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Autonomous vehicles need to localize themselves within the environment in order to effectively perform most tasks. In situations where a Global Navigation Satellite System such as the Global Positioning System cannot be used for localization, other methods are required. One self-localization method is to use signals transmitted by beacons at known locations to determine the relative distance and bearing of the vehicle from the beacons. Estimation performance is influenced by the beacon&ndash, vehicle geometry and the investigation into the optimal placement of beacons is of interest to maximize the estimation performance. In this article, a new solution to the optimal beacon placement problem for self-localization of a vehicle on a two-dimensional plane using angle-of-arrival measurements is proposed. The inclusion of heading angle in the estimation problem differentiates this work from angle-of-arrival target localization, making the optimization problem more difficult to solve. First, an expression of the determinant of the Fisher information matrix for an arbitrary number of beacons is provided. Then, a procedure for analytically determining the optimal angular separations for the case of three beacons is presented. The use of three beacons is motivated by practical considerations. Numerical simulations are used to demonstrate the optimality of the proposed method.

The World Health Organization (WHO) has declared COVID-19 a pandemic. We review and reduce the clinical literature on diagnosis of COVID-19 through symptoms that might be remotely detected as of early May 2020. Vital signs associated with respiratory distress and fever, coughing,and visible infections have been reported. Fever screening by temperature monitoring is currently popular. However, improved noncontact detection is sought. Vital signs including heart rate and respiratory rate are affected by the condition. Cough, fatigue, and visible infections are also reported as common symptoms. There are non-contact methods for measuring vital signs remotely that have been shown to have acceptable accuracy, reliability, and practicality in some settings. Each has its pros and cons and may perform well in some challenges but be inadequate in others. Our review shows that visible spectrum and thermal spectrum cameras offer the best options for truly noncontact sensing of those studied to date, thermal cameras due to their potential to measure all likely symptoms on a single camera, especially temperature, and video cameras due to their availability, cost, adaptability, and compatibility. Substantial supply chain disruptions during the pandemic and the widespread nature of the problem means that cost-effectiveness and availability are important considerations. Refereed/Peer-reviewed

The article contains sections titled: 1. Introduction 2. Companies, Markets, and Products 3. Legal Requirements 3.1. General 3.2. Definitions 3.3. Requirements Relating to the Development of Drugs 3.4. Marketing Approval 3.5. Requirements for the Manufacture and Quality Control of Drugs 3.6. Requirements for the Placing of a Drug on the Market 3.7. Drug Liability 3.8. International Non-Proprietary Names (INN) 4. Drug Testing 4.1. Preclinical Testing 4.1.1. Introduction 4.1.2. Animal Experiments 4.1.3. Pharmacological Testing 4.1.4. Toxicological Testing 4.2. Clinical Trials 4.2.1. Phases of Clinical Drug Development 4.2.2. Methods for Proving Effectiveness 4.2.3. Adverse Drug Reactions 4.2.4. Good Clinical Practice 4.2.5. Clinical Application Dossier 4.3. Quality Control of Pharmaceutical Products 4.3.1. Manufacturing of Drug Substances - Test of Starting Materials 4.3.2. Control of Drug Substances: Impurities 4.3.3. Control of Drug Products: Impurities 4.3.4. Validation of Analytical Procedures 4.3.5. Process Validation and Qualification 4.3.6. Batch Release 4.3.7. Stability Testing 4.3.8. Documentation 4.3.9. Variations - Changes 4.3.10. Change Control 4.3.11. Compliance 4.3.12. Changes Requiring New Applications - Line Extension 4.3.13. Inspections 4.3.14. The Mutual Recognition Agreement (MRA) 4.3.15. Pharmaceutical Inspection Convention (PIC) 4.3.16. Pharmaceutical Inspection Cooperation Scheme (PIC/S) 4.3.17. Pharmacopeias 4.3.18. The EP Certificate of Suitability

Publisher Summary This chapter reviews convenient assay methods for retinoids against phorbol ester-induced effects in the skin. The chapter describes methods for measuring 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced edema, ornithine decarboxylase (ODC) activity, and DNA synthesis. Measurements of TPA-induced ear edema, ODC activity, and DNA synthesis provide convenient methods to assess the effects of retinoids on phorbol ester-mediated events in the skin. The antiinflammatory effects of retinoids in the TPA ear edema model may be due to their action as inhibitors of arachidonic acid metabolism, all-trans-Retinoic acid and 13-cis-retinoic acid are reported to act as inhibitors of snake venom phospholipase A 2 and to inhibit the release and metabolism of arachidonic acid in calcium ionophore-stimulated rat peritoneal macrophages. In TPAtreated mouse skin, phospholipase A 2 activity is elevated and would provide a source of free arachidonic acid for metabolism into prostaglandin E 2 (PGE 2 )and 15-hydroxyeicosatetraenoic acids (HETE).

