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1.  Moderately and Heavily Used Biomedical Journals * 
The purpose of this investigation was to produce a title list of current journals supplying upwards of 75 percent of demand at the Columbia and Yale Medical Libraries. Columbia received nearly 2,000 journals and Yale over 1,500; findings are based upon an analysis of canceled charge slips for issues published from 1959 through June 1962. This combined study of recorded usage for six months in the Columbia Medical Library (12.9 percent of circulation during January through June 1962) and for one year in the Yale Medical Library (12.5 percent of 1961/62 circulation) revealed that a core of 262 journals supplied 80 percent of use of titles published in the 1959 to mid-1962 period. However, it is probable that current issues of all titles received were used at least once within the libraries. Titles of sixty-seven journals which supplied slightly more than 50 percent of use are listed.
PMCID: PMC198101  PMID: 14119296
2.  Harvey Cushing’s Ghosts: Death and Hauntings in Modern Medicine 
The passing of Yale School of Medicine’s 2010 Bicentennial occasions a moment of reflecting on the past, present, and future of medical education and research at Yale and beyond. Last June, a ribbon-cutting ceremony inaugurated the opening of the Cushing Center in the Cushing-Whitney Medical Library. Named after Harvey Cushing, an early 20th-century neurosurgeon and former Yale College alum, the dual education/exhibition space now houses hundreds of gross brain specimens constituting the Cushing Tumor Registry. Originally a personal collection, Cushing donated his numerous medical specimens, photographs, and other medical relics from his deathbed, relinquishing the brains to Yale only under the condition that a suitable space be erected to preserve the many specimens. Some 70 years later and after nearly being destroyed, Cushing’s wish is fully realized: The once desiccated, hidden brains have been painstakingly restored and are now on view in the Cushing Center. The brains express Cushing’s singular and spectral worldview as a surgeon, artist, athlete, soldier, book collector, and historian.
PMCID: PMC3117422  PMID: 21698039
Harvey Cushing; anatomy; brains; ghosts; hauntings; surgery; death; collection; history; humanities
3.  Cost analysis of a project to digitize classic articles in neurosurgery* 
In summer 2000, the Cushing/Whitney Medical Library at Yale University began a demonstration project to digitize classic articles in neurosurgery from the late 1800s and early 1900s. The objective of the first phase of the project was to measure the time and costs involved in digitization, and those results are reported here. In the second phase, metadata will be added to the digitized articles, and the project will be publicized. Thirteen articles were scanned using optical character recognition (OCR) software, and the resulting text files were carefully proofread. Time for photocopying, scanning, and proofreading were recorded. This project achieved an average cost per item (total pages plus images) of $4.12, a figure at the high end of average costs found in other studies. This project experienced high costs for two reasons. First, the articles contained many images, which required extra processing. Second, the older fonts and the poor condition of many of these articles complicated the OCR process. The average article cost $84.46 to digitize. Although costs were high, the selection of historically important articles maximized the benefit gained from the investment in digitization.
PMCID: PMC100769  PMID: 11999182
4.  Building Health Literacy Among an Urban Teenage Population by Creating Online Health Videos for Public and School Health Curriculum Use 
Healthflicks is a 2010-2011 National Network of Libraries of Medicine outreach project conducted in New Haven, CT, targeting health information literacy among urban teens through the creation of web videos. Students from a public magnet school with a health careers curriculum track volunteered. Yale University students were hired as video mentors. Partners included the Cushing/Whitney Medical Library, Hill Regional Career High School, the New Haven Free Public Library, and Yale University’s Office of New Haven and State Affairs. Outcomes included a Healthflicks YouTube channel and an ongoing partnership between an academic medical library and a high school with a health careers curriculum track.
doi:10.1080/15398285.2012.673459
PMCID: PMC3410668  PMID: 22866023
5.  Online bibliographic information: integration into an emerging IAIMS environment. 
The Medical Library at Yale University has developed an online free-text database containing Current Contents citations. The database was designed to be integrated into an emerging campus-wide information environment. To this end Current Contents at Yale was designed with a user interface familiar to the Yale community, an alerting service based on electronic mail, and search expansion using the National Library of Medicine's Meta-1 metathesaurus.
PMCID: PMC2248136  PMID: 1336416
6.  Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma 
PLoS Medicine  2007;4(4):e122.
