cssi/SciSciGPT-SciSciNet huggingface dataset:
Solving the chemical master equation for monomolecular reaction systems and beyond: a Doi-Peliti path integral view.

The chemical master equation (CME) is a fundamental description of interacting molecules commonly used to model chemical kinetics and noisy gene regulatory networks. Exact time-dependent solutions of the CME—which typically consists of infinitely many coupled differential equations—are rare, and are valuable for numerical benchmarking and getting intuition for the behavior of more complicated systems. Jahnke and Huisinga’s landmark calculation of the exact time-dependent solution of the CME for monomolecular reaction systems is one of the most general analytic results known; however, it is hard to generalize, because it relies crucially on special properties of monomolecular reactions. In this paper, we rederive Jahnke and Huisinga’s result on the time-dependent probability distribution and moments of monomolecular reaction systems using the Doi-Peliti path integral approach, which reduces solving the CME to evaluating many integrals. While the Doi-Peliti approach is less intuitive, it is also more mechanical, and hence easier to generalize. To illustrate how the Doi-Peliti approach can go beyond the method of Jahnke and Huisinga, we also find an explicit and exact time-dependent solution to a problem involving an autocatalytic reaction that Jahnke and Huisinga identified as not solvable using their method. Most interestingly, we are able to find a formal exact time-dependent solution for any CME whose list of reactions involves only zero and first order reactions, which may be the most general result currently known. This formal solution also yields a useful algorithm for efficiently computing numerical solutions to CMEs of this type.
Assessment of retinal oxygen metabolism, visual function, thickness and degeneration markers after variable ischemia/reperfusion in rats.

Abstract After total retinal ischemia induced experimentally by ophthalmic vessel occlusion followed by reperfusion, studies have reported alterations in retinal oxygen metabolism (MO2), delivery (DO2), and extraction fraction (OEF), as well as visual dysfunction and cell loss. In the current study, under variable durations of ischemia/reperfusion, changes in these oxygen metrics, visual function, retinal thickness, and degeneration markers (gliosis and apoptosis) were assessed and related. Additionally, the prognostic value of MO2 for predicting visual function and retinal thickness outcomes was reported. Sixty-one rats were divided into 5 groups of ischemia duration (0 [sham], 60, 90, 120, or 180 min) and 2 reperfusion durations (1 h, 7 days). Phosphorescence lifetime and blood flow imaging, electroretinography, and optical coherence tomography were performed. MO2 reduction was related to visual dysfunction, retinal thinning, increased gliosis and apoptosis after 7-days reperfusion. Impairment in MO2 after 1-hour reperfusion predicted visual function and retinal thickness outcomes after 7-days reperfusion. Since MO2 can be measured in humans, findings from analogous studies may find value in the clinical setting.
Small fish, big fish: the impact of venture capital portfolio composition on affiliation benefits

This study argues and empirically demonstrates that the value of a venture’s affiliations depends in part on its relative standing in the portfolio of affiliations held by its partners. Relative standing is determined by how the venture ranks among other ventures in the partner’s portfolio with respect to observable signals of quality. We argue that the relative standing of a venture in its partner’s portfolio influences the focal venture’s access to the partner’s resources and, subsequently, the venture’s performance. We also argue that a venture’s relative standing becomes a more important predictor of performance when the partner has a larger portfolio or higher status. An empirical test of the equity investments by venture capital firms in 1011 private biotechnology ventures between 1980 and 2004 provides support for the hypothesized relationships.
An exact solution to general SISO mixed /spl Hscr//sub 2///spl Hscr//sub /spl infin// problems via convex optimization

The mixed /spl Hscr//sub 2///spl Hscr//sub /spl infin// control problem can be motivated as a nominal LQG optimal control problem, subject to robust stability constraints, expressed in the form of an /spl Hscr//sub /spl infin// norm bound. A related modified problem consisting on minimizing an upper bound of the /spl Hscr//sub 2/ cost subject to /spl Hscr//sub /spl infin// constraints was introduced by Bernstein-Haddad (1989). Although there presently exist efficient methods to solve this modified problem, the original problem remains, to a large extent, still open. In this paper we propose a method for solving general discrete-time SISO /spl Hscr//sub 2///spl Hscr//sub /spl infin// problems. This method involves solving a sequence of problems, each one consisting of a finite-dimensional convex optimization and an unconstrained Nehari approximation problem. >
Evacuation of People with Disabilities

