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Article: 'Fly-ing' from rare to common neurodegenerative disease mechanisms.

Ma, Mengqi / Moulton, Matthew J / Lu, Shenzhao / Bellen, Hugo J

2022 Volume 38, Issue 9, Page(s) 972–984

Abstract: Advances in genome sequencing have enabled researchers and clinicians to probe vast numbers of human variants to distinguish pathogenic from benign variants. Model organisms have been crucial in variant assessment and in delineating the molecular ... ...

Abstract	Advances in genome sequencing have enabled researchers and clinicians to probe vast numbers of human variants to distinguish pathogenic from benign variants. Model organisms have been crucial in variant assessment and in delineating the molecular mechanisms of some of the diseases caused by these variants. The fruit fly, Drosophila melanogaster, has played a valuable role in this endeavor, taking advantage of its genetic technologies and established biological knowledge. We highlight the utility of the fly in studying the function of genes associated with rare neurological diseases that have led to a better understanding of common disease mechanisms. We emphasize that shared themes emerge among disease mechanisms, including the importance of lipids, in two prominent neurodegenerative diseases: Alzheimer's disease (AD) and Parkinson's disease (PD).
MeSH term(s)	Alzheimer Disease/genetics ; Animals ; Disease Models, Animal ; Drosophila ; Drosophila melanogaster/genetics ; Humans ; Neurodegenerative Diseases/genetics ; Parkinson Disease/genetics
Language	English
Publishing date	2022-04-25
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2022.03.018
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Article ; Online: Lnc-ing pluripotency maintenance and early differentiation in human pluripotent stem cells.

Lu, Pei / Li, Mao / Zhang, Donghui / Jiang, Wei

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 4, Page(s) e21438

Abstract: Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self-renewal or differentiation is under the exquisite control of the gene regulatory network, ... ...

Abstract	Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self-renewal or differentiation is under the exquisite control of the gene regulatory network, which is composed of transcription factors, signaling pathways, metabolic factors, chromatin or histone modifiers, miRNAs, and lncRNAs. Growing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in epigenetic, transcriptional, and posttranscriptional gene regulation during the cell fate determination of pluripotent stem cells. Here, we summarize recent reports of lncRNA functions in pluripotency maintenance/exit and the early germ layer specification of human pluripotent stem cells. We also illustrate four major lncRNA functional mechanisms according to different types of cofactors: chromatin or histone modifiers, transcription factors, canonical and noncanonical RNA-binding proteins, and miRNAs. Further understanding of lncRNA-based regulation will provide more insights into the drivers manipulating cell fate and promote the therapeutic and research potential of human embryonic and induced pluripotent stem cells.
MeSH term(s)	Cell Differentiation/physiology ; Humans ; Pluripotent Stem Cells/physiology ; RNA, Long Noncoding/physiology
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2021-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202002278R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The fission yeast inhibitor of growth (ING) protein Png1p functions in response to DNA damage.

Chen, Jian-Qiang / Li, Yang / Pan, Xian / Lei, Bing-Kun / Chang, Cheng / Liu, Zheng-Xun / Lu, Hong

The Journal of biological chemistry

2010 Volume 285, Issue 21, Page(s) 15786–15793

Abstract: In budding yeast and human cells, ING (inhibitor of growth) tumor suppressor proteins play ... with histone acetyltransferase or histone deacetylase complexes. However, the biological functions of ING family proteins ... in fission yeast are poorly defined. Here, we report that Png1p, a fission yeast ING homolog protein, is required ...

