaneous test) are more appropriate for the assessment of relative skin-sensitizing potency. (3) The LLNA is suitable for the determination of relative skin sensitizing potency, and the adaptation of this method for derivation of comparative criteria such as EC3 values (the estimated concentration of test chemical required to induce a stimulation index of 3 in the LLNA) provides an effective and quantitative basis for such measurements. (4) For all the methods identified above, potency is assessed relative to other chemical allergens of known skin sensitizing potential. The estimation of likely threshold concentrations is dependent upon the availability of suitable benchmark chemicals of known potency for human sensitization. (5) Human testing (and specifically, the Human Repeat Insult Patch Test) can provide information of value in confirming the absence of skin sensitizing activity of formulations and products under specific conditions of use and exposure. Based on the above, the following recommendations are made. (1) If results are already available from suitable guinea pig tests, then judicious interpretation of the data may provide information of value in assessing relative skin sensitizing potency. This option should be explored before other analyses are conducted. (2) The LLNA is the recommended method for new assessments of relative potency, and/or for the investigation of the influence of vehicle or formulation on skin sensitizing potency. (3) Whenever available, human skin sensitization data should be incorporated into an assessment of relative potency. With respect to risk assessment, the conclusion drawn is that all the available data on skin-sensitizing activity in animals and man should be integrated into the risk-assessment process. Appropriate interpretation of existing data from suitable guinea pig studies can provide valuable information with respect to potency, as the first step in the development of a risk assessment. However, for de novo investigations, the LLNA is the method favored for providing quantitative estimations of skin-sensitizing potency that are best suited to the risk assessment process. Finally, human testing is of value in the risk assessment process, but is performed only for the purposes of confirming product safety.

Experimental studies on acute and chronic action of azelastine on nasal mucosa in guinea pigs, rats and dogs.

Azelastine (CAS 37932-96-0) nasal spray (Allergodil, Rhinolast, Astelin) was investigated in acute experiments in guinea pigs and after a 26-week local application period with daily repeated administration for effects on ciliary beat activity (acute experiments) and morphology of nasal mucosa. The commercially available spray did not inhibit ciliary beat activity in guinea pigs nor did it cause any inflammatory or atrophic changes after 26-week daily local application on nasal mucosa in rats and dogs.

[Effect of long-chain polyunsaturated fatty acids on arachidonate and docosahexaeonic acid in healthy infants in the first four months of life]. / Hosszú szénláncú, többszörösen telítetlen zsírsavak hatása egészséges csecsemók arachidonsav-és dokozahexénsav-ellátottságára 92 eletelsonegy honapjaban.

Fatty acid compositions of plasma phospholipids (PL), triglycerides (TG) and sterol esters (STE) were measured by high resolution capillary gas-liquid chromatography in formula fed healthy infants at the ages of 5 days and 1, 2, 3 and 4 months. The infants were randomly assigned to receive either conventional infant formula (F, n = 10) without long-chain polyunsaturates (LCP) or the same formula supplemented with LCP (LCP-F, n = 12) in amounts and ratios similar to those characteristic to human milk. From the age of 1 month onwards, percentage contributions of the principal omega-6 LCP, arachidonic acid were significantly higher in plasma lipids of infants fed LCP-F than in those receiving conventional formula without dietary LCP. Values of the principal omega-3 LCP, docosahexaenoic acid were also significantly lower in the infants fed conventional formula than in those receiving LCP-F throughout the study. The data obtained indicate that from the formula supplemented with LCP both arachidonic and docosahexaenoic acids were effectively absorbed and incorporated into infantile plasma lipids. Recent data of the literature suggest that supplementation of infant formula with LCP may beneficially influence visual and psychomotor development also in healthy, term infants.

[Long-chain polyunsaturated fatty acids in breast-fed and formula fed healthy infants]. / Szoptatott és tápszerrel táplált egészséges csecsemök ellátottsága hosszú szénláncú, többszörösen telítetlen zsírsavakkal.

