bluuebunny/crossref_metadata_2025 huggingface dataset:
SYMPOSIUM: Clearance of Aβ from the Brain in Alzheimer' Disease: The Role of the Immune System in Clearance of Aβ from the Brain
Authors: Boche Delphine , Nicoll James A.R.
Published: March 2008

In Alzheimer's disease (AD), there is abnormal accumulation of Aβ and tau proteins in the brain. There is an associated immunological response, but it is still unclear whether this is beneficial or harmful. Inflammation in AD, specifically in the form of microglial activation, has, for many years, been considered to contribute to disease progression. However, two types of evidence suggest that it may be appropriate to revise this view: first, the disappointing results of prospective clinical trials of anti‐inflammatory agents and, second, the observation that microglia can clear plaques in AD following Aβ immunization. Although Aβ immunization alters AD pathology, there is limited evidence so far of benefit to cognitive function. Immunization against microorganisms is almost always used as a method of disease prevention rather than to treat a disease process that has already started. In animal models, immunotherapy at an early age can protect against Aβ accumulation and it will be interesting to see if this can usefully be applied to humans to prevent AD.
Topical Treatment with OGG1 Enzyme Affects UVB‐induced Skin Carcinogenesis†
Authors: Wulff Brian C. , Schick Jonathan S. , Thomas‐Ahner Jennifer M. , Kusewitt Donna F. , Yarosh Daniel B. , Oberyszyn Tatiana M.
Published: March 2008

Nonmelanoma skin cancer resulting from UVB exposure is a large and growing problem in the United States. Production of reactive oxygen species (ROS) during the UVB‐induced inflammatory response results in the formation of oxidative DNA adducts such as 8‐hydroxy‐2‐deoxyguanine (8‐oxo‐dG), which have been shown to contribute to the development of this cancer. The 8‐oxoguanine DNA glycosylase (OGG1) enzyme repairs 8‐oxo‐dG adducts, suggesting that enhancing its activity in the skin might increase 8‐oxo‐dG repair thus preventing skin cancer development. We therefore used the SKH‐1 murine model to examine the effect of topically applied OGG1 on UVB‐induced skin cancer development. Mice were exposed three times weekly to UVB followed immediately by topical treatment with a formulation of liposome‐encapsulated OGG1 enzyme for 25 weeks. While this treatment did not affect UVB‐induced tumor multiplicity, it did reduce tumor size and dramatically reduced tumor progression, as indicated by tumor grade. These results suggest that oxidative DNA damage contributes to the progression of UVB‐induced skin tumors and that a topical formulation containing OGG1, perhaps in conjunction with other DNA repair enzymes such as T4 endonuclease V, could be used in populations at high risk for skin cancer development.
Cyclo‐oxygenase‐2 Plays a Critical Role in UV‐induced Skin Carcinogenesis†
Authors: Rundhaug Joyce E. , Fischer Susan M.
Published: March 2008

Besides induction of DNA damage and p53 mutations, chronic exposure to UV irradiation leads to the constitutive up‐regulation of cyclo‐oxygenase‐2 (COX‐2) expression and to increased production of its primary product in skin, prostaglandin E2 (PGE2). COX‐2 has also been shown to be constitutively overexpressed in mouse, as well as human, UV‐induced skin cancers and premalignant lesions. UV exposure results in ligand‐independent activation of the epidermal growth factor receptor and subsequent activation of mitogen‐activated protein kinase and phosphatidylinositol 3‐kinase/Akt pathways leading to transcriptional activation of the COX‐2 gene. Use of COX‐2‐specific inhibitors and genetic manipulation of COX‐2 expression have demonstrated that UV induction of COX‐2 in the skin contributes to the induction of epidermal hyperplasia, edema, inflammation, and counters the induction of apoptosis after UV exposure. Likewise, inhibition of COX‐2 activity or reduced expression in COX‐2 knockout mice resulted in significantly reduced UV‐induced tumorigenesis, while overexpression of COX‐2 in transgenic mice enhanced UV‐induced tumor development. A combination of signaling from the PGE2 EP1, EP2 and/or EP4 receptors mediates the effects of COX‐2 overexpression. These studies demonstrate the crucial role of COX‐2 in the development of UV‐related nonmelanoma skin cancers.
Hypothesis—Ultraviolet‐B Irradiance and Vitamin D Reduce the Risk of Viral Infections and thus Their Sequelae, Including Autoimmune Diseases and some Cancers†
Authors: Grant William B.
Published: March 2008

