Auswahl der wissenschaftlichen Literatur zum Thema „Herman@s (Association)“

The Centre des livres d’artistes (cdla), which has been based in S aint-Yrieix-la-Perche since 1994, is the culmination of a project initiated at the end of the 1980s by the association Pays-paysage. After many years during which it lacked anywhere to develop its activities fully, the cdla has at last been installed in a refurbished building and opened early in 2005 with a new exhibition of books and publications by herman de vries. The two principal activities of the cdla are the creation and management of a collection of artists’ books (currently nearly 3000 items), and the organisation of exhibitions in France and also abroad.

Cisolok Village is a village with a geographical location bordering the Indonesian Ocean. It has the potential for marine tourism and supporting MSMEs. The digital marketing branding seminar with the theme of optimizing social media in introducing local products digitally is one of the efforts made in Community Service activities to be able to increase the insight of Cisolok Village MSME players to recognize digital marketing branding in the hope of increasing product recognition to the wider community and increasing sales profits. The Cisolok Village digital marketing branding seminar was held on Tuesday, August 08, 2023 at the Cisolok Village Office Hall with presenters Imelda D.S SE (Mother of UMKM Sukabumi), Herman Subandi S,Ip M.Si (DKUKM representative), and Rosita Juliyanti, S.I.Kom (online import clothing entrepreneur). The seminar was attended by participants from the Sukabumi UMKM association in Cisolok Village, as well as village officials, hamlet heads, neighborhood heads, PKK cadres and Posyandu cadres. Digital marketing branding is important for UMKM players because it can more easily promote their businesses due to wider reach, more efficient costs, direct interaction online (cyberspace) with consumers, and also the ease for entrepreneurs in choosing specific targets or potential customers according to the criteria of the business being undertaken.

Abstract Selpercatinib (LOXO-292, LY3527723) and pralsetinib (BLU-667) are first-in-class RET-targeted cancer therapy drugs. However, secondary RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation RET Tyrosine kinase inhibitors (TKIs). While the G810C/R/S/V mutations located at the RET kinase solvent-front site were detected in selpercatinib-treated patients, it was unclear whether all of these and other potential G810 mutants are resistant to selpercatinib and pralsetinib. We profiled selpercatinib and pralsetinib on all six possible G810 mutants derived from single nucleotide substitution. Surprisingly, the G810V mutant found in a clinical study was not resistant to selpercatinib or pralsetinib. Besides G810C/R/S, G810D also conferred selpercatinib/pralsetinib resistance. We found that alkynyl nicotinamide compounds such as HSN608 have better drug-like properties than alkynyl benzamides. HSN608 inhibited RET and RET V804M gatekeeper mutant, and all six G810 mutants with low nanomolar IC50s in the BaF3/KIF5B-RET mutant cell model. In cell derived xenograft (CDX) tumors driven by KIF5B-RET(G810C), HSN608 caused regression of the selpercatinib-resistant tumors. This study clarifies the sensitivities of different RET solvent-front mutants to selpercatinib and pralsetinib, and identifies an alkylnyl nicotinamide-based RET TKI for inhibiting selpercatinib/pralsetinib-resistant G810 mutants. Citation Format: Ujjwol Khatri, Neetu Dayal, Xueqing Hu, Elizabeth Larocque, Nimishetti Naganna, Tao Shen, Xuan Liu, Frederick W. Holtsberg, M. Javad Aman, Herman O. Sintim, Jie Wu. Targeting RET solvent-front mutants with an alkynyl nicotinamide-based inhibitor. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3851.