Background
The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes of oncoproteins (e.g., transcription factors) are not amenable to conventional small-molecule screening. Despite the identification of tumor-specific somatic mutations, most cancer therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is the treatment of Ewing sarcoma. Although the EWS/FLI oncoprotein, present in the vast majority of Ewing tumors, was characterized over ten years ago, it has never been exploited as a target of therapy. Previously, this target has been intractable to modulation with traditional small-molecule library screening approaches. Here we describe a gene expression–based approach to identify compounds that induce a signature of EWS/FLI attenuation. We hypothesize that screening small-molecule libraries highly enriched for FDA-approved drugs will provide a more rapid path to clinical application.
Methods and Findings
A gene expression signature for the EWS/FLI off state was determined with microarray expression profiling of Ewing sarcoma cell lines with EWS/FLI-directed RNA interference. A small-molecule library enriched for FDA-approved drugs was screened with a high-throughput, ligation-mediated amplification assay with a fluorescent, bead-based detection. Screening identified cytosine arabinoside (ARA-C) as a modulator of EWS/FLI. ARA-C reduced EWS/FLI protein abundance and accordingly diminished cell viability and transformation and abrogated tumor growth in a xenograft model. Given the poor outcomes of many patients with Ewing sarcoma and the well-established ARA-C safety profile, clinical trials testing ARA-C are warranted.
Conclusions
We demonstrate that a gene expression–based approach to small-molecule library screening can identify, for rapid clinical testing, candidate drugs that modulate previously intractable targets. Furthermore, this is a generic approach that can, in principle, be applied to the identification of modulators of any tumor-associated oncoprotein in the rare pediatric malignancies, but also in the more common adult cancers.
Todd Golub and colleagues show that a gene expression-based screen of small-molecule libraries can identify candidate drugs that modulate cancer-associated oncoproteins.
Editors' Summary
Background.
Cancer occurs when cells accumulate genetic changes (mutations) that allow them to divide uncontrollably and to travel throughout the body (metastasize). Chemotherapy, a mainstay of cancer treatments, works by killing rapidly dividing cells. Because some normal tissues also contain dividing cells and are therefore sensitive to chemotherapy drugs, it is hard to treat cancer without causing serious side effects. In recent years, however, researchers have identified some of the mutations that drive the growth of cancer cells. This raises the possibility of designing drugs that kill only cancer cells by specifically targeting “oncoproteins” (the abnormal proteins generated by mutations that transform normal cells into cancer cells). Some “targeted” drugs have already reached the clinic, but unfortunately medicinal chemists do not know how to inhibit the function of many classes of oncoproteins with the small organic molecules that make the best medicines. One oncoprotein in this category is EWS/FLI. This contains part of a protein called EWS fused to part of a transcription factor (a protein that controls cell behavior by telling the cell which proteins to make) called FLI. About 80% of patients with Ewing sarcoma (the second commonest childhood cancer of bone and soft tissue) have the mutation responsible for EWS/FLI expression. Localized Ewing sarcoma can be treated with nontargeted chemotherapy (often in combination with surgery and radiotherapy), but treatment for recurrent or metastatic disease remains very poor.
Why Was This Study Done?
Researchers have known for years that EWS/FLI expression drives the development of Ewing sarcoma by activating the expression of target genes needed for tumor formation. However, EWS/FLI has never been exploited as a target for therapy of this cancer—mainly because traditional approaches used to screen libraries of small molecules do not identify compounds that modulate the activity of transcription factors. In this study, the researchers have used a new gene expression–based, high-throughput screening (GE-HTS) approach to identify compounds that modulate the activity of EWS/FLI.
What Did the Researchers Do and Find?
The researchers used a molecular biology technique called microarray expression profiling to define a 14-gene expression signature that differentiates between Ewing sarcoma cells in which the EWS/FLI fusion protein is active and those in which it is inactive. They then used this signature to screen a library of about 1,000 chemicals (many already approved for other clinical uses) in a “ligation-mediated amplification assay.” For this, the researchers grew Ewing sarcoma cells with the test chemicals, extracted RNA from the cells, and generated a DNA copy of the RNA. They then added two short pieces of DNA (probes) specific for each signature gene to the samples. In samples that expressed a given signature gene, both probes bound and were then ligated (joined together) and amplified. Because one of each probe pair also contained a unique “capture sequence,” the signature genes expressed in each sample were finally identified by adding colored fluorescent beads, each linked to DNA complementary to a different capture sequence. The most active modulator of EWS/FLI activity identified by this GE-HTS approach was cytosine arabinoside (ARA-C). At levels achievable in people, this compound reduced the abundance of EWS/FLI protein in and the viability and cancer-like behavior of Ewing sarcoma cells growing in test tubes. ARA-C treatment also slowed the growth of Ewing sarcoma cells transplanted into mice.
