Publications by authors named "Matthias Hofmann"

100 Publications

Unraveling the Way Acetaldehyde is Formed from Acetylene: A Study Based on DFT.

ACS Omega 2021 Mar 2;6(10):6924-6933. Epub 2021 Mar 2.

Anorganisch Chemisches Institüt, Ruprecht-Karls-Universität, Heidelberg 69120, Germany.

Acetylene hydratase (AH) of is a tungsten (W)-containing iron-sulfur enzyme that catalyzes the transformation of acetylene to acetaldehyde, the exact/true reaction mechanism of which is still in question. Scientists utilized different computational approaches to understand the reaction mechanism of acetylene hydration. Some identified it as a multistep (4-16) process that starts with the displacement of a water molecule present at the active site of AH with acetylene. However, some said that there is no need to displace water with acetylene at the active site of AH. As the reaction mechanism for the conversion of acetylene to acetaldehyde is still controversial and needs to be investigated further, DFT studies were performed on the model complexes derived from the native protein X-ray crystal structure of AH. Based on the computational results, here we are proposing the nucleophilic reaction mechanism where the water (Wat1424) molecule is coordinated to the W center and Asp13 is assumed to be in an anionic form. The Wat1424 molecule is activated by W and then donates one of its protons to the anionic Asp13, forming the W-bound hydroxide and protonated Asp13. The W-bound hydroxide then attacks the C1 atom of acetylene together with the transfer of a proton from Asp13 to its C2 atom, resulting in the formation of a vinyl alcohol intermediate complex. The energy barrier associated with this step is 14.4 kcal/mol. The final, rate-limiting, step corresponds to the tautomerization of the vinyl alcohol intermediate to acetaldehyde via intermolecular assistance of two water molecules, associated with an energy barrier of 18.9 kcal/mol. Also, the influence of the metal on the hydration of acetylene is studied when W is replaced with Mo.
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http://dx.doi.org/10.1021/acsomega.0c06159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970554PMC
March 2021

Safety and Performance of Etermis 3 and 4 in Wrinkles/Folds Treatment and Facial Volume Enhancement: A Prospective, Evaluator-Blinded, Open-Label Study.

Clin Cosmet Investig Dermatol 2020 19;13:591-599. Epub 2020 Aug 19.

Merz North America, Inc., Raleigh, NC, USA.

Background: Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas.

Objective: To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement.

Methods: Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment.

Results: In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥76.6%, marionette lines ≥61%, lips ≥36%) and ET3 (marionette lines ≥50% and lips ≥21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions.

Conclusion: Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.
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http://dx.doi.org/10.2147/CCID.S244598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443462PMC
August 2020

Simultaneous measurement of the thickness and the lifetime of a foam lamella.

Rev Sci Instrum 2019 Dec;90(12):124102

Institute of Physical and Theoretical Chemistry, University of Regensburg, D-93053 Regensburg, Germany.

Despite the important role of foams in industrial applications, few methods for determining the stability are present. By extending the existing light reflection-based apparatus, additional information about a single foam lamella can be obtained. Evaluation of these data delivers insight into the thinning process of the lamella. The potential of this technique is shown for the analysis of two surfactants with different head group lengths (Lutensol XP 100 and Lutensol XP 140).
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http://dx.doi.org/10.1063/1.5119192DOI Listing
December 2019

Probing Trions at Chemically Tailored Trapping Defects.

ACS Cent Sci 2019 Nov 16;5(11):1786-1794. Epub 2019 Oct 16.

Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, Maryland 20742, United States.

Trions, charged excitons that are reminiscent of hydrogen and positronium ions, have been intensively studied for energy harvesting, light-emitting diodes, lasing, and quantum computing applications because of their inherent connection with electron spin and dark excitons. However, these quasi-particles are typically present as a minority species at room temperature making it difficult for quantitative experimental measurements. Here, we show that by chemically engineering the well depth of sp quantum defects through a series of alkyl functional groups covalently attached to semiconducting carbon nanotube hosts, trions can be efficiently generated and localized at the trapping chemical defects. The exciton-electron binding energy of the trapped trion approaches 119 meV, which more than doubles that of "free" trions in the same host material (54 meV) and other nanoscale systems (2-45 meV). Magnetoluminescence spectroscopy suggests the absence of dark states in the energetic vicinity of trapped trions. Unexpectedly, the trapped trions are approximately 7.3-fold brighter than the brightest previously reported and 16 times as bright as native nanotube excitons, with a photoluminescence lifetime that is more than 100 times larger than that of free trions. These intriguing observations are understood by an efficient conversion of dark excitons to bright trions at the defect sites. This work makes trions synthetically accessible and uncovers the rich photophysics of these tricarrier quasi-particles, which may find broad implications in bioimaging, chemical sensing, energy harvesting, and light emitting in the short-wave infrared.
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http://dx.doi.org/10.1021/acscentsci.9b00707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891859PMC
November 2019

Facial skin revitalization with CPM-HA20G: an effective and safe early intervention treatment.