Abstract Rearranged during transfection (RET) is a protein tyrosine kinase that is aberrantly activated by gene fusions or mutations in many types of human cancer including thyroid cancer and non-small cell lung cancer (NSCLC). Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are FDA approved RET-selective tyrosine kinase inhibitors (TKIs) being used to treat RET-altered cancer. However, these tumors develop selpercatinib/pralsetinib-resistance via acquisition of RET(G810C/R/S) mutations located at the solvent front of the ATP binding pocket. The overall goal of our research is to discover next-generation of RET kinase inhibitors to inhibit selpercatinib/pralsetinib-resistant RET solvent-front mutants. In this study, we characterized one of the nicotinamide-based RET kinase inhibitor, HSN748, in vitro and in vivo. HSN748 was able to inhibit selpercatinib/pralsetinib-resistant RET(G810C/R) solvent-front mutations. In BaF3/KIF5B-RET(G810C) tumor xenograft experiment, HSN748 treatment resulted in tumor regression. In immune competent transgenic mice, KIF5B-RET-induced lung tumors regressed after HSN748 treatment by oral gavage for one month (10-15 mg/kg, QD) without affecting body weight. These results identify HSN748 as an orally available RET inhibitor capable of inhibiting KIF5B-RET and its solvent-front mutant-driven tumors. Citation Format: Ujjwol Khatri, Neetu Dayal, Tao Shen, Xueqing Hu, Herman Sintim, Jie Wu. Characterization of a nicotinamide-based kinase inhibitor HSN748 for inhibition of RET-driven tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4660.

Abstract Introduction: Identification of human subjects who qualify for a cancer trial can be challenging, particularly given narrow time frames for enrollment and highly specific criteria for eligibility. We sought to identify patients on a timely basis by matching trial criteria to data present in both the Pathology and clinical information systems. In a separate abstract submitted to the AACR meeting, we described the enrollment outcomes of our effort for two clinical trials. In this companion abstract, we describe the query methods that we employed. Methods: Method #1 involved querying structured data fields in the EMR, using dashboards or SQL queries of relational databases. Method #2 utilized natural language processing (NLP) queries of narrative text in pathology reports. We assessed the useability of each query approach, on a near-real-time basis, against eligibility criteria for open clinical trials at our institution. Results: We examined the first 25 open clinical trials for treatment of solid tumors listed publicly on our institutional website. For each trial, eligibility and query criteria were compiled by two reviewers (DC,YZ); discrepancies between reviewers were resolved by a third reviewer (NY). We found that of the 33 trials examined: 26 trials (79%) could be successfully analyzed by NLP in the pathology report. 2 trials (6%) required SQL query of discrete data fields in clinical databases. 2 trials (6%) required both methods to be used together. 3 trials (9%) required data elements outside the scope of either method. The data fields provided by NLP were: tumor morphology; tumor stage; specimen margin; and tumor receptor status. The data fields provided by SQL were: ICD 10 codes, CPT codes, Chemotherapy, and quantitative lab results. The data fields not accessible by either approach were: tumor resectability and risk calculation. Conclusion: There is no single method that is best for all trials, and availability of a broad set of tools is needed to craft a fitting query for each trial. However, 26 of 33 trials (79%) required NLP to parse eligibility criteria from narrative pathology reports. Cancer clinical trials enrollment may be substantially enhanced by NLP extraction of structured data from pathology reports as part of a near-real-time workflow for identifying eligible Human Subjects. Citation Format: Nalan Yurtsever, Yonah Ziemba, Daniel A. King, Dylan J. Cooper, Sergio Garza, Cheryl B. Schleicher, Sharon S. Fox, James M. Crawford, Joseph Herman. The need for structured pathology data in matching human subjects to cancer clinical trial criteria: A methodological approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3167.