What Do These Findings Mean?
These findings identify ARA-C, which is already used to treat children with some forms of leukemia, as a potent modulator of EWS/FLI activity. More laboratory experiments are needed to discover how ARA-C changes the behavior of Ewing sarcoma cells. Nevertheless, given the poor outcomes currently seen in many patients with Ewing sarcoma and the historical reluctance to test new drugs in children, these findings strongly support the initiation of clinical trials of ARA-C in children with Ewing sarcoma. These results also show that the GE-HTS approach is a powerful way to identify candidate drugs able to modulate the activity of some of the oncoproteins (including transcription factors and other previously intractable targets) that drive cancer development.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040122.
Cancerquest from Emory University, provides information on cancer biology (also includes information in Spanish, Chinese and Russian)
The MedlinePlus encyclopedia has pages on Ewing sarcoma
Information for patients and health professionals on Ewing sarcoma is available from the US National Cancer Institute
Cancerbackup offers information for patients and their parents on Ewing sarcoma
Wikipedia has pages on DNA microarrays and expression profiling (note that Wikipedia is a free online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0040122
PMCID: PMC1851624  PMID: 17425403
7.  History of the Department of Cell Biology at Yale School of Medicine, 1813-2010 
The Department of Cell Biology at the Yale University School of Medicine was established in 1983. It was preceded by the Section of Cell Biology, which was formed in 1973 when George E. Palade and collaborators came to Yale from the Rockefeller University. Cell Biology at Yale had its origins in the Department of Anatomy that existed from the beginning of classes at the Medical Institution of Yale College in 1813. This article reviews the history of the Department of Anatomy at Yale and its evolution into Cell Biology that began with the introduction of histology into the curriculum in the 1860s. The formation and development of the Section and Department of Cell Biology in the second half of the 20th century to the present time are described. Biographies and research activities of the chairs and key faculty in anatomy and cell biology are provided.
PMCID: PMC3117420  PMID: 21698037
8.  Medicus Deus: a review of factors affecting hospital library services to patients between 1790–1950 
Question: What are some of the historical societal, medical, and public health trends leading to today's provision of hospital library services to patients?
Data Sources: Literature from the archives of the Bulletin of the Medical Library Association and other library sources, medical journals, primary historical documents, and texts from the history of medicine form the core of this review.
Study Selection: The period of review extends from about 1790 through 1950 and focuses solely on trends in the United States. Of primary concern are explicitly documented examples that appear to illustrate the patient-physician relationship and those between librarians and their patient-patrons during the earliest years of the profession's development.
Data Extraction: An historical timeline was created to allow the identification of major trends that may have affected library services. Multiple literature searches were conducted using library, medical, and health anthropology resources. When possible, primary sources were preferred over reviews.
Main Results: Juxtapositioning historical events allows the reader to obtain an overview of the roots of consumer health services in medical libraries and to consider their potential legacy in today's health care libraries.
Conclusion: This review article highlights early developments in hospital library service to patients. Further research is needed to verify a preliminary conclusion that in some medical library settings, services to the general public are shaped by the broader health care environment as it has evolved.
PMCID: PMC1525305  PMID: 16888658
9.  Realizing what's essential: a case study on integrating electronic journal management into a print-centric technicalservices department 
Objective: To support migration from print to electronic resources, the Cushing/Whitney Medical Library at Yale University reorganized its Technical Services Department to focus on managing electronic resources.
Methods: The library hired consultants to help plan the changes and to present recommendations for integrating electronic resource management into every position. The library task force decided to focus initial efforts on the periodical collection. To free staff time to devote to electronic journals, most of the print subscriptions were switched to online only and new workflows were developed for e-journals.
Results: Staff learned new responsibilities such as activating e-journals, maintaining accurate holdings information in the online public access catalog and e-journals database (“electronic shelf reading”), updating the link resolver knowledgebase, and troubleshooting. All of the serials team members now spend significant amounts of time managing e-journals.