Abstract Since people with disabilities obtained the right to access the built environment, emergency evacuation of people with functional limitations has been an issue in building design and code development activities. Recent events, however, have emphasized that evacuation problems for this group extend beyond building design to include preparedness, the process of evacuation and the recovery efforts as well. This paper describes the extent of the problem and identifies key research and development issues. An argument is advanced for universal design approaches that will integrate concern for disability into all evacuation practices and benefit not just people with disabilities, but all stakeholders.
Forefathers' Day Dinners and Martha Washington Teas: Commemorative Consumption and the Colonial Revival

As early as a half-century before the 1876 national centennial, the point at which many scholars have marked the beginning of the colonial revival movement, historicized foodways appeared at centennial celebrations and homecoming gatherings across Northeast America. Commemorative consumption, the communal participation in anachronistic foodways, provided a vehicle for inscription into heritage-based groups, thus catalyzing the coalescence of collective self-consciousness during a time of cultural upheaval and social dislocation. Early discrete examples of commemorative consumption provided a seedbed for more widespread, popular expressions of the same. Through clambakes, centennial picnics, and Forefathers' Day dinners, New Englanders appropriated Native American foodways and re-enacted European settlement, symbolically laying claim to a region and a nation. Later, through Martha Washington teas, middle and upper-class Anglo-American women in the Northeast and beyond asserted their prerogative as ...
Silicon-Based Tracking System: Mechanical Engineering and Design

The Silicon Tracking System (STS) is composed of silicon strip detectors arranged both in a cylindrical array and in an array of flatpanels about the interaction region. The cylindrical array denotes the central region and the flat panel arrays, which are normal to the beam axis, denote the forward regions. The overall length of the silicon array is 5.16 m, and the maximum diameter is 0.93 m. The Silicon Tracking System Conceptual Design Report1 should be consulted for the body of analysis performed to quantify the present design concept. For the STS to achieve its physics goals, the mechanical structures and services must • support 17 m2 of silicon detectors and stabilize their positions to within 5 μm, • uniformly cool the detector system to 0°C, while potentially removing up to 13 kW of waste heat generated by the detector electronics, • provide up to 3400 A of current to supply the 6.5 million electronics channels, and • supply all control and data transmission lines for those channels.
Phylogenetic group-specific oligodeoxynucleotide probes for identification of single microbial cells.

Abstract Examination of collections of 16S rRNA sequences revealed sequence domains that were unique to (and invariant within) the three primary lines of cellular descent: the archaebacteria, the eubacteria, and the eucaryotes. Oligodeoxynucleotides complementary to these conserved sequence domains were synthesized and used as hybridization probes. Each of the radiolabeled probes specifically hybridized to nylon membrane-bound 16S rRNA from the targeted kingdom. A probe complementary to a universally conserved sequence in 16S rRNAs was used as a positive control, while its complement provided a negative control for nonspecific binding. The abilities of the probes to bind specifically to whole, fixed cells representing a broad array of phylogenetic diversity were tested in whole-cell dot blot assays. Again, all of the probes specifically bound the targeted groups. By microautoradiography, the method was extended to permit phylogenetic identification of single cells microscopically.
The American Cancer Society National Prostate Cancer Detection Project and National patterns of prostate cancer detection and treatment

The ACS National Prostate Cancer Detection Project was established in 1987 to demonstrate the feasibility of early detection as a cancer control strategy for prostate cancer. Ten years later, the compliance results suggest that early detection programs can achieve long-term participation in a healthy population.
Response of epidermoid and non-epidermoid cancers of the head and neck to fast neutron irradiation: the Fermilab experience.

Abstract One hundred and six patients with locally advanced cancers of the head and neck were treated with neutrons at the Fermilab Neutron Therapy Facility. Of these, 44 patients were previously untreated, 33 were recurrent following attempted surgery and 29 patients had previously received a full course of radiation therapy with conventional radiation. Results were analyzed to study the influence of stage, previous management, site of origin and tumor histology on local control of the disease. The most significant factor determining the outcome in this series of patients is the histological type. For epidermoid carcinoma, long term local control was achieved in 1735 patients (49%) in the previously unirradiated group. With non-epidermoid tumors (adenocarcinoma, cylindroma, muco-epidermoid carcinoma), the local control rate was 2839 (72%). Disease-free survival analysis also shows a survival advantage in non-epidermoid lesions treated with neutrons. It is concluded that neutron beam therapy may probably be the treatment of choice for non-resectable or recurrent non-epidermoid cancers of the head and neck and requires a clinical trial to establish this observation.
Evaluation of Guillain-Barré Syndrome Among Recipients of Influenza Vaccine in 2000 and 2001