Abstract The purpose of this study was to improve the identification and solicitation of human subject candidates to augment patient enrollment to clinical trials. In the past, our enrollment efforts involved manual mechanisms that began at the time that cancer patients were presented for care, most commonly at our chemotherapy clinics. We reasoned that computational review of pathology records may be far more efficient, allowing us to screen larger numbers of patients, and may allow us to intercept patients at the time of diagnosis, rather than time of care. We thus implemented a new workflow: (1) computational query of pathology database to filter candidates based on key eligibility criteria; (2) validation of the query using a clinical research coordinator, who can then (3) navigate the patient to the trial. As a proof of concept, starting in August of 2022, we selected two gastrointestinal oncology trials, the COBRA and PACES trial, based on trial eligibility that could be easily extracted using pathologic criteria, and because these trials had low enrollment. We designed computational queries to extract cohorts of potential patients whose surgery dates and pathology staging identified potential clinical trial candidates. A coordinator performed chart-review to validate these candidates. The trial coordinator then contacted the patient’s surgical oncologist, facilitated referral to a medical oncologist, and tracked the number of patients approached and consented. Whereas in a 12-month period preceding this new workflow, we had 0 and 1 patients approached for the PACES and COBRA trial, in the 3-month period following the new intervention, we had 8 and 2 patients approached. These data suggest computational cohort building and subsequent navigation have the potential to improve enrollment onto clinical trials and motivate extension of this work to additional trials. Table(s) Trial # of patients approached pre-intervention Computational Criteria Meeting computational criteria Coordinator validation criteria # of patients validated by coordinator # of patients connected with medical oncologist # of patients approached post-intervention PACES 0 Colorectal cancer, stage T0-T3,N0-1 Date Aug 2021 – July 2022 23 Facility location, No evidence of disease on colonoscopy performed 120 -456 days post-surgery, No chemotherapy, No other malignancy 18 8 8 COBRA 1 Colorectal cancer pT3N0resection date August 2022 – October 2022 18 ≥ 12 lymph nodes assessedPatient locationIf the subject appropriate for active surveillanceSurgery within 14-60 days of randomization 4 0 2 Citation Format: Yonah Ziemba, Kaitlin Parnahay, Paul Ward, Nalan Yurtsever, Sharon Fox, Cheryl Schleicher, Priya Singh-Shiwsankar, Vincent Vinciguerra, Joseph Herman, James M. Crawford, Daniel A. King. Computational cohort discovery and coordinator-led validation to navigate potential research candidates to clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3150.

Abstract Osteosarcoma (OS) is an aggressive pediatric solid tumor that is difficult to treat with established therapies. We performed CRISPR/Cas9 screening in 13 OS cell lines as part of the Dependency Map project. Mining this data to identify genes whose knockout (KO) leads to selective anti-viability in OS, we observed the helicase SMARCAL1 as a selective dependency in OS (p<0.0001; effect size = -0.275). Given the genomic instability of OS and SMARCAL1’s related, established role in replication stress, we first validated our screens by CRISPR KO in OS lines in vitro. This demonstrated