Many viral infections reach clinical significance in winter, when it is cold, relative humidity is lowest and vitamin D production from solar ultraviolet‐B irradiation is at its nadir. Several autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus and asthma, are linked to viral infections. Vitamin D, through induction of cathelicidin, which effectively combats both bacterial and viral infections, may reduce the risk of several autoimmune diseases and cancers by reducing the development of viral infections. Some types of cancer are also linked to viral infections. The cancers with seemingly important risk from viral infections important in winter, based on correlations with increasing latitude in the United States, an index of wintertime solar ultraviolet‐B dose and vitamin D, are bladder, prostate, testicular and thyroid cancer, Hodgkin’s and non‐Hodgkin’s lymphoma, and, perhaps, gastric cancer. The evidence examined includes the role of viruses in the etiology of these diseases, the geographic and seasonal variation of these diseases, and the time of life when vitamin D is effective in reducing the risk of disease. In general, the evidence supports the hypothesis. However, further work is required to evaluate this hypothesis.
A Behavioral Model for Estimating Population Exposure to Solar Ultraviolet Radiation†
Authors: Diffey Brian
Published: March 2008

Determining the variability of solar UV exposure of different members of a population by direct measurement demands high compliance over an extended period of time by a large number of people. An alternative approach is to model the variables that affect personal exposure and this is the basis of the method reported here, which uses a random sampling technique to explore variability of exposure at different times of the year by habitués. It is shown that there are large variations in daily personal erythemal exposure, more so for indoor workers living in northern Europe than those resident in Florida, which are due not only to seasonal changes in ambient, but just as importantly to seasonal variation in behavior. Not surprisingly, holiday and summer weekend exposure account for the largest daily UV doses. Northern Europeans who take their summer vacation in Florida can double their exposure during this period compared with holidaying at home and this illustrates just how important sun protection measures should be during recreational exposure in areas of high insolation if the annual UV burden is to be sensibly controlled.
Inhibition of β‐TrCP Function Potentiates UVB‐induced Apoptosis in hTERT‐immortalized Normal Human Keratinocytes†
Authors: Bhatia Neehar , Demmer Tara A. , Spiegelman Vladimir S.
Published: March 2008

Chronic skin exposure to UV radiation manifests in a score of biochemical events, DNA damage and mutations which can potentially cause skin cancer. The ubiquitin proteasome pathway controls the degradation of a majority of regulatory eukaryotic proteins including those which play a key role in tumorigenesis. SCFβTrCP E3 ubiquitin ligases mediate ubiquitination and proteasomal degradation of phosphorylated substrates that play a key role in signal transduction. Activation of several signaling pathways involved in tumorigenesis was shown to elevate expression and activity of β‐TrCP1/2. In this study, we established and characterized human neonatal foreskin keratinocytes, rendered immortal by retroviral introduction of human telomerase reverse transcriptase (hTERT). These skin hTERT immortalized normal keratinocytes (STINKs) maintain characteristic traits of keratinocytes, such as expression of keratins, cytoplasmic localization of basonuclin and susceptibility to high concentration of calcium. We analyzed the response of STINKs to UVB radiation and its classical markers, such as p53 and nuclear factor (NF)‐κB. We also demonstrate that inhibition of β‐TrCP2 function, by induction of dominant negative β‐TrCP2 (β‐TrCP2ΔN), accentuates UVB induced apoptosis, and this phenomenon is independent of NF‐κB and p53 pathways.
Oligonol Inhibits UVB‐induced COX‐2 Expression in HR‐1 Hairless Mouse Skin—AP‐1 and C/EBP as Potential Upstream Targets†
Authors: Kundu Joydeb Kumar , Chang Eun‐Jin , Fujii Hajime , Sun Buxiang , Surh Young‐Joon
Published: March 2008

Oxidative stress and inflammatory tissue damage are two major events frequently implicated in carcinogenesis. Numerous polyphenolic compounds derived from plants possess antioxidant and anti‐inflammatory activities and are hence effective in preventing cancer. Oligonol is a polyphenol formulation enriched with catechin‐type oligomers. As an initial approach to assess the chemopreventive potential of oligonol, we have determined its effects on inflammatory as well as oxidative damage in mouse skin irradiated with UVB. Topical application of oligonol onto the dorsal skin of male HR‐1 hairless mice 30 min prior to UVB exposure diminished epidermal hyperplasia and formation of 4‐hydroxynonenal, a biochemical hallmark of lipid peroxidation. Topical application of oligonol also significantly inhibited UVB‐induced cyclooxygenase (COX‐2) expression in mouse skin. Oligonol diminished the DNA binding of activator protein‐1 (AP‐1) and CCAAT/enhancer binding protein (C/EBP), and the expression of C/EBPδ in mouse skin exposed to UVB. Our study also revealed that oligonol attenuated UVB‐induced catalytic activity as well as expression of p38 mitogen‐activated protein (MAP) kinase. Moreover, UVB‐induced phosphorylation of another upstream kinase Akt was attenuated by oligonol. Taken together, oligonol showed antioxidative and anti‐inflammatory effects in UVB‐irradiated mouse skin by inhibiting COX‐2 expression via blockade of the activation of AP‐1 and C/EBP, and upstream kinases including p38 MAP kinase and Akt.
Apoptosis Mechanisms Related to the Increased Sensitivity of Jurkat T‐cells vs A431 Epidermoid Cells to Photodynamic Therapy with the Phthalocyanine Pc 4†‡
Authors: Ke Malcolm S. , Xue Liang‐yan , Feyes Denise K. , Azizuddin Kashif , Baron Elma D. , McCormick Thomas S. , Mukhtar Hasan , Panneerselvam Ashok , Schluchter Mark D. , Cooper Kevin D. , Oleinick Nancy L. , Stevens Seth R.
Published: March 2008

