Discovery and characterization of a novel non-competitive inhibitor of the divalent metal transporter DMT1/SLC11A2

Divalent metal transporter-1 (SLC11A2/DMT1) uses the H+ electrochemical gradient as the driving force to transport divalent metal ions such as Fe2+, Mn2+ and others metals into mammalian cells. DMT1 is ubiquitously expressed, most notably in proximal duodenum, immature erythroid cells, brain and kidney. This transporter mediates H+-coupled transport of ferrous iron across the apical membrane of enterocytes. In addition, in cells such as to erythroid precursors, following transferrin receptor (TfR) mediated endocytosis; it mediates H+-coupled exit of ferrous iron from endocytic vesicles into the cytosol. Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery. In the present study, we performed a ligand-based virtual screening of the Princeton database (700,000 commercially available compounds) to search for pharmacophore shape analogs of recently reported DMT1 inhibitors. We discovered a new compound, named pyrimidinone 8, which mediates a reversible linear non-competitive inhibition of human DMT1 (hDMT1) transport activity with a Ki of ∼20 μM. This compound does not affect hDMT1 cell surface expression and shows no dependence on extracellular pH. To our knowledge, this is the first experimental evidence that hDMT1 can be allosterically modulated by pharmacological agents. Pyrimidinone 8 represents a novel versatile tool compound and it may serve as a lead structure for the development of therapeutic compounds for pre-clinical assessment.

The Chemical Space Project

One of the simplest questions that can be asked about molecular diversity is how many organic molecules are possible in total? To answer this question, my research group has computationally enumerated all possible organic molecules up to a certain size to gain an unbiased insight into the entire chemical space. Our latest database, GDB-17, contains 166.4 billion molecules of up to 17 atoms of C, N, O, S, and halogens, by far the largest small molecule database reported to date. Molecules allowed by valency rules but unstable or nonsynthesizable due to strained topologies or reactive functional groups were not considered, which reduced the enumeration by at least 10 orders of magnitude and was essential to arrive at a manageable database size. Despite these restrictions, GDB-17 is highly relevant with respect to known molecules. Beyond enumeration, understanding and exploiting GDBs (generated databases) led us to develop methods for virtual screening and visualization of very large databases in the form of a “periodic system of molecules” comprising six different fingerprint spaces, with web-browsers for nearest neighbor searches, and the MQN- and SMIfp-Mapplet application for exploring color-coded principal component maps of GDB and other large databases. Proof-of-concept applications of GDB for drug discovery were realized by combining virtual screening with chemical synthesis and activity testing for neurotransmitter receptor and transporter ligands. One surprising lesson from using GDB for drug analog searches is the incredible depth of chemical space, that is, the fact that millions of very close analogs of any molecule can be readily identified by nearest-neighbor searches in the MQN-space of the various GDBs. The chemical space project has opened an unprecedented door on chemical diversity. Ongoing and yet unmet challenges concern enumerating molecules beyond 17 atoms and synthesizing GDB molecules with innovative scaffolds and pharmacophores.

Stereoselective virtual screening of the ZINC database using atom pair 3D-fingerprints

Background Tools to explore large compound databases in search for analogs of query molecules provide a strategically important support in drug discovery to help identify available analogs of any given reference or hit compound by ligand based virtual screening (LBVS). We recently showed that large databases can be formatted for very fast searching with various 2D-fingerprints using the city-block distance as similarity measure, in particular a 2D-atom pair fingerprint (APfp) and the related category extended atom pair fingerprint (Xfp) which efficiently encode molecular shape and pharmacophores, but do not perceive stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable rapid stereoselective searches in the ZINC database (23.2 million 3D structures). Results Molecular fingerprints counting atom pairs at increasing through-space distance intervals were designed using either all atoms (16-bit 3DAPfp) or different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring functions) of 110,000 compounds from the Cambridge Structural Database with equal or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp or 3DAPfp similarity was stereoselective and gave very different analogs when starting from different diastereomers of the same chiral drug. Results were also different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D-fingerprints also gave very different results in LBVS of folded molecules where through-space distances between atom pairs are much shorter than topological distances. Conclusions 3DAPfp and 3DXfp are suitable for stereoselective searches for shape and pharmacophore analogs of query molecules in large databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are accessible at www.gdb.unibe.ch webcite and should provide useful assistance to drug discovery projects.