selective antiviability of SMARCAL1 KO in dependent OS lines. To orthogonally validate SMARCAL1 dependency, we deployed a dTAG system, utilizing a hetero-bifunctional small molecule targeting the tagged protein for degradation by an E3 ubiquitin ligase. We observed antiviability of dependent lines after SMARCAL1 degradation. In parallel, in order to ascertain importance of this gene in vivo, we performed a barcoded CRISPR pooled screen against pre-selected OS dependencies in an OS cell line xenograft in NSG mice. After sequencing of tumor gDNA, we identified SMARCAL1 as a top hit, suggesting relevance in vivo.We next investigated biomarkers of SMARCAL1 dependency. A role for SMARCAL1 has been described in alternative lengthening of telomeres (ALT). We asked whether ALT+ OS cell lines are enriched for SMARCAL1 dependency. We found a correlation between ALT+ OS and SMARCAL1 dependence in our CRISPR screens. We then asked if this extends to other ALT+ tumors. Neuroblastoma (NB), the most common extracranial pediatric solid tumor, is enriched for ALT. When we looked specifically at NB models, we observed that SMARCAL1 was the most enriched dependency in ALT+ NB compared with other NB lines (p<0.0001; effect size = -0.785). We then performed SMARCAL1 KO in 2 ALT+ ATRX-altered NB lines and one ALT+ ATRX-WT NB line. We found that SMARCAL1 KO led to antiviability in the ATRX-altered ALT+ cell lines, while the ALT+ ATRX-WT cell line was unaffected. This suggests that dependency on SMARCAL1 is specific to ATRX alteration, rather than ALT alone.In order to confirm synthetic lethality between ATRX and SMARCAL1, we next utilized a human OS line not included in the DepMap screen, which has biallelic inactivation of SMARCAL1. We infected this line with our SMARCAL1 dTAG, leading to constitutive overexpression of SMARCAL1, and then performed ATRX KO. We observed that SMARCAL1 overexpression rescued the antiviability effect of ATRX KO. This could be reversed by degradation of exogenous SMARCAL1, suggesting that ATRX and SMARCAL1 can compensate for one another. Taken together, these findings demonstrate that SMARCAL1 is a selective dependency engendered by the loss of WT ATRX in OS and NB and that SMARCAL1 is playing a critical role in mediating ALT. Studies are ongoing to determine the mechanism of SMARCAL1’s activity and potential for targeting this enzyme for therapeutic benefit. Citation Format: Monika Wierdl, Jerrel L. Catlett, Nicole Ocasio-Martinez, Jon D. Johnson, Amy Herman, Neekesh V. Dharia, Gabriela Alexe, E. Alejandro Sweet-Cordero, Emily Bernstein, Kimberly Stegmaier, Lillian M. Guenther. SMARCAL1 is a novel synthetic lethal target in ALT+ osteosarcoma and neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3949.

- Jet Bakels, Robert Layton, The anthropology of art. Cambridge: Cambridge University Press, 1991, 258 pp. - J.M.S. Baljon, Herman Leonard Beck, De Islam in Nederland: Romancing religion? [Inaugurele rede theologische faculteit Tilburg 14.2.1992.] Tilburg: Tilburg University Press 1992. - R.H. Barnes, J.D.M. Platenkamp, North Halmahera: Non-Austronesian Languages, Austronesian cultures?, Lecture presented to the Oosters Genootschap in Nederland at Leiden on 23 May 1989, Leiden: Oosters Genootschap in Nederland, 1990. 33 pp. - Hans Borkent, Directory of Southeast Asianists in the Pacific Northwest. Compiled by: Northwest Regional Consortium for Southeast Asian Studies. Seattle, WA: University of Washington [et al.], 1990. 