To examine the clinical applicability of Pc 4, a promising second‐generation photosensitizer, for the photodynamic treatment of lymphocyte‐mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte‐derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose–response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4‐PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl‐2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl‐2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl‐1 was extensively cleaved in a dose‐ and caspase‐dependent manner in Jurkat, but not in A431, cells exposed to Pc 4‐PDT. Thus, the greater killing by Pc 4‐PDT in Jurkat compared with A431 cells correlated with greater Bcl‐2 photodamage and more strongly to the more extensive Mcl‐1 degradation. Pc 4‐PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T‐cell‐mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl‐2 family proteins, especially Mcl‐1, in the therapeutic response.
Resveratrol Imparts Photoprotection of Normal Cells and Enhances the Efficacy of Radiation Therapy in Cancer Cells†
Authors: Reagan‐Shaw Shannon , Mukhtar Hasan , Ahmad Nihal
Published: March 2008

Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin‐related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV‐mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure‐mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB‐mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.
Interactions Between Chromophore and Protein in Phytochrome Identified by Novel Oxa‐, Thia‐ and Carba‐Chromophores
Authors: Bongards Christian , Gärtner Wolfgang
Published: March 2008

Six new bilin chromophores of the plant photoreceptor phytochrome have been synthesized, carrying at the photoisomerizing ring D an oxygen or a sulfur atom or a methylene group instead of the pyrrole nitrogen atom. These furanone‐, thiophenone‐ or cyclopentenone‐containing compounds bound covalently to the recombinant apophytochrome phyA of Avena sativa. The novel chromoproteins showed hypsochromically shifted absorption spectra with respect to native phytochrome and a strongly diminished photochemical activity, but a three‐ to four‐fold higher fluorescence quantum yield. These results demonstrate that, on the one hand, also ring D‐modified chromophores can be forced into a partially extended structure, required for incorporation into the apoprotein binding pocket and covalent binding. On the other hand, the modifications introduced into ring D of the chromophores strongly impede the formation of stable far red‐absorbing forms of plant photoreceptor phytochrome (Pfr‐form) of the chromoproteins, highlighting especially the role of the pyrrole nitrogen atom and hydrogen bonding for the precise interactions between that part of the chromophore and the protein for the Pfr‐formation.
Fluorescence Kinetics of Protoporphyrin‐IX Induced from 5‐ALA Compounds in Rabbit Postballoon Injury Model for ALA‐Photoangioplasty
Authors: Kwon Oh‐Choon , Yoon Hyeok‐Joon , Kim Ki‐Hong , Kim Hong‐Tae , Yoon Yeon‐Hee , Kim Jong‐Ki
Published: March 2008

Protoporphyrin IX (PpIX) is one of the photodynamically active substances that are endogenously synthesized in the metabolic pathway for heme as a precursor. Aminolevulinic acid‐esters are more lipophilic than conventional 5‐aminolevulinic acid (ALA) and some of them are currently being approved as new drugs for photodynamic diagnosis (PDD) and photodynamic therapy (PDT). In order to investigate the pharmacokinetics of ALA and ALA‐ethyl ester (ALA‐ethyl) in the atheromatous plaque and normal aortic wall of rabbit postballoon injured artery, each 60 mg kg−1 of ALA or ALA‐ethyl was injected intravenously followed by serial detection of PpIX fluorescence of harvested arteries at 0–48 h post‐injection. Maximum PpIX build‐up in the atheromatous plaque was seen at 2 h after injecting ALA. In contrast, it occurred at 9 h after injecting ALA‐ethyl. In addition, the selective build‐up of ALA in the atheromatous plaque compared to normal vessel wall was much higher (10 times) than that of ALA‐ethyl. The time of maximum fluorescence intensity of PpIX was employed as drug‐light‐interval for subsequent PDT treatment of the atheromatous plaque with 50–150 J cm−1 of light dose. Significant reduction in plaque was observed without damage of the medial wall at both groups, but smooth muscle cell (SMC) was still present in the media region below the PDT‐treated atheromatous plaque. In conclusion, ALA may be a more effective compound for endovascular PDT treatment of the atheromatous plaque compared with ALA‐ethyl based on their pharmacokinetics, but further optimization of PDT methodology remains to remove completely residual SMC in the media for preventing potential restenosis.
Dynamics Change of Phoborhodopsin and Transducer by Activation: Study Using D75N Mutant of the Receptor by Site‐directed Solid‐state 13C NMR†
Authors: Kawamura Izuru , Yoshida Hideaki , Ikeda Yoichi , Yamaguchi Satoru , Tuzi Satoru , Saitô Hazime , Kamo Naoki , Naito Akira
Published: March 2008