Pituitary sensitivity to a gonadotropin-releasing hormone (GnRH) challenge test before, during, and after GnRH antagonist administration was compared in four ovariectomized female monkeys receiving GnRH antagonist intramuscularly (IM) at increasing doses of 0.3, 1.0, and 3.0 mg/kg/day over 9 days. Three days before and 3 days after treatment, monkeys received vehicle alone. On experiment days 4, 7, 10, 13, and 16, 100 micrograms of GnRH was administered intravenously (IV) and blood drawn at 0 and 30 minutes. Before treatment, tonic follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were 248 +/- 105 and 178 +/- 31 ng/ml, respectively; after 0.3 mg/kg/day of GnRH antagonist, FSH and LH decreased to 30 +/- 6 and 41 +/- 4 ng/ml, respectively. After treatment with either 1 mg/kg/day or 3 mg/kg/day of GnRH antagonist, both gonadotropins were undetectable in serum. Monkeys with lower initial levels of gonadotropins were suppressed by 48 hours after GnRH antagonist, while those with higher tonic gonadotropins were suppressed 6 days later (FSH: r = 0.992; LH: r = 0.833). The data show that initial physiologic status is predictive of the rapidity of the suppression response induced by a GnRH antagonist and that, after achieving pituitary suppression, responsivity to an IV GnRH challenge test may be restored before normal tonic FSH/LH secretion is regained.

Suprofen is a potent, peripherally-acting, non-narcotic analgesic agent. The mechanism of action of the compound involves inhibition of prostaglandin biosynthesis and, perhaps, direct antagonism of the peripheral, pain inducing actions of prostaglandins, bradykinin and other pain mediators. Suprofen at a dose of 200 mg appears to be equal or greater in efficacy as an analgesic modality than those of ibuprofen, propoxyphene, naproxen and diflunisal or a combination of 650 mg aspirin plus 60 mg codeine. Its clinical utility has been amply demonstrated in the treatment of a number of types of pain including general and orthopedic surgery, episiotomy, post-partum pain, dysmenorrhea, dental pain and musculoskeletal disorders. Suprofen represents a new class of orally effective nonnarcotic analgesics with potential for effective clinical use in the treatment of pain.

Two different progesterone binding macromolecules have been identified in the cytosol fraction of rat and rabbit uteri. One is apparently the binder earlier reported by Milgrom and Baulieu. It is not specific in its binding. The second macromolecule is apparently that which has been reported by McGuire and DeDella and Milgrom et al. It apparently binds only to progestogens and has been termed a progestogen receptor. These two binders can be separated on the basis of binding specificity and by ammonium sulfate fractionation. Kinetic studies indicate the presence of two binders. Attempts to characterize the progestogen specific binder demonstrate that the binder is a protein with a molecular weight of about 85,000. Tissue specificity studies indicate that this binder exists in the cytosol fraction of uterus and vagina but not in the cytosol fraction of spleen, stomach, liver, kidney, intestine, leg muscle, or arm muscle. No evidence was found for its presence in blood. Optimal progesterone binding occurs be...

A preliminary isolation of an estrogen specific binding macromolecule from the human uterus is described. Tritiated-estradiol-17beta was incubated with uterine cytosol fractions (273,000 g supernatant) and various nonradioactive steroids. Sucrose gradient centrifugation was employed in isolating the human estrogen, and bound steroids were separated from the unbound by dextran-coated charcoal. Only nonlabeled estrogens depressed the quantity of bound estradiol. Ethynyl estradiol, estriol, and estradiol-17beta competitively inhibited tritiated-estradiol binding, whereas, cholesterol, cortisol, testosterone, progesterone, and norethindrone did not. Sucrose density gradient ultracentrifugation also revealed binding of estradiol to uterine cytosol. It is concluded that these data sugges t the presence of an estrogen-binding macromolecule in the human uterus similar to that in lower mammals making various hormone receptor studies applicable to both man and mammals.