Conclusions: The serials staff now spends its time managing the materials most important to the library's clientele (e-journals and databases). The team's proactive approach to maintenance work and rapid response to reported problems should improve patrons' experiences using e-journals. The library is taking advantage of new technologies such as an electronic resource management system, and library workflows and procedures will continue to evolve as technology changes.
doi:10.3163/1536-5050.95.2.147
PMCID: PMC1852630  PMID: 17443247
10.  The Library of the Royal Society of Physicians in Budapest becomes today's Semmelweis Medical History Library 
Objectives:
The 170-year history of the library of the Royal Society of Medicine in Budapest illustrates both that political and cultural context matter and that “medical” libraries, if they survive, in due course become primarily “medical history” libraries.
Methods:
Two of the authors are on the staff of the Semmelweis Medical History Library; the third is a US scholar who makes frequent use of the library. Together, they avail themselves of archival and published materials—and personal experience with the collection—to establish the context that produced the original library, trace its evolution, and describe its present-day incarnation.
Results:
A tale of transformation emerges that reflects how collections are likely to change. The authors present events and individuals in the life of the Royal Society's library and paint a picture of the value of today's Semmelweis Medical History Library. Unique treasures in the collection are described.
Conclusion:
The story told here is of how a particular nineteenth-century library became a twenty-first–century institution. The authors establish its peculiarly Hungarian context and potential value to librarians and historians from outside Hungary. The overall message is that general medical libraries everywhere are perforce likely to become medical historical libraries over time.
doi:10.3163/1536-5050.99.1.007
PMCID: PMC3016667  PMID: 21243053
11.  Evaluating IAIMS at Yale 
Abstract Objective: To evaluate use of information resources during the first year of IAIMS implementation at the Yale—New Haven Medical Center. The evaluation asked: (1) Which information resources are being used? (2) Who uses information resources? (3) Where are information resources used? (4) Are multiple sources of information being integrated?
Design: Measures included monthly usage data for resources delivered network-wide, in the Medical Library, and in the Hospital; online surveys of library workstation users; an annual survey of a random, stratified sample of Medical Center faculty, postdoctoral trainees, students, nurses, residents, and managerial and professional staff; and user comments.
Results: Eighty-three percent of the Medical Center community use networked information resources, and use of resources is increasing. Both status (faculty, student, nurse, etc.) and mission (teaching, research, patient care) affect use of individual resources. Eighty-eight percent of people use computers in more than one location, and increases in usage of traditional library resources such as MEDLINE are due to increased access from outside the Library. Both survey and usage data suggest that people are using multiple resources during the same information seeking session.
Conclusions: Almost all of the Medical Center community is using networked information resources in more settings. It is necessary to support increased demand for information access from remote locations and to specific populations, such as nurses. People are integrating information from multiple sources, but true integration within information systems is just beginning. Other institutions are advised to incorporate pragmatic evaluation into their IAIMS activities and to share evaluation results with decision-makers.
PMCID: PMC61503  PMID: 9067879
12.  History of the Department of Pediatrics Yale University School of Medicine. 
The history of pediatrics at the Yale University School of Medicine can be divided into eight historical eras. The "Paleohistorical Era" included colonial figures such as Governor John Winthrop and Hezekiah Beardsley who wrote about children's disease in colonial times. Eli Ives, Professor of the Diseases of Children at Yale Medical School gave the first systematic pediatric course in America in the first half of the nineteenth century. During the second era, from 1830-1920, the New Haven Hospital was opened. An affiliation between Yale University and the New Haven Hospital led to the formal establishment of clinical departments including pediatrics in the early 20th century. Six eras coinciding with successive pediatric chairman have led the department to its present respected position in American pediatrics. The department's 75th anniversary in 1996 is an occasion to recognize many of the department's accomplishments and leaders over the years. It is also a time to reaffirm the mission of the department: to the health needs of the children of Connecticut and beyond, to the advancement of scientific knowledge of infants and children and their diseases, and to the training and educational of the pediatric clinicians, educators and investigators of the future.
Images
PMCID: PMC2589094  PMID: 9544489
13.  Portability issues for a structured clinical vocabulary: mapping from Yale to the Columbia medical entities dictionary. 