Background The 1976–1977 swine influenza vaccine was associated with an elevated risk of Guillain-Barre Syndrome (GBS), especially within 6 weeks after vaccination. A 2004 IOM report concluded that evidence was inadequate to accept or reject a causal relationship between subsequent influenza vaccine formulations and GBS. Studies published after the IOM report have been limited by passively reported data or lack of validation of coded diagnoses. Purpose To evaluate whether influenza vaccine is associated with GBS. Methods Controlled observational study using national data from the Medicare program, which ensures a predominantly elderly population. People included had a Medicare claim for influenza vaccination during September–December in 2000 or 2001. Medical records were reviewed to classify definite, probable, or possible GBS (or not a case) using a standardized case definition. In a risk interval design, the incidence rate of GBS during Weeks 0–6 after vaccination (exposed period) was compared to Weeks 9–14 after vaccination (comparison period). Data collection occurred during 2003–2007, and analysis was conducted during 2007–2009. Results Primary analysis included 22.2 million vaccinees, among whom 164 definite or probable GBS cases with onset during Weeks 0–6 or 9–14 were identified. The incidence rate ratio (IRR [95% CIs]) based on the GBS rate in the vaccine-exposed versus comparison periods, was 1.04 (0.76, 1.43) for combined years; 0.86 (0.52, 1.41) among people vaccinated in 2000; and 1.21 (0.79, 1.86) among people vaccinated in 2001. Secondary analysis additionally included 74 possible GBS cases; results were similar. Conclusions Overall, the results do not support an association between influenza vaccine receipt and GBS among the elderly for the years studied (2000–2001 and 2001–2002 formulations).
Helical assembly in the death domain (DD) superfamily

Death domain (DD) superfamily members play a central role in apoptotic and inflammatory signaling through formation of oligomeric molecular scaffolds. These scaffolds promote the activation of proinflammatory and apoptotic initiator caspases, as well as Ser/Thr kinases. Interactions between DDs are facilitated by a conserved set of interaction surfaces, type I, type II, and type III. Recently structural information on a ternary complex containing the DDs of MyD88, IRAK4, and IRAK2 and a binary complex containing Fas and FADD DDs has become available. This review will focus on how the three DD interaction surfaces cooperate to facilitate the assembly of these oligomeric signaling complexes.
Inscriptions as artifacts: Precolonial south india and the analysis of texts

This paper examines one assemblage of texts from southern India, stone inscriptions of the Vijayanagara period, and considers both how these texts have been studied and how that history of research has structured our understanding of the past. We ask how these texts might be interpreted differently, (1) under different conditions of sampling and recovery, with a specific focus on in-field locations of inscriptions, and (2) as sources of information combined with archaeological data. We suggest that traditional source-side criticism of texts might be profitably expanded routinely to include contextual analysis, such as archaeologists apply to studies of artifacts.
Excited-State Ions in Femtosecond Time-Resolved Mass Spectrometry: An Investigation of Highly Excited Chloroamines

We have investigated the processes induced by femtosecond laser pulses in chloroamines, with a focus on the generation and observation of a highly reactive radical and on the involvement and general importance of excited-state ions in time-resolved mass spectrometry investigations of gaseous molecules. We have found that 280 nm femtosecond pulses lead to an ultrafast breakage of the N-Cl bond on the repulsive S1 surface, and that resulting radical is long-lived. When exposing the molecule to 420 nm photons a multiphoton ionization takes place to generate ions; these ions can then be excited with a 280 nm photon. The evidence is unambiguous since we observe a distinct temporal evolution of the ion current with no photoelectrons to match. We suggest that the involvement of excited-state ions is a general phenomenon in time-resolved photoionization studies.
The Sorting Signals for Peroxisomal Membrane-bound Ascorbate Peroxidase Are within Its C-terminal Tail