Clin Cosmet Investig Dermatol 2019 13;12:563-572. Epub 2019 Aug 13.

University of Hamburg, Division of Biochemistry and Molecular Biology, Cosmetic Science, D-20146 Hamburg, Germany.

Background: Hyaluronic acid (HA) fillers are popular for the treatment of signs of facial skin aging.

Objective: The objective of this study was to confirm the performance and safety of a new cohesive polydensified matrix HA filler ([CPM-HA20G, Belotero Revive, lidocaine-free], Merz Pharmaceuticals GmbH, Frankfurt, Germany) for the treatment of early signs of facial skin aging by use of biophysical measurements as well as subject and investigator satisfaction.

Methods: Twenty-five healthy female subjects with signs of facial skin aging were enrolled in this open-label, rater-blinded, observational post-market clinical follow-up study, and received 20 micropuncture treatments of 50 µL CPM-HA20G each into the lower cheek area at three injection visits 4 weeks apart. Objective biophysical assessments were conducted to demonstrate effects on viscoelastic properties of the skin, surface roughness, tone and radiance, and hydration, at baseline and at all follow-up visits up to 36 weeks.

Results: CPM-HA20G significantly increased gross elasticity of the skin (at weeks 9 and 12), skin firmness (up to week 24), skin tone and radiance and skin hydration (all up to 36 weeks). Significant reduction of skin fatigue (up to 9 weeks), skin roughness (up to 28 weeks), and redness (up to 36 weeks) was also observed. Subjects and blinded investigator were highly satisfied with the treatment outcomes. The treating investigator reported a high level of satisfaction with the ease of injection and the clinical performance of the device. Moreover, data demonstrated a good safety profile of the device.

Conclusion: CPM-HA20G is considered to be an effective and safe HA injectable for skin revitalization in patients suffering from signs of skin aging and loss of skin elasticity. It seems to be a perfect early intervention approach in patients that do not need volumizing treatment and a combination approach in older patients with more pronounced aging.
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http://dx.doi.org/10.2147/CCID.S209256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698156PMC
August 2019

The influence of lanthanide-(III)-nitrates on adsorbed monolayers of dodecylphosphorylcholine at the air-water interface.

J Colloid Interface Sci 2019 Jul 8;548:217-223. Epub 2019 Apr 8.

Institut für Physikalische und Theoretische Chemie, Universität Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany. Electronic address:

Adsorption layers at the air-water interface formed from the soluble zwitterionic surfactant dodecylphosphorylcholine (DPC) serving as a soluble model substance for phospho-lipids were characterized with respect to their equilibrium and dynamic surface properties. To clarify the effect of ionic interactions with electrolyte present in the bulk phase, surface rheological properties upon addition of Ce(NO) and Yb(NO) were determined. In order to account for the surface activity of the nitrate ion, comparative measurements using NaNO were carried out additionally. Further experimental information on the bulk hydration characteristics of the aqueous solutions was obtained using dielectric relaxation spectroscopy (DRS). A possible mechanism causing the deviating surface dilatational modulus E in terms of ion specificity is suggested.
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http://dx.doi.org/10.1016/j.jcis.2019.03.065DOI Listing
July 2019

Assessment of Melanogenesis in a Pigmented Human Tissue-Cultured Skin Equivalent.

Indian J Dermatol 2019 Mar-Apr;64(2):85-89

Department of Dermatology, Venereology, and Allergology, Goethe University Hospital, Frankfurt/Main, Germany.

Background: Organotypic tissue-cultured skin equivalents are used for a broad range of applications either as possible substitute for animal tests or for transplantation in patient-centered care.

Aims: In this study, we implemented melanocytes in a tissue-cultured full-thickness skin equivalent, consisting of epidermis and dermis. The versatility of this skin-like model with respect to pigmentation and morphological criteria was tested.