Pharaonis phoborhodopsin (ppR or sensory rhodopsin II) is a negative phototaxis receptor of Natronomonas pharaonis, and forms a complex, which transmits the photosignal into cytoplasm, with its cognate transducer (pHtrII). We examined a possible local dynamics change of ppR and its D75N mutant complexed with pHtrII, using solid‐state 13C NMR of [3‐13C]Ala‐ and [1‐13C]Val‐labeled preparations. We distinguished Ala Cβ13C signals of relatively static stem (Ala221) in the C‐terminus of the receptors from those of flexible tip (Ala228, 234, 236 and 238), utilizing a mutant with truncated C‐terminus. The local fluctuation frequency at the C‐terminal tip was appreciably decreased when ppR was bound to pHtrII, while it was increased when D75N, that mimics the signaling state because of disrupted salt bridge between C and G helices prerequisite for the signal transfer, was bound to pHtrII. This signal change may be considered with the larger dissociation constant of the complex between pHtrII and M‐state of ppR. At the same time, it turned out that fluctuation frequency of cytoplasmic portion of pHtrII is lowered when ppR is replaced by D75N in the complex with pHtrII. This means that the C‐terminal tip partly participates in binding with the linker region of pHtrII in the dark, but this portion might be released at the signaling state leading to mutual association of the two transducers in the cytoplasmic regions within the ppR/pHtrII complex.
First Cytoplasmic Loop of Glucagon‐like Peptide‐1 Receptor Can Function at the Third Cytoplasmic Loop Position of Rhodopsin†
Authors: Yamashita Takahiro , Tose Koji , Shichida Yoshinori
Published: March 2008

G protein‐coupled receptors (GPCRs) are classified into several families based on their amino acid sequences. In family 1, GPCRs such as rhodopsin and adrenergic receptor, the structure–function relationship has been extensively investigated to demonstrate that exposure of the third cytoplasmic loop is essential for selective G protein activation. In contrast, much less is known about other families. Here we prepared chimeric mutants between Gt‐coupled rhodopsin and Gi/Go‐ and Gs‐coupled glucagon‐like peptide‐1 (GLP‐1) receptor of family 2 and tried to identify the loop region that functions at the third cytoplasmic loop position of rhodopsin. We succeeded in expressing a mutant having the first cytoplasmic loop of GLP‐1 receptor and found that this mutant activated Gi and Go efficiently but did not activate Gt. Moreover, the rhodopsin mutant having the first loop of Gs‐coupled secretin receptor of family 2 decreased the Gi and Go activation efficiencies. Therefore, the first loop of GLP‐1 receptor would share a similar role to the third loop of rhodopsin in G protein activation. This result strongly suggested that different families of GPCRs have maintained molecular architectures of their ancestral types to generate a common mechanism, namely exposure of the cytoplasmic loop, to activate peripheral G protein.
An Introduction to Multilevel Modeling for Social and Personality Psychology
Authors: Nezlek John B.
Published: March 2008

Multilevel modeling is a technique that has numerous potential applications for social and personality psychology. To help realize this potential, this article provides an introduction to multilevel modeling with an emphasis on some of its applications in social and personality psychology. This introduction includes a description of multilevel modeling, a rationale for this technique, and a discussion of applications of multilevel modeling in social and personality psychological research. Some of the subtleties of setting up multilevel analyses and interpreting results are presented, and software options are discussed.
Subjectivity, Not Personality: Combining Discourse Analysis and Psychoanalysis
Authors: Branney Peter
Published: March 2008

Mainstream psychology can often be criticized for turning the liberal concerns of psychologists into conservative practices focusing on the individual. In the United Kingdom, the discursive turn in social psychology has been marked by an audacious body of work critical of cognitive attempts to theorize the social. A particular psycho‐discursive strand has emerged, which combines discourse analysis and psychoanalytic theory in an attempt to change both the subject of, and the subjectivity (re)produced by, mainstream psychology. This paper reviews three different psycho‐discursive approaches: (i) Hollway and Jefferson's Free Association Narrative Interview method; (ii) Billig's Psychoanalytic Discursive Psychology; (iii) Parker's Lacanian excursions into social psychology. In these psycho‐discursive approaches, ‘subjectivity’ replaces personality as the key theoretical construct where the social forms part of who we are and these approaches seem to offer social psychologists the theoretical tools to start to appreciate how individual personality and social context are intimately connected.
Psychoneuroimmunology
Authors: Byrne‐Davis L. M. T. , Vedhara K.
Published: March 2008

