bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical characteristics of one-dimensional Si∕SiO2 photonic crystals for thermophotovoltaic applications
Authors: O’Sullivan Francis , Celanovic Ivan , Jovanovic Natalija , Kassakian John , Akiyama Shoji , Wada Kazumi
Published: January 2005

This article presents a detailed exploration of the optical characteristics of various one-dimensional photonic crystal structures designed for use as a means of improving the efficiency and power density of thermophotovoltaic (TPV) devices. The crystals being investigated have a ten-layer quarter-wave periodic structure, and are based on Si∕SiO2 and Si∕SiON material systems. For TPV applications the crystals are designed to act as filters, transmitting photons with wavelengths below 1.78μm to a GaSb photodiode, while reflecting photons of longer wavelengths back to the source of thermal radiation. In the case of the Si∕SiO2 structure, the Si and SiO2 layers were designed to be 170 and 390nm thick, respectively. This structure was fabricated using low-pressure chemical vapor deposition. Reflectance and transmittance measurements of the fabricated Si∕SiO2 photonic crystals were taken from 0.8to3.3μm for both polarizations and for a range of incident angles. Measurement results were found to correlate well with simulation results for the ideal structure. Measurement results were used to predict the TPV system efficiency, power density and spectral efficiency using an ideal thermodynamic model of a TPV system.
Ferroelectric domain morphologies of (001) PbZr1−xTixO3 epitaxial thin films
Authors: Li Y. L. , Hu S. Y. , Chen L. Q.
Published: January 2005

Ferroelectric domain morphologies in (001) PbZr1−xTixO3 epitaxial thin films were studied using the phase-field approach. The film is assumed to have a stress-free top surface and is subject to a biaxial substrate constraint. Both the electrostatic open-circuit and short-circuit boundary conditions on the film surfaces were considered. The phase-field simulations indicated that in addition to the known tetragonal and rhombohedral phases, an orthorhombic phase becomes stable in films under large tensile constraints. The orthorhombic domain structure contains (100) and (010) 90° domain walls and (110) and (1–10) 180° domain walls. For the rhombohedral phase in a thin film, the domain walls are found to be along {101}, (100), and (010) of the prototypical cubic cell. It is shown that the short-circuit boundary condition and compressive substrate constraint enhance the out-of-plane polarization component while the open-circuit boundary condition and tensile substrate constraint suppress it. It is also shown that the depolarization field promotes the formation of herringbonelike morphology for the rhombohedral phase.
On the two-dimensional flow in a sudden expansion with large expansion ratios
Authors: Revuelta Antonio
Published: January 2005

In this Brief Communication, the two-dimensional laminar flow of an incompressible viscous jet through a channel with a sudden expansion is analyzed in the case of a large expansion ratio. It is shown that, when the jet Reynolds number is sufficiently large, the momentum exchange between the incoming jet and the recirculating fluid determines the structure and the scales of the resulting flow, as well as the critical conditions for appearance of asymmetric solutions.
Effects of repetition, interval between treatments and season on the results from laparoscopic ovum pick-up in goats
Authors: Pierson J. , Wang B. , Neveu N. , Sneek L. , Côté F. , Karatzas C. N. , Baldassarre H.
Published: January 2005

The present study was conducted to evaluate the follicular response and oocyte yield following repeated gonadotrophin stimulation and laparoscopic aspiration in goats and to assess the effects of the time interval between procedures and season. A total of 98 adult goats were subjected to laparoscopic ovum pick-up (LOPU) five consecutive times in a transgenic production programme. Oestrus was synchronised by means of intravaginal sponges inserted for 10 days coupled with 125 μg cloprostenol 36 h before sponge removal and LOPU, and follicular development was stimulated with 80 mg follicle stimulating hormone and 300 IU equine chorionic gonadotrophin administered 36 h before LOPU. No difference was detected in the response for LOPUs 1, 2, 3 and 4. Although a small decrease in response was detected at LOPU 5 (P < 0.05), the numbers of follicles aspirated and oocytes recovered were not different from those at LOPU 1 and LOPUs 1 and 4, respectively. With respect to time interval between LOPU and season, all intervals and seasons produced acceptable responses, with no difference in follicles aspirated and oocytes recovered between intervals and seasons. These results indicate that LOPU may be repeated up to five times in goats at different intervals and in different seasons with little or no important change in overall response.
Macedonian Border Closings in the Kosovo Refugee Crisis: A Game-Theoretic Perspective
Authors: Williams John H.P. , Zeager Lester A.
Published: January 2005