While human milk contains considerable amounts of long-chain polyunsaturated fatty acids (LCP), most formulae contain only the precursors of LCP synthesis (linoleic and alpha-linolenic acids) but are devoid of preformed dietary LCP such as are arachidonic and docosahexaenoic acids. LCP contents in plasma phospholipids (PL), triglycerides (TG) and sterol esters (STE) were measured by high resolution capillary gas-liquid chromatography in healthy, term infants fed human milk of formula. Percentage contributions of the precursor fatty acids were similar or higher in plasma lipids in formula fed than in breast-fed infants, meanwhile values of the intermediary metabolites of LCP synthesis did not differ between the two groups. Percentage contributions of arachidonic acid were higher in breast-fed than in formula fed infants at the ages of 2 weeks (PL: 9.39 +/- 1.00 vs. 6.91 +/- 0.38, TG: 0.61 +/- 0.03 vs. 0.41 +/- 0.05, %weight/weight, mean +/- SEM), 1 month (PL: 9.06 +/- 1.04 vs. 6.16 +/- 0.35, TG: 0.62 +/- 0.10 vs. 0.32 +/- 0.04, STE: 4.50 +/- 0.45 vs. 2.84 +/- 0.39) and 2 months (PL: 8.41 +/- 1.19 vs. 5.74 +/- 0.37). Similarly, docosahexaenoic acid values were at the ages of 1 month (PL: 1.94 +/- 0.21 vs. 1.19 +/- 0.21, TG: 0.12 +/- 0.03 vs. 0.04 +/- 0.02) and 2 months (PL: 2.02 +/- 0.36 vs. 0.99 +/- 0.07) significantly higher in breast-fed infants than in those receiving formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity of cysteine S-conjugates: structure-activity relationships.

The cytotoxicity of cysteine S-conjugates was investigated in freshly isolated rat renal proximal tubule cells. The study was designed to determine the contribution of the thiols and of the acylating intermediates formed by cysteine conjugate beta-lyase to the initiation of cytotoxicity. Cell viability was determined by trypan blue exclusion and by lactate dehydrogenase leakage. The S-conjugates S-(1,2,2-trichlorovinyl)-L-cysteine, S-(1,2,3,3,3-pentachloro-prop-1-enyl)-L-cysteine and S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine, at a concentration of 0.2 mM, reduced cell viability compared to controls from 85% to less than 50% after 3 h. The alpha-chlorinated enethiols formed from these S-conjugates are transformed to acylating intermediates. The S-conjugate S-(2-chlorovinyl)-L-cysteine forms an enethiol, which cannot transform to an acylating intermediate and did not reduce cell viability at 0.2 mM; at 1 mM, it resulted in a very slight reduction of cell viability after 3 h. S-(pentachlorophenyl)-L-cysteine and S-benzyl-L-cysteine, which form stable thiols after metabolism by beta-lyase, were not cytotoxic at a concentration of 1 mM. The direct acting S-(2-chloroethyl)-L-cysteine (0.2 mM) reduced cell viability after 3 h from 85% to 90% (control) to 40%. The results obtained suggest that reactions of the initial thiol-metabolites with biological macromolecules do not contribute to the induction of cytotoxicity by cysteine S-conjugates and indicate that acylating intermediates formed by cysteine conjugate R-lyase induce cytotoxic effects by non-selective acylation of cellular macromolecules.

Thioacylating intermediates as metabolites of S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2,2-trichlorovinyl)-L-cysteine formed by cysteine conjugate beta-lyase.

The bioactivation mechanism of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) was studied with cysteine conjugate beta-lyase (beta-lyase) from Salmonella typhimurium and with the pyridoxal phosphate model N-dodecylpyridoxal bromide (PL-Br) as catalysts and with GC/MS to identify the metabolites formed. PL-Br converted S-2-benzothiazolyl-L-cysteine to 2-mercaptobenzothiazole and S-benzyl-L-cysteine to benzyl mercaptan, demonstrating the ability of PL-Br to serve as a model for beta-lyase. PL-Br and bacterial beta-lyase converted DCVC to chloroacetic acid and chlorothionoacetic acid and TCVC to dichloroacetic acid. Incubations of PL-Br with the S-conjugates in the presence of diethylamine resulted in the formation of N,N-diethylchlorothioacetamide from DCVC and of N,N-diethyldichlorothioacetamide from TCVC. Attempts to trap the enethiols, which are the expected initial products formed by beta-elimination, by reaction with methyl iodide in incubations with the beta-lyase model were not successful. The formation of thioacylating agents from the enethiols may contribute to the cytotoxic and mutagenic effects of DCVC and TCVC.