Psychoneuroimmunology (PNI) is concerned with the processes that mediate the relationships between psychological and social factors and disease or health. The focus of PNI is particularly the bidirectional relationships between these factors and the immune system, through nervous system and endocrine system pathways. This paper will provide an introduction to PNI. This will include a brief tour of the immune system and its measurement and the physiology of mind–body connections. Two pertinent questions will then arise: whether social and psychological factors can make healthy people sick and how these factors influence the course of diseases. These questions will be discussed using evidence from observational, experimental, and intervention studies.
Research Artifacts and the Social Psychology of Psychological Experiments
Authors: Strohmetz David B.
Published: March 2008

In psychological research with human subjects, experimenters need to anticipate potential artifacts that may be attributable to the social context of such research. Called research artifacts in this review, they are essentially uncontrolled, systematic errors (or biases) that threaten the degree of validity of statements made about whether changes in one variable result in changes in another variable. This discussion focuses on a proposed Markov‐like model emphasizing three mediating variables that operate in a theoretical chain of events. One variable refers to the likelihood of the subject's receptivity to task‐orienting cues (called demand characteristics), or incidental hints about the experimenter's expectations. A second variable refers to the likelihood of the subject's motivation (or willingness) to comply with those cues or hints. A third variable refers to the likelihood of the subject's capability of responding in accordance with the cues or hints. These three variables are discussed along with strategies that researchers can use to break the chain of events.
Culture and Personality: Variability across Universal Motives as the Missing Link
Authors: Higgins E. Tory
Published: March 2008

What is the relation between culture and personality? I argue that to address this question, it is necessary to meet five criteria: (1) to identify universal principles of human functioning that underlie both culture and personality; (2) to treat those principles at different levels of analysis for culture and personality; (3) to define culture and personality in terms of those principles in a manner that maintains the integrity of these concepts; (4) to select specific psychological factors that, because of their survival value, are present in every culture and individual, although to varying degrees; and (5) to postulate how different cultures and personalities emerge from variability in the predominance of those specific psychological factors. I then propose that these criteria can be met by identifying specific human motives that are both universal and vary across individuals, situations, and groups. I propose a five‐step model that describes how cultures influence the personalities that emerge among its members, with particular emphasis on the human‐defining period of development between 3 and 6 years of age, and how those personalities in turn influence the culture (from effects of regulatory fit). As initial support for the model, evidence is reviewed for commonality among cultures in the existence of promotion, prevention, locomotion, and assessment motives; for variability across cultures in the predominance of these motives as modal personalities; and for universality in the relations between each motive and Big Five and self‐esteem trait characteristics. Combining the latter universal relations with the cultural variability in modal personalities yields cultural differences in manners of goal pursuit.
Estimation of effective number of breeders from molecular coancestry of single cohort sample
Authors: Nomura Tetsuro
Published: March 2008

The effective population size, Ne, is an important parameter in population genetics and conservation biology. It is, however, difficult to directly estimate Ne from demographic data in many wild species. Alternatively, the use of genetic data has received much attention in recent years. In the present study, I propose a new method for estimating the effective number of breeders Neb from a parameter of allele sharing (molecular coancestry) among sampled progeny. The bias and confidence interval of the new estimator are compared with those from a published method, i.e. the heterozygote‐excess method, using computer simulation. Two population models are simulated; the noninbred population that consists of noninbred and nonrelated parents and the inbred population that is composed of inbred and related parents. Both methods give essentially unbiased estimates of Neb when applied to the noninbred population. In the inbred population, the proposed method gives a downward biased estimate, but the confidence interval is remarkably narrowed compared with that in the noninbred population. Estimate from the heterozygote‐excess method is nearly unbiased in the inbred population, but suffers from a larger confidence interval. By combining the estimates from the two methods as a harmonic mean, the reliability is remarkably improved.
Increase in maturation size after the closure of a high seas gillnet fishery on hatchery‐reared chum salmon Oncorhynchus keta
Authors: Fukuwaka Masa‐aki , Morita Kentaro
Published: March 2008

Gillnet fisheries are strongly size‐selective and seem to produce changes in size at maturity for exploited fishes. After Word War II, large‐scale gillnet fisheries targeted Pacific salmon (Oncorhynchus spp.) in the high seas area of the North Pacific and the Bering Sea, but these fisheries were closed in 1993. To assess the effects of this high seas gillnet fishery (and its closing) on size at maturity, we examined long‐term trends in size at 50% probability of maturing (L50) for chum salmon (O. keta) from three populations in Hokkaido, Japan. The L50 trends were statistically different among rivers, but showed similar temporal patterns with decreases in the 1970s and early 1980s and increases after the 1985 brood year. While fishery‐induced evolution seemed largely responsible for this temporal change in L50 during the fishing period, natural selection and phenotypic plasticity induced by environmental changes could contribute to the increases in L50 after the relaxation of fishing pressure.
The impact of the brand in the success of a mobile game
Authors: Stenbacka Björn
Published: March 2008

A short value chain, strong brand, strong game concept, broad porting, strong language support (EFIGS, i.e., English, French, Italian, German and Spanish), combined with short time to market and powerful global distribution machinery, are key components in building a successful mobile game and gaming business. But which of these components and factors affect success when success is defined as high revenue per download and high download volumes of the game? Or does the combination of all these factors decide the outcome? These are two central research questions in this study.

We specifically describe the effects of using a brand in the mobile games' value chain. The comparative analysis of three J2ME-branded racing games points to the fact that the brand has a significant impact on the value chain and the success of a game. The stronger the brand the shorter the value chain, and the higher the revenue per download and the download volume.

To some extent, a strong brand compensates for a lack in game quality, and even game porting. The other way around, we find that if the brand is weak even a good-quality game and very broad porting cannot compensate for the negative impact of a weak brand.
Embedded noninteractive continuous bot detection
Authors: Yampolskiy Roman V. , Govindaraju Venu
Published: March 2008

Multiplayer online computer games are quickly growing in popularity, with millions of players logging in every day. While most play in accordance with the rules set up by the game designers, some choose to utilize artificially intelligent assistant programs, a.k.a. bots, to gain an unfair advantage over other players. In this article we demonstrate how an embedded noninteractive test can be used to prevent automatic artificially intelligent players from illegally participating in online game-play. Our solution has numerous advantages over traditional tests, such as its nonobtrusive nature, continuous verification, and simple noninteractive and outsourcing-proof design.
PyTrilinos
Authors: Sala Marzio , Spotz W. F. , Heroux M. A.
Published: March 2008

PyTrilinos is a collection of Python modules that are useful for serial and parallel scientific computing. This collection contains modules that cover serial and parallel dense linear algebra, serial and parallel sparse linear algebra, direct and iterative linear solution techniques, domain decomposition and multilevel preconditioners, nonlinear solvers, and continuation algorithms. Also included are a variety of related utility functions and classes, including distributed I/O, coloring algorithms, and matrix generation. PyTrilinos vector objects are integrated with the popular NumPy Python module, gathering together a variety of high-level distributed computing operations with serial vector operations.

PyTrilinos is a set of interfaces to existing, compiled libraries. This hybrid framework uses Python as front-end, and efficient precompiled libraries for all computationally expensive tasks. Thus, we take advantage of both the flexibility and ease of use of Python, and the efficiency of the underlying C++, C, and FORTRAN numerical kernels. Out numerical results show that, for many important problem classes, the overhead required by the Python interpreter is negligible.

To run in parallel, PyTrilinos simply requires a standard Python interpreter. The fundamental MPI calls are encapsulated under an abstract layer that manages all interprocessor communications. This makes serial and parallel scripts using PyTrilinos virtually identical.
Algorithm 873
Authors: Rojas Marielba , Santos Sandra A. , Sorensen Danny C.
Published: March 2008

A MATLAB 6.0 implementation of the LSTRS method is presented. LSTRS was described in Rojas et al. [2000]. LSTRS is designed for large-scale quadratic problems with one norm constraint. The method is based on a reformulation of the trust-region subproblem as a parameterized eigenvalue problem, and consists of an iterative procedure that finds the optimal value for the parameter. The adjustment of the parameter requires the solution of a large-scale eigenvalue problem at each step. LSTRS relies on matrix-vector products only and has low and fixed storage requirements, features that make it suitable for large-scale computations. In the MATLAB implementation, the Hessian matrix of the quadratic objective function can be specified either explicitly, or in the form of a matrix-vector multiplication routine. Therefore, the implementation preserves the matrix-free nature of the method. A description of the LSTRS method and of the MATLAB software, version 1.2, is presented. Comparisons with other techniques and applications of the method are also included. A guide for using the software and examples are provided.
Reverse-mode AD in a functional framework
Authors: Pearlmutter Barak A. , Siskind Jeffrey Mark
Published: March 2008

We show that reverse-mode AD (Automatic Differentiation)—a generalized gradient-calculation operator—can be incorporated as a first-class function in an augmented lambda calculus, and therefore into a functional-programming language. Closure is achieved, in that the new operator can be applied to any expression in the augmented language, yielding an expression in that language. This requires the resolution of two major technical issues: (a) how to transform nested lambda expressions, including those with free-variable references, and (b) how to support self application of the AD machinery. AD transformations preserve certain complexity properties, among them that the reverse phase of the reverse-mode AD transformation of a function have the same temporal complexity as the original untransformed function. First-class unrestricted AD operators increase the expressive power available to the numeric programmer, and may have significant practical implications for the construction of numeric software that is robust, modular, concise, correct, and efficient.
Exceptional situations and program reliability
Authors: Weimer Westley , Necula George C.
Published: March 2008

It is difficult to write programs that behave correctly in the presence of run-time errors. Proper behavior in the face of exceptional situations is important to the reliability of long-running programs. Existing programming language features often provide poor support for executing clean-up code and for restoring invariants.

We present a data-flow analysis for finding a certain class of exception-handling defects: those related to a failure to release resources or to clean up properly along all paths. Many real-world programs violate such resource usage rules because of incorrect exception handling. Our flow-sensitive analysis keeps track of outstanding obligations along program paths and does a precise modeling of control flow in the presence of exceptions. Using it, we have found over 1,300 exception handling defects in over 5 million lines of Java code.

Based on those defects we propose a programming language feature, the compensation stack, that keeps track of obligations at run time and ensures that they are discharged. We present a type system for compensation stacks that tracks collections of obligations. Finally, we present case studies to demonstrate that this feature is natural, efficient, and can improve reliability.
Normalize, transpose, and distribute
Authors: Cooke Daniel E. , Rushton J. Nelson , Nemanich Brad , Watson Robert G. , Andersen Per
Published: March 2008

SequenceL is a concise, high-level language with a simple semantics that provides for the automatic derivation of many iterative and parallel control structures. The semantics repeatedly applies a “Normalize-Transpose-Distribute” operation to functions and operators until base cases are discovered. Base cases include the grounding of variables and the application of built-in operators to operands of appropriate types. This article introduces the results of a 24-month effort to reduce the language to a very small set of primitives. Included are comparisons with other languages, the formal syntax and semantics, and the traces of several example problems run with a prototype interpreter developed in 2006.
Dynamic slicing on Java bytecode traces
Authors: Wang Tao , Roychoudhury Abhik
Published: March 2008

Dynamic slicing is a well-known technique for program analysis, debugging and understanding. Given a program
P
and input I, it finds all program statements which directly/indirectly affect the values of some variables' occurrences when
P
is executed with I. In this article, we develop a dynamic slicing method for Java programs. Our technique proceeds by backwards traversal of the bytecode trace produced by an input I in a given program
P
. Since such traces can be huge, we use results from data compression to compactly represent bytecode traces. The major space savings in our method come from the optimized representation of (a) data addresses used as operands by memory reference bytecodes, and (b) instruction addresses used as operands by control transfer bytecodes. We show how dynamic slicing algorithms can directly traverse our compact bytecode traces without resorting to costly decompression. We also extend our dynamic slicing algorithm to perform “relevant slicing”. The resultant slices can be used to explain omission errors that is, why some events did not happen during program execution. Detailed experimental results on space/time overheads of tracing and slicing are reported in the article. The slices computed at the bytecode level are translated back by our tool to the source code level with the help of information available in Java class files. Our
JSlice
dynamic slicing tool has been integrated with the Eclipse platform and is available for usage in research and development.
Alice
Authors: Pausch Randy
Published: March 2008

I have spent the last fifteen years of my life leading an incredible team. Our quest (which we did not even realize in the beginning) was to revolutionize the way computer programming is taught. Current versions of the Alice system (Alice v2.0, and Caitlin Kelleher's "Storytelling Alice") have been very effective in the college classroom and in tests with middle school girls. The use of drag-and-drop authoring to create 3D movies has proved to be a powerful motivator for students of all ages and both genders. In 2008, we will release Alice v3.0, which provides "real Java" programming and the characters from EA's "The Sims," the most popular PC video game in history.

Damn shame I won't be there to see it. As you probably know, I'm dying of pancreatic cancer, as became widely known in my "Last Lecture." Like Moses, I get to see the promised land, but not set foot in it. But the vision is clear. Long before I became ill, Dennis Cosgrove took over the responsibility for the design of Alice v3.0, and he's doing a whale of a job. Steve Cooper (of St. Joseph's University), Wanda Dann, and Don Slater are handling the pedagogic materials for college and high school, and Caitlin Kelleher (now junior faculty at Washington University in St. Louis) is heading the efforts regarding middle school girls.

This talk will address the history, philosophy, and future of the Alice project, and will include a behind-the-scenes look at a pre-release version of Alice v3.0. I will give this address in person if I am still alive and able, or by a combination of pre-taped video and help from the Alice team. I cannot imagine a better professional legacy than what the Alice team is currently building.
Learning from wrong and creative algorithm design
Authors: Ginat David
Published: March 2008

We all are aware of the relevance of examining a task from diverse angles. We also are aware of the potential relevance of learning from one's mistakes. Yet computer science (CS) textbooks and teaching materials fall short in embedding these two notions. In this paper, we present an approach of elaborating divergent thinking in algorithm design, while capitalizing on erroneous solutions. Using a collected set of non-routine algorithmic tasks, we developed and applied a scheme of class activities, in which initial faulty solutions (due to novice tendencies) are carefully examined, and their falsifying inputs and characteristics are used for creative reasoning that yields fruitful outcomes. We present and illustrate our activities, refer to their cognitive aspects, and describe our experience with applying them in (an Introduction-to-Algorithms) class.
Language engineering in the context of a popular, inexpensive robot platform
Authors: Xu Li
Published: March 2008

Language engineering - the theory and practice of building language processors and compilers, has long been recognized as important subject in Computer Science curricula. However, due to lack of suitable target systems, educators face significant challenges to teach language engineering classes effectively.