Peroxisomal ascorbate peroxidase (APX) is a carboxyl tail-anchored, type II (Ncytosol-Cmatrix) integral membrane protein that functions in the regeneration of NAD+ in glyoxysomes of germinated oilseeds and protection of peroxisomes in other organisms from toxic H2O2. Recently we showed that cottonseed peroxisomal APX was sorted post-translationally from the cytosol to peroxisomes via a novel reticular/circular membranous network that was interpreted to be a subdomain of the endoplasmic reticulum (ER), named peroxisomal ER (pER). Here we report on the molecular signals responsible for sorting peroxisomal APX. Deletions or site-specific substitutions of certain amino acid residues within the hydrophilic C-terminal-most eight-amino acid residues (includes a positively charged domain found in most peroxisomal integral membrane-destined proteins) abolished sorting of peroxisomal APX to peroxisomes via pER. However, the C-terminal tail was not sufficient for sorting chloramphenicol acetyltransferase to peroxisomes via pER, whereas the peptide plus most of the immediately adjacent 21-amino acid transmembrane domain (TMD) of peroxisomal APX was sufficient for sorting. Replacement of the peroxisomal APX TMD with an artificial TMD (devoid of putative sorting sequences) plus the peroxisomal APX C-terminal tail also sorted chloramphenicol acetyltransferase to peroxisomes via pER, indicating that the peroxisomal APX TMD does not possess essential sorting information. Instead, the TMD appears to confer the proper context required for the conserved positively charged domain to function within peroxisomal APX as an overlapping pER sorting signal and a membrane peroxisome targeting signal type 2.
An Impedance Study of Curved Sandwich Trim Panels Driven by Piezoelectric Patch Actuators

Recent research in the area of structural acoustic control for aircraft interior noise suppression has been focused on developing active trim panels. Active trim panels being part of non-critical structures offer many advantages over active controls applied to load critical structures such as aircraft frames and skins. Because there are many flanking paths for the noise to get into the cabin, and because it is not realistic to apply active controls to the entire interior trim panel, the part of the trim that is instrumented with structural controls will inevitably be driven hard enough to cancel the cabin noise. This probably entails high power requirements for active trim panels. The present paper presents an analytical study of cylindrically curved sandwich composite trim and aluminum panels driven by piezoelectric path actuators. An impedance formulation is taken in the study. This paper studies the effect of curvature on the dynamics of the trim panel and the uniform aluminum panel, and has found that...
Software engineering problems in the design of an integrated modelling system

Integrative modelling is a concept which suggests that the modelling and simulation enterprise can best be advanced within a framework which provides a strong theory and software domain for dealing with many models at many levels of specification and application at once. This approach to modelling is important for several reasons; first, and perhaps most important, the appraoch will provide for a more cumulative development of the modelling and simulation enterprise, and thus indirectly more cumulative development of the ultimately desired knowledge and understanding of large-scale complex systems. Secondly, once the required computer software is designed and implemented, the system of integrated models should enable the development of additional related models for a lower total "cost" in terms of total effort. The lower cost is due to the fact that new models will also be integrated and therefore derived from earlier available ones. Third, this approach, when implemented, will tend to centralize the data and models of a particular large-scale system thus making it more readily available in responding to the needs of public policymaking.
Development and Implementation of Micro Autonomous Systems and Technologies (MAST) Interactive Reconfigurable Matrix of Alternatives (M-IRMA) for Concept Selection

Abstract Army Research Laboratory sponsored Micro Autonomous Systems and Technologies (MAST) project seeks to collaboratively develop new technologies to enhance warfighter's small unit's tactical situation awareness in complex terrain. The development consists of multifunctional, autonomous and collaborative microsystem swarms. To analyze the large concept space, a specialized tool, MAST Interactive Reconfigurable Matrix of Alternatives (M-IRMA) has been developed. A convoy assistance mission scenario based on the movie’Black Hawk Down’ is analyzed and evaluated using the tool. Results include the selection of families of concepts, among the defined alternatives, that accomplish the mission optimally. The system components reflect fundamental requirements of the mission, namely high endurance, adaptability, path planning, and communication ability. Moreover, a database-driven web-based implementation of M-IRMA enables online definition of problems and conceptualization of solutions. WM-IRMA (Web-based MAST Interactive Reconfigurable Matrix of Alternatives) provides a dynamic online platform for MAST researchers to remotely access, view, modify, and evaluate alternatives simultaneously.
A Hyperprior for Sparse Signal Estimation

The problem of estimating a sparse signal from compressive sampling data is addressed by utilizing a conditionally independent Gaussian prior for the sparse signal parameters, and a novel hyperprior for the signal variances.
Indoor positioning system using geo-magnetic field

In this paper we address the problem of non-adversarial co-operative localization using the Earth's ambient magnetic field. We demonstrate the feasibility of using magnetic field to perform localization and tracking. A three-axis magnetic field sensor is employed to locate and track a target. The algorithm estimates the position using the magnitude of the current magnetic field readings. Our technique depends on the local distortions in the Earth's magnetic field created by presence of various magnetic or metallic objects in the local workspace. These objects may be manmade or naturally occurring. The magnetic field data corresponding to known locations is stored in a database. A reverse lookup is used to estimate the position of the target. The localization techniques described in this paper have demonstrated successful target tracking with the average error radius of 2.5 feet.
My culture made me do it: Media, identity and the politics of recognition