The 1999 Kosovo crisis generated more than 800,000 refugees, the majority of whom fled into Albania or Macedonia. While Albanians welcomed their ethnic kin, Macedonia closed its border three times. We provide a game-theoretic perspective on strategic interactions between Macedonia and NATO. We use narrative accounts of the crisis to eliminate many configurations of payoffs. Among those remaining, the theory of moves isolates one game that can satisfy the necessary conditions for credible threats: the prisoners' dilemma. Credible threats of border closings in a prisoners' dilemma alter donor incentives and lead to international sharing of asylum burdens in repeated play.
Testing Competing Institutional Explanations of the Democratic Peace: The Case of Dispute Duration
Authors: Bueno De Mesquita Bruce , Koch Michael T. , Siverson Randolph M.
Published: January 2005

Drawing upon two alternative versions of the institutional explanation for the democratic peace, we suggest competing hypotheses about the relationship between democratic political institutions and the length of dispute participation. One set of hypotheses originates in the argument that because of the bargaining arrangements internal to democratic states, disputes between democratic states will necessarily be drawn out, so that in the time that it takes to secure the domestic political base for war, diplomats have time to find nonwar solutions. A second set of hypotheses, derived from the selectorate argument about how institutions shape the behavior of leaders who want to remain in power, leads to the expectation that selection effects over which disputes to participate in make disputes between democracies shorter than disputes between pairs of other types of states. Using a Weibull survival model we analyze data on the length of Militarized Interstate Disputes during the period 1816 to 1992; we find clear support for the selectorate explanation. Two ancillary hypotheses from the selectorate argument are also tested and supported by the data.
Politics and National Security: The Battles for Britain
Authors: Lobell Steven E.
Published: January 2005

Between 1889 and 1939 Britain created security for itself through alliances, rearmament, or appeasement (either alone or in some combination). The existing literature emphasizes the role of geopolitics, domestic characteristics, and individual idiosyncrasies to explain Britain's choices. I argue that within Britain, two broad and logrolled coalitions (outward-looking internationalist bloc and inward-oriented nationalist faction) battled to advance their faction's preferred security strategy and to capture the associated distributive benefits. Supporters and opponents understood that how Britain secured itself would create internal winners and losers. Supporters and opponents also recognized that any changes in the security strategy would have domestic redistributional consequences. I apply this model to Britain and use a longitudinal controlled comparison over three periods: 1889—1914, 1914—1919, and 1919—1939.
“The Enemy of My Enemy Is My Friend” Is the Enemy: Dealing with the War-Provoking Rules of Intent
Authors: Saperstein Alvin M.
Published: January 2005

A set of rules often invoked to explain or justify the evolution of intentions and the consequent behavior of competitive systems consists of the following:

1. The friend of my friend is my friend.

2. The friend of my enemy is my enemy.

3. The enemy of my friend is my enemy.

4. The enemy of my enemy is my friend.

These rules have been modeled as a set of nonlinear, coupled differential equations from which predictions can be derived as to eventual alliance building or conflict in the system, predictions which are quite ominous for the behavior of simple three-body systems. This paper presents illustrations of the application of the rules to international behavior and discusses the relationship between the rules as usually verbally applied and the associated mathematical models.

Not all of these rules are equally desirable: behavior in accordance to the fourth rule has led to major difficulties in the “real world.” This fourth rule cannot just be dropped, since the four rules are not independent of each other in the mathematical model. Hence the model must be altered. A simple mathematical modification is suggested which implies increased flexibility in the verbal statement and application of the rules; e.g., the fourth now reads “The enemy of my enemy may be my friend.” The altered model leads to altered predictions of the evolution of intent which are much less ominous for the outcome of three-body competitions.
Aegean Territorial Waters Conflict: An Evolutionary Narrative
Authors: Güner Serdar Ş.
Published: January 2005

Delimitation of the territorial waters and continental shelf in the Aegean Sea constitutes a constant source of conflict and produces recurrent crises between Greece and Turkey. This article explores directions that the Greek—Turkish dispute over the delimitation of territorial waters can take through an evolutionary game framework. Crises are found to follow routines and practices involving challenges to the status quo and reactions preceding mutual retreat. Hence, the status quo in the Aegean Sea can persist even in the form of aggressive behavior. It is also possible that the dispute will evolve into a stable state of conflict where no cooperative foreign policy can survive.
ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation
Authors: Lee Stella Y. , Yang Jia-Shu , Hong Wanjin , Premont Richard T. , Hsu Victor W.
Published: January 2005