Materials And Methods: Pigmented skin equivalents were morphologically characterized, and melanogenesis was evaluated after treatment with kojic acid - a tyrosinase inhibitor and forskolin - a well-known activator of the cyclic adenosine 3,5-monophosphate pathway. Pigmentation was measured either by determination of the extinction at 400 nm after melanin extraction with KOH correlated to a melanin standard curve or by reflectance colorimetric analysis, monitoring reflectance of 660 nm and 880 nm emitting diodes.

Results: The morphological analysis revealed characteristic epidermal stratification with melanocytes located at the basal layer. Stimulation with forskolin increased the pigmentation, whereas treatment with kojic acid caused bleaching.

Conclusion: The present study demonstrates that the herein-introduced organotypic tissue-cultured skin equivalent is comparable to the normal human skin and its versatility in tests regarding skin pigmentation. Therefore, this model might help understand diseases with dysfunctional pigmentation such as melasma, vitiligo, and postinflammatory hyperpigmentation.
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http://dx.doi.org/10.4103/ijd.IJD_410_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440179PMC
April 2019

The surface rheological signature of the geometric isomers of an azobenzene-surfactant.

Phys Chem Chem Phys 2018 May;20(18):12659-12663

Universitätsstraße 31, 93053 Regensburg, Germany.

The equilibrium and dynamic surface properties of a photosensitive azobenzene-surfactant subject to illumination with UV and Vis-light leading to the respective geometric cis- and trans-isomers were studied. The adsorption layers formed by the soluble surfactant were characterized by pendant drop tensiometry and surface rheology using the oscillating bubble technique. Aqueous solutions corresponding to the geometric isomers could clearly be distinguished in terms of both their equilibrium and dynamic surface properties. The frequency dependence of the surface dilatational modulus could be described by the extended Lucassen-van den Tempel (LvdT)-model. These findings can be interpreted in terms of the changes of the dipole moment. Furthermore, they shed some light on the relation between the molecular structure and macroscopic properties of the adsorption layer.
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http://dx.doi.org/10.1039/c8cp01025kDOI Listing
May 2018

Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective.

J Am Assoc Nurse Pract 2017 May 24;29(5):294-303. Epub 2017 Apr 24.

Division of Oncodermatology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.

Purpose: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies.

Data Sources: Data for drug-related skin AEs were summarized from phase 3 nivolumab and nivolumab + ipilimumab trials and phase 2 and 3 pembrolizumab trials. Patient case studies were provided by the lead (M.T.) and senior (J.N.C.) authors.

Conclusions: The recommendations presented here, based on accumulated clinical trial and clinical practice experience are consistent with established treatment guidelines and reach beyond established guidelines and recommendations for the management of AEs associated with immune checkpoint inhibitors.

Implications For Practice: The practical treatment guidance presented here may help familiarize medical teams with the recognition and management of skin AEs associated with these recently approved agents. The enclosed recommendations may contribute to optimized treatment through awareness of typical time to onset and clinical presentation, knowledge of management options, and appropriate application of treatment.
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http://dx.doi.org/10.1002/2327-6924.12458DOI Listing
May 2017

Influence of Biodentine® - A Dentine Substitute - On Collagen Type I Synthesis in Pulp Fibroblasts In Vitro.

PLoS One 2016 9;11(12):e0167633. Epub 2016 Dec 9.

Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.

Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167633PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147936PMC
July 2017

Measurement of the lifetime of individual foam lamellae.

Rev Sci Instrum 2016 Sep;87(9):094101

Institute of Physical and Theoretical Chemistry, University of Regensburg, D-93053 Regensburg, Germany.

Foams play a crucial role in a number of practical applications. Their analysis in terms of stability is subject to a large number of parameters. An automated, light reflection based device for the measurement of the lifetime of a single foam lamella of aqueous surfactant solutions in contact with the liquid and gas phases is proposed. The capability of the method is shown for the analysis of the cationic and anionic model surfactants hexadecyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS) with saturated humidity, respectively. A statistical approach for analysis of the individual foam lamella lifetimes is presented and a comparison to the foam stability parameters obtained from a foam column device is presented.
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http://dx.doi.org/10.1063/1.4962404DOI Listing
September 2016

Cavity-enhanced Raman microscopy of individual carbon nanotubes.

Nat Commun 2016 07 12;7:12155. Epub 2016 Jul 12.