Abstract	In budding yeast and human cells, ING (inhibitor of growth) tumor suppressor proteins play important roles in response to DNA damage by modulating chromatin structure through collaborating with histone acetyltransferase or histone deacetylase complexes. However, the biological functions of ING family proteins in fission yeast are poorly defined. Here, we report that Png1p, a fission yeast ING homolog protein, is required for cell growth under normal and DNA-damaged conditions. Png1p was further confirmed to regulate histone H4 acetylation through collaboration with the MYST family histone acetyltransferase 1 (Mst1). Additionally, both fission yeast PNG1 and MST1 can functionally complement their budding yeast correspondence homologs YNG2 and ESA1, respectively. These results suggest that ING proteins in fission yeast might also conserve function, similar to ING proteins in budding yeast and human cells. We also showed that decreased acetylation in Deltapng1 cells resulted in genome-wide down-regulation of 756 open reading frames, including the central DNA repair gene RAD22. Overexpression of RAD22 partially rescued the png1 mutant phenotype under both normal and DNA-damaged conditions. Furthermore, decreased expression of RAD22 in Deltapng1 cells was confirmed to be caused by decreased H4 acetylation at its promoter. Altogether, these results indicate that Png1p is required for histone H4 acetylation and functions upstream of RAD22 in the DNA damage response pathway.
MeSH term(s)	Acetylation ; Chromatin/genetics ; Chromatin/metabolism ; DNA Damage/physiology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Deletion ; Gene Expression Regulation, Fungal/physiology ; Histone Acetyltransferases/genetics ; Histone Acetyltransferases/metabolism ; Histone Deacetylases/genetics ; Histone Deacetylases/metabolism ; Histones/genetics ; Histones/metabolism ; Humans ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Chromatin ; DNA-Binding Proteins ; Histones ; Png1 protein, S pombe ; Schizosaccharomyces pombe Proteins ; Tumor Suppressor Proteins ; rad52 protein, S pombe ; Histone Acetyltransferases (EC 2.3.1.48) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2010-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M110.101832
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Article: The Fission Yeast Inhibitor of Growth (ING) Protein Png1p Functions in Response to DNA Damage

Chen, Jian-Qiang / Li, Yang / Pan, Xian / Lei, Bing-Kun / Chang, Cheng / Liu, Zheng-Xun / Lu, Hong

Journal of biological chemistry. 2010 May 21, v. 285, no. 21

2010

Abstract	In budding yeast and human cells, ING (inhibitor of growth) tumor suppressor proteins play important roles in response to DNA damage by modulating chromatin structure through collaborating with histone acetyltransferase or histone deacetylase complexes. However, the biological functions of ING family proteins in fission yeast are poorly defined. Here, we report that Png1p, a fission yeast ING homolog protein, is required for cell growth under normal and DNA-damaged conditions. Png1p was further confirmed to regulate histone H4 acetylation through collaboration with the MYST family histone acetyltransferase 1 (Mst1). Additionally, both fission yeast PNG1 and MST1 can functionally complement their budding yeast correspondence homologs YNG2 and ESA1, respectively. These results suggest that ING proteins in fission yeast might also conserve function, similar to ING proteins in budding yeast and human cells. We also showed that decreased acetylation in Δpng1 cells resulted in genome-wide down-regulation of 756 open reading frames, including the central DNA repair gene RAD22. Overexpression of RAD22 partially rescued the png1 mutant phenotype under both normal and DNA-damaged conditions. Furthermore, decreased expression of RAD22 in Δpng1 cells was confirmed to be caused by decreased H4 acetylation at its promoter. Altogether, these results indicate that Png1p is required for histone H4 acetylation and functions upstream of RAD22 in the DNA damage response pathway.
Language	English
Dates of publication	2010-0521
Size	p. 15786-15793.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
Database	NAL-Catalogue (AGRICOLA)

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Article: A similar ecological development historical city: The study on the spatial distribution and pattern evolution of the planning history of the Manchu city in the Ch'ing Dynasty of Ancient China

Lu, Chuan / Li, Baihao

Ecological informatics. 2021 Sept., v. 64

2021

Abstract: ... of urban sites conforming to nature and the natural attributes of cities.The rulers of the Ch'ing Dynasty ... In order to consolidate the monarchy and colonize new territories, the Ch'ing Dynasty implemented the Eight ... is based on the official documents of the Ch'ing Dynasty, investigating the history of overall ...