OBJECTIVE: To examine the issues involved in mapping an existing structured controlled vocabulary, the Medical Entities Dictionary (MED) developed at Columbia University, to an institutional vocabulary, the laboratory and pharmacy vocabularies of the Yale New Haven Medical Center. DESIGN: 200 Yale pharmacy terms and 200 Yale laboratory terms were randomly selected from database files containing all of the Yale laboratory and pharmacy terms. These 400 terms were then mapped to the MED in three phases: mapping terms, mapping relationships between terms, and mapping attributes that modify terms. RESULTS: 73% of the Yale pharmacy terms mapped to MED terms. 49% of the Yale laboratory terms mapped to MED terms. After certain obsolete and otherwise inappropriate laboratory terms were eliminated, the latter rate improved to 59%. 23% of the unmatched Yale laboratory terms failed to match because of differences in granularity with MED terms. The Yale and MED pharmacy terms share 12 of 30 distinct attributes. The Yale and MED laboratory terms share 14 of 23 distinct attributes. CONCLUSION: The mapping of an institutional vocabulary to a structured controlled vocabulary requires that the mapping be performed at the level of terms, relationships, and attributes. The mapping process revealed the importance of standardization of local vocabulary subsets, standardization of attribute representation, and term granularity.
PMCID: PMC116288  PMID: 8750391
14.  Laws, leaders, and legends of the modern National Library of Medicine 
Purpose: The paper is an expanded version of the 2007 Joseph Leiter National Library of Medicine (NLM)/Medical Library Association Lecture presented at MLA ‘07, the Medical Library Association annual meeting in Philadelphia in May 2007. It presents an historical accounting of four major pieces of legislation, beginning with the NLM Act of 1956 up through the creation of the National Center for Biotechnology Information.
Brief Description: The transition from the United States Armed Forces Medical Library to the United States National Library of Medicine in 1956 was a major turning point in NLM's history, scope, and direction. The succeeding landmark legislative achievements—namely, the 1965 Medical Library Assistance Act, the 1968 Joint Resolution forming the Lister Hill National Center for Biomedical Communications, and the 1988 authorization for the National Center for Biotechnology Information— transformed the library into a major biomedical communications institution and a leader and supporter of an effective national network of libraries of medicine. The leaders of the library and its major advocates—including Dr. Michael DeBakey, Senator Lister Hill, and Senator Claude Pepper—together contributed to the creation of the modern NLM.
doi:10.3163/1536-5050.96.2.121
PMCID: PMC2268223  PMID: 18379667
15.  TRIPLES: a database of gene function in Saccharomyces cerevisiae 
Nucleic Acids Research  2000;28(1):81-84.
Using a novel multipurpose mini-transposon, we have generated a collection of defined mutant alleles for the analysis of disruption phenotypes, protein localization, and gene expression in Saccharomyces cerevisiae. To catalog this unique data set, we have developed TRIPLES, a Web-accessible database of TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces. Encompassing over 250 000 data points, TRIPLES provides convenient access to information from nearly 7800 transposon-mutagenized yeast strains; within TRIPLES, complete data reports of each strain may be viewed in table format, or if desired, downloaded as tab-delimited text files. Each report contains external links to corresponding entries within the Saccharomyces Genome Database and International Nucleic Acid Sequence Data Library (GenBank). Unlike other yeast databases, TRIPLES also provides on-line order forms linked to each clone report; users may immediately request any desired strain free-of-charge by submitting a completed form. In addition to presenting a wealth of information for over 2300 open reading frames, TRIPLES constitutes an important medium for the distribution of useful reagents throughout the yeast scientific community. Maintained by the Yale Genome Analysis Center, TRIPLES may be accessed at http://ycmi.med.yale.edu/ygac/triples.htm
PMCID: PMC102388  PMID: 10592187
16.  The Moody Medical Library and Its Historical Relevance 
The historical development of the Medical Branch Library from the Medical Department of Soulé University, established in 1861, to the present is traced. The powerful growth stimulus that was provided by Dr. Chauncey Leake is recognized as is the important influence more recently of Dr. Truman G. Blocker, Jr. The new Moody Medical Library Building and the services and financing of the library are described.