Fakultät für Physik, Ludwig-Maximilians-Universität, Schellingstraβe 4, München 80799, Germany.

Raman spectroscopy reveals chemically specific information and provides label-free insight into the molecular world. However, the signals are intrinsically weak and call for enhancement techniques. Here, we demonstrate Purcell enhancement of Raman scattering in a tunable high-finesse microcavity, and utilize it for molecular diagnostics by combined Raman and absorption imaging. Studying individual single-wall carbon nanotubes, we identify crucial structural parameters such as nanotube radius, electronic structure and extinction cross-section. We observe a 320-times enhanced Raman scattering spectral density and an effective Purcell factor of 6.2, together with a collection efficiency of 60%. Potential for significantly higher enhancement, quantitative signals, inherent spectral filtering and absence of intrinsic background in cavity-vacuum stimulated Raman scattering render the technique a promising tool for molecular imaging. Furthermore, cavity-enhanced Raman transitions involving localized excitons could potentially be used for gaining quantum control over nanomechanical motion and open a route for molecular cavity optomechanics.
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http://dx.doi.org/10.1038/ncomms12155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945868PMC
July 2016

The Role of Surface Viscosity in the Escape Mechanism of the Stenus Beetle.

J Phys Chem B 2016 07 18;120(29):7143-7. Epub 2016 Jul 18.

Institute of Physical and Theoretical Chemistry, University of Regensburg , D-93053 Regensburg, Germany.

Beetles of the species Stenus comma live and hunt close to ponds and rivers, where they occasionally fall on the water surface. To escape this jeopardized state, the beetle developed a strategy relying on the excretion of a secretion containing the substances stenusine and norstenusine. They reduce surface tension and propel the bug to the saving river bank. These substances were synthesized and analyzed with respect to their equilibrium and dynamic adsorption properties at the air-water interface (pH 7, 23 ± 1 °C). The surface dilatational rheological characteristics in a frequency range from 2 to 500 Hz at molar bulk concentrations of 20.6 mmol L(-1) were studied using the oscillating bubble technique. Both alkaloids formed surface viscoelastic adsorption layers. The frequency dependence of the surface dilatational modulus E could successfully be described by the extended Lucassen-van den Tempel model accounting for a nonzero intrinsic surface viscosity κ. The findings confirmed a dual purpose of the spreading alkaloids in the escape mechanism of the Stenus beetle. Next to generating a surface pressure, a transition to surface viscoelastic behavior of the adsorbed layers was observed.
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http://dx.doi.org/10.1021/acs.jpcb.6b04871DOI Listing
July 2016

Scanning Acoustic Microscopy-A Novel Noninvasive Method to Determine Tumor Interstitial Fluid Pressure in a Xenograft Tumor Model.

Transl Oncol 2016 Jun 22;9(3):179-83. Epub 2016 Apr 22.

Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.

Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values.
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http://dx.doi.org/10.1016/j.tranon.2016.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856858PMC
June 2016

Ubiquity of Exciton Localization in Cryogenic Carbon Nanotubes.

Nano Lett 2016 05 27;16(5):2958-62. Epub 2016 Apr 27.

Fakultät für Physik, Munich Quantum Center, and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München , Geschwister-Scholl-Platz 1, D-80539 München, Germany.

We present photoluminescence studies of individual semiconducting single-wall carbon nanotubes at room and cryogenic temperatures. From the analysis of spatial and spectral features of nanotube photoluminescence, we identify characteristic signatures of unintentional exciton localization. Moreover, we quantify the energy scale of exciton localization potentials as ranging from a few to a few tens of millielectronvolts and stemming from both environmental disorder and shallow covalent side-wall defects. Our results establish disorder-induced crossover from the diffusive to the localized regime of nanotube excitons at cryogenic temperatures as a ubiquitous phenomenon in micelle-encapsulated and as-grown carbon nanotubes.
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http://dx.doi.org/10.1021/acs.nanolett.5b04901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918963PMC
May 2016

Impact of Different Spa Waters on Inflammation Parameters in Human Keratinocyte HaCaT Cells.

Ann Dermatol 2015 Dec 7;27(6):709-14. Epub 2015 Dec 7.

Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.

Background: The treatment of different skin conditions with spa waters is a long tradition dating back to at least late Hellenism. Interestingly, independent scientific examinations studying the effect of spa waters are scarce.