(1999). My culture made me do it: Media, identity and the politics of recognition. International Journal of Cultural Policy: Vol. 6, No. 1, pp. 69-90.
Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Summary Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.
TRENDS IN SURGICAL AND NONSURGICAL PERIODONTAL TREATMENT

ABSTRACT Background New research is demonstrating that a person's total health is indeed related to his or her oral health. Elimination of all oral infections, including gingivitis and periodontis, is important to overall health. Clinical Implications This article reviews recent evidence on the systemic and oral connection and discusses these findings as they relate to patient care. The article examines trends in nonsurgical and surgical therapy that will successfully arrest periodontal infections. Opportunities for early diagnosis and prevention will play an increasing role in dental practice in the future as patients understand the importance of oral health to overall health.
Wardianum catoptrophori n. sp. (Digenea: Cyclocoelidae: Haematotrephinae) from the Willet, Catoptrophorus semipalmatus (scolopacidae), from the Galveston, Texas area of the Gulf of Mexico, U.S.A

Abstract During a study of the endohelminths of wading birds from the Texas Gulf coast, 4 specimens of an undescribed species of Wardianum (Cyclocoelidae: Haematotrephinae) were collected from willets, Catoptrophorus semipalmatus, from the Galveston, Texas, area. Wardianum catoptrophori n. sp. can be distinguished from all the other species in the genus (Wardianum chauhani, Wardianum. facioi, Wardianum lateriovari, Wardianum taxorchis, Wardianum triangulare, and Wardianum wilsoni) by having a pharynx that is wider than long. It can be distinguished from all other species in the genus except W. facioi by having uterine loops that extend laterally beyond the outer margin of the ceca approaching the body wall and that extend posteriorly along the lateral margins of both testes to the level of the posttesticular space but that do not invade the intertesticular space. The new species differs from W. facioi by having a larger body size (14.0 [12.5–16.5] mm long by 3.5 [3.0–4.0] mm wide compared with 6.6–7.5 mm ...
The Unconserved Groucho Central Region Is Essential for Viability and Modulates Target Gene Specificity

Groucho (Gro) is a Drosophila corepressor required by numerous DNA-binding repressors, many of which are distributed in gradients and provide positional information during development. Gro contains well-conserved domains at its N- and C-termini, and a poorly conserved central region that includes the GP, CcN, and SP domains. All lethal point mutations in gro map to the conserved regions, leading to speculation that the unconserved central domains are dispensable. However, our sequence analysis suggests that the central domains are disordered leading us to suspect that the lack of lethal mutations in this region reflects a lack of order rather than an absence of essential functions. In support of this conclusion, genomic rescue experiments with Gro deletion variants demonstrate that the GP and CcN domains are required for viability. Misexpression assays using these same deletion variants show that the SP domain prevents unrestrained and promiscuous repression by Gro, while the GP and CcN domains are indispensable for repression. Deletion of the GP domain leads to loss of nuclear import, while deletion of the CcN domain leads to complete loss of repression. Changes in Gro activity levels reset the threshold concentrations at which graded repressors silence target gene expression. We conclude that co-regulators such as Gro are not simply permissive components of the repression machinery, but cooperate with graded DNA-binding factors in setting borders of gene expression. We suspect that disorder in the Gro central domains may provide the flexibility that allows this region to mediate multiple interactions required for repression.
Further application of the statistical thermodynamics of curved surfaces to scaled particle theory

The thermodynamics of curved boundary layers is combined with scaled particle theory to determine the rigid-sphere equation of state. In particular, the boundary analog of the Gibbs-Tolman-Koenig-Buff equation is solved for a rigid-sphere fluid, using the approximation that the distance between the surface of a cavity and its surface of tension is a function of the density only (the first-order approximation). This, in conjunction with several exact conditions onG, the central function of scaled particle theory, leads to an approximate rigid-sphere fluid equation of state and a qualitatively correct rigid-sphere solid equation of state. The fluid isotherm compares favorably with previous results (2.9 % error in the fourth virial coefficient), but due to the inaccuracy of the solid isotherm, no phase transition is obtained. The theory described here is to be contrasted with previous approaches in that a less arbitrary functional form forG is assumed, and the surface of tension and cavity surface are not assumed to be coincident. The “cycle equation” of Reiss and Tully-Smith is rederived by a simpler route and shown to be correct to all orders of cavity curvature, rather than only first order as was originally thought. A new exact condition, obtained from the compressibility equation of state, is used as a boundary condition for the “cycle equation” to determine the location of the equimolecular surface. This molecular calculation compares favorably (discrepancy of <2 %) with a thermodynamic calculation based on the boundary analog of the Gibbs adsorption equation and indicates the accuracy and consistency of the first-order approximation.
HEPARIN AND THE ELECTROPHORETIC MOBILITY OF BETA-LIPOPROTEIN IN CORONARY DISEASE.