Privacy-preserving genomic testing in the clinic: a model using HIV treatment

PURPOSE The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical issues in clinical genomics. METHODS We genotyped 4,149 markers in HIV-positive individuals. Variants allowed for prediction of 17 traits relevant to HIV medical care, inference of patient ancestry, and imputation of human leukocyte antigen (HLA) types. Genetic data were processed under a privacy-preserving framework using homomorphic encryption, and clinical reports describing potentially actionable results were delivered to health-care providers. RESULTS A total of 230 patients were included in the study. We demonstrated the feasibility of encrypting a large number of genetic markers, inferring patient ancestry, computing monogenic and polygenic trait risks, and reporting results under privacy-preserving conditions. The average execution time of a multimarker test on encrypted data was 865 ms on a standard computer. The proportion of tests returning potentially actionable genetic results ranged from 0 to 54%. CONCLUSIONS The model of implementation presented herein informs on strategies to deliver genomic test results for clinical care. Data encryption to ensure privacy helps to build patient trust, a key requirement on the road to genomic-based medicine.Genet Med advance online publication 14 January 2016Genetics in Medicine (2016); doi:10.1038/gim.2015.167.

Primary prevention of peri-implantitis: managing peri-implant mucositis

AIMS Over the past decades, the placement of dental implants has become a routine procedure in the oral rehabilitation of fully and partially edentulous patients. However, the number of patients/implants affected by peri-implant diseases is increasing. As there are--in contrast to periodontitis--at present no established and predictable concepts for the treatment of peri-implantitis, primary prevention is of key importance. The management of peri-implant mucositis is considered as a preventive measure for the onset of peri-implantitis. Therefore, the remit of this working group was to assess the prevalence of peri-implant diseases, as well as risks for peri-implant mucositis and to evaluate measures for the management of peri-implant mucositis. METHODS Discussions were informed by four systematic reviews on the current epidemiology of peri-implant diseases, on potential risks contributing to the development of peri-implant mucositis, and on the effect of patient and of professionally administered measures to manage peri-implant mucositis. This consensus report is based on the outcomes of these systematic reviews and on the expert opinion of the participants. RESULTS Key findings included: (i) meta-analysis estimated a weighted mean prevalence for peri-implant mucositis of 43% (CI: 32-54%) and for peri-implantitis of 22% (CI: 14-30%); (ii) bleeding on probing is considered as key clinical measure to distinguish between peri-implant health and disease; (iii) lack of regular supportive therapy in patients with peri-implant mucositis was associated with increased risk for onset of peri-implantitis; (iv) whereas plaque accumulation has been established as aetiological factor, smoking was identified as modifiable patient-related and excess cement as local risk indicator for the development of peri-implant mucositis; (v) patient-administered mechanical plaque control (with manual or powered toothbrushes) has been shown to be an effective preventive measure; (vi) professional intervention comprising oral hygiene instructions and mechanical debridement revealed a reduction in clinical signs of inflammation; (vii) adjunctive measures (antiseptics, local and systemic antibiotics, air-abrasive devices) were not found to improve the efficacy of professionally administered plaque removal in reducing clinical signs of inflammation. CONCLUSIONS Consensus was reached on recommendations for patients with dental implants and oral health care professionals with regard to the efficacy of measures to manage peri-implant mucositis. It was particularly emphasized that implant placement and prosthetic reconstructions need to allow proper personal cleaning, diagnosis by probing and professional plaque removal.