108 pp. - Roy Ellen, Frans Hüsken, Cognation and social organization in Southeast Asia. Verhandelingen van het Koninklijk Instituut voor Taal-, Land- en Volkenkunde 145. Leiden: KITLV Press, 1991, 221 pp. figs. tables, index., Jeremy Kemp (eds.) - C. de Jonge, Huub J.W.M. Boelaars, Indonesianisasi. Het omvormingsproces van de katholieke kerk in Indonesië tot de Indonesische katholieke kerk, Kerk en Theologie in Context, 13, Kampen: Kok, 1991, ix + 472 pp. - Nico de Jonge, Gregory Forth, Space and place in eastern Indonesia, University of Kent at Canterbury, Centre of South-east Asian Studies (Occasional Paper no. 16) 1991. 85 pp., ills. - J. Kommers, Bernard Juillerat, Oedipe chasseur. Une mythologie du sujet en Nouvelle-Guinée, P.U.F., Le fil rouge, section 1 Psychanalyse. Paris, 1991. - Gerco Kroes, Signe Howell, Society and cosmos, the Chewong of Peninsular Malaysia, University of Chicago Press, 1989, xv + 294 pp. - Daniel S. Lev, S. Pompe, Indonesian Law 1949-1989: A bibliography of foreign-language materials with brief commentaries on the law, Van Vollenhoven Institute for Law and Administration in Non-Western Countries. Nijhoff, 1992. - A. M. Luyendijk-Elshout, H. den Hertog, De militair geneeskundige verzorging in Atjeh, 1873-1904. Amsterdam, Thesis Publishers, 1991. - G.E. Marrison, Wolfgang Marschall, The Rejang of South Sumatra. Hull: Centre for South-east Asian Studies, 1992, iii + 93 pp., ill. (Occasional Papers no. 19: special issue)., Michele Galizia, Thomas M. Psota (eds.) - Harry A. Poeze, Marijke Barend-van Haeften, Oost-Indie gespiegeld; Nicolaas de Graaff, een schrijvend chirurgijn in dienst van de VOC. Zutphen: Walburg Pers, 1992, 279 pp. - Ratna Saptari, H. Claessen, Het kweekbed ontkiemd; Opstellen aangeboden aan Els Postel. Leiden: VENA, Faculty of Social Sciences, University of Leiden, P.O. Box 9555, 2300 RA., M. van den Engel, D. Plantenga (eds.) - Jerome Rousseau, James J. Fox, The heritage of traditional agriculture among the western Austronesians. Occasional paper of the department of Anthropology. Comparitive Austronesian Project. Research school of Pacific studies. Australian National University, Canberra, Australia, 1992. 89 pp. - Oscar Salemink, Gehan Wijeyewardene, Ethnic groups acrss National boundaries in mainland Southeast Asia. Singapore 1990, Institute of Southeast Asian studies (Social issues in Southeast Asia series). x + 192 pp. - Henk Schulte Nordholt, U. Wikan, Managing turbulent hearts. A Balinese formula for living, Chicago: University of Chicago Press. 1990, xxvi + 343 pp. photos. - Mary Somers Heidhues, Claudine Salmon, Le moment ‘sino-malais’ de la litterature indonesienne. [Cahier d’Archipel 19.] Paris: Association Archipel, 1992. - Heather Sutherland, J.N.F.M. à Campo, Koninklijke Paketvaart Maatschappij; Stoomvaart en staatsvorming in de Indonesische archipel 1888-1914, Hilversum: Verloren, (Erasmus Universiteit Rotterdam, Publikaties van de Faculteit der Historische en Kunstwetenschappen III), 1992, 756 pp., tables, graphics, photographs. - Gerard Termorshuizen, Robin W. Winks, Asia in Western fiction. Honolulu: University of Hawaii Press, 1990. x + 229 pp., James R. Rush (eds.) - John Verhaar, Lourens de Vries, The morphology of Wambon of the Irian Jaya Upper-Digul area. Leiden: KITLV Press, 1992, xiv + 98 pp., Robinia de Vries-Wiersma (eds.) - Maria van Yperen, Cornelia N. Moore, Translation East and West: A cross-cultural approach, Honolulu: University of Hawaii Press. xxv + 259 pp., Lucy Lower (eds.) - Harvey Whitehouse, Klaus Neumann, Not the way it really was: constructing the Tolai past. Honolulu: University of Hawaii Press, 1992.