Abstract The mobility of beta-lipoprotein in an electrical field is greatly increased by administration of heparin and is decreased in patients subjected to emotional tension and in patients whose blood contains detectible amounts of lipid mobilizer factor. Shortened beta-lipoprotein mobility and the presence of lipid mobilizer factor seem to be associated with coronary disease in young and middle-aged patients, especially those subjected to severe emotional stress.
Direct Assessment of Behavioral and Emotional Problems.

New procedures for assessing the behavior of children in an environmental context are available to the school psychologist. The procedures, which are sometimes called psychosituational or informal assessments, examine the influence of the external environment as setting the occasion for emotional and behavioral problems. Covert speech of children also is viewed as an event which can occasion behavioral problems and can serve to reinforce and/or punish the behavior. Procedures are outlined for conducting the direct assessment.
Techniques to demonstrate immunoproteasome in retinal functions

The catalytic core of the proteasome contains three pair of catalytic subunits that perform distinct proteolytic activities referred to as caspase-like, trypsin-like, and chymotrypsin-like. In the standard proteasome, the catalytic subunits are β1, β2, and β5. These subunits can be replaced in nascent proteasomes by the subunits LMP2 (β1i), MECL-1 (β2i), and LMP7 (β5i), which form the core of the immunoproteasome. The immunoproteasome is a proteasome subtype that is abundant in immune cells and also present, albeit in low concentrations, in cells outside the immune system. A well-described function of immunoproteasome is to generate peptides for MHC class I for display on the cell surface. Functions of immunoproteasome that go beyond its role in generating antigenic peptides are emerging from studies in immunoproteasome-deficient mice and from human diseases linked to mutations in immunoproteasome subunits. Notably, oxidative stress and pro-inflammatory cytokines, conditions that predominate in retinal diseases, are associated with immunoproteasome upregulation. Multiple methods used to investigate immunoproteasome function in the retina and in cultured retinal pigment epithelial cells will be discussed in detail.
Conditional Abatement of Tissue Fibrosis Using Nucleoside Analogs to Selectively Corrupt DNA Replication in Transgenic Fibroblasts

Progressive tissue fibrosis can compromise epithelial function resulting in organ failure. Appreciating evidence suggests that fibroblasts provide fibrogenic collagens during such injury. We further tested this notion by attempting to reduce the physiologic consequences of organ fibrosis through the selective killing of fibroblasts at sites of injury. Here, we report the conditional reduction of tissue fibroblasts using the coding sequence for herpesvirus thymidine kinase (DeltaTK) put under the control of a cell-specific promoter from the gene encoding fibroblast-specific protein 1 (FSP1). Transgenic fibroblasts from mice carrying FSP1.DeltaTK minigenes expressed thymidine kinase concordantly with native FSP1 and, compared to transgenic epithelium, were selectively susceptible to the lethal effects of nucleoside analogs either in culture or during experimental renal fibrosis. The numbers of fibroblasts in fibrogenic kidney tissue were reduced on exposure to nucleoside analogs as was the degree of type I collagen deposition and the extent of fibrosis. Fibroblast reduction following the stress of DNA chain termination highlights the important contribution of cell division during fibrogenesis. Our findings convey a proof of principle regarding the importance of FSP1(+) fibroblasts in fibrosis as well as providing a new approach to treating the relentless scarification of tissue.
Screening for Obstructive Sleep Apnea on the Internet: Randomized Trial