Editorial genesis: From comparing texts (product) to interpreting rewritings (process)

In literary genetics, “editorial genetics” deals with the “public life” of texts, whereas the writing process is affected by edition and diffusion. Editorial genetics frequently has to deal with cases of “editorial rewriting”: in the literary domain for example, authors frequently modify previously published works, so that several versions may co-exist. We are especially interested in Balzac’s La Bourse (translated in English as The Purse) since we know three authorized versions of this specific work.By comparing different texts associated with a single work, the literary geneticist is facing different products that are themselves the result of a writing process. However, different specificities should be outlined: (1) the writing process does not leave any trace: we just have access to different products/texts and (2) since the texts we compare seem to be achieved, differences must be referred, not to programmatic or temporary linguistic structures, but to the reconfiguration of a pre-existing textuality.Do such products still reflect the processes that have given birth to them? Does the comparison between two texts considered as variations of a same text give access to this transformation’s processes? After describing the objects of this particular textual comparison and the terminology that permits to give an account of such phenomenon, this contribution suggests to express these questions differently, as a matter of poetics of transitions between texts, or, further digging, an hermeneutics of the transition between texts.

Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth

myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na(+)- or H(+)-linked myo-inositol transporters. While Na(+)-coupled myo-inositol transporters are found exclusively in the plasma membrane, H(+)-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo-synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi complex. We now provide evidence that the Golgi complex-localized T. brucei H(+)-linked myo-inositol transporter (TbHMIT) is essential in bloodstream-form T. brucei. Downregulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It tolerates only a single modification on the inositol ring, such as the removal of a hydroxyl group or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol.

X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair

DNA duplexes containing unnatural base-pair surrogates are attractive biomolecular nanomaterials with potentially beneficial photophysical or electronic properties. Herein we report the first X-ray structure of a duplex containing a phen-pair in the center of the double helix in a zipper like stacking arrangement.

Expression and distribution of a vacuolar aquaporin in young and mature leaf tissues of Brassica napus in relation to water fluxes

Recently, it has been shown that water fluxes across biological membranes occur not only through the lipid bilayer but also through specialized water-conducting proteins, the so called aquaporins. In the present study, we investigated in young and mature leaves of Brassica napus L. the expression and localization of a vacuolar aquaporin homologous to radish γ-tonoplast intrinsic protein/vacuolar-membrane integral protein of 23 kDa (TIP/VM 23). In-situ hybridization showed that these tonoplast aquaporins are highly expressed not only in developing but also in mature leaves, which export photosynthates. No substantial differences could be observed between different tissues of young and mature leaves. However, independent of the developmental stage, an immunohistochemical approach revealed that the vacuolar membrane of bundle-sheath cells contained more protein cross-reacting with antibodies raised against radish γ-TIP/VM 23 than the mesophyll cells. The lowest labeling was detected in phloem cells. We compared these results with the distribution of plasma-membrane aquaporins cross-reacting with antibodies detecting a domain conserved among members of the plasma-membrane intrinsic protein 1 (PIP1) subfamily. We observed the same picture as for the vacuolar aquaporins. Furthermore, a high density of gold particles labeling proteins of the PIP1 group could be observed in plasmalemmasomes of the vascular parenchyma. Our results indicate that γ-TIP/VM 23 and PIP1 homologous proteins show a similar expression pattern. Based on these results it is tempting to speculate that bundle-sheath cells play an important role in facilitating water fluxes between the apoplastic and symplastic compartments in close proximity to the vascular tissue.

Na 1 Nachlass Max Horkheimer, 96 - Korrespondenzen u.a. mit Jürgen Habermas (p. III 6, 1-421)