Objective: In the present in vitro study, we compared the effect of culture media supplemented with (a) thermal spa waters (La Roche-Posay, Avène) and (b) two natural mineral drinking waters (Heppinger, Adelholzener) on physiological parameters in HaCaT keratinocytes.

Methods: The different medium preparations were investigated with regard to cell proliferation and cell damage. Moreover, the impact on inflammation parameters with and without ultraviolet B (UVB) irradiation was examined.

Results: Two popular thermal spring waters were found to suppress cell proliferation and cell damage. Moreover, these waters reversed the induction of interleukin-6, as measured using enzyme-linked immunosorbent assay and promoter transactivation, and the formation of reactive oxygen species after UVB stimulation. Of note, the two natural mineral waters, which are distributed as drinking waters, had some effect on the above-mentioned parameters but to a lesser extent.

Conclusion: In summary, our results show that spa waters, and particularly those derived from thermal springs, reduce parameters associated with inflammation. It seems likely that trace elements such as selenium and zinc are critical for the observed effects.
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http://dx.doi.org/10.5021/ad.2015.27.6.709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695423PMC
December 2015

Retrieval of complex χ((2)) parts for quantitative analysis of sum-frequency generation intensity spectra.

J Chem Phys 2015 Oct;143(13):134112

Department of Bioengineering, National ESCA and Surface Analysis Center for Biomedical Problems, University of Washington, Seattle, Washington 98105, USA.

Vibrational sum-frequency generation (SFG) spectroscopy has become an established technique for in situ surface analysis. While spectral recording procedures and hardware have been optimized, unique data analysis routines have yet to be established. The SFG intensity is related to probing geometries and properties of the system under investigation such as the absolute square of the second-order susceptibility χ((2)) (2). A conventional SFG intensity measurement does not grant access to the complex parts of χ((2)) unless further assumptions have been made. It is therefore difficult, sometimes impossible, to establish a unique fitting solution for SFG intensity spectra. Recently, interferometric phase-sensitive SFG or heterodyne detection methods have been introduced to measure real and imaginary parts of χ((2)) experimentally. Here, we demonstrate that iterative phase-matching between complex spectra retrieved from maximum entropy method analysis and fitting of intensity SFG spectra (iMEMfit) leads to a unique solution for the complex parts of χ((2)) and enables quantitative analysis of SFG intensity spectra. A comparison between complex parts retrieved by iMEMfit applied to intensity spectra and phase sensitive experimental data shows excellent agreement between the two methods.
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http://dx.doi.org/10.1063/1.4932180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600082PMC
October 2015

Development and Characterization of an Engraftable Tissue-Cultured Skin Autograft: Alternative Treatment for Severe Electrical Injuries.

Cells Tissues Organs 2014 21;200(3-4):227-39. Epub 2015 Aug 21.

Department of Dermatology, Venereology and Allergology, University Hospital, Goethe University, Frankfurt am Main, Germany.

Background/aims: Optimizing the treatment regimens of extensive or nonhealing defects is a constant challenge. Tissue-cultured skin autografts may be an alternative to mesh grafts and keratinocyte suspensions that are applied during surgical defect coverage.

Methods: Autologous epidermal and dermal cells were isolated, in vitro expanded and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically and electron microscopically characterized. Subsequently, it was transplanted onto lesions of a severely burned patient.

Results: Comparability of the skin equivalent to healthy human skin could be shown due to the epidermal strata, differentiation, proliferation markers and development of characteristics of a functional basal lamina. Approximately 2 weeks after skin equivalent transplantation the emerging new skin correlated closely to the adjacent normal skin.

Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and its versatility for clinical applications.
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http://dx.doi.org/10.1159/000433519DOI Listing
March 2016

STAT6-Dependent Collagen Synthesis in Human Fibroblasts Is Induced by Bovine Milk.

PLoS One 2015 2;10(7):e0131783. Epub 2015 Jul 2.

Department of Dermatology, Venereology and Allergy, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.

