Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of α‐Melanocyte Stimulating Hormone†

Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle⁴‐d‐Phe⁷‐α‐MSH), a synthetic analog of α‐melanocyte stimulating hormone and agonist of the melanocortin‐1‐receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained‐release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60‐day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low‐grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open‐label study, confirmation by a large‐scale trial is required.     

Cerebrospinal fluid promotes survival and astroglial differentiation of adult human neural progenitor cells but inhibits proliferation and neuronal differentiation

Background  

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existing in vitro studies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).     

Reversible formation of alcohol solvates and their potential use for heat storage

Journal of Thermal Analysis and Calorimetry - The influence of temperature and magnesia content on the formation of phases and their transformation kinetics in stoichiometric and non-stoichiometric...     

Copper‐Catalyzed Regio‐ and Enantioselective Addition of Silicon Grignard Reagents to Alkenes Activated by Azaaryl Groups

A new application of silicon Grignard reagents in C(sp³)?Si bond formation is reported. With the aid of BF₃?OEt₂, these silicon nucleophiles add across alkenes activated by various azaaryl groups under copper catalysis. An enantioselective version employing benzoxazole‐activated alkenes as substrates and a CuI‐josiphos complex as catalyst has been developed, forming the C(sp3)?Si bond with good to high enantiomeric ratios (up to 97:3). The method expands the toolbox for “conjugate addition” type C(sp³)?Si bond formation.     

Evolution of surface characteristics of two industrial 7xxx aluminium alloys exposed to humidity at moderate temperature

This study analyses the evolution of surface characteristics of two industrial high-strength 7xxx aluminium alloys with a focus on alloy composition and environmental parameters. Based on storage and transport conditions of as-machined products, the effect of humidity—as liquid and vapour phase—on the natural oxide layer has been studied. The evolution of the natural oxide layer has been analysed by scanning electron microscopy and X-ray photoelectron spectroscopy. The growth behaviour of the surface layer is dominated by environmental conditions, while microgalvanic activity depends mainly on the alloys' chemical composition and differs significantly for tested alloys. Scanning transmission electron microscopy images demonstrated that the long-term exposure at moderate temperatures affects the microstructure near the surface, which differs for the analysed alloy compositions. An anomalous precipitation of zinc-rich particles at the surface and along the precipitate-free zone is observed for the alloy with higher Zn/Mg ratio and lower Cu content.     

Seasonal variations and sources of mass and chemical composition for PM10 aerosol in Hangzhou,China

Aerosol observation was conducted for four seasons from September 2001 to August 2002 at five sampling sites in Hangzhou, South China, on PM10 mass, 22 elements （Na, Mg, AI, Si, P, S, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As. Se, Br, Cd, Ba, and Pb）, 5 major ions （F^-, Cl^ , NO3^-, SO4^2- , and NH4^＋）, and organic and elemental carbon （OC and EC）, showing that PM10 mass ranged from 46.7 to 270.8 μg/m^3, with an annual average of 119.2 μg/m^3. Na, AI, Si, S, K, Ca, and Fe were the most abundant elements in PM10, most of S being in the form of SO4^2- . SO4^2-, NO3^-, and NH4^＋ were the major ions, which contributed to about 20% of the PM10 mass. The mean seasonal concentrations for SO4^2- , averaged over all sites, were found to be 18.0, 18.5, 24,Z and 21.4 μg/m^3, for spring, summer, autumn, and winter, respectively, while the corresponding loadings for NO3^- were 7.2, 4.7, 7.1, and 11.2 μg/m^3, and for NH4^＋ were 6.0, 5.9, 8.2, and 9.3 μg/m^3, in the form mostly of NH4NO3 in spring, autumn, and winter, and mostly of （NH4）2SO4 in summer. The low NO3^-/SO4^2- ratio found indicates coal combustion as the major source throughout the year. The mean annual concentrations of OC and EC in PM10 were found to be 21.4, and 4.1 μg/m^3, respectively. Material balance calculation indicated that fugitive dust, the secondary aerosol, and carbonaceous matter were the most abundant species in PM10 for the four seasons, as is characteristic for cities in South China.     

Seasonal variations and sources of mass and chemical composition for PM10 aerosol in Hangzhou,China

Aerosol observation was conducted for four seasons from September 2001 to August 2002 at five sampling sites in Hangzhou, South China, on PM10 mass, 22 elements (Na, Mg, Al, Si, P, S, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Cd, Ba, and Pb), 5 major ions (F-, Cl-, NO3-, SO42-, and NH4+), and organic and elemental carbon (OC and EC), showing that PM10 mass ranged from 46.7 to 270.8 μg/m3, with an annual average of 119.2 μg/m3. Na, AI, Si, S. K, Ca, and Fe were the most abundant elements in PM10, most ors being in the form of SO42-. SO42-, NO4-, and NH4+ were the major ions, which contributed to about 20%; of the PM10 mass. The mean seasonal concentrations for SO42- , averaged over all sites, were found to be 18.0, 18.5, 24.Z and 21.4 μg/m3. for spring, summer, autumn, and winter, respectively, while the corresponding Ioadings for NO3- were 72, 4.7, 7.1, and 11.2μg/m3. and for NH4+ were 6.0, 5.9, 8.2. and 9.3 μg/m3, in the form mostly of NH4NO3 in spring, autumn, and winter, and mostly of (NH4)2SO4 in summer. The low NO3-/SO42- ratio found indicates coal combustion as the major source throughout the year. The mean annual concentrations of OC and EC in PM10 were found to be 21A, and 4.1 μg/m3, respectively. Material balance calculation indicated that fugitive dust, the secondary aerosol, and carbonaceous matter were the most abundant species in PM10 for the four seasons, as is characteristic for cities in South China.     

Methan im Gashydrat. Gefangen im Wasserkäfig

This article shows the variety of gas hydrates regarding their occurrences, composition, characterization and potential usability. Synthetic clathrate hydrates are described as well as those hydrates occurring in nature. Different methods, embracing the spectrum from laboratory analytic methods to field use are described.     

Mathematics of pulsed vocalizations with application to killer whale biphonation

Formulas for the spectra of pulsed vocalizations for both the continuous and discrete cases are rigorously derived from basic formulas for Fourier analysis, a topic discussed qualitatively in Watkins' classic paper on "the harmonic interval" ["The harmonic interval: Fact or artifact in spectral analysis of pulse trains," in Marine Bioacoustics 2, edited by W. N. Tavogla (Pergamon, New York, 1967), pp. 15-43]. These formulas are summarized in a table for easy reference, along with most of the corresponding graphs. The case of a "pulse tone" is shown to involve multiplication of two temporal wave forms, corresponding to convolution in the frequency domain. This operation is discussed in detail and shown to be equivalent to a simpler approach using a trigonometric formula giving sum and difference frequencies. The presence of a dc component in the temporal wave form, which implies physically that there is a net positive pressure at the source, is discussed, and examples of the corresponding spectra are calculated and shown graphically. These have application to biphonation (two source signals) observed for some killer whale calls and implications for a source mechanism. A MATLAB program for synthesis of a similar signal is discussed and made available online.