5 Briefe mit Antwort an Inga Haag, 1951-1955; 1 Brief mit Antwort von Jürgen Habermas an Max Horkheimer, 1955; 1 Brief von Ministerialrat i. R. Theodor Häbich an Max Horkheimer, 1957; 2 Briefe mit Antwort von cand. phil. Walter Hähnle an Max Horkheimer, 1955, 1957; 1 Brief mit Antwort von Sekretärin Jutta Hagen an Max Horkheimer, 1956; 1 Dissertationsauszug von Volker Freiherr von Hagen, 1954; 1 Brief mit Antwort von Julia Hagenbucher an Max Horkheimer, 1951/1952; 1 Entwurf zu einem Gratulationsschreiben von Max Horkheimer an Professor Otto Hahn, ohne Jahr; 2 Drucksachen von Obermagistratsrat Julius Hahn, 1953, 1955; 1 Brief mit Antwort von Theodor W. Adorno, von Dr. Hans Hahn an Max Horkheimer, 1952; 1 Brief von Theodor W. Adorno an Dr. Hans Hahn, 1952; 1 Danksagung von Rabbi Hugo Hahn, 1955; 3 Briefe mit Antwort von Paul Hahn an Max Horkheimer, 1951-1958; 1 Brief von Max Horkheimer an die Gebrüder Haldy, 1952; 1 Brief mit Antwort und Beilage von Professor George W. F. Hallgarten an Max Horkheimer, 1950; 1 Rundschreiben von Arzt und Psychotherapeut Hans Hammer, 1957; 1 Brief von Max Horkheimer an Margarete Hampf-Solm, 1955; 1 Brief mit Antwort von Professor Eduardo Hamuy an Max Horkheimer, 1952; 1 Brief von der Stadtärztin Dr. med. Carola Hannappel an Max Horkheimer, 1951; 1 Brief von Hansenmeister an Max Horkheimer, 1951; 1 Brief mit Antwort und Beilage von der Buchhandlung Ludwig Häntzschel an Max Horkheimer, 1958; 1 Brief von Professor Frederick Harris Harbison an Max Horkheimer, 1952; 3 Briefe mit Antwort von Robert Harcourt an Max Horkheimer, 1958; 1 Brief von Karl Hardach an Max Horkheimer, 1957; 1 Brief mit Antwort von Emilie Harlacher an Max Horkheimer, 1952; 1 Drucksache mit Antwort von Oberkirchenrat Otto L. A. von Harling an Max Horkheimer, 1955; 1 Brief mit Antwort von Gertrud Harms an Max Horkheimer, 1955; 2 Brief mit Antwort von Professor Wolfgang Hartke an Max Horkheimer, 1954-1956; 2 Briefe mit antwort von Max Horkheimer an Senator Georg Hartmann, 1951, 1954; 3 briefe mit Antwort und Beilage von Ökonom Heinz Hartmann an Max Horkheimer, 1956-1958; 1 Brief mit Antwort von Professor Wilbert E. Moore an Max Horkheimer, 1957; 3 Briefe mit Antwort und Beilage von Dr. phil. Leo Hartmann an Max Horkheimer, 1957-1858; 1 Brief mit Antowort von Dr. phil. Eckardt Mesch an Max Horkheimer, 1957; 1 Brief mit Antwort von Luzie Hatch an Max Horkheimer, 1954; 1 Brief von Max Horkheimer an den Direktor H. W. Haupt, 1950; 1 Drucksache von Haus Schwalbach, 1951; 4 Briefe mit Antwort von Professor Gottfried und Ellen Hausmann an Max Horkheimer, 1951-1958; 6 Briefe mit Antwort von Eva Haussner an Max Horkheimer, 1957, 1958; 1 Brief mit Antwort von Professor Robert J. Havighurst an Max Horkheimer, 1951; 1 Brief mit Beilage von Herbert Hax an Max Horkheimer, 1955; 2 Briefe mit Antwort und Beilage von Jean Louis Hébarre an Max Horkheimer, 1950-1952; 1 Brief mit Antwort von dem Hebedienst für Elektrizität, Gas und Wasser an Max Horkheimer, 1951; 5 Briefe mit Antwort und Beilage von Professor Otto Heckmann an Max Horkheimer, 1952, 1954; 1 Brief von Melvin J. Lasky an August Heckscher, 1957; 3 Briefe mit Antwort von Marie Heep an Max Horkheimer, 1956-1858; 1 Brief von der Buchhandlung Thekla Heer an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Verleger Jakob Hegner an Max Horkheimer, 1955; 1 Brief von Dr. phil. Rudolf M. Heilbrunn an Max