Abstract Introduction: Emergence of resistance to immune checkpoint blockade (ICB) mandates the development of strategies for ICB sensitization. Here we employed a multi-omic approach to understand the effects of epigenetic priming in re-shaping the tumor microenvironment, together with genomic drivers of therapeutic response of epigenetic therapy followed by ICB in non-small cell lung cancer (NSCLC). Methods: We performed whole exome sequencing (WES) on 39 baseline tumors and bulk RNA sequencing (RNAseq) on 18 serial tumors across 42 patients with metastatic immunotherapy-naïve NSCLC, who received azacitidine and entinostat followed by nivolumab (NCT01928576). WES was utilized to assess co-mutations, mutation signatures and genome-wide structural changes. RNAseq was utilized for gene and gene set enrichment analysis (GSEA) and repeat element analysis. Response after nivolumab initiation was assessed using RECIST 1.1 criteria. Patients who were progression-free at 6 months or alive at 2 years after initial treatment were defined as exceptional responders. Results: We found an enrichment in inactivating mutations in homologous recombination genes in radiographic responders (Fisher’s exact, p=0.0007). Higher germline and somatic HLA class II diversity (Mann-Whitney U-test, p=0.05 and p=0.03 respectively), and an enrichment of smoking and DNA damage mutational signatures were noted in radiographic responders (Mann-Whitney U-test, p=0.03 and p=0.15 respectively). Radiographically responding tumors harbored a higher number of mutations in genomic regions that were haploid or present in multiple copies (persistent tumor mutation burden; Mann-Whitney U-test, p=0.018). GSEA revealed an upregulation of inflammatory response gene sets post-epigenetic therapy in patients attaining an exceptional response. Antigen presentation, interferon-alpha, and interferon-gamma related gene sets were upregulated in exceptional responders post epigenetic priming (FDR-adjusted p=0.005, p=0.009, and p=0.011 respectively). Additionally, we observed an enrichment in interferon-alpha, cancer testis antigens, and interferon-gamma related gene sets in patients with a longer progression-free survival (FDR-adjusted p=0.007, p=0.011, and p=0.013 respectively). Repeat element analysis showed an increase in long terminal repeats on-therapy in exceptional responders, suggesting induction of repeat element expression with epigenetic therapy. A higher expression of MAGE family tumor associated antigens (MAGEA10, MAGEB1, MAGEB2) was noted post-epigenetic therapy in exceptional responders. Conclusions: Genomic and transcriptomic analyses reveal the potential of epigenetic-priming to re-shape the tumor microenvironment and highlight patients that could benefit from combination epigenetic therapy with immunotherapy. Citation Format: Blair V. Landon, Kristen A. Marrone, Michael J. Topper, Akshaya Annapragada, Hua-Ling Tsai, Archana Balan, Noushin Niknafs, Christopher Cherry, James R. White, Gavin Pereira, Vilmos Adleff, Chen Hu, Joanne Riemer, Margaret Fitzpatrick, Patrick Forde, Christine L. Hann, Ronan J. Kelly, David S. Ettinger, Benjamin Levy, Jorge Nieva, James Herman, Victor E. Velculescu, Stephen Baylin, Julie Brahmer, Valsamo Anagnostou. Comprehensive genomic and transcriptomic analyses capture the effects of epigenetic therapy priming on immune checkpoint blockade response in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6551.

- Tim Behrend, Nancy K. Florida, Javanese literature in Surakarta manuscripts; Volume 2; Manuscripts of the Mangkunagaran palace. Ithaca, New York: Cornell University Southeast Asia Program, 2000, 575 pp. - Harold Brookfield, Judith M. Heimann, The most offending soul alive; Tom Harrisson and his remarkable life. Honolulu: University of Hawai’i Press, 1998, 468 pp. - Harold Brookfield, Victor T. King, Rural development and social science research; Case studies from Borneo. Phillips, Maine: Borneo Research Council, 1999, xiii + 359 pp. [Borneo Research Council Proceedings Series 6.] - J.G. de Casparis, Roy E. Jordaan, The Sailendras in Central Javanese history; A survey of research from 1950 to 1999. Yogyakarta: Penerbitan Universitas Sanata Dharma, 1999, iv + 108 pp. - H.J.M. Claessen, Francoise Douaire-Marsaudon, Les premiers fruits; Parenté, identité sexuelle et pouvoirs en Polynésie occidentale (Tonga, Wallis et Futuna). 