Abstract Background Obstructive sleep apnea is underdiagnosed. We conducted a pilot randomized controlled trial of an online intervention to promote obstructive sleep apnea screening among members of an Internet weight-loss community. Methods Members of an Internet weight-loss community who have never been diagnosed with obstructive sleep apnea or discussed the condition with their healthcare provider were randomized to intervention (online risk assessment+feedback) or control. The primary outcome was discussing obstructive sleep apnea with a healthcare provider at 12 weeks. Results Of 4700 members who were sent e-mail study announcements, 168 (97% were female, age 39.5 years [standard deviation 11.7], body mass index 30.3 [standard deviation 7.8]) were randomized to intervention (n=84) or control (n=84). Of 82 intervention subjects who completed the risk assessment, 50 (61%) were low risk and 32 (39%) were high risk for obstructive sleep apnea. Intervention subjects were more likely than control subjects to discuss obstructive sleep apnea with their healthcare provider within 12 weeks (11% [9/84] vs 2% [2/84]; P =.02; relative risk=4.50; 95% confidence interval, 1.002-20.21). The number needed to treat was 12. High-risk intervention subjects were more likely than control subjects to discuss obstructive sleep apnea with their healthcare provider (19% [6/32] vs 2% [2/84]; P =.004; relative risk=7.88; 95% confidence interval, 1.68-37.02). One high-risk intervention subject started treatment for obstructive sleep apnea. Conclusion An online screening intervention is feasible and likely effective in encouraging members of an Internet weight-loss community to discuss obstructive sleep apnea with their healthcare provider.
The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs

Indolealkylamine and phenethylamine hallucinogens disrupted responding maintained under a fixed-ratio 40 (FR-40) schedule of reinforcement. LSD, DMT, mescaline and DOM produced dose-dependent decreases in number of reinforcers and increases in 10-sec periods of non-responding (pause-intervals). The 5HT agonist quipazine, as well as the LSD congener lisuride, altered response patterns in a similar manner. The effects of these drugs were examined after pretreatment with pirenperone, an antagonist with specificity toward the 5HT2 receptor with reference to the 5HT1 receptor. The dose-response curves for the phenethylamine hallucinogens were shifted significantly to the right and to a greater degree than were those for the indolealkylamine hallucinogens. Pirenperone also antagonized the effects of quipazine to a degree similar to that observed with the phenethylamine-type hallucinogens. Pirenperone did not significantly shift the dose-response pattern to lisuride. These data suggest that the behavioral disruption induced by these hallucinogens and quipazine relates at least in part to an effect on 5HT2 receptors, while the effects of lisuride do not involve a significant interaction at the 5HT2 receptor.
Visceral adipose tissue: a critical review of intervention strategies.

OBJECTIVE: To review the published literature regarding the effect of caloric restriction, pharmacologic intervention, and exercise to promote the loss of visceral adipose tissue (VAT) DESIGN: A review was conducted of published studies which measured VAT using computed tomography or magnetic resonance imaging before and after caloric restriction, pharmacologic therapy, or exercise. STUDIES REVIEWED: 23 separate studies were reviewed. Men represented 38% and women 63% of the 599 volunteers. There were 17 black volunteers and 30 patients with NIDDM included in these studies. MEASUREMENTS: Data regarding the baseline and change in VAT, body fat, and body weight were collected. RESULTS: Most interventions demonstrated a preferential loss of VAT regardless of the intervention applied. When expressed as percent change in VAT/percent change in body fat, a ratio can be calculated which we call the Selectivity Index (SI). When this index is applied to the literature reviewed, two observations can be made. First, the Selectivity Index is higher when baseline body fat is higher. Second, there is a direct relationship between the Selectivity Index and the baseline visceral fat ratio. These two observations suggest that individuals with greater visceral fat mass, either through an increase in the body weight or the propensity to store fat in the visceral depot, lose more visceral fat when adjusted to the loss of body fat. CONCLUSION: In conclusion, the Selectivity Index is useful to compare the ability of an intervention to specifically target the loss of AT. This simple index can serve as a benchmark for comparing intervention studies to each other.
Job Change Patterns and the Wages of Young Men

This study uses data from the National Longitudinal Survey of Youth to distinguish empirically between mover—stayer, “search good,” and “experience good” models of job mobility. We estimate wage models in which the pattern of overall job mobility affects both the level and tenure slope of the log-wage path. After controlling for the correlation between mobility patterns and time-constant person- and job-specific unobservables, we find that workers who undergo persistent mobility have lower log-wage paths than less mobile workers. This finding is consistent with models in which job mobility is driven by time-varying unobservables, such as “experience good” models, where changes in perceived match quality cause turnover.
History of the Lamme Medal

Once again we have the pleasure of awarding the Lamme Medal to a man who well deserves this coveted honor. In presenting the award, we honor not only its recipient, but also the memory of its founder — Benjamin Garver Lamme.
Drinking in Antarctic fishes