Horkheimer, 1953; 1 Brief mit Antwort von Professor Eduard Heimann an Max Horkheimer, 1952; 1 Brief von Professor Eduard Heimann an Theodor W. Adorno, 1957; 1 Brief mit Antwort von stud. phil. Wolfgang Heinrich an Max Horkheimer, 1958; 1 Brief von Max Horkheimer an den Direktor Helmuth Heintzmann, 1955; 1 Aktennotiz von Professor Bernhard Heller, 1956; 1 Brief mit Antwort von Philipp A. Heller an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an Assistent Winfried Hellmann, 1957; 2 Briefe mit Antwort von Professor Arthur Henkel an Max Horkheimer, 1953/1954; 1 Brief von Max Horkheiemr an Dorothy Henkel, 1952; 2 Briefe mit Antwort von Dr. jur. Werner Hennig an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Professor Wilhelm Hennis, 1957; 3 Briefe mit Antwort und Beilage von Professor Fritz Hepner an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an den Hessischer Minister für Erziehung und Volksbildung, 1950; 1 Brief mit Antwort von Professor Henrietta Herbolsheimer an Max Horkheimer, 1957/1958; 2 Briefe mit Antwort von P. G. Herbst an Max Horkheimer, 1952; 1 Brief von Max Horkheimer an den Herder Verlag, 1953; 2 Briefe mit Antwort, Beilagen und Aktennotizen von Guenter R. Herz an Max Horkheimer, 1956-1957; 2 Briefe mit Antwort unv Beilagen von Professor Theodor W. Adorno, von Dr. phil. Günther Herzberg an Max Horkheimer, 1951-1953; 1 Brief von Professor Theodor W. Adrono an Dr. phil. Günther Herzberg, 1951; 1 Brief von Dr. phil. G. Herzfeld an Max Horkheimer, 1952; 1 Brief von dem Herzog-Film an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor Theodor W. Adorno, von Professor Erich Herzog an Max Horkheimer, 1952; 1 Brief von Professor Theodor W. Adorno an Professor Erich Herzog, 1952; 1 Brief mit Antwort von dem Verlag Otto H. Hess an Max Horkheimer, 1954; 1 Brief von Professor Gerhard Hess an Max Horkheimer, 1953; 1 Drucksachevon dem Hessischer Arbeitsausschuss gegen Rekrutierung, 1952; 1 Brief mit Beilage von dem Hotel Hessischer Hof an Max Horkheimer, 1956; 1 Brief mit Antwort von dem Hessischer Landesverband für Erwachsenenbildung an Max Horkheimer, 1956; 2 Briefe mit Antwort und Beilage von Marc Heurgon an Max Horkheimer, 1958; 1 Brief mit Beilage von Ruth Heydebrand an Max Horkheimer, [1955]; 1 Brief mit Antwort von Professor Frederick W. J. Heuser an Max Horkheimer, 1954; 2 Briefe mit Antwort von Professor Joh Erich Heyde an Max Horkheimer, 1958; 1 Befürwortung von Wolf von Heydebrand an Max Horkheimer, 1954; 1 Brief mit Antwort von Professor Heinz Joachim Heydorn an Max Horkheimer, 1953; 1 Brief mit Antwort und Beilage von dem Arzt Otto Heymann an Max Horkheimer, 1955; 5 Briefe zwischen dem Devisenberater und Steuerhelfer Joseph Christ und Max Horkheimer, 1955, 1956, 1961; 1 Brief von dem Office of the United States High Commissioner for Germany an Max Horkheimer, 1953; 1 Lebenslauf von Elen B. Hill, ohne Jahr; 1 Brief von Kurt H. Wolff an Max Horkheimer, 1952; 1 Brief von Rolf Himmelreich an Max Horkheimer, 1956; 1 Brief mit Antwort von Dr. Rolf Hinder an Max Horkheimer, 1953; 1 Brief mit Antwort von Anton Hinsinger an Max Horkheimer, 1953; 1 Brief mit Antwort von dem Hippokrates-Verlag an Max Horkheimer, 1952; 1 Brief von Bernice L. Hirsch anMax Horkheimer, 1957; 4 Briefe und Beilagen zwischen dem Historiker und Soziologe Helmut Hirsch an Max Horkheimer, 1951-1954, 25.05.1951; 3 Briefe mit Antwort von Lux Hirsch