1. 1. Gas-liquid chromatographic analyses of Blaberus discoidalis fat bodies and diets indicate that fatty acids are biosynthesized by the insects, their occurrence being independent of diet. 2. 2. Palmitate and oleate are the predominant fat body fatty acids, with the palmitoleate, stearate, and linoleate being less abundant. This pattern holds even in insects reared on fat-free diet. 3. 3. Unusual lipid constituents in the diet may be incorporated directly into fat body fatty acids.

In order to gain insight into the chemical interaction between steroid and macromolecule a study was undertaken to define some of the steric requirements for steroid binding to the rabbit uterine progestogen receptor. 45 steroidal compounds derivatives of both progesterone and testosterone were investigated. Introduction of a hydroxyl group in the 17-alpha 16-alpha 6-alpha 11-alpha or 14-alpha position precipitously reduced the affinity of progesterone for the macromolecule whereas introduction in the 11-beta position had no effect. If the polarity of the hydroxyl groups were altered by acylation binding affinity was not depressed. When an alkyl group was added at carbon-6 alpha or carbon-16 alpha binding affinity increased whereas a beta-alkyl group at carbon-16 prevented binding. Although the carbon-3 keton was not required for binding affinity introduction of a bulky thioketal group at carbon-3 completely prevented binding. Reduction of the delta 45 double bond of progesterone to yield a compound with A/B trans juncture had no effect on binding affinity but the isomer with a nonplanar A/B cis juncture possessed lower binding affinity. Removal of carbon-19 from progesterone resulted in a slightly greater binding affinity for the uterine macromolecule. The 2 modifications of testosterone which most dramatically increased binding affinity were removal of the carbon-10 methyl group and introduction of an alkyl group in the 17-alpha position. In the latter case binding affinity increased as the electron-donating power of the group was increased. The d-isomer of norgestrel binds whereas the 1-isomer does not bind to the uterine progestogen receptor.

SummaryThe para-hydroxy metabolites of 2-methyl-3-ethyl-4-phenyl-Δ4-cyclohexene carboxylic acid and known estrogens all depressed uptake of 3H-estradiol-17β into uterus but not intestine. In contrast no evidence for competition was seen with ORF 3858 and nonestrogenic compounds. Little incorporation of ORF 3858-3H was seen in target tissues, and neither estradiol-17β nor ORF 3858 competed for label uptake. Sucrose gradient centrifugation of uterine soluble fractions incubated with 3H-estradiol-17β produced a peak of radioactivity believed to be the estrogen receptor complex. Neither cholesterol nor ORF 3858 depressed this peak; in contrast, incubation with estradiol-17β or the para-hydroxy metabolites of ORF 3858 did depress the peak. Incubation of uterine soluble fractions with ORF 38S8-3H did not result in any peak of activity which could be correlated with the estrogen receptor peak. These data indicate that ORF 3858 is not estrogenic at the target tissue level, but that the para-hydroxylated metabolit...

TREATMENT of pubertal female rats with androgen or oestrogen produces sterility and reduces sexual receptivity in a high percentage of the animals. These hormones seem to alter the normal function of the preoptic—anterior hypothalamic region1–3, which—apparently undifferentiated at birth—is involved in: (1) producing the cyclic ovulatory surge of gonadotropin resulting in ovulation2, and (2) regulating mating behaviour in the female rat4. When allowed to differentiate normally, it regulates the cyclic release of gonadotropin, which is necessary for the normal pattern of sexual behaviour in the female rat. Early treatment with oestrogen or androgen causes the preoptic area to become refractory to both intrinsic and extrinsic activation by stimuli which would usually result in ovulation5.

Tissue incubation of rat uteri and samples of intestine with 3 H-progesterone re- sulted in preferential uptake of label by uteri. Concomitant incubation with nonlabeled pro- gestogens but not other compounds depressed uptake of 3 H-progesterone in uterus but not in- testine. When labeled hormone and potential competitors were added directly to the 273,000 g supernatant fraction of rabbit uteri, binding of 3 H-progesterone and competition by unlabeled progestogens appears to be identical with that which was observed for the uterus in the tissue incubation experiments. The 273,000 g super- natant fraction contains a progesterone binding component which sediments at a rate consistent with 4s proteins. Since 1) both 3 H-progesterone and 3 H-norethindrone were found in the same region of the sucrose density gradient and 2) binding of 3 H-progesterone to this component is competitively antagonized by known progesto- gens only, we consider it to have the properties of a progestogen receptor. (Endocrinology 88: 1099, 1971)