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When Caxton Foster of the University of Massachusetts published his book Computer Architecture in 1970, this term was only just being recognized, reluctantly, by the computing community. This despite an influential paper published in 1964 by a group of IBM engineers on the “Architecture of the IBM System/360.” For instance, ACM’s “Curriculum 68” made no mention of the term in its elaborate description of the entire scope of computing as an academic discipline. Rather, in the late 1960s and well into the ’70s terms such as computer organization, computer structures, logical organization, computer systems organization, or, most blandly, computer design were preferred to describe computers in an abstract sort of way, independent of the physical (hardware) details. Thus a widely referenced paper by Michael Flynn of Stanford University, published in 1974, was titled “Trends and Problems in Computer Organization.” And Maurice Wilkes, even in the third edition of his Time-Sharing Computer Systems (1975) declined to use the term computer architecture. Yet, computer architecture as both an abstract way of looking at, understanding, and designing computers, and as a field of computer science emerged in the first years of the ’70s. The Institute of Electrical and Electronics Engineers (IEEE) founded a Technical Committee on Computer Architecture (TCCA) in 1970 to join the ranks of other specialist IEEE TCs. The Association for Computing Machinery (ACM) followed suit in 1971 by establishing, alongside other special-interest groups, the Special Interest Group on Computer Architecture (SIGARCH). And in 1974, the first of what came to be the annual International Symposium on Computer Architecture (ISCA) was held in Gainesville, Florida. By the end of the decade a series of significant textbooks and articles bearing the term computer architecture(s) had appeared. The reason for naming an aspect of the computer its “architecture” and the reason for naming an academic and research discipline “computer architecture” can be traced back to the mid-1940s and the paradigm-shaping unpublished reports by John von Neumann of the Institute of Advanced Study, Princeton, and his collaborators, Arthur Burks and Herman Goldstine.

Abstract The free-standing company (FSC) was studied initially in the context of British economic history. Soon the question was raised, to what extent were FSCs headquartered in other states? In Chapter 11, Ben Gales and Keetie Sluyterman considered Holland as home to FSCs; my interest is in Belgium, Germany, and Switzerland. I have noted in an earlier book that the majority of Belgian foreign direct investment (FDI) was carried out through FSCs. In Chapter 5 herein, Peter Hertner showed that Belgian FSCs ‘ investment in Italy was substantial, second only to the British interest. By contrast, other nations with a sizeable share of the FDI in Italy, such as Switzerland or Germany, played a small or even insignificant role there in foreign investments made by FSCs.My opening question is, to what extent are my prior findings on Belgium and Peter Hertner ‘s evidence, which was gathered for one major host nation, confirmed by further research? Thus, my first sec-tion will offer data on FSCs headquartered in Belgium, Germany, and Switzerland, providing information on numbers, destinations, periods of foundation, branches of industries, finance, and so forth. The second part of this chapter will be devoted to special problems that arose during my research and also the association of my empirical materials with the emerging theory on the FSC.

Alessandro Camiz ¹ ¹ Department of Architecture, Girne American University, Cyprus, Association for Historical Dialogue and Research, Home for Cooperation (H4C), 28 Marcou Dracou Street, Nicosia, Cyprus, 1102. E-mail: alessandrocamiz@gau.edu.tr Keywords (3-5): urban tissues, urban morphology, urban routes, theory, history Conference topics and scale: Tools of analysis in urban morphology Recent urban morphology studies consider urban tissues as living organisms changing in time (Strappa, Carlotti, Camiz, 2016), following this assumption the theory should examine more analytically what Muratori called ‘medievalisation’ (Muratori, 1959), a term describing some of the transformations of urban routes happened in the middle ages. The paper considers the diachronic deformation of routes, and other multi-scalar occurrences of the attraction phenomena (Charalambous, Geddes, 2015), introducing the notion of attractors and repellers. Archaeological studies already do consider attractors and repellers as a tool to interpret some territorial transformations, following the assumption that “the trajectory that a system follows through time is the result of a continuous dynamic interaction between that system and the multiple 'attractors' in its environment” (Renfrew, Bahn, 2013, p. 184). There are different elements that can act as attractors in an urban