bluuebunny/crossref_metadata_2025_split huggingface dataset:
Speech synthesis for computer assisted instruction
Authors: Sanders William R. , Benbassat Gerard V. , Smith Robert L. 
Published: November 2005

The Institute for Mathematical Studies in the Social Sciences at Stanford (IMSSS) has developed a synthesis system, MISS (Microprogrammed Intoned Speech Synthesizer), designed to test the effectiveness of computer-generated speech in the context of complex CAI programs. No one method of computer controlled speech production is completely satisfactory for all the uses of computer-assisted instruction (CAI). The choice of synthesis method is strongly related to the kinds of curriculums and instructional designs that will use speech. We chose to use acoustic modelling by linear predictive coding as the method of synthesis for MISS.(1)
In Section 2 we describe criteria appropriate for organizing the comparison of voice response systems for use with instructional computers. Then we describe the particular requirements imposed by curriculums at IMSSS, review general voice synthesis techniques, and finally discuss our actual choice. In Sections 3 and 4 we outline the hardware and software that have been created to support MISS in operational CAI at Stanford.
In Section 5 we discuss the applications of audio to CAI.
On the uses of models in education
Authors: Kirbach Jürgen , Schmidt Joachim W. 
Published: November 2005

Some preliminary observations may demonstrate some of man's motivation for using models: Generally science is concerned with causal systems, which are systems the states of which do not depend on future inputs to the system. It is this class of systems which is pretty well understood (differential equations, automata, deterministic or not). The purpose for engaging in science about causal systems is - besides pure curiosity - mainly to aid man's desire to behave in a goal-directed manner.
Since a modern society has a need for goal-directed behavior of its members, e.g. in problem solving, there is also the need to teach people the associated structures. They need
- to get to know existing models (knowledge),
- to learn the way models are used (methods),
- to get to know the tools for modelling (theories), and
- to be able to use strategies for developing them (science).
The introduction may give the impression that we favor a very loose use of the term “model”. This is not so, however. On the contrary since this term is so loosely used presently, it should find a refinement by explication which can be done by examining the associated structures further. That this may not be a waste of effort may have been demonstrated by the central role models play for man's goal-directed behavior.
Another look at the discrete structures course
Authors: Prather Ronald E. 
Published: November 2005

Over the last several years since the introduction of B3 (Discrete Structures) into the undergraduate computer science curriculum, the course has been the subject of continuing controversy. The major difficulties later found in implementing the course were easy to foresee from the most casual reading of its original description in Curriculum '68 [1]. The necessary placement of the course in the sophomore year, the relative sophistication of the intended subject matter, and the lack of sufficient preparation of most beginning students in these areas and in appropriate computer science areas of application, all have contributed to problems in the implementation of the ACM Curriculum Committee recommendations.
We will discuss each of these problems in turn, and hope to provide new insights toward achieving a satisfactory solution.
A proposed course on data processing economics
Authors: Phister M. 
Published: November 2005

Universities are often criticized for being too academic—too far removed from society's real problems. One reason for this remoteness is the academic preoccupation with analysis, despite the fact that the solution to many practical problems requires synthesis or invention. Another reason—and this is the one I want to discuss—is that faculties in science and engineering by and large are interested in the science of technology, and devote little or no time to teaching the economics of technology.
The problem is a general one and I believe it deserves attention by all scientific and engineering faculties of the university (?). It is particularly important in the computer field, where growth and change are the norm, and where we all must be careful, in making decisions, to take into account trends and directions in the economics of data processing. I propose a course entitled “Data Processing Technology and Economics” as a solution to the problems described above, and in this paper I will describe the course, which is based on a textbook I have been preparing for the past several years. The course has been taught twice: at Harvard University in the Fall Semester 1974-1975; and at the University of Sydney, in Australia, in the Michaelmas Term, ]975. However, before describing the course in detail, I would like to explain, with the help of some examples, why I believe this subject is important to the student of Computer Science.
Report on acm's activity on community and junior college curriculum career program in computer programming
Authors: Little Joyce Currie , Seeds Harice , Lenhardt Ronald , Dineen John , Maniotes John 
Published: November 2005