Images
PMCID: PMC198746  PMID: 4591132
17.  The early years of coeducation at the Yale University School of Medicine. 
The Yale School of Medicine began accepting women as candidates for the degree of medicine in the fall of 1916. This decision was consistent with the trend in medical education at the time. While Yale was not the first prestigious Eastern medical school to admit women, joining Johns Hopkins (1893) and the University of Pennsylvania (1914), it was not one of the last. Columbia University College of Physicians and Surgeons admitted women a year later, but Harvard Medical School held out until 1945. The years 1916--1920 saw the number of women enrolled in medical school almost double. Yale's decision to admit women seems to have been made with little resistance from the faculty. The final decision was made through the encouragement and financial help of Henry Farnam, a professor of economics at Yale, who agreed to pay for the women's bathrooms. His daughter, Louise, was in the first class of women. At graduation she was awarded the highest scholastic honors, the Campbell Gold Prize. From Yale she travelled to the Yale-sponsored medical school in Changsha, China, where she became the first female faculty member, a position she held for twelve years. The impressions of Ella Clay Wakeman Calhoun, the only woman to graduate in the second class of women, are presented here. Since 1916 the Yale School of Medicine has undergone extensive physical and philosophical changes, developments in which women have participated.
PMCID: PMC2595889  PMID: 6996342
18.  Analysis of Recorded Biomedical Book and Journal Use in the Yale Medical Library Part II. Subject and User Relations* 
Cancelled charge slips collected over a one-year period supply the data for this analysis of circulation in the Yale Medical Library. Full-time teaching faculty are the heaviest users of journal literature, and students, of monograph literature. Faculties of Medical School departments are compared in terms of their use of material in individual subjects. Subject literatures are analyzed in terms of groups of users borrowing from them. The extent to which journal titles used by medical students are also used by Medical School faculty is examined. One of the products of the study is a rank list of journal titles used in the Library. Results are presented in several tables.
PMCID: PMC199083  PMID: 6041835
19.  Analysis of Recorded Biomedical Book and Journal Use in the Yale Medical Library Part I: Date and Subject Relations* 
Analysis of book and journal circulation is based on cancelled charge slips collected over a one-year period in the Yale Medical Library. About two-fifths of material circulated were monographs. Books and journals in seven subject fields provided over half of the circulation. Approximately two-thirds of both books and journals used had been published during the most recent nine years. A subject-by-subject examination of the ratio of books to journals circulating revealed that, in subjects where proportionally more journals than books were taken out of the Library, books were of more recent imprint dates than were journals, contrary to the overall pattern. Date distribution of books and journals by subject was also studied. Results are illustrated with graphs and tables.
PMCID: PMC199082  PMID: 6041834
20.  How Biomedical Investigators Use Library Books * 
Relatively few studies have been concerned with the use of biomedical books. This paper reports an investigation into use made of library books by biomedical investigators. Based on cancelled charge slips collected at the Yale Medical Library circulation desk, telephone appointments were made to interview those research investigators whose books had been returned the previous day. The interviewer obtained answers from the investigator to a questionnaire to discover how the investigator had learned of a book, if the book had been useful, and, if useful, how it had been used. During the six-month study period, 30.4 percent of researchers' volumes returned were monographs. Almost four-fifths of books borrowed supplied information wanted, and about four-fifths of books used had been printed in the previous decade. Nine-tenths of the use of books was research-related, the other tenth being for lecture preparation.
PMCID: PMC198398  PMID: 5910382
21.  Cancer-selective antiproliferative activity is a general property of some G-rich oligodeoxynucleotides 
Nucleic Acids Research  2009;38(5):1623-1635.
Oligodeoxynucleotide libraries containing randomly incorporated bases are used to generate DNA aptamers by systematic evolution of ligands by exponential enrichment (SELEX). We predicted that combinatorial libraries with alternative base compositions might have innate properties different from the standard library containing equimolar A + C + G + T bases. In particular, we hypothesized that G-rich libraries would contain a higher proportion of quadruplex-forming sequences, which may impart desirable qualities, such as increased nuclease resistance and enhanced cellular uptake. Here, we report on 11 synthetic oligodeoxynucleotide libraries of various base combinations and lengths, with regard to their circular dichroism, stability in serum-containing medium, cellular uptake, protein binding and antiproliferative activity. Unexpectedly, we found that some G-rich libraries (composed of G + T or G + C nucleotides) strongly inhibited cancer cell growth while sparing non-malignant cells. These libraries had spectral features consistent with G-quadruplex formation, were significantly more stable in serum than inactive libraries and showed enhanced cellular uptake. Active libraries generally had strong protein binding, while the pattern of protein binding suggested that G/T and G/C libraries have distinct mechanisms of action. In conclusion, cancer-selective antiproliferative activity may be a general feature of certain G-rich oligodeoxynucleotides and is associated with quadruplex formation, nuclease resistance, efficient cellular uptake and protein binding.
doi:10.1093/nar/gkp1088
PMCID: PMC2836550  PMID: 20008101
22.  Health sciences libraries in the United States: II. Medical school libraries, 1960-1980. 
Surveys of medical school libraries made over a twenty-year period (1960-61 through 1980-81) were analyzed. As indicated by growth in both number and support, medical school libraries have evolved from a period of stability through expansive growth and subsequent leveling off. Expenditures and resource development have been affected by historical developments, especially recent massive federal and state aid to medical education.