Since the domestication of the urus, 10.000 years ago, mankind utilizes bovine milk for different purposes. Besides usage as a nutrient also the external application of milk on skin has a long tradition going back to at least the ancient Aegypt with Cleopatra VII as a great exponent. In order to test whether milk has impact on skin physiology, cultures of human skin fibroblasts were exposed to commercial bovine milk. Our data show significant induction of proliferation by milk (max. 2,3-fold, EC50: 2,5% milk) without toxic effects. Surprisingly, bovine milk was identified as strong inducer of collagen 1A1 synthesis at both, the protein (4-fold, EC50: 0,09% milk) and promoter level. Regarding the underlying molecular pathways, we show functional activation of STAT6 in a p44/42 and p38-dependent manner. More upstream, we identified IGF-1 and insulin as key factors responsible for milk-induced collagen synthesis. These findings show that bovine milk contains bioactive molecules that act on human skin cells. Therefore, it is tempting to test the herein introduced concept in treatment of atrophic skin conditions induced e.g. by UV light or corticosteroids.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131783PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489876PMC
April 2016

Statistical approaches for the determination of cut points in anti-drug antibody bioassays.

J Immunol Methods 2015 Mar 27;418:84-100. Epub 2015 Feb 27.

Institute of Biostatistics, Leibniz Universität Hannover, Herrenhaeuser Str. 2, D-30419 Hannover, Germany.

Cut points in immunogenicity assays are used to classify future specimens into anti-drug antibody (ADA) positive or negative. To determine a cut point during pre-study validation, drug-naive specimens are often analyzed on multiple microtiter plates taking sources of future variability into account, such as runs, days, analysts, gender, drug-spiked and the biological variability of un-spiked specimens themselves. Five phenomena may complicate the statistical cut point estimation: i) drug-naive specimens may contain already ADA-positives or lead to signals that erroneously appear to be ADA-positive, ii) mean differences between plates may remain after normalization of observations by negative control means, iii) experimental designs may contain several factors in a crossed or hierarchical structure, iv) low sample sizes in such complex designs lead to low power for pre-tests on distribution, outliers and variance structure, and v) the choice between normal and log-normal distribution has a serious impact on the cut point. We discuss statistical approaches to account for these complex data: i) mixture models, which can be used to analyze sets of specimens containing an unknown, possibly larger proportion of ADA-positive specimens, ii) random effects models, followed by the estimation of prediction intervals, which provide cut points while accounting for several factors, and iii) diagnostic plots, which allow the post hoc assessment of model assumptions. All methods discussed are available in the corresponding R add-on package mixADA.
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http://dx.doi.org/10.1016/j.jim.2015.02.004DOI Listing
March 2015

Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor.

Cancer Chemother Pharmacol 2015 May 27;75(5):887-95. Epub 2015 Feb 27.

South Texas Accelerated Research Therapeutics, 4383 Medical Drive, Suite 4021, San Antonio, TX, 78229, USA,

Purpose: TAS266 is a novel agonistic tetravalent Nanobody(®) targeting the DR5 receptor. In preclinical studies, TAS266 was more potent than a cross-linked DR5 antibody or TRAIL. This first-in-human study was designed to evaluate the safety and tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of TAS266.

Methods: Adult patients with advanced solid tumors were to receive assigned doses of TAS266 (3, 10, 15, or 20 mg/kg) intravenously on days 1, 8, 15, and 22 of a 28-day treatment cycle.

Results: Grade ≥3 elevations in aspartate aminotransferase and/or alanine aminotransferase levels, occurring during cycle 1 in three of four patients at the 3 mg/kg dose level, were attributed to TAS266 and led to early study termination. Liver enzyme levels quickly returned to grade ≤1 following TAS266 discontinuation. Evidence of preexisting antibodies able to bind to TAS266 was found in the three patients who experienced these dose-limiting toxicities. Immunogenic responses remained elevated and strengthened at end-of-treatment (EOT). In the one patient who did not develop hepatotoxicity, no evidence of immunogenicity was observed at baseline or following administration of 4 TAS266 doses; however, incipient positive immunogenicity was observed at the EOT visit.

Conclusion: TAS266 was associated with unexpected, significant but reversible hepatotoxicity. Although the underlying mechanism is not fully elucidated, factors including the molecule's high potency, immunogenicity to TAS266, and possibly increased DR5 expression on hepatocytes further enhancing the activity of the Nanobody(®) may have contributed to enhanced DR5 clustering and activation of hepatocyte apoptosis.
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http://dx.doi.org/10.1007/s00280-015-2712-0DOI Listing
May 2015

Impact of the imaginary part of the surface dilatational modulus on the splashing behavior of drops.

Langmuir 2015 Feb 4;31(6):1874-8. Epub 2015 Feb 4.

Institute of Physical and Theoretical Chemistry, University of Regensburg , D-93040 Regensburg, Germany.