A Workshop in Two Year College Programs in Computer Science was held August 11-13, 1975 in Gloucester Point, Virginia. Sponsored by the ACM's Special Interest Group in Computer Science Education (SIGCSE), it brought thirteen community and junior college participants together at the Virginia Institute for Marine Science (VIMS) to work toward recommendations for a two year program.
Representing ACM were Dr. Richard Austing, Chairman, SIGCSE, Associate Professor in the Computer Science Department of the University of Maryland, and Dr. Gerald L. Engel, Executive Secretary of the ACM Curriculum Committee on Computer Science (C S), Director of Computing and Statistical Services at VIMS, Dr. Bruce Barnes of the National Science Foundation also attended.
Joyce C. Little, Chairman of the ACM's Two Year College Subcommittee of C S and Professor and Chairman of the Data Processing and Computing Sciences Department at the Community College of Baltimore, served as Chairman of the Workshop.
This panel presentation, given by participants in the workshop, is the first public discussion of the material under development by this group, being chaired by Joyce Currie Little, Chairman of the Ad Hoc Subcommittee for 3 Community and Junior College Curriculum, serving under the Curriculum Committee in Computer Science (C S). Reaction to, and discussion of, the preliminary findings of this group, will been couraged from the audience.
Computer science and minority colleges & universities
Authors: Lewis Jesse 
Published: November 2005

Jackson State University is the lead institution in a Cooperative Regional Educational Computing Network. The network is funded by the National Science Foundation. When it began operating in January, 1974, it involved eleven (11) other participating institutions. Now there are seventeen (17).
The purpose of the network is to provide appropriate equipment, with an accompanying massive educational effort, so as to allow each of the participating institutions to become more aware of the academic implications of computers. The ultimate goal is to profoundly affect basic curricula.
The results have been positive. Some faculty at participating institutions have reconstructed course content so as to include the use of the computer at appropriate points in their courses. More positive is the fact that a large number of students from disadvantaged educational and cultural backgrounds now have access to interactive computing.
CCAAT/Enhancer Binding Protein α Knock-in Mice Exhibit Early Liver Glycogen Storage and Reduced Susceptibility to Hepatocellular Carcinoma
Authors: Tan Ee Hong , Hooi Shing Chuan , Laban Mirtha , Wong Esther , Ponniah Sathivel , Wee Aileen , Wang Nai-dy 
Published: November 2005

Abstract
The CCAAT/enhancer binding protein α (C/EBPα) is vital for establishing normal hepatic energy homeostasis and moderating hepatocellular growth. CEBPA loss-of-function mutations identified in acute myeloid leukemia patients support a tumor suppressor role for C/EBPα. Recent work showed reductions of C/EBPα levels in human hepatocellular carcinoma with the reductions correlating to tumor size and progression. We investigated the potential of reactivating c/ebpα expression during hepatic carcinogenesis to prevent tumor cell growth. We have developed a c/ebpα knock-in mouse in which a single-copy c/ebpα is regulated by one allele of the α-fetoprotein (AFP) gene promoter. The knock-in mice are physically indistinguishable from wild-type (WT) controls. However, knock-in animals were found to deposit fetal hepatic glycogen earlier than WT animals. Quantitative real-time PCR confirmed early c/ebpα expression and early glycogen synthase gene activation in knock-in fetuses. We then used diethylnitrosamine to induce hepatocellular carcinoma in our animals. Diethylnitrosamine produced half the number of hepatocellular nodules in knock-in mice as in WT mice. Immunohistochemistry showed reduced C/EBPα content in WT nodules whereas knock-in nodules stained strongly for C/EBPα. The p21 protein was examined because it mediates a C/EBPα growth arrest pathway. Nuclear p21 was absent in WT nodules whereas cytoplasmic p21 was abundant; knock-in nodules were positive for nuclear p21. Interestingly, only C/EBPα-positive nodules were positive for nuclear p21, suggesting that C/EBPα may be required to direct p21 to the cell nucleus to inhibit growth. Our data establish that controlled C/EBPα production can inhibit liver tumor growth in vivo.
A Comparative Study on the Protection Profile of Lidocaine, Amifostine, and Pilocarpin on the Parotid Gland during Radiotherapy
Authors: Hakim Samer G. , Kosmehl Hartwig , Lauer Isabel , Nadrowitz Roger , Wedel Thilo , Sieg Peter 
Published: November 2005