Abstract	Ancient China attached great importance to urban ecology, which is reflected in the selection of urban sites conforming to nature and the natural attributes of cities.The rulers of the Ch'ing Dynasty paid full attention to the cities of the Ming Dynasty, took the military as the driving force and paid attention to the urban ecology, and built a large number of military and national cities accordingly. In order to consolidate the monarchy and colonize new territories, the Ch'ing Dynasty implemented the Eight Banners Garrison System and built Manchu cities in the interior and parts of the border areas. This paper is based on the official documents of the Ch'ing Dynasty, investigating the history of overall planning of the Manchu City, gradually collecting and analyzing its analogical biological evolution from the northeast region to the whole nation of the Ch'ing Dynasty. Besides, the paper argues that the spatial pattern of Manchu city is characterized by its hierarchy, defensiveness and connectivity, and summarizes the integrated planning of Manchu city, and reveal the intrinsic correlation between its planning and the changes of territory in the Ch'ing Dynasty. The planning and construction of Manchu cities implied the use of natural and social attributes of historical cities.At the same time, the military and urban planning of the Ch'ing Dynasty also provide useful insights and historical thoughts for homeland space security and land planning nowadays.
Keywords	ecology ; evolution ; China
Language	English
Dates of publication	2021-09
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2212016-6
ISSN	1878-0512 ; 1574-9541
ISSN (online)	1878-0512
ISSN	1574-9541
DOI	10.1016/j.ecoinf.2021.101394
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E)

Ing Ni Lu / Spoorthy Kulkarni / Marie Fisk / Michalis Kostapanos / Edward Banham-Hall / Sonakshi Kadyan / Simon Bond / Sam Norton / Andrew Cope / James Galloway / Frances Hall / David Jayne / Ian B. Wilkinson / Joseph Cheriyan

Trials, Vol 21, Iss 1, Pp 1-

A structured summary of a study protocol for a randomized controlled trial

2020 Volume 3

Abstract: Abstract Objectives To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ... ...

Abstract	Abstract Objectives To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Trial design Randomised, parallel arm, open-label, adaptive platform Phase 2/3 trial of potential disease modifying therapies in patients with late stage 1/stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical, laboratory and radiological assessment. Participants Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a risk count (as defined below) >3 OR ≥3 if risk count includes “Radiographic severity score >3”. A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x109/L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator and are able to swallow capsules or tablets. The complete inclusion and exclusion criteria as detailed in the Additional file 1 should be fulfilled. Drug specific inclusion and exclusion criteria will also be applied to the active arms. Patients will be enrolled prior to the need for invasive mechanical ventilation, cardiac or renal support. Participants will be recruited across multiple centres in the UK including initially at Cambridge University Hospitals NHS Foundation Trust and St George’s University NHS Foundation Trust. Other centres will be approached internationally in view of the evolving pandemic. Intervention and ...
Keywords	COVID-19 ; Randomised controlled trial ; Protocol ; Open-label ; Adaptive trial ; EDP1815 ; Medicine (General) ; R5-920 ; covid19
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial.

Lu, Ing Ni / Kulkarni, Spoorthy / Fisk, Marie / Kostapanos, Michalis / Banham-Hall, Edward / Kadyan, Sonakshi / Bond, Simon / Norton, Sam / Cope, Andrew / Galloway, James / Hall, Frances / Jayne, David / Wilkinson, Ian B / Cheriyan, Joseph

Trials

2020 Volume 21, Issue 1, Page(s) 690

Abstract: Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ... ...