Drinking rates have never been measured in Antarctic fish. Drinking rates were measured in four species of notothenioid fish, including a hemoglobinless icefish, found in the near-freezing waters of the Ross Sea of the Southern Ocean. All of the fish, with the exception of the icefish, had low drinking rates and high serum osmolalities relative to temperate seawater fish. The icefish had significantly higher drinking rates and serum osmolalities relative to the Antarctic fishes containing hemoglobin, including Trematomus bernacchii. Warm acclimation of T. bernacchii, from −1.5°C to +4°C for 4 weeks, significantly increased their drinking rates 4.6-fold, significantly decreased their serum and intestinal osmolality by 11% and 12%, respectively, relative to cold-acclimated fish. These results indicate that increased drinking rates in Antarctic fish at elevated temperatures are involved in maintaining a lower serum osmolality.
On the power of secondary confession evidence

Research on primary confessions has demonstrated that it is a powerful form of evidence. The goal of the current research was to investigate whether secondary confessions – the suspect confesses to another individual who in turn then reports the confession to the police – could be as persuasive. In Experiments 1 and 2, participants read a murder trial containing an eyewitness identification, a secondary confession, and character testimony, and made midtrial assessments of the evidence. Results indicated that the secondary confession was evaluated as the most incriminating. In Experiment 3, participants read summaries of four criminal trials, each of which contained a primary confession, a secondary confession, eyewitness identification, or none of the above. The two confession conditions produced significantly higher conviction rates. Our findings suggest that secondary confessions are another powerful and potentially dangerous form of evidence.
Integrity and moral development

Analyse de la notion d'integrite en reference au niveau developpemental de l'agent moral. Examinant le statut de l'egocentrisme, du conformisme et du desinteressement chez L. Kohlberg et C. Gilligan, l'A. definit l'integrite de l'individu comme principe d'autonomie et comme principe de balance des vertus
Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB- and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.
Simulation modeling of carcinogenesis.

Abstract A discrete-time simulation model of carcinogenesis is described mathematically using recursive relationships between time-varying model variables. The dynamics of cellular behavior is represented within a biological framework that encompasses two irreversible and heritable genetic changes. Empirical data and biological supposition dealing with both control and experimental animal groups are used together to establish values for model input variables. The estimation of these variables is integral to the simulation process as described in step-by-step detail. Hepatocarcinogensis in male F344 rats provides the basis for seven modeling scenarios which illustrate the complexity of relationships among cell proliferation, genotoxicity, and tumor risk.
When and why do retrieval attempts enhance subsequent encoding

Unsuccessful retrieval attempts can enhance subsequent encoding and learning. In three experiments, subjects either attempted to retrieve word pairs prior to studying them (e.g., attempting to recall tide–? before studying tide–beach) or did not attempt retrieval and retention of the studied targets was assessed on a subsequent cued recall test. Experiment 1 showed that attempting retrieval enhanced subsequent encoding and recall relative to not attempting retrieval when the word pairs were semantically related, but not when the pairs were unrelated. In Experiment 2, studying a different word pair prior to the correct pair (e.g., studying tide–wave prior to tide–beach) did not produce the same effect as attempting retrieval prior to studying. Constraining retrieval to a particular candidate word prior to study (e.g., recalling tide–wa__ before studying tide–beach) produced a negative effect on subsequent recall. Experiment 3 showed that attempting retrieval did not enhance encoding when a brief delay occurred between the retrieval attempt and the subsequent study trial. The results support the idea that a search set of candidates related to the retrieval cue is activated during retrieval and that this retrieval-specific activation can enhance subsequent encoding of those candidates.
U.S. College Student Activism during an Era of Neoliberalism: A Qualitative Study of Students Against Sweatshops.

This article sets out to examine the experiences of college student activists involved in Students Against Sweatshops on the Beautiful River University campus. Based on observation and interview fieldwork, the paper explores how students negotiate and understand their activism against the backdrop of neoliberalism. The paper concludes that being a contemporary student activist requires advanced time management skills and the capacity to ascribe multiple meanings to activities (for example, hanging out and doing activism simultaneously). This emphasis on using one’s time wisely resonates with students who are surrounded by the language of neoliberal reform. By analysing how students prioritise activism, outreach to new members and develop friendships, and position themselves as part of an international network, I show that student activism is influenced by the neoliberal environment at Beautiful River University at the same time that student activists are working to resist and counter such practices.
The effect of atovaquone on etoposide pharmacokinetics in children with acute lymphoblastic leukemia.

Purpose: The use of trimethoprim/sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia in patients with acute lymphoblastic leukemia (ALL) may cause undesirable adverse effects: fungal overgrowth, neutropenