The rise and ruin of a medieval port town: A reconsideration of the development of Julfar

Arabian Archaeology and Epigraphy published by John Wiley & Sons Ltd Julfar was a major port town of the Persian Gulf during the fourteenth and fifteenth centuries AD. A possession of the Hormuzi empire, it was a lucrative source of taxes and pearls, and a port of trade for northern Oman, tapping into maritime trading networks connecting the Middle East with Africa, India, Southeast Asia and China. The site is found north of modern Ras Al-Khaimah, UAE. Julfar Al-Nudud was previously considered to be a late suburb of an urban core, Julfar Al-Mataf, and is located on a creek opposite the latter. However, excavations in 2010 indicated that Al-Nudud was part of the original urban core, which had grown up on either side of the creek. Moreover, re-examination of previous work in Al-Mataf, where a large mosque and fortification were excavated (by British and French teams), shows that the two areas followed different trajectories. Significant occupation in Al-Nudud and southern Al-Mataf (revealed by previous Japanese excavations) ended before the start of the sixteenth century, while use of the mosque and fort in central Al-Mataf continued into the seventeenth century, albeit discontinuously. A revised concordance of the phases derived from the work of various archaeological teams is therefore proposed

Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

BackgroundEvidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated.MethodsAnalyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White).ResultsOf 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54).ConclusionsOur findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers

Topical delivery of 3-O-ethyl L-ascorbic acid from complex solvent systems

3-O-ethyl l-ascorbic acid (EA), an ether derivative of Vitamin C, is widely used in skincare formulations. Previously, we reported the effects of neat solvents on EA percutaneous absorption and observed that 0.6–7.5% of the applied EA was delivered through the skin over 24 h. In this work, we designed complex formulations using combinations of solvents that may act synergistically and examined their impact on EA permeation in porcine skin in vitro under finite dose conditions. Binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML) were effective in enhancing skin permeation of EA compared with individual solvents (p 0.05). Addition of the volatile solvent isopropyl alcohol (IPA) to PG solutions also did not improve EA skin delivery compared with neat PG. Ternary solvent systems containing PG:PGML were subsequently prepared by the addition of a lipophilic solvent, either isopropyl myristate (IPM), medium-chain triglycerides (MCT) or isostearyl isostearate (ISIS). The optimum vehicle, PG:PGML:IPM, promoted up to 70.9% skin delivery of EA. The PG:PGML:ISIS vehicles also promoted EA permeation across the skin, but to a significantly lesser extent than the IPM-containing vehicles. No enhancement of EA delivery was noted for the PG:PGML:MCT mixtures. These results will inform the development of targeted formulations for EA in the future

The skinny on CCN2

The CCN family of matricellular proteins directly or indirectly affects development and differentiation. A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740–C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations

Integrating timescales with time-transfer functions: A practical approach for an INTIMATE database

© 2014 Elsevier Ltd.The purpose of the INTIMATE project is to integrate palaeo-climate information from terrestrial, ice and marine records so that the timing of environmental response to climate forcing can be compared in both space and time. One of the key difficulties in doing this is the range of different methods of dating that can be used across different disciplines. For this reason, one of the main outputs of INTIMATE has been to use an event-stratigraphic approach which enables researchers to co-register synchronous events (such as the deposition of tephra from major volcanic eruptions) in different archives (Blockley etal., 2012). However, this only partly solves the problem, because it gives information only at particular short intervals where such information is present. Between these points the ability to compare different records is necessarily less precise chronologically. What is needed therefore is a way to quantify the uncertainties in the correlations between different records, even if they are dated by different methods, and make maximum use of the information available that links different records. This paper outlines the design of a database that is intended to provide integration of timescales and associated environmental proxy information. The database allows for the fact that all timescales have their own limitations, which should be quantified in terms of the uncertainties quoted. It also makes use of the fact that each timescale has strengths in terms of describing the data directly associated with it. For this reason the approach taken allows users to look at data on any timescale that can in some way be related to the data of interest, rather than specifying a specific timescale or timescales which should always be used. The information going into the database is primarily: proxy information (principally from sediments and ice cores) against depth, age depth models against reference chronologies (typically IntCal or ice core), and time-transfer functions that relate different timescales to each other, through the use of event stratigraphies or global phenomena such as cosmogenic isotope production rate variations

3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin

L-ascorbic acid (AA), commonly known as vitamin C, has been widely used in topical formulations for many years as an antioxidant and anti-aging ingredient. However, the physicochemical properties of AA are not optimal for skin uptake and the molecule is also unstable, readily undergoing oxidation on exposure to air. The compound 3-o-ethyl-l-ascorbic acid (EA) has been developed as a stable vitamin C derivative and has been used in topical products. The aims of this work were to conduct a comprehensive characterisation of physicochemical properties of EA as well as to investigate the influence of various neat solvents on EA skin delivery. Nuclear magnetic resonance (NMR), mass spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterise the molecule. The pKa of the compound and the partition coefficient logP(o/w) were experimentally determined. A new HPLC method for analysis of the molecule was also developed and validated. A number of solvents for topical preparations were selected based on their wide use as excipients in topical formulations, their potential to act as skin penetration enhancers and their favourable safety profiles. The solubility and stability of EA was examined. Skin permeation of the molecule in full thickness porcine skin in vitro was investigated using Franz-type diffusion cells. The melting point, log P(o/w) value and pKa value of EA were determined to be 114.39 ± 0.5°C, -1.07 ± 0.03 and 7.72 ± 0.01 respectively. Skin penetration of EA was evident for the following vehicles 1,2 hexanediol (HEX), glycerol (GLY), propylene glycol (PG), 1,2 pentanediol (1-2P), isopropyl alcohol (IPA), propylene glycol monolaurate (PGML) and propylene glycol monocaprylate (PGMC). Skin uptake but no permeation through the skin was observed for Transcutol® (TC) and dipropylene glycol (DiPG), while no penetration was observed for the solvents 1,5 pentanediol (1-5P) and tripropylene glycol (TriPG). The findings of the permeation experiments confirm the potential of simple formulations to deliver EA to the skin. Studies are ongoing to identify complex vehicles for synergistic enhancement of EA skin penetration. To our knowledge this is the first study to conduct a comprehensive characterization of EA and examine its skin uptake and permeation properties in porcine skin

Information Dynamics in Living Systems: Prokaryotes, Eukaryotes, and Cancer

BACKGROUND: Living systems use information and energy to maintain stable entropy while far from thermodynamic equilibrium. The underlying first principles have not been established. FINDINGS: We propose that stable entropy in living systems, in the absence of thermodynamic equilibrium, requires an information extremum (maximum or minimum), which is invariant to first order perturbations. Proliferation and death represent key feedback mechanisms that promote stability even in a non-equilibrium state. A system moves to low or high information depending on its energy status, as the benefit of information in maintaining and increasing order is balanced against its energy cost. Prokaryotes, which lack specialized energy-producing organelles (mitochondria), are energy-limited and constrained to an information minimum. Acquisition of mitochondria is viewed as a critical evolutionary step that, by allowing eukaryotes to achieve a sufficiently high energy state, permitted a phase transition to an information maximum. This state, in contrast to the prokaryote minima, allowed evolution of complex, multicellular organisms. A special case is a malignant cell, which is modeled as a phase transition from a maximum to minimum information state. The minimum leads to a predicted power-law governing the in situ growth that is confirmed by studies measuring growth of small breast cancers. CONCLUSIONS: We find living systems achieve a stable entropic state by maintaining an extreme level of information. The evolutionary divergence of prokaryotes and eukaryotes resulted from acquisition of specialized energy organelles that allowed transition from information minima to maxima, respectively. Carcinogenesis represents a reverse transition: of an information maximum to minimum. The progressive information loss is evident in accumulating mutations, disordered morphology, and functional decline characteristics of human cancers. The findings suggest energy restriction is a critical first step that triggers the genetic mutations that drive somatic evolution of the malignant phenotype