environment, such as bridges, city walls, city gates, water systems, markets, special buildings, and it is possible to consider each of these anthropic attractors as equivalent to a morphological attractor at the geographical scale. We can even interpret the ridge-top theory (Caniggia, 1976) as the result of attraction and repellence of geographic features on anthropic routes. The territorial scale analysis is the methodological base of the theory, but the attractors herein considered operate at the urban scale, deviating locally across time from a rectilinear trajectory and defining a specific urban fabric. The research interprets and reads the effects of attractors on urban routes and fabrics as a method for the reconstruction of Nicosia’s medieval city walls, in continuity between the Conzenian approach (Whitehand, 2012) and the Italian School of Urban Morphology (Marzot, 2002). References:, Muratori, S. (1959) Studi per un’operante storia urbana di Venezia (Istituto Poligrafico dello Stato, Roma). Caniggia, G. (1976) Strutture dello spazio antropico. Studi e note (Uniedit, Firenze). Marzot, N. (2002) ‘The study of urban form in Italy’, Urban Morphology 6.2, 59-73. Whitehand, J.W.R. (2012) ‘Issues in urban morphology’, Urban Morphology 16.1, 55-65. Renfrew, C., Bahn, P. (eds.) (2013) Archaeology: The Key Concepts, (London, Routledge). Charalambous, N., Geddes, I. (2015) ‘Making Spatial Sense of Historical Social Data’, Journal of Space Syntax 6.1, 81-101. Strappa, G., Carlotti, P., Camiz, A. (2016) Urban Morphology and Historical Fabrics. Contemporary design of small towns in Latium (Gangemi, Roma).

Objectives: We seek to establish the basis for improving cotton productivity under arid conditions, by studying the water use efficiency - evaporative cooling interrelationship. Specifically, we will test the hypothesis that cotton productivity under arid conditions can be improved by combining high seasonal WUE with efficient evaporative cooling, evaluate whether high WUE and/or evaporative cooling are based on specific physiological factors such as diurnal flexibility in stomatal conductance, stomatal density, photosynthetic capacity, chlorophyll fluorescence, and plant water status. Genes influencing both WUE and evaporative cooling, as well as other parameters such as economic products (lint yield, quality, harvest index) of cotton will also be mapped, in order to evaluate influences of water relations on these parameters. Approach: Carbon isotope ratio will be used to evaluate WUE, accompanied by additional parameters to elucidate the relationship between WUE, evaporative cooling, and cotton productivity. A detailed RFLP map will be used to determine the number, location, and phenotypic effects of genes underlying genetic variation in WUE between cultivated cottons, as well as test associations of these genes with traits of economic importance such as harvest index, lint yield, and lint quality. Major Conclusions: Productivity and quality of cotton grown under well-watered versus water-limited conditions was shown to be partly accounted for by different quantitative trait loci (QTLs). Among a suite of physiological traits often found to differ between genotypes adapted to arid versus well-watered conditions, genetic mapping implicated only reduced plant osmotic potential in improved cotton productivity under arid conditions. Our findings clearly implicate OP as a major component of cotton adaptation to arid conditions. However, testing of further physiological hypotheses is clearly needed to account for additional QTL alleles conferring higher seed-cotton yield under arid conditions, such as three of the five we found. Near-isogenic lines being made for QTLs discovered herein will offer a powerful new tool useful toward identification of the underlying gene(s) by using fine-scale mapping approaches (Paterson et al 1990). Implications: Adaptation to both arid and favorable conditions can be combined into the same genotype. We have identified diagnostic DNA markers that are being applied to creation of such desirable genotypes. Simultaneous improvement of productivity (and/or quality) for both arid and irrigated conditions will require more extensive field testing and the manipulation of larger numbers of genes, reducing the expected rate of genetic gain These difficulties may be at least partly ameliorated by efficiencies gained through identification and use of diagnostic DNA markers. Genomic tools and approaches may expedite adaptation of crops to arid cultivation, help to test roles of additional physiological factors, and guide the isolation of the underlying genes that protect crop performance under arid conditions.