an Max Horkheimer, 1958; 1 Brief mit Antwort von Trude Hirschberg an Max Horkheimer, 1951; 1 Brief mit Antwort von Ingineur Paul F. Hirschfelder an Max Horkheimer, 1952; 1 Brief von Johannes Hirzel an Max Horkheimer, 1955; 1 Brief mit Antwort von dem Historisches Seminar Köln an Max Horkheimer, 1956; 1 Brief mit Antwort und Beilage von Professor Wolfgang Hochheimer an Professor Theodor W. Adorno, 1952; 2 Briefe von Max Horkheimer an Professor Wolfgang Hochheimer, 1953, 1954; 2 Memoranden von der Deutschen Gesellschaft für Psychologie, 1953; 1 Brief mit Beilage von Stud. phil. Erna Hochleitner an Max Horkheimer, 1956; 1 Brief mit Antwort von Professor Helmut Coing an Max Horkheimer, 1957; 3 Briefe mit Antwort von der Hochschule für Sozialwissenschaften Wilhelmshaven an Max Horkheimer, 1957, 1958; 1 Brief von Max Horkheimer an die Hochschule für Wirtschafts- und Sozialwissenschaften Nürnberg, 1953; 2 Drucksachen von dem Hochschul-Dienst, 1952; 2 Drucksachen von der Hochschule für politische Wissenschaften München, 1952; 1 Brief mit Antwort von Dr. Wolfram Hodermann an Max Horkheimer, 1951; 4 Briefe zwischen Dr. phil. Walter Höllerer und Max Horkheimer, 1956; 1 Brief mit Antwort von Privatdozent Dr. phil. Walter Hoeres anMax Horkheimer, 1956; 2 Briefe mit Antwort von Stud. phil. Charlotte Hoffmann an Max Horkheimer, 1950; 3 Briefe mit Antwort und Beilage von Professor Walter Hoffmann an Max Horkheimer, 1950-1955; 1 Brief mit Antwort von Wolfhart E. V. Hoffmann an Max Horkheimer, 1953; 1 Brief von Max Horkheimer an Dr. Werner Hofmann, 1956; 1 Glückwunschtelegramm mit Antwort von Ernst und Karl Hohner, 1953; 1 Brief von Dozent Uvo Hölscher an Max Horkheimer, 1950; 2 Briefe mit Antwort von Professor Dr. med. K. Holldack an Max Horkheimer, 1957; 2 Briefe mit Antwort von Dipl. Landwirt Bernhard Hollenhorst an Max Horkheimer, 1956; 1 Brief von Hans Heinz Holz an Max Horkheimer, 1951; 2 Briefe mit Antwort und Beilage von Dr. phil. Rudolf Holzinger an Max Horkheimer, 1951, 1952; 1 Brief mit Antwort von Jakob Hommen an Max Horkheimer, 1953; 1 Brief von Adele Hoppe anMax Horkheimer, 1953; 1 Brief mit Antwort von Dr. jur. Anton Horn an Max Horkheimer, 1954; 1 Brief mit Antwort von Dr. phil. Emil Horn an Max Horkheimer, 1953; 1 Brief von der Landesabgeordneten Ruth Horn an H. Maidon, 1953; 1 Brief mit Antwort von Reg.-Direktor Dr. phil. Kurt Horstmann an Max Horkheimer, 1953; 1 Brief von dem Hotel Baur au Lac an H. Maidon, 1958; 2 Briefe mit 1 Antwort von dem Hotel Frankfurter Hof an Max Horkheimer, 1956, 1958; 1 Brief mit Antwort von dem Hotel Stafflenberg an H. Maidon, 1953; 1 Brief von dem Hotel Vier Jahreszeiten, München an Max Horkheimer, 1951; 1 Brief von Max Horkheimer an Jean J. Hubener, 1951; 2 Briefe mit Antwort und Beilage von Susanna Huber-Weisser an Max Horkheimer, 1956; 1 Todesanzeige von dem Sozialgerichtsdirektor Gustav Adolf Hünniger, 1955; 1 Brief von dem Oberstudiendirektor F. Huf an Max Horkheimer, 1952; 1 Brief mit Antwort von Professor H. D. Huggins an Max Horkheimer, 1954; 2 Briefe mit 1 Antwort und 1 Beilage von dem Humboldt-Verlag, Wien-Stuttgart an Max Horkheimer, 1951; 1 Brief von Helge Pross an stud. rer. pol. Kristian Hungar, 1957; 1 Brief von Helmut Hungerland an Max Horkheimer, 1950; 1 Brief mit Antwort von James R. Huntley an Max Horkheimer, 1954; 1 Brief von Professor Robert Maynard Hutchins an Max Horkheimer, 1957;