Leveraging the emerging inexpensive robot devices, this paper presents a new approach of using robots as system context to teach language engineering topics. We designed the Chirp-Scribbler Language, which targets the popular Scribbler robot; combined together, they provide an engaging and feature-rich platform to teach a wide range of topics in language engineering.

This paper describes the Chirp-Scribbler Language, its integration with the target robot, and the teaching practice of using them to teach language translation basics in an undergraduate programming course.
Multi-player soccer and wireless embedded systems
Authors: Borriello Gaetano , Hartung Carl , Hemingway Bruce , Koscher Karl , Mayton Brian
Published: March 2008

Embedded systems are increasingly becoming connected through wireless networking. These devices now form the basis of many of today's consumer products including cell phones and video game controllers. In the "Software for Embedded Systems" class in the Department of Computer Science & Engineering at the University of Washington, we used the design of a multi-player video game as motivation for the principal concepts in wireless embedded systems. Each student in the class designed an accelerometer-based game controller and then, the class as a whole, developed a multi-player video game that allowed 28 players (the number of students in the course) to play simultaneously. In this paper, we first describe the context of the course and its goals followed by the hardware/software platform we used to realize the game controller. We then detail the pedagogical approach we used to collectively design the video game (loosely based on soccer) and conclude with the lessons learned from this group design experience and how we would enhance the project and course in the future.
A new paradigm for programming competitions
Authors: Bowring James F.
Published: March 2008

The annual ACM International Collegiate Programming Contest produces a competitive paradigm that is at odds with the pedagogical goals of modern computer science and software engineering degree programs. This paradigm stresses the fast completion of a programming task and evaluates the results solely with black-box testing specified by the judges. In contrast, the pedagogical goals of contemporary college degree programs in computing emphasize the quality of processes inherent in software development and implementation. In 2007, the College of Charleston student chapter of the ACM hosted its annual high school programming competition by turning the conventional programming paradigm on its head to focus on quality-of-process rather than time-to-complete. The judging criteria included both technical and artistic merit. The implementation of the competition emphasized success by giving students working skeleton solution programs. This paper presents the motivation for the new paradigm, the details of its implementation for the 2007 competition, and the details of the new techniques for judging technical and artistic merit.
Computer science olympiad
Authors: Kearse Iretta B. , Hardnett Charles R.
Published: March 2008

Generating interest in specialized areas of Computer Science (CS) is one of the goals of the department of Computer and Information Science at Spelman College as with most departments. Achieving this goal in a new, exciting, and innovative manner provided the inspiration to establish the Spelman College Computer Science Olympiad (SC CS Olympiad). The SC CS Olympiad is patterned after the Olympics athletic event. Students participate in the Olympiad as a part of a team as with the Olympics. In addition, there are several events for competition as there are in the Olympics. The events are designed to expose students to the interesting breadth of CS over several days. In this paper, the events are in the following categories: Cryptography, Robotics, Website Design, Hardware and Software Integration, and Programming. Teams use their CS knowledge and problem-solving skills to complete hands-on exercises in each area. Each teams receives points based on the quality of their results from the exercise. In this paper, we present the implementation, results, and future directions of the Spelman College Computer Science Olympiad.
Cluster computing for web-scale data processing
Authors: Kimball Aaron , Michels-Slettvet Sierra , Bisciglia Christophe
Published: March 2008

In this paper we present the design of a modern course in cluster computing and large-scale data processing. The defining differences between this and previously published designs are its focus on processing very large data sets and its use of Hadoop, an open source Java-based implementation of MapReduce and the Google File System as the platform for programming exercises. Hadoop proved to be a key element for successfully implementing structured lab activities and independent design projects. Through this course, offered at the University of Washington in 2007, we imparted new skills on our students, improving their ability to design systems capable of solving web-scale problems.
Microwulf
Authors: Adams Joel C. , Brom Tim H.
Published: March 2008

A Beowulf cluster is a distributed memory multiprocessor built from commodity off-the-shelf PC hardware, an inexpensive network for inter-process communication, and open-source software. Today's multi-core CPUs make it possible to build a Beowulf cluster that is powerful, small, and inexpensive. This paper describes Microwulf, a Beowulf cluster that cost just $2470 to build, but provides 26.25 Gflops of measured performance. (For comparison: a 1996 Cray T3D MC256-8/464 provided 25.3 Gflops.) This makes Microwulf the first Beowulf with a price/performance ratio below $100/Gflop (for double-precision operations). The system measures just 11" x 12" x 17" (27.9 cm x 30.5 cm x 43.2 cm), runs at room temperature, and plugs into a standard wall outlet. These desirable characteristics combine to make Microwulf an attractive design for most computer science departments and/or individuals.