Examining how key components of coat protein I (COPI) transport participate in cargo sorting, we find that, instead of ADP ribosylation factor 1 (ARF1), its GTPase-activating protein (GAP) plays a direct role in promoting the binding of cargo proteins by coatomer (the core COPI complex). Activated ARF1 binds selectively to SNARE cargo proteins, with this binding likely to represent at least a mechanism by which activated ARF1 is stabilized on Golgi membrane to propagate its effector functions. We also find that the GAP catalytic activity plays a critical role in the formation of COPI vesicles from Golgi membrane, in contrast to the prevailing view that this activity antagonizes vesicle formation. Together, these findings indicate that GAP plays a central role in coupling cargo sorting and vesicle formation, with implications for simplifying models to describe how these two processes are coupled during COPI transport.
Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model
Authors: Dobrowolny Gabriella , Giacinti Cristina , Pelosi Laura , Nicoletti Carmine , Winn Nadine , Barberi Laura , Molinaro Mario , Rosenthal Nadia , Musarò Antonio
Published: January 2005

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle. Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. Here, we show that muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1G93A transgenic mice, inducing calcineurin-mediated regenerative pathways. Muscle-specific expression of local Igf-1 (mIgf-1) isoform also stabilized neuromuscular junctions, reduced inflammation in the spinal cord, and enhanced motor neuronal survival in SOD1G93A mice, delaying the onset and progression of the disease. These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival.
Cell growth–dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p
Authors: Faulhammer Frank , Konrad Gerlinde , Brankatschk Ben , Tahirovic Sabina , Knödler Andreas , Mayinger Peter
Published: January 2005

The integral membrane lipid phosphatase Sac1p regulates local pools of phosphatidylinositol-4-phosphate (PtdIns(4)P) at endoplasmic reticulum (ER) and Golgi membranes. PtdIns(4)P is important for Golgi trafficking, yet the significance of PtdIns(4)P for ER function is unknown. It also remains unknown how localization of Sac1p to distinct organellar membranes is mediated. Here, we show that a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p. The interaction with Dpm1p persists during exponential cell division but is rapidly abolished when cell growth slows because of nutrient limitation, causing translocation of Sac1p to Golgi membranes. Cell growth–dependent shuttling of Sac1p between the ER and the Golgi is important for reciprocal control of PtdIns(4)P levels at these organelles. The fraction of Sac1p resident at the ER is also required for efficient dolichol oligosaccharide biosynthesis. Thus, the lipid phosphatase Sac1p may be a key regulator, coordinating the secretory capacity of ER and Golgi membranes in response to growth conditions.
Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast
Authors: Pozniakovsky Andrei I. , Knorre Dmitry A. , Markova Olga V. , Hyman Anthony A. , Skulachev Vladimir P. , Severin Fedor F.
Published: January 2005

Although programmed cell death (PCD) is extensively studied in multicellular organisms, in recent years it has been shown that a unicellular organism, yeast Saccharomyces cerevisiae, also possesses death program(s). In particular, we have found that a high doses of yeast pheromone is a natural stimulus inducing PCD. Here, we show that the death cascades triggered by pheromone and by a drug amiodarone are very similar. We focused on the role of mitochondria during the pheromone/amiodarone-induced PCD. For the first time, a functional chain of the mitochondria-related events required for a particular case of yeast PCD has been revealed: an enhancement of mitochondrial respiration and of its energy coupling, a strong increase of mitochondrial membrane potential, both events triggered by the rise of cytoplasmic [Ca2+], a burst in generation of reactive oxygen species in center o of the respiratory chain complex III, mitochondrial thread-grain transition, and cytochrome c release from mitochondria. A novel mitochondrial protein required for thread-grain transition is identified.
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Authors: Langrish Claire L. , Chen Yi , Blumenschein Wendy M. , Mattson Jeanine , Basham Beth , Sedgwick Jonathan D. , McClanahan Terrill , Kastelein Robert A. , Cua Daniel J.
Published: January 2005

Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-γ–producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4+ T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23–driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12–driven T cells. Using passive transfer studies, we confirm that these IL-23–dependent CD4+ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.
Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen
Authors: Lurquin Christophe , Lethé Bernard , De Plaen Etienne , Corbière Véronique , Théate Ivan , van Baren Nicolas , Coulie Pierre G. , Boon Thierry
Published: January 2005