Radiocarbon dates of sediments from ODP Site 161-976

Multiproxy paleoenvironmental records (pollen and planktonic isotope) from Ocean Drilling Program Site 976 (Alboran Sea) document rapid ocean and climate variations during the last glacial that follow the Dansgaard-Oeschger climate oscillations seen in the Greenland ice core records, thus suggesting a close link of the Mediterranean climate swings with North Atlantic climates. Continental conditions rapidly oscillated through cold-arid and warm-wet conditions in the course of stadial-interstadial climate jumps. At the time of Heinrich events, i.e., maximum meltwater flux to the North Atlantic, western Mediterranean marine microflora and microfauna show rapid cooling correlated with increasing continental dryness. Enhanced aridity conceivably points to prolonged wintertime stability of atmospheric high-pressure systems over the southwestern Mediterranean in conjunction with cooling of the North Atlantic.

Ice and snow measurements during Nathaniel B. Palmer cruise NBP0709 (SIMBA experiment)

The Sea Ice Mass Balance in the Antarctic (SIMBA) experiment was conducted from the RVIB N.B. Palmer in September and October 2007 in the Bellingshausen Sea in an area recently experiencing considerable changes in both climate and sea ice cover. Snow and ice properties were observed at 3 short-term stations and a 27-day drift station (Ice Station Belgica, ISB) during the winter-spring transition. Repeat measurements were performed on sea ice and snow cover at 5 ISB sites, each having different physical characteristics, with mean ice (snow) thicknesses varying from 0.6 m (0.1 m) to 2.3 m (0.7 m). Ice cores retrieved every five days from 2 sites and measured for physical, biological, and chemical properties. Three ice mass-balance buoys (IMBs) provided continuous records of snow and ice thickness and temperature. Meteorological conditions changed from warm fronts with high winds and precipitation followed by cold and calm periods through four cycles during ISB. The snow cover regulated temperature flux and controlled the physical regime in which sea ice morphology changed. Level thin ice areas had little snow accumulation and experienced greater thermal fluctuations resulting in brine salinity and volume changes, and winter maximum thermodynamic growth of ~0.6 m in this region. Flooding and snow-ice formation occurred during cold spells in ice and snow of intermediate thickness. In contrast, little snow-ice formed in flooded areas with thicker ice and snow cover, instead nearly isothermal, highly permeable ice persisted. In spring, short-lived cold air episodes did not effectively penetrate the sea ice nor overcome the effect of ocean heat flux, thus favoring net ice thinning from bottom melt over ice thickening from snow-ice growth, in all cases. These warm ice conditions were consistent with regional remote sensing observations of earlier ice breakup and a shorter sea ice season, more recently observed in the Bellingshausen Sea.