PMCID: PMC227094  PMID: 6831082
23.  Are health science faculty interested in medical history? An evaluative case study. 
This paper deals with the efforts of a medical library to stimulate interest in the history of medicine by utilizing its historical resources. It is based on a survey designed to evaluate the monthly publication of the library, the Bookman, and to determine the response of health science faculty to historical essays as well as to other sections of the publication. The results show that a large percentage of the faculty reads historical essays either regularly or occasionally, and reveal a trend contrary to the common belief that the teaching staff in health science centers is not interested in medical history. The authors suggest that a library with historical resources can contribute to the educational process in a medical community by actively publicizing its collections and providing opportunities for informal and self-initiated reading.
PMCID: PMC199450  PMID: 656659
24.  Impact of the Pacific Southwest Regional Medical Library Service on hospital library development. 
A study was designed to evaluate the progress of hospital libraries within Region 7 since the Pacific Southwest Regional Medical Library Services (PSRMLS) began in 1969. Library progress was defined as an increase in extent and types of services and resources offered. The study assessed the impact of Regional Medical Library programs on hospital libraries and compared resources and services reported in 1969, 1971, and 1984. The 1984 data were also measured against a set of core library services and resources that should be provided by a full-service hospital library. In addition to assessing the quality of PSRMLS programs and their effect on Region 7 hospital libraries, the study documented extensive growth in staffing, collection size, and services. PSRMLS programs were highly rated by the respondents, who also indicated that participation in PSRMLS programs improved specific library resources and services.
PMCID: PMC227685  PMID: 3676532
25.  Interlibrary loan in primary access libraries: challenging the traditional view 
Introduction: Primary access libraries serve as the foundation of the National Network of Libraries of Medicine (NN/LM) interlibrary loan (ILL) hierarchy, yet few published reports directly address the important role these libraries play in the ILL system. This may reflect the traditional view that small, primary access libraries are largely users of ILL, rather than important contributors to the effectiveness and efficiency of the national ILL system.
Objective: This study was undertaken to test several commonly held beliefs regarding ILL system use by primary access libraries.
Hypotheses: Three hypotheses were developed. H1: Colorado and Wyoming primary access libraries comply with the recommended ILL guideline of adhering to a hierarchical structure, emphasizing local borrowing. H2: The closures of two Colorado Council of Medical Librarians (CCML) primary access libraries in 1996 resulted in twenty-three Colorado primary access libraries' borrowing more from their state resource library in 1997. H3: The number of subscriptions held by Colorado and Wyoming primary access libraries is positively correlated with the number of items they loan and negatively correlated with the number of items they borrow.
Methods: The hypotheses were tested using the 1992 and 1997 DOCLINE and OCLC data of fifty-four health sciences libraries, including fifty primary access libraries, two state resource libraries, and two general academic libraries in Colorado and Wyoming. The ILL data were obtained electronically and analyzed using Microsoft Word 98, Microsoft Excel 98, and JMP 3.2.2.
Results: CCML primary access libraries comply with the recommended guideline to emphasize local borrowing by supplying each other with the majority of their ILLs, instead of overburdening libraries located at higher levels in the ILL hierarchy (H1). The closures of two CCML primary access libraries appear to have affected the entire ILL system, resulting in a greater volume of ILL activity for the state resource library and other DOCLINE libraries higher up in the ILL hierarchy and highlighting the contribution made by CCML primary access libraries (H2). CCML primary access libraries borrow and lend in amounts that are proportional to their collection size, rather than overtaxing libraries at higher levels in the ILL hierarchy with large numbers of requests (H3).
Limitations: The main limitations of this study were the small sample size and the use of data collected for another purpose, the CCML ILL survey.
Conclusions: The findings suggest that there is little evidence to support several commonly held beliefs regarding ILL system use by primary access libraries. In addition to validating the important contributions made by primary access libraries to the national ILL system, baseline data that can be used to benchmark current practice performance are provided.
PMCID: PMC35251  PMID: 11055297

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