Melanoma patients have high frequencies of T cells directed against antigens of their tumor. The frequency of these antitumor T cells in the blood is usually well above that of the anti-vaccine T cells observed after vaccination with tumor antigens. In a patient vaccinated with a MAGE-3 antigen presented by HLA-A1, we measured the frequencies of anti-vaccine and antitumor T cells in several metastases to evaluate their respective potential contribution to tumor rejection. The frequency of anti–MAGE-3.A1 T cells was 1.5 × 10−5 of CD8 T cells in an invaded lymph node, sixfold higher than in the blood. An antitumor cytotoxic T lymphocyte (CTL) recognizing a MAGE-C2 antigen showed a much higher enrichment with a frequency of ∼10%, 1,000 times higher than its blood frequency. Several other antitumor T clonotypes had frequencies >1%. Similar findings were made on a regressing cutaneous metastasis. Thus, antitumor T cells were ∼10,000 times more frequent than anti-vaccine T cells inside metastases, representing the majority of T cells present there. This suggests that the anti-vaccine CTLs are not the effectors that kill the bulk of the tumor cells, but that their interaction with the tumor generates conditions enabling the stimulation of large numbers of antitumor CTLs that proceed to destroy the tumor cells. Naive T cells appear to be stimulated in the course of this process as new antitumor clonotypes arise after vaccination.
High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens
Authors: Germeau Catherine , Ma Wenbin , Schiavetti Francesca , Lurquin Christophe , Henry Emmanuelle , Vigneron Nathalie , Brasseur Francis , Lethé Bernard , De Plaen Etienne , Velu Thierry , Boon Thierry , Coulie Pierre G.
Published: January 2005

After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10−5 of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10−4 to 3 × 10−3, which is 10–10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethé, V. Corbière, I. Théate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249–257).
Yellow fever 17D as a vaccine vector for microbial CTL epitopes
Authors: Tao Deng , Barba-Spaeth Giovanna , Rai Urvashi , Nussenzweig Victor , Rice Charles M. , Nussenzweig Ruth S.
Published: January 2005

The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human vaccines in underdeveloped countries is the need for multiple injections to achieve full efficacy. To examine 17D as a vector for microbial T cell epitopes, we inserted the H-2Kd–restricted CTL epitope of the circumsporozoite protein (CS) of Plasmodium yoelii between 17D nonstructural proteins NS2B and NS3. The recombinant virus, 17D-Py, was replication competent and stable in vitro and in vivo. A single subcutaneous injection of 105 PFU diminished the parasite burden in the liver by ∼70%. The high level of protection lasted between 4 and 8 wk after immunization, but a significant effect was documented even 24 wk afterwards. Thus, the immunogenicity of a foreign T cell epitope inserted into 17D mimics some of the remarkable properties of the human vaccine. Priming with 17D-Py followed by boosting with irradiated sporozoites conferred sterile immunity to 90% of the mice. This finding indicates that the immune response of vaccine-primed individuals living in endemic areas could be sustained and magnified by the bite of infected mosquitoes.
Detection, identification and mapping of iron anomalies in brain tissue using X-ray absorption spectroscopy
Authors: Mikhaylova A , Davidson M , Toastmann H , Channell J.E.T , Guyodo Y , Batich C , Dobson J
Published: January 2005

This work describes a novel method for the detection, identification and mapping of anomalous iron compounds in mammalian brain tissue using X-ray absorption spectroscopy. We have located and identified individual iron anomalies in an avian tissue model associated with ferritin, biogenic magnetite and haemoglobin with a pixel resolution of less than 5 μm. This technique represents a breakthrough in the study of both intra- and extra-cellular iron compounds in brain tissue. The potential for high-resolution iron mapping using microfocused X-ray beams has direct application to investigations of the location and structural form of iron compounds associated with human neurodegenerative disorders—a problem which has vexed researchers for 50 years.
Cayley kinematics and the Cayley form of dynamic equations
Authors: Sinclair Andrew J. , Hurtado John E.
Published: January 2005

The Cayley transform and the Cayley–transform kinematic relationships are an important and fascinating set of results that have relevance in
N
–dimensional orientations and rotations. In this paper these results are used in two significant ways. First, they are used in a new derivation of the matrix form of the generalized Euler equations of motion for
N
–dimensional rigid bodies. Second, they are used to intimately relate the motion of general mechanical systems to the motion of higher–dimensional rigid bodies. This approach can be used to describe an enormous variety of systems, one example being the representation of general motion of an
N
–dimensional body as pure rotations of an (
N
+ 1)–dimensional body.
The stability of nonlinear neutral modes in Hagen–Poiseuille flow
Authors: Walton Andrew G.
Published: January 2005

The nonlinear stability of Hagen–Poiseuille flow through a pipe of circular crosssection subjected to non–symmetric disturbances is studied asymptotically at large Reynolds number. By introducing unsteady effects into the nonlinear critical layer, an evolution equation for the disturbance amplitude is derived and is found to possess an equilibrium solution first identified by Smith and Bodonyi. This solution is shown to provide a threshold amplitude, above which, on this scaling, perturbations experience finite–time blow–up, while, below the threshold, disturbances of all wavenumbers decay to zero.
Adaptation of brain regions to habitat complexity: a comparative analysis in bats (Chiroptera)
Authors: Safi Kamran , Dechmann Dina K. N.
Published: January 2005

Vertebrate brains are organized in modules which process information from sensory inputs selectively. Therefore they are probably under different evolutionary pressures. We investigated the impact of environmental influences on specific brain centres in bats. We showed in a phylogenetically independent contrast analysis that the wing area of a species corrected for body size correlated with estimates of habitat complexity. We subsequently compared wing area, as an indirect measure of habitat complexity, with the size of regions associated with hearing, olfaction and spatial memory, while controlling for phylogeny and body mass. The inferior colliculi, the largest sub-cortical auditory centre, showed a strong positive correlation with wing area in echolocating bats. The size of the main olfactory bulb did not increase with wing area, suggesting that the need for olfaction may not increase during the localization of food and orientation in denser habitat. As expected, a larger wing area was linked to a larger hippocampus in all bats. Our results suggest that morphological adaptations related to flight and neuronal capabilities as reflected by the sizes of brain regions coevolved under similar ecological pressures. Thus, habitat complexity presumably influenced and shaped sensory abilities in this mammalian order independently of each other.
Sperm competition and sexually size dimorphic brains in birds
Authors: Garamszegi László Zsolt , Eens Marcel , Erritzøe Johannes , Møller Anders Pape
Published: January 2005

Natural selection may favour sexually similar brain size owing to similar selection pressures in males and females, while sexual selection may lead to sexually dimorphic brains. For example, sperm competition involves clear–cut sex differences in behaviour, as males display, mate guard and copulate with females, while females choose among males, and solicit or reject copulations. These behaviours may require fundamentally different neural government in the two sexes leading to sex–dependent brain evolution. Using two phylogenetic approaches in a comparative study, we tested for roles of both natural and sexual–selection pressures on brain size evolution of birds. In accordance with the natural–selection theory, relative brain size of males coevolved with that of females, which may be the result of adaptation to similar environmental constraints such as feeding innovation. However, the mode of brain size evolution differed between the sexes, and factors associated with sperm competition as reflected by extra–pair paternity may give rise to sexually size dimorphic brains. Specifically, species in which females have larger brains than males were found to have a higher degree of extra–pair paternity independently of potentially confounding factors, whereas species in which males have relatively larger brains than females appeared to have lower rates of extra–pair paternity. Hence, the evolution of sperm competition may select for complex behaviours together with the associated neural substrates in the sex that has a higher potential to control extra–pair copulations at the observed levels. Brain function may thus be affected differently in males and females by sexual selection.
The cosmic history of the X–ray background
Authors: Barger Amy J.
Published: January 2005

The
Chandra
and
XMM–Newton
X–ray observatories have detected obscured active galactic nuclei (AGN) and almost fully resolved the X–ray background into discrete sources. Ground–based observations of the X–ray sources enable the reconstruction of the history of supermassive black hole accretion from the earliest times to the present. A dramatic cosmic downsizing of AGN luminosities is seen at recent times. Correspondingly, the production rate of the AGN radiation drops rapidly, and the dominant period of supermassive black hole production is seen to be at redshifts near z = 1.
Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle
Authors: Hutchin Mark E. , Kariapper Muhammed S.T. , Grachtchouk Marina , Wang Aiqin , Wei Lebing , Cummings Donelle , Liu Jianhong , Michael L. Evan , Glick Adam , Dlugosz Andrzej A.
Published: January 2005

Temporally and spatially constrained Hedgehog (Hh) signaling regulates cyclic growth of hair follicle epithelium while constitutive Hh signaling drives the development of basal cell carcinomas (BCCs), the most common cancers in humans. Using mice engineered to conditionally express the Hh effector Gli2, we show that continued Hh signaling is required for growth of established BCCs. Transgene inactivation led to BCC regression accompanied by reduced tumor cell proliferation and increased apoptosis, leaving behind a small subset of nonproliferative cells that could form tumors upon transgene reactivation. Nearly all BCCs arose from hair follicles, which harbor cutaneous epithelial stem cells, and reconstitution of regressing tumor cells with an inductive mesenchyme led to multilineage differentiation and hair follicle formation. Our data reveal that continued Hh signaling is required for proliferation and survival of established BCCs, provide compelling support for the concept that these tumors represent an aberrant form of follicle organogenesis, and uncover potential limitations to treating BCCs using Hh pathway inhibitors.
Exonic splicing enhancers in fission yeast: functional conservation demonstrates an early evolutionary origin
Authors: Webb Christopher J. , Romfo Charles M. , van Heeckeren Willem J. , Wise Jo Ann
Published: January 2005

Discrete sequence elements known as exonic splicing enhancers (ESEs) have been shown to influence both the efficiency of splicing and the profile of mature mRNAs in multicellular eukaryotes. While the existence of ESEs has not been demonstrated previously in unicellular eukaryotes, the factors known to recognize these elements and mediate their communication with the core splicing machinery are conserved and essential in the fission yeast Schizosaccharomyces pombe. Here, we provide evidence that ESE function is conserved through evolution by demonstrating that three exonic splicing enhancers derived from vertebrates (chicken ASLV, mouse IgM, and human cTNT) promote splicing of two distinct S. pombe pre-messenger RNAs (pre-mRNAs). Second, as in extracts from mammalian cells, ESE function in S. pombe is compromised by mutations and increased distance from the 3′-splice site. Third, three-hybrid analyses indicate that the essential SR (serine/arginine-rich) protein Srp2p, but not the dispensable Srp1p, binds specifically to both native and heterologous purine-rich elements; thus, Srp2p is the likely mediator of ESE function in fission yeast. Finally, we have identified five natural purine-rich elements from S. pombe that promote splicing of our reporter pre-mRNAs. Taken together, these results provide strong evidence that the genesis of ESE-mediated splicing occurred early in eukaryotic evolution.
A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling
Authors: Chuang Chiou-Fen , Bargmann Cornelia I.
Published: January 2005

A stochastic lateral signaling interaction between two developing Caenorhabditis elegans AWC olfactory neurons causes them to take on asymmetric patterns of odorant receptor expression, called AWCOFF and AWCON. Here we show that the AWC lateral signaling gene tir-1 (previously known as nsy-2) encodes a conserved post-synaptic protein that specifies the choice between AWCOFF and AWCON. Genetic evidence suggests that tir-1 acts downstream of a voltage-gated calcium channel and CaMKII (UNC-43) to regulate AWC asymmetry via the NSY-1(ASK1) p38/JNK MAP (mitogen-activated protein) kinase cascade. TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression. Temperature-shift experiments indicate that tir-1 affects AWC during a critical period late in embryogenesis, near the time of AWC synapse formation. TIR-1 is a multidomain protein with a TIR (Toll-interleukin-1 receptor) domain that activates signaling, SAM repeats that mediate localization to post-synaptic regions of axons, and an N-terminal inhibitory domain. TIR-1 and other TIR proteins are implicated in vertebrate and invertebrate innate immunity, as are NSY-1/ASK1 kinases, so this pathway may also have a conserved function in immune signaling.
The control of Spo11's interaction with meiotic recombination hotspots
Authors: Prieler Silvia , Penkner Alexandra , Borde Valérie , Klein Franz
Published: January 2005

Programmed double-strand breaks (DSBs), which initiate meiotic recombination, arise through the activity of the evolutionary conserved topoisomerase homolog Spo11. Spo11 is believed to catalyze the DNA cleavage reaction in the initial step of DSB formation, while at least a further 11 factors assist in Saccharomyces cerevisiae. Using chromatin-immunoprecipitation (ChIP), we detected the transient, noncovalent association of Spo11 with meiotic hotspots in wild-type cells. The establishment of this association requires Rec102, Rec104, and Rec114, while the timely removal of Spo11 from chromatin depends on several factors, including Mei4 and Ndt80. In addition, at least one further component, namely, Red1, is responsible for locally restricting Spo11's interaction to the core region of the hotspot. In chromosome spreads, we observed meiosis-specific Spo11-Myc foci, independent of DSB formation, from leptotene until pachytene. In both rad50S and com1Δ/sae2Δ mutants, we observed a novel reaction intermediate between Spo11 and hotspots, which leads to the detection of full-length hotspot DNA by ChIP in the absence of artificial cross-linking. Although this DNA does not contain a break, its recovery requires Spo11's catalytic residue Y135. We propose that detection of uncross-linked full-length hotspot DNA is only possible during the reversible stage of the Spo11 cleavage reaction, in which rad50S and com1Δ/sae2Δ mutants transiently arrest.
Modified reconstructability analysis for many‐valued functions and relations
Authors: Al‐Rabadi Anas N. , Zwick Martin
Published: January 2005