The relation between the complex surface dilatational modulus E of aqueous surfactant solutions and the splashing behavior of their drops on liquid surfaces was investigated. The surface dilatational modulus E of selected surfactant systems has been determined in the frequency range of 3 to 500 Hz by means of the oscillating bubble technique. According to the functional dependence of the phase ϕ of the complex modulus E(ω, c)exp[iϕ(ω, c)] at higher frequencies, adsorption layers can be classified as surface elastic or surface viscoelastic. Each behavior shows pronounced differences in drop splashing experiments. The impact of a drop on the liquid was monitored with a high-speed camera. The splash of a drop is a rather complex phenomenon, so the focus of this article is to establish a relationship between the imaginary part of the surface dilatational modulus E and the height of the drop rebound. These findings may be of importance for formulations in crop protection, introducing a chemical way to influence the impact of drops on solid and liquid interfaces.
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http://dx.doi.org/10.1021/la5050128DOI Listing
February 2015

Clinical application of a tissue-cultured skin autograft: an alternative for the treatment of non-healing or slowly healing wounds?

Dermatology 2014 6;229(3):190-8. Epub 2014 Sep 6.

Department of Dermatology, Venereology and Allergology, Goethe University Medical School, Frankfurt/Main, Germany.

Background: The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied.

Objective: Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface.

Methods: Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin.

Results: Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin.

Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.
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http://dx.doi.org/10.1159/000362927DOI Listing
July 2015

Direct real-time quantitative PCR for measurement of host-cell residual DNA in therapeutic proteins.

J Pharm Biomed Anal 2014 Nov 12;100:123-130. Epub 2014 Aug 12.

Novartis Pharma AG, TRD Biologics Process R&D, Basel, Switzerland. Electronic address:

Real-time quantitative PCR (qPCR) is important for quantification of residual host cell DNA (resDNA) in therapeutic protein preparations. Typical qPCR protocols involve DNA extraction steps complicating sample handling. Here, we describe a "direct qPCR" approach without DNA extraction. To avoid interferences of DNA polymerase with a therapeutic protein, proteins in the samples were digested with proteinase K (PK) in the presence of sodium dodecyl sulfate (SDS). Tween 20 and NaCl were included to minimize precipitation of therapeutic proteins in the PK/SDS mix. After PK treatment, the solution was applied directly for qPCR. Inhibition of DNA polymerase by SDS was prevented by adding 2% (v/v) of Tween 20 to the final qPCR mix. The direct qPCR approach was evaluated for quantification of resDNA in therapeutic proteins manufactured in Chinese hamster ovary (CHO) host cells. First, direct qPCR was compared with qPCR applied on purified DNA ("extraction qPCR"). For both qPCRs, the same CHO-specific primers and probes were used. Comparable residual DNA levels were detected with both PCR approaches in purified and highly concentrated drug proteins as well as in in-process-control samples. Finally, the CHO-specific direct qPCR protocol was validated according to ICH guidelines and applied for 25 different therapeutic proteins. The specific limits of quantification were 0.1-0.8ppb for 24 proteins, and 2.0ppb for one protein. General applicability of the direct qPCR was demonstrated by applying the sample preparation protocol for quantification of resDNA in therapeutic proteins manufactured in other hosts such as Escherichia coli and mouse cells.
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http://dx.doi.org/10.1016/j.jpba.2014.07.032DOI Listing
November 2014

Antenna-enhanced optoelectronic probing of carbon nanotubes.

Nano Lett 2014 Jul 5;14(7):3773-8. Epub 2014 Jun 5.

Department Chemie und Center for NanoScience (CeNS), Ludwig-Maximilians-Universität , 81377 München, Germany.

We report on the first antenna-enhanced optoelectronic microscopy studies on nanoscale devices. By coupling the emission and excitation to a scanning optical antenna, we are able to locally enhance the electroluminescence and photocurrent along a carbon nanotube device. We show that the emission source of the electroluminescence can be pointlike with a spatial extension below 20 nm. Topographic and antenna-enhanced photocurrent measurements reveal that the emission takes place at the location of highest local electric field indicating that the mechanism behind the emission is the radiative decay of excitons created via impact excitation.
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http://dx.doi.org/10.1021/nl5006959DOI Listing
July 2014

Topically applied glycyrrhizic acid causes hair removal in rats.

Pharm Biol 2014 Oct 2;52(10):1362-5. Epub 2014 May 2.

Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany and.

