Antiovulatory antagonists of LHRH related to antide

We report 104 analogues of the potent antiovulatory antagonist of LHRH, N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Nic)-D-Lys(Nic)-Leu-Ilys-Pro-D-Ala- NH2, Antide. We replaced the Nic group in Antide with other acyl substituents to modulate size, hydrophilicity or basicity of the molecule, we also replaced the Lys residues with shorter basic amino acids, and made cyclic 5/6 analogues as well as position 5 or 6 dimers. We substituted Ilys8 with other alkyl groups and acyl derivatives. When injected in 0.1% DMSO in water in a typical antiovulatory (AO) assay. Antide gives six rats ovulating out of eight (6/8) at 2 micrograms, 4/8 at 4 micrograms, and in the histamine release assay (HRA). ED50 is > 300 micrograms/ml; [Lys(N-Isobutyl)8]Antide gave 2/8 at 2 micrograms/rat; [Lys (8-Qis)5]Antide gave 1/8 at 1 microgram, and 0/8 at 2 micrograms, and in the HRA ED50. 22 micrograms/ml; [D-Lys(8-Qis)5]Antide gave 4/8 at 1 microgram and 0/8 at 2 micrograms, and in the HRA, ED50 was 27 micrograms/ml; [Lys(8-Qic)8] gave 5/8 at 1 microgram 1/8 at 2 micrograms/ [Lys(2-Pyc)6]Antide gave 3/8 at 1 microgram, and 0/8 at 2 micrograms, and in the HRA ED50 was 116 micrograms/ml; [D-Lys (2-Pyc)5]Antide gave 5/8 at 1 microgram and in the HRA, ED50 was 100- > 300 micrograms/ml; [Lys(2-Pyc)5.D-Lys(2-Pyc)6]Antide gave 2/8 at 1 microgram. The substitutions of the Nic groups of Antide at Lys5 or D-Lys6 with 8-Qis or with 2-Pyc groups seem to give highly potent antiovulatory antagonists of LHRH and constitute significant new leads to generate potent antiovulatory compounds endowed with moderate or low histamine release.     

Formulation optimization of a drug in adhesive transdermal analgesic patch

Abstract

Context: Conventional pain management approaches have limitations such as gastrointestinal side effects, frequent dosing, and difficulties in swallowing medications. Hence, to overcome these limitations, we developed a transdermal analgesic patch.

Objective: This study was designed to formulate a drug in adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may potentially treat moderate pain in children.

Materials and methods: Three analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide crystallization study using polarized light microscope and their permeation profiles were studied using vertical Franz diffusion cells across porcine ear skin, dermatomed human skin and epidermis for 24?h, and the samples were quantified by high performance liquid chromatography. Patches used for permeation studies were prepared by dissolving sub-saturation concentration of the drug(s) in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting knife.

Results and discussion: Among the three drugs screened, CDB demonstrated the best permeation profile (660.21?µg/cm²), and shortest lag time (4.35?±?0.01?h), and hence was chosen for patch studies. The highest concentration of CDB in the patch at which drug does not crystallize was determined as 40% of its saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB standalone patch delivered 105.48?µg/cm² of CDB, while the CDB–APAP combination patch with 5% w/w OA delivered 151.40?µg/cm² CDB and 58.12?µg/cm² APAP in 24?h.

Conclusion: Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.     

Leather-Based Multi-Stimuli Responsive Chromisms

Leather is made from the skin of animals and possesses special micro- and nanostructures. Due to the high breathability, durability, strength, elasticity, and softness, leather is widely used in daily life, and is an ideal substrate for future multi-functional wearable smart devices. Herein, two leather-based multi-stimuli responsive chromic devices denoted as UV/thermo/electro chromic device and UV sensor are developed. The UV/thermo/electro chromic device demonstrates instantaneous and reversible chromic responses to applied UV radiation, heat, and electrical voltage with different color changing styles. The pattern design with the assistance of 3D printed molds and the broad selection of dyes/pigments endow the device with high design flexibility and wide applicability. The leather-based UV sensor exhibits a change in color gradient when exposed to UV radiation with different intensities. For more versatile color options, inactive pigments/dyes can be mixed with stimuli-responsive ones in this system. Coating the leather surface with a polyacrylic finishing agent is also conducted, which is a practical and effective method to protect the pigments and/or dyes in the leather, and improves the usability/durability of the devices. This study opens a new avenue to design and develop wearable devices and individual customization/anti-counterfeiting of leather products.     

Web video classification with visual and contextual semantics

On the social Web, the amount of video content either originated from wireless devices or previously received from media servers has increased enormously in the recent years. The astounding growth of Web videos has stimulated researchers to propose new strategies to organize them into their respective categories. Because of complex ontology and large variation in content and quality of Web videos, it is difficult to get sufficient, precisely labeled training data, which causes hindrance in automatic video classification. In this paper, we propose a novel content‐ and context‐based Web video classification framework by rendering external support through category discriminative terms (CDTs) and semantic relatedness measure (SRM). Mainly, a three‐step framework is proposed. Firstly, content‐based video classification is proposed, where twofold use of high‐level concept detectors is leveraged to classify Web videos. Initially, category classifiers induced from VIREO‐374 detectors are trained to classify Web videos, and then concept detectors with high confidence for each video are mapped to CDT through SRM‐assisted semantic content fusion function to further boost the category classifiers, which intuitively provide a more robust measure for Web video classification. Secondly, a context‐based video classification is proposed, where twofold use of contextual information is also harnessed. Initially, cosine similarity and then semantic similarity are measured between text features of each video and CDT through vector space model (VSM)‐ and SRM‐assisted semantic context fusion function, respectively. Finally, classification results from content and context are fused to compensate for the shortcomings of each other, which enhance the video classification performance. Experiments on large‐scale video dataset validate the effectiveness of the proposed solution.     

Performance comparison of M-QAM and DQPSK modulation schemes in a 2 × 20 Gbit/s–40 GHz hybrid MDM–OFDM-based radio over FSO transmission system

Photonic Network Communications - This work is focused on the modeling and performance investigation of a 2?×?20 Gbit/s–40 GHz hybrid mode division...     

Numerical investigation of combustion characteristics in an oxygen transport reactor

The paper presents a numerical investigation of thermal characteristics of oxyfuel combustion in an oxygen transport reactor (OTR). The reactor is made of a combustion chamber of tubular shape and surrounded by an annular air flow compartment. The walls of the combustion chamber are made of dense, nonporous, mixed‐conducting ceramic membranes that only allow oxygen permeation from the annular air compartment into the combustion chamber. A mixture of CO₂ and CH₄ (sweep gas) enters the reactor from one side and mixes with the oxygen permeating through the ion transport membrane. The resulting combustion products (composed of H₂O and CO₂) are discharged from the other side of the reactor. The modeling of the flow process is based on a numerical solution of the conservation equations of mass, momentum, energy and species in the axi‐symmetric flow domain. The membrane is modeled as a selective layer in which the oxygen permeation depends on the prevailing temperatures as well as the oxygen partial pressure at both sides of the membrane. The comparison between reactive and separation‐only OTR units showed that combining reaction and separation increases significantly O₂ permeation rate to about 2.5 times under the assumptions given herein. Uniform axial temperature of about 1250 K is achieved in most of the reactor length with high CH₄ conversion of 75% to 35% for CH₄/CO₂ mass ratio ranging from 0.5/0.5 to 1.0/0. Since the thermal resistance of these membranes is low, the heat of reaction is mostly transferred to the air side with a portion used to heat the O₂ permeating flux. Copyright © 2013 John Wiley & Sons, Ltd.     

RAPD profile variation amongst provenances of neem

Neem, described as a tree for solving global problems, is an evergreen, long-lived, multipurpose tree of the tropics with a wide distribution range in India. It is believed to be highly cross-pollinated. Inter-provenance variations have been reported in neem in case of morphological and physiological characters. Yet no reports about the genetic determinism for these variations are available to our knowledge. In order to have an idea about the extent and/or nature of genetic (DNA) variation in neem, the powerful RAPD technique has been employed. RAPD profiles of 34 accessions/provenances of neem were generated with 200 decamer random primers, of which the data from the 49 primers, that resulted in reproducible amplification products, were considered for analysis. Based on the presence/absence of bands, a similarity matrix was computed. Dendrogram was constructed by UPGMA method based on the pairwise similarities amongst the RAPD profiles. The similarities in RAPD profiles amongst the different DNAs was more than that expected due to the cross-pollinated nature of the tree and furthermore, these more-than-expected similarities were not due to random chance. These results suggest that neem may have a narrow genetic base.     

Intra-operative parathyroid hormone assay for simplified localization of parathyroid adenomas

Lack of success in parathyroid surgery is usually due to failure to identify the abnormal parathyroid gland correctly at operation. The surgeon may be helped by rapid parathyroid hormone (PTH) assay in peripheral blood after removal of a suspected adenoma, and by frozen section histology, but these are not true localization techniques. We have adapted a non-isotopic immunoassay for rapid measurement of PTH in samples from the upper, middle and lower thyroid veins taken at operation, before exploration begins. Fifteen patients with primary hyperparathyroidism were operated on. In 10 the parathyroid adenoma was located easily, and was associated with high local venous PTH levels. In four patients the abnormal parathyroid was not immediately apparent but the assay indicated its location, which was confirmed after further exploration. In one patient there was no difference in PTH levels in the six venous samples. An ectopic adenomatous gland was successfully identified behind the thymus. The operation was successful in all patients as shown by a fall in the plasma calcium to the normal range. We conclude that intra-operative selective venous sampling and rapid PTH assay facilitates operative localization of parathyroid adenomas.     

Performance investigation of a 3.84 Tb/s WDM-based FSO transmission system incorporating 3-D orthogonal modulation scheme

Photonic Network Communications - The present work discusses the development and simulative investigation of a high-capacity wavelength division multiplexed free space optics (FSO) transmission...