A novel many‐valued decomposition within the framework of lossless reconstructability analysis (RA) is presented. In previous work, modified reconstructability analysis (MRA) was applied to Boolean functions, where it was shown that most Boolean functions not decomposable using conventional reconstructability analysis (CRA) are decomposable using MRA. Also, it was previously shown that whenever decomposition exists in both MRA and CRA, MRA yields simpler or equal complexity decompositions. In this paper, MRA is extended to many‐valued logic functions, and logic structures that correspond to such decomposition are developed. It is shown that many‐valued MRA can decompose many‐valued functions when CRA fails to do so. Since real‐life data are often many‐valued, this new decomposition can be useful for machine learning and data mining. Many‐valued MRA can also be applied for the decomposition of relations.
Reversible modified reconstructability analysis of Boolean circuits and its quantum computation
Authors: Al‐Rabadi Anas N. , Zwick Martin
Published: January 2005

Modified reconstructability analysis (MRA) can be realized reversibly by utilizing Boolean reversible (3,3) logic gates that are universal in two arguments. The quantum computation of the reversible MRA circuits is also introduced. The reversible MRA transformations are given a quantum form by using the normal matrix representation of such gates. The MRA‐based quantum decomposition may play an important role in the synthesis of logic structures using future technologies that consume less power and occupy less space.
A comparison of modified reconstructability analysis and Ashenhurst‐Curtis decomposition of Boolean functions
Authors: Al‐Rabadi Anas N. , Perkowski Marek , Zwick Martin
Published: January 2005

Modified reconstructability analysis (MRA), a novel decomposition technique within the framework of set‐theoretic (crisp possibilistic) reconstructability analysis, is applied to three‐variable NPN‐classified Boolean functions. MRA is superior to conventional reconstructability analysis, i.e. it decomposes more NPN functions. MRA is compared to Ashenhurst‐Curtis (AC) decomposition using two different complexity measures: log‐functionality, a measure suitable for machine learning, and the count of the total number of two‐input gates, a measure suitable for circuit design. MRA is superior to AC using the first of these measures, and is comparable to, but different from AC, using the second.
Multi‐level decomposition of probabilistic relations
Authors: Grygiel Stanislaw , Zwick Martin , Perkowski Marek
Published: January 2005

Two methods of decomposition of probabilistic relations are presented in this paper. They consist of splitting relations (blocks) into pairs of smaller blocks related to each other by new variables generated in such a way so as to minimize a cost function which depends on the size and structure of the result. The decomposition is repeated iteratively until a stopping criterion is met. Topology and contents of the resulting structure develop dynamically in the decomposition process and reflect relationships hidden in the data.
The k‐systems glitch: granulation of predictor variables
Authors: Hoeppner Susanne S. , Shaffer Gary P.
Published: January 2005

Ecosystem behavior is complex and may be controlled by many factors that change in space and time. Consequently, when exploring system functions such as ecosystem “health”, scientists often measure dozens of variables and attempt to model the behavior of interest using combinations of variables and their potential interactions. This methodology, using parametric or nonparametric models, is often flawed because ecosystems are controlled by events, not variables, and events are comprised of (often tiny) pieces of variable combinations (states and substates). Most events are controlled by relatively few variables (≤4) that may be modulated by several others, thereby creating event distributions rather than point estimates. These event distributions may be thought of as comprising a set of fuzzy rules that could be used to drive simulation models. The problem with traditional approaches to modeling is that predictor variables are dealt with in total, except for interactions, which themselves must be static. In reality, the “low” piece of one variable may influence a particular event differently than another, depending on how pieces of other variables are shaping the event, as demonstrated by the k‐systems state model of algal productivity. A swamp restoration example is used to demonstrate the changing faces of predictor variables with respect to influence on the system function, depending on particular states. The k‐systems analysis can be useful in finding potent events, even when region size is very small. However, small region sizes are the result of using many variables and/or many states and substates, which creates a high probability of extracting falsely‐potent events by chance alone. Furthermore, current methods of granulating predictor variables are inappropriate because the information in the predictor variables rather than that of the system function is used to form clusters. What is needed is an iterative algorithm that granulates the predictor variables based on the information in the system function. In most ecological scenarios, few predictor variables could be granulated to two or three categories with little loss of predictive potential.
Directed extended dependency analysis for data mining
Authors: Shannon Thaddeus T. , Zwick Martin
Published: January 2005

Extended dependency analysis (EDA) is a heuristic search technique for finding significant relationships between nominal variables in large data sets. The directed version of EDA searches for maximally predictive sets of independent variables with respect to a target dependent variable. The original implementation of EDA was an extension of reconstructability analysis. Our new implementation adds a variety of statistical significance tests at each decision point that allow the user to tailor the algorithm to a particular objective. It also utilizes data structures appropriate for the sparse data sets customary in contemporary data mining problems. Two examples that illustrate different approaches to assessing model quality tests are given in this paper.
Instant modelling and data‐knowledge processing by reconstructability analysis
Authors: Shu Guangfu
Published: January 2005