Abstract	Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Trial design: Randomised, parallel arm, open-label, adaptive platform Phase 2/3 trial of potential disease modifying therapies in patients with late stage 1/stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical, laboratory and radiological assessment. Participants: Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a risk count (as defined below) >3 OR ≥3 if risk count includes "Radiographic severity score >3". A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x10 Intervention and comparator: There is increasing evidence of the role of immunomodulation in altering the course of COVID-19. Additionally, various groups have demonstrated the presence of pulmonary shunting in patients with COVID-19 as well as other cardiovascular complications. TACTIC-E will assess the efficacy of the novel immunomodulatory agent EDP1815 versus the approved cardio-pulmonary drugs, Dapagliflozin in combination with Ambrisentan versus the prevailing standard of care. EDP1815 will be given as 2 capsules twice daily (1.6 x 10 Main outcomes: The primary outcome is the incidence (from baseline up to Day 14) to the occurrence of the any one of the following events: death, invasive mechanical ventilation, extra corporeal membrane oxygenation, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Randomisation: Eligible patients will be randomised using a central web-based randomisation service (Sealed Envelope) in a 1:1:1 ratio, stratified by site to one of the treatment arms or standard of care. Blinding (masking): This is an open-label trial. Data analysis will not be blinded. Numbers to be randomised (sample size): There is no fixed sample size for this study. There will be an early biomarker-based futility analysis performed at a point during the study. If this biomarker futility analysis is not conclusive, then a second futility analysis based on clinical endpoints will be performed after approximately 125 patients have been recruited per arm. Provisionally, further analyses of clinical endpoints will be performed after 229 patients per active arm and later 469 patients per arm have been recruited. Further additional analyses may be triggered by the independent data monitoring committee. Trial status: TACTIC-E Protocol version number 1.0 date May 27 Trial registration: Registered on EU Clinical Trials Register EudraCT Number: 2020-002229-27 registered: 9 June 2020. The trial was also registered on ClinicalTrials.gov (NCT04393246) on 19 May 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
MeSH term(s)	Humans ; Benzhydryl Compounds/administration & dosage ; COVID-19 ; COVID-19 Drug Treatment ; Glucosides/administration & dosage ; Immunologic Factors/therapeutic use ; Intensive Care Units ; Pandemics ; Phenylpropionates/administration & dosage ; Pyridazines/administration & dosage ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; Standard of Care ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Adult
Chemical Substances	ambrisentan (HW6NV07QEC) ; Benzhydryl Compounds ; dapagliflozin (1ULL0QJ8UC) ; Glucosides ; Immunologic Factors ; Phenylpropionates ; Pyridazines
Keywords	covid19
Language	English
Publishing date	2020-07-31
Publishing country	England
Document type	Clinical Trial Protocol ; Letter
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-020-04618-2
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Article ; Online: muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E)

Trials

A structured summary of a study protocol for a randomized controlled trial

2020 Volume 21, Issue 1

Keywords	Medicine (miscellaneous) ; Pharmacology (medical) ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2040523-6
ISSN	1468-6694 ; 1745-6215 ; 1468-6708
ISSN (online)	1468-6694 ; 1745-6215
ISSN	1468-6708
DOI	10.1186/s13063-020-04618-2
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: muLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E)

A structured summary of a study protocol for a randomized controlled trial.

2020

Keywords	Humans ; Pneumonia ; Viral ; Coronavirus Infections ; Phenylpropionates ; Benzhydryl Compounds ; Pyridazines ; Glucosides ; Immunologic Factors ; Respiration ; Artificial ; Intensive Care Units ; Randomized Controlled Trials as Topic ; Pandemics ; Standard of Care ; Betacoronavirus ; covid19
Language	English
Publishing date	2020-07-31
Publisher	Trials
Publishing country	uk
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A critique of Teng Hsiao-P' ing's compradorbourgesois economic thought

Kao, Lu / Ch'ang Ko

Chinese economic studies : a journal of translations Vol. 11, No. 1 , p. 52-63

1977 Volume 11, Issue 1, Page(s) 52–63

Author's details	Lu Kao and Ch'ang Ko
Keywords	Teng, Hsiao-P'ing
Publisher	Sharpe
Publishing place	New York, NY
Document type	Article
Note	Übers. aus: Jen-min jih-pao People's Daily. 1976, July ; über: Teng Hsiao-P'ing
ZDB-ID	422715-3
Database	ECONomics Information System

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