Context: Anecdotic reports from Turkmenistan suggest an epilatory effect of sweet licorice extract after topical application.

Objective: This study examines hair removal after topical application of glycyrrhizic acid, the main compound of sweet licorice.

Materials And Methods: An aqueous solution containing 15% of the ammonium salt of glycyrrhizic acid, 10% urea, and 20% ethanol was topically applied two times per day on the neck areas of Wistar rats using a toothbrush.

Results: After 3 d, 20-30% of the treated areas were free of hair. After treatment for 6-12 d, 90-95% of the hair was gone. Clinical as well as immunohistological examinations showed no signs of inflammation even after long-term treatment for more than 9 months. Interestingly, long-term treatment reduced the regrowth of hair of about 20%. Examination by scanning electron microscopy showed a smoothed hair cuticle that might facilitate detachment of the hair shaft from the follicular wall.

Discussion And Conclusion: Our findings suggest glycyrrhizic acid as an interesting molecule for treating hypertrichosis in humans.
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http://dx.doi.org/10.3109/13880209.2014.884608DOI Listing
October 2014

ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cell-specific VEGF receptor.

Exp Cell Res 2014 May 11;323(2):263-75. Epub 2014 Mar 11.

Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; International Center, Okayama University, Okayama, Japan. Electronic address:

Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy.
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http://dx.doi.org/10.1016/j.yexcr.2014.03.002DOI Listing
May 2014

Effects of sea surface warming on marine plankton.

Ecol Lett 2014 May 28;17(5):614-23. Epub 2014 Feb 28.

Marine Ecology, GEOMAR Helmholtz Center for Ocean Research Kiel, Düsternbrooker Weg 20, 24105, Kiel, Germany; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Deutscher Platz 5e, 04103, Leipzig, Germany.

Ocean warming has been implicated in the observed decline of oceanic phytoplankton biomass. Some studies suggest a physical pathway of warming via stratification and nutrient flux, and others a biological effect on plankton metabolic rates; yet the relative strength and possible interaction of these mechanisms remains unknown. Here, we implement projections from a global circulation model in a mesocosm experiment to examine both mechanisms in a multi-trophic plankton community. Warming treatments had positive direct effects on phytoplankton biomass, but these were overcompensated by the negative effects of decreased nutrient flux. Zooplankton switched from phytoplankton to grazing on ciliates. These results contrast with previous experiments under nutrient-replete conditions, where warming indirectly reduced phytoplankton biomass via increased zooplankton grazing. We conclude that the effect of ocean warming on marine plankton depends on the nutrient regime, and provide a mechanistic basis for understanding global change in marine ecosystems.
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http://dx.doi.org/10.1111/ele.12265DOI Listing
May 2014

Visible light is a better co-inducer of apoptosis for curcumin-treated human melanoma cells than UVA.

PLoS One 2013 8;8(11):e79748. Epub 2013 Nov 8.

Department of Dermatology, Venereology, and Allergology, University Hospital, J.W. Goethe-University, Frankfurt/Main, Germany.

Curcumin attracts worldwide scientific interest due to its anti-proliferative and apoptosis inducing effects on different tumor cells at concentrations ranging from 10 to 150 µM (3.7-55 µg/ml). Unfortunately, because of a low oral bioavailability, only low and pharmacologically ineffective serum levels are achievable. In this study, an alternative treatment concept consisting of low concentration curcumin (0.2-5 µg/ml) and irradiation with UVA or visible light (VL) has been tested. The experimental results show clearly that this treatment decreases the proliferation and the viability of human melanoma cells while the cell membrane integrity remains intact. We identified the onset of apoptosis characterized by typical markers such as active caspases 8, 9 and 3 as well as DNA fragmentation accompanied by the loss of cell adhesion. The mitochondrial apoptosis signaling pathway is predominant due to an early activation of caspase-9. The present data indicate a higher efficacy of a combination of curcumin and VL than curcumin and UVA. Reduced effects as a result of light absorption by heavily pigmented skin are unlikely if VL is used. These results indicate that a combination of curcumin and light irradiation may be a useful additional therapy in the treatment of malignant disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079748PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821844PMC
July 2014

Modeling conditions of pigmented integument by dissipative structures.

J Dermatol Sci 2014 Jan 3;73(1):80-3. Epub 2013 Sep 3.

Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.

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http://dx.doi.org/10.1016/j.jdermsci.2013.08.012DOI Listing
January 2014