This paper first reviews factor reconstructability analysis (RA) modelling completely by data. Gives a description of levelled variable factor reconstruction analysis model generation process and its further extension to forecasting, evaluation and optimisation. It introduces RA modelling with multi‐variety information and knowledge. From generation of mixed variable RA models to generation of models with both data and knowledge, the paper gives a related table and a figure on “Information flow of reconstructability analysis with multi‐variety information and knowledge” which included database, RA relational knowledge base, and interfaces for input of experts' knowledge. Finally, it gives some examples and prospects.
Application of reconstructability analysis in system structure
Authors: Wang Pengtao , Yu Changyun
Published: January 2005

In the development research of talent resource, the most important topics of talent resource forecasting and optimization are the structure of talent resource, requirement number and talent quality. This paper establishes factor reconstruction analysis forecasting and talent quality model on the basis of system reconstruction analysis and ensures most effective factor level in the system. The method is based on works of G.J. Klir, B. Jones, and performs dynamic analysis of example ration.
A software architecture for reconstructability analysis
Authors: Willett Kenneth , Zwick Martin
Published: January 2005

Software packages for reconstructability analysis (RA), as well as for related log linear modeling, generally provide a fixed set of functions. Such packages are suitable for end‐users applying RA in various domains, but do not provide a platform for research into the RA methods themselves. A new software system, Occam3, is being developed which is intended to address three goals which often conflict with one another to provide: a general and flexible infrastructure for experimentation with RA methods and algorithms; an easily‐configured system allowing methods to be combined in novel ways, without requiring deep software expertise; and a system which can be easily utilized by domain researchers who are not computer specialists. Meeting these goals has led to an architecture which strictly separates functions into three layers: the core, which provides representation of data sets, relations, and models; the management layer, which provides extensible objects for development of new algorithms; and the script layer, which allows the other facilities to be combined in novel ways to address a particular domain analysis problem.
Forecast entropy
Authors: Yao W. , Essex C. , Yu P. , Davison M.
Published: January 2005

A technique, called forecast entropy, is proposed to measure the difficulty of forecasting data from an observed time series. When the series is chaotic, this technique can also determine the delay and embedding dimension used in reconstructing an attractor. An ideal random system is defined. An observed time series from the Lorenz system is used to show the results.
Reconstructability analysis with Fourier transforms
Authors: Zwick Martin
Published: January 2005

Fourier methods used in two‐ and three‐dimensional image reconstruction can be used also in reconstructability analysis (RA). These methods maximize a variance‐type measure instead of information‐theoretic uncertainty, but the two measures are roughly collinear and the Fourier approach yields results close to that of standard RA. The Fourier method, however, does not require iterative calculations for models with loops. Moreover, the error in Fourier RA models can be assessed without actually generating the full probability distributions of the models; calculations scale with the size of the data rather than the state space. State‐based modeling using the Fourier approach is also readily implemented. Fourier methods may thus enhance the power of RA for data analysis and data mining.
State‐based reconstructability analysis
Authors: Zwick Martin , Johnson Michael S.
Published: January 2005

Reconstructability analysis (RA) is a method for detecting and analyzing the structure of multivariate categorical data. While Jones and his colleagues extended the original variable‐based formulation of RA to encompass models defined in terms of system states, their focus was the analysis and approximation of real‐valued functions. In this paper, we separate two ideas that Jones had merged together: the “g to k” transformation and state‐based modeling. We relate the idea of state‐based modeling to established variable‐based RA concepts and methods, including structure lattices, search strategies, metrics of model quality, and the statistical evaluation of model fit for analyses based on sample data. We also discuss the interpretation of state‐based modeling results for both neutral and directed systems, and address the practical question of how state‐based approaches can be used in conjunction with established variable‐based methods.
Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis
Authors: Ménasché Gael , Feldmann Jérôme , Fischer Alain , De Saint Basile Geneviève
Published: January 2005

Summary:  Hemophagocytic syndrome (HS) is a severe and often fatal syndrome resulting from potent and uncontrolled activation and proliferation of T‐lymphocytes, leading to excessive macrophage activation and multiple deleterious effects. The onset of HS characterizes several inherited disorders in humans. In each condition, the molecular defect impairs the granule‐dependent cytotoxic activity of lymphocytes, thus highlighting the determinant role of this function in driving the immune system to a state of equilibrium following infection. It has also been shown that some of the proteins required for lytic granule secretion are required for melanocyte function, leading to associated hypopigmentation in these conditions. This review focuses on several effectors of this secretory pathway, recently identified, because their defects cause these disorders, and discusses their role and molecular interactions in granule‐dependent cytotoxic activity.