Abstract
The aim of this study was to evaluate the individual and the synergetic radioprotective effect of lidocaine, amifostine, and pilocarpin on the parotid gland. Forty-nine rabbits were randomized into seven groups (n = 7)—control, irradiated sham-treated, irradiated/lidocaine–pretreated, irradiated/amifostine–pretreated, irradiated/pilocarpin–pretreated, irradiated/lidocaine + pilocarpin–pretreated, and irradiated/amifostine + pilocarpin–pretreated groups. One week before irradiation (15 Gy) and 72 hours as well as 1 month afterward, the parotid gland was investigated morphologically, sialoscintigraphically, and immunohistochemically with the use of tenascin-C and α smooth muscle actin. Compared with control animals, there was a significant reduction of the salivary ejection fraction in the irradiated untreated group 72 hours following radiation. Only animals pretreated with lidocaine or amifostine (alone or combined with pilocarpin) showed a slight nonsignificant reduction of salivary ejection fraction. Immunohistochemically, we observed a significant loss of α smooth muscle actin and an up-regulation of tenascin-C expression in irradiated/untreated glands. These changes were less evident in animals pretreated with lidocaine or lidocaine + pilocarpin. Amifostine and pilocarpin did not show any influence on tenascin-C or α smooth muscle actin expression. Ultrastructural damage was observed in irradiated untreated and pilocarpin–pretreated glands. In contrast, lidocaine and amifostine could largely preserve the glandular ultrastructure. One month postradiation, all changes were regressive regardless of treatment protocol. Potential radioprotective agents show different effects on both morphology and function of the parotid gland. Associated immunohistochemical and ultrastructural findings could prove the prevailed protection profile of lidocaine. This may provide a prophylactic approach in the field of radioprotection of salivary glands.
Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing α(1,3)-Galactosyl Epitopes
Authors: Rossi Gabriela R. , Mautino Mario R. , Unfer Robert C. , Seregina Tatiana M. , Vahanian Nicholas , Link Charles J. 
Published: November 2005

Abstract
The hyperacute immune response in humans is a potent mechanism of xenograft rejection mediated by complement-fixing natural antibodies recognizing α(1,3)-galactosyl epitopes (αGal) not present on human cells. We exploited this immune mechanism to create a whole cell cancer vaccine to treat melanoma tumors. B16 melanoma vaccines genetically engineered to express αGal epitopes (B16αGal) effectively treated preexisting s.c. and pulmonary αGal-negative melanoma (B16Null) tumors in the α(1,3)-galactosyltransferase knockout mouse model. T cells from mice vaccinated with B16αGal recognized B16Null melanoma cells measured by detection of intracellular tumor necrosis factor-α. We showed successful adoptive transfer of immunity to recipient mice bearing lung melanoma metastasis. Mice receiving lymphocytes from donors previously immunized with B16αGal had reduced pulmonary metastases. The transfer of lymphocytes from mice vaccinated with control vaccine had no effect in the pulmonary metastasis burden. This study unequivocally establishes for the first time efficacy in the treatment of preexisting melanoma tumors using whole cell vaccines expressing αGal epitopes. Vaccination with B16αgal induced strong long-lasting cell-mediated antitumor immunity extended to B16Null. These data formed the basis for the testing of this therapeutic strategy in human clinical trials currently under way.
The Inflammatory Cytokine Tumor Necrosis Factor-α Regulates Chemokine Receptor Expression on Ovarian Cancer Cells
Authors: Kulbe Hagen , Hagemann Thorsten , Szlosarek Piotr W. , Balkwill Frances R. , Wilson Julia L. 
Published: November 2005

Abstract
Epithelial ovarian cancer cells express the chemokine receptor, CXCR4, which may be associated with increased survival and metastatic potential, but the regulation of this receptor is not understood. The inflammatory cytokine tumor necrosis factor-α (TNF-α) is found in ovarian cancer biopsies and is associated with increased tumor grade. In this report, we show that CXCR4 expression on human epithelial ovarian cancer cells is associated with, and can be modulated by, TNF-α. Ovarian cancer cells with high endogenous expression of TNF-α expressed higher levels of CXCR4 mRNA and protein than cells with low TNF-α expression. Stimulation of ovarian cancer cell lines and primary epithelial cancer cells with TNF-α resulted in increased CXCR4 mRNA and protein. The TNF-α–stimulated increase in CXCR4 mRNA was due partly to de novo synthesis, and up-regulation of CXCR4 cell surface protein increased migration to the CXCR4 ligand CXCL12. CXCR4 mRNA and protein was down-regulated by anti-TNF-α antibody or by targeting TNF-α mRNA using RNAi. TNF-α stimulation activated components of the nuclear factor κB pathway, and overexpression of the inhibitor of κB also reduced CXCR4 expression. Coculture of macrophages with ovarian cancer cells also resulted in cancer cell up-regulation of CXCR4 mRNA in a TNF-α–dependent manner. Finally, there was a correlation between the levels of TNF-α and CXCR4 mRNA in clinical biopsies of ovarian cancer, and TNF-α protein was expressed in CXCR4-positive tumor cells. TNF-α is a critical mediator of tumor promotion in a number of experimental cancers. Our data suggest that one mechanism may be through nuclear factor κB–dependent induction of CXCR4.
Activated Tyrosine Kinase Ack1 Promotes Prostate Tumorigenesis: Role of Ack1 in Polyubiquitination of Tumor Suppressor Wwox
Authors: Mahajan Nupam P. , Whang Young E. , Mohler James L. , Earp H. Shelton 
Published: November 2005

Abstract
Aberrant activation of tyrosine kinases is linked causally to human cancers. Activated Cdc42-associated kinase (Ack1), an intracellular tyrosine kinase, has primarily been studied for its signaling properties but has not been linked to specific pathologic conditions. Herein, we report that expression of activated Ack1 in LNCaP cells, while minimally increasing growth in culture, enhanced anchorage-independent growth in vitro and dramatically accelerated tumorigenesis in nude mice. Molecular chaperone heat shock protein 90β (Hsp90β)–bound Ack1 and treatment of cells with geldanamycin, a Hsp90 inhibitor, inhibited Ack1 kinase activity and suppressed tumorigenesis. Further, we identify the tumor suppressor WW domain containing oxidoreductase (Wwox) as an Ack1-interacting protein. Activated Ack1 tyrosine phosphorylated Wwox, leading to rapid dissociation of the Ack1-Wwox complex and concomitant Wwox polyubiquitination followed by degradation. Tyrosine phosphorylation of Wwox was critical for its degradation, as splice variant WwoxΔ5-8 that was not phosphorylated by Ack1 failed to undergo polyubiquitination and degradation. It has been reported that phosphorylation of Wwox at Tyr33 stimulated its proapoptotic activity. We observed that Y33F Wwox mutant was still tyrosine phosphorylated and polyubiquitinated by Ack1 action. Site-directed mutagenesis revealed that activated Ack1 primarily phosphorylated Wwox at Tyr287, suggesting that phosphorylation of distinct tyrosine residues activate or degrade Wwox. Primary androgen-independent prostate tumors but not benign prostate showed increased tyrosine-phosphorylated Ack1 and decreased Wwox. Taken together, these data indicate that Ack1 stimulated prostate tumorigenesis in part by negatively regulating the proapoptotic tumor suppressor, Wwox. Further, these findings suggest that Ack1 could be a novel therapeutic target for prostate cancer.
Efficient Deletion of Normal Brca2-Deficient Intestinal Epithelium by Poly(ADP-Ribose) Polymerase Inhibition Models Potential Prophylactic Therapy
Authors: Hay Trevor , Jenkins Helen , Sansom Owen J. , Martin Niall M.B. , Smith Graeme C.M. , Clarke Alan R. 
Published: November 2005

Abstract
The genes encoding the BRCA1 and BRCA2 tumor suppressors are the most commonly mutated in human familial breast cancers. Both have separate roles in the maintenance of genomic stability through involvement in homologous recombination, an error-free process enabling cells to repair DNA double-strand breaks. We have previously shown that cre-mediated conditional deletion of Brca2 within the mouse small intestine sensitizes the tissue to DNA damage. Eventually, the tissue repopulates via stem cells in which recombination at the floxed Brca2 allele has not taken place. In this study, we have treated Brca2-deficient small intestine with a potent small-molecule inhibitor of poly(ADP-ribose) polymerase 1 (PARP1), an enzyme predominantly involved in the recognition of DNA single-strand breaks. Brca2 deficiency rendered otherwise normal cells exquisitely sensitive to PARP inhibition, resulting in very high levels of apoptosis as early as 6 hours after treatment, with evidence for repopulation of the tissue at 12 hours. Furthermore, the intestines of animals treated with serial injections of the inhibitor repopulated very rapidly in comparison with those from untreated mice. Our results represent the first in vivo demonstration that inhibition of PARP1 activity confers exquisite sensitivity to death in physiologically normal Brca2-deficient cells, suggesting that such a regimen may be extremely potent prophylactically in women heterozygous for the BRCA2 gene, as well as against established tumors lacking functional BRCA2.
The p53 Tumor Suppressor Network Is a Key Responder to Microenvironmental Components of Chronic Inflammatory Stress
Authors: Staib Frank , Robles Ana I. , Varticovski Lyuba , Wang Xin W. , Zeeberg Barry R. , Sirotin Michail , Zhurkin Victor B. , Hofseth Lorne J. , Hussain S. Perwez , Weinstein John N. , Galle Peter R. , Harris Curtis C. 
Published: November 2005

Abstract
Activation of the p53 network plays a central role in the inflammatory stress response associated with ulcerative colitis and may modulate cancer risk in patients afflicted with this chronic disease. Here, we describe the gene expression profiles associated with four microenvironmental components of the inflammatory response (NO•, H2O2, DNA replication arrest, and hypoxia) that result in p53 stabilization and activation. Isogenic HCT116 and HCT116 TP53−/− colon cancer cells were exposed to the NO• donor Sper/NO, H2O2, hypoxia, or hydroxyurea, and their mRNA was analyzed using oligonucleotide microarrays. Overall, 1,396 genes changed in a p53-dependent manner (P &lt; 0.001), with the majority representing a “unique” profile for each condition. Only 14 genes were common to all four conditions. Included were eight known p53 target genes. Hierarchical sample clustering distinguished early (1 and 4 hours) from late responses (8, 12, and 24 hours), and each treatment was differentiated from the others. Overall, NO• and hypoxia stimulated similar transcriptional responses. Gene ontology analysis revealed cell cycle as a key feature of stress responses and confirmed the similarity between NO• and hypoxia. Cell cycle profiles analyzed by flow cytometry showed that NO• and hypoxia induced quiescent S-phase and G2-M arrest. Using a novel bioinformatic algorithm, we identified several putative p53-responsive elements among the genes induced in a p53-dependent manner, including four [KIAA0247, FLJ12484, p53CSV (HSPC132), and CNK (PLK3)] common to all exposures. In summary, the inflammatory stress response is a complex, integrated biological network in which p53 is a key molecular node regulating gene expression.
Kisspeptin-10-Induced Signaling of GPR54 Negatively Regulates Chemotactic Responses Mediated by CXCR4: a Potential Mechanism for the Metastasis Suppressor Activity of Kisspeptins
Authors: Navenot Jean-Marc , Wang Zixuan , Chopin Michael , Fujii Nobutaka , Peiper Stephen C. 
Published: November 2005

Abstract
The product of the KiSS-1 gene is absent or expressed at low level in metastatic melanoma and breast cancer compared with their nonmetastatic counterparts. A polypeptide derived from the KiSS-1 product, designated kisspeptin-10 (Kp-10), activates a receptor coupled to Gαq subunits (GPR54 or KiSS-1R). To study the mechanism by which Kp-10 antagonizes metastatic spread, the effect on CXCR4-mediated signaling, which has been shown to direct organ-specific migration of tumor cells, was determined. Kp-10 blocked chemotaxis of tumor cells expressing CXCR4 in response to low and high concentrations of SDF-1/CXCL12 and inhibited mobilization of calcium ions induced by this ligand. Pretreatment with Kp-10 did not induce down-modulation of cell surface CXCR4 expression, reduce affinity for SDF-1/CXCL12, or alter Gαi subunit activation stimulated by this ligand. Although Kp-10 stimulated prolonged phosphorylation of extracellular signal-regulated kinase 1/2, it inhibited the phosphorylation of Akt induced by SDF-1. The ability of Kp-10 to inhibit signaling and chemotaxis induced by SDF-1 indicates that activation of GPR54 signaling may negatively regulate the role of CXCR4 in programming tumor metastasis.