Bacterial cysteine conjugate beta-lyase and the metabolism of cysteine S-conjugates: structural requirements for the cleavage of S-conjugates and the formation of reactive intermediates.

The cysteine conjugate beta-lyase mediated metabolism and the mutagenicity of the synthetic cysteine conjugates S-(2-chloroethyl)-L-cysteine (CEC), S-(2-chlorovinyl)-L-cysteine (CVC), S-(1,2,3,3,3-pentachloroprop-1-enyl)-L-cysteine (PCPC), S-(pentachlorophenyl)-L-cysteine (PCPhC), S-(chloro-1,2,2-trifluoroethyl)-L-cysteine (CTFEC), S-benzyl-L-cysteine (SBC) and S-methyl-L-cysteine (SMC) were investigated in Salmonella typhimurium strains TA100, TA2638, TA102 and TA98 to establish structure/activity relationships. Bacterial 100,000 X g supernatants cleaved CTFEC, PCPC, CVC, PCPhC and SBC to pyruvate; pyruvate formation was inhibited by the beta-lyase inhibitor aminooxyacetic acid (AOAA) in all cases. Of the compounds tested, CEC, PCPC and CVC were mutagenic in the Ames-test. CTFEC, PCPhC and SBC failed to increase the number of revertants above control levels. The mutagenicity of PCPC and CVC could be inhibited by AOAA. CEC exerted a potent mutagenic effect in the Ames-test which was not affected by AOAA; CEC was not transformed to pyruvate by bacterial beta-lyase. Neither pyruvate formation nor mutagenicity were observed with SMC. These results indicate that the structure of the substituent on the sulfur atom is an important determinant for the biological activity of cysteine S-conjugates. Electronegative and/or unsaturated substituents are required for beta-lyase catalysed beta-elimination reactions. The formation of chemically unstable thiols, which may be converted to thioacylating intermediates, seems to be a prerequisite for beta-lyase dependent mutagenicity of S-conjugates.

Thioacylating agents as ultimate intermediates in the beta-lyase catalysed metabolism of S-(pentachloro-butadienyl)-L-cysteine.

The transformation of the hexachloro-1,3-butadiene metabolite S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (PCBC) by bacterial cysteine conjugate beta-lyase (beta-lyase) and by N-dodecylpyridoxal bromide (PLP-Br) was investigated using GC/MS to identify products formed. PCBC was transformed by both bacterial beta-lyase and PLP-Br to the major products 2,3,4,4-tetrachlorobutenoic acid and 2,3,4,4-tetrachlorothiobutenoic acid, and to the minor metabolites trichloroacetic acid and S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-mercaptoacetic acid. In the presence of diethylamine as model nucleophile, PLP-Br transformed PCBC to yield 2,3,4,4-tetrachlorothiobutenoic acid diethylamide; attempts to trap 1,2,3,4,4-pentachlorobutadienyl thiol, the initial metabolite formed by beta-elimination from PCBC, were unsuccessful. The results obtained suggest that the formation of a thioacylating intermediate (a thioketene or a thiono acyl chloride) may be the decisive reaction during the beta-lyase dependent activation of PCBC.

Enzymatic transformation of mercapturic acids derived from halogenated alkenes to reactive and mutagenic intermediates.

The metabolism of the mercapturic acids S-pentachlorobutadienyl-N-acetylcysteine (N-Ac-PCBC), S-trichlorovinyl-N-acetylcysteine (N-Ac-TCVC) and S-dichlorovinyl-N-acetylcysteine (N-Ac-DCVC) by subcellular fractions from male rat liver and kidney homogenates was studied. As a model compound, N-Ac-PCBC, 14C labelled, was synthesised. It was intensively metabolised by cytosolic but not by microsomal enzymes from rat liver and kidney. The major metabolite identified by GC/MS was pentachlorobutadienylcysteine, the amount produced being highest in kidney cytosol. Metabolic conversion of 14C-N-Ac-PCBC by kidney and liver cytosol resulted in covalent binding of radioactivity to protein, binding was strongly inhibited by the beta-lyase inhibitor aminooxyacetic acid (AOAA). N-Ac-TCVC and N-Ac-DCVC were also transformed by cytosolic enzymes to the corresponding cysteine conjugates (trichlorovinylcysteine and dichlorovinylcysteine). The three mercapturic acids tested were strong mutagens in the Ames-test after addition of rat kidney cytosol. In the absence of cytosol, N-Ac-TCVC and N-Ac-DCVC were weakly but definitely mutagenic, whereas N-Ac-PCBC was not. In contrast to N-Ac-PCBC, the "direct" mutagens N-Ac-TCVC and N-Ac-DCVC were both transformed to pyruvate by bacterial (S. typhimurium TA100) homogenate 100,000 g supernatants. It is concluded that mercapturic acids are deacetylated to the corresponding cysteine conjugates by cytosolic (N-Ac-PCBC, N-Ac-TCVC and N-Ac-DCVC) and bacterial enzymes (N-Ac-TCVC and N-Ac-DCVC) and further cleaved to reactive and mutagenic intermediates by mammalian and/or bacterial beta-lyase. The observed activation mechanisms for the mercapturic acids, whose formation from hexachlorobutadiene, tetrachloroethylene and trichloroethylene has been proven, might contribute to the nephrotoxicity and nephrocarcinogenicity of the parent alkenes.

Frequency- and polarization-selective Schottky detectors in the visible and near ultraviolet.

The influence of dielectric coatings on the photoresponsivity of metal-insulator-semiconductor structures on holographic submicrometer sinusoidal grating structures is investigated. Narrow-band photodetectors are realized based on the excitation of transverse electric modes and surface plasmon polaritons in the vacuum-MgF(2)-Al or vacuum-SiO(2)-A1 layer system on Si substrates. These detectors are sensitive to either s- or p-polarized light. Quantum efficiencies up to 20% and a linewidth of 18 mm were achieved with transverse electric modes at a wavelength lambda = 325 nm. The resonances are tunable from the ultraviolet into the visible regime by variation of the dielectric film thickness.

Bacterial beta-lyase mediated cleavage and mutagenicity of cysteine conjugates derived from the nephrocarcinogenic alkenes trichloroethylene, tetrachloroethylene and hexachlorobutadiene.

The metabolism of beta-lyase and the mutagenicity of the synthetic cysteine conjugates S-1,2-dichlorovinylcysteine (DCVC), S-1,2,2-trichlorovinylcysteine (TCVC), S-1,2,3,4,4-pentachlorobuta-1,3-dienylcysteine (PCBC) and S-3-chloropropenylcysteine (CPC) were investigated in Salmonella typhimurium strains TA100, TA2638 and TA98. The bacteria contained significantly higher concentrations of beta-lyase than mammalian subcellular fractions. Bacterial 100,000 X g supernatants cleaved benzthiazolylcysteine to equimolar amounts of mercaptobenzthiazole and pyruvate. DCVC, TCVC and PCBC produced a linear time-dependent increase in pyruvate formation when incubated with bacterial 100,000 X g supernatants; pyruvate formation was inhibited by the beta-lyase inhibitor aminooxyacetic acid (AOAA). CPC was not cleaved by bacterial enzymes to pyruvate. DCVC, TCVC and PCBC were mutagenic in three strains of S. typhimurium (TA100, TA2638 and TA98) in the Ames-test without addition of mammalian subcellular fractions; their mutagenicity was decreased by the addition of AOAA to the preincubation mixture. CPC was not mutagenic in any of the strains of bacteria tested. These results indicate that beta-lyase plays a key role in the metabolism and mutagenicity of haloalkenylcysteines when tested in S. typhimurium systems. The demonstrated formation in mammals of the mutagens DCVC, TCVC and PCBC during biotransformation of trichloroethylene (Tri), tetrachloroethylene (Tetra) and hexachlorobutadiene (HCBD) may provide a molecular explanation for the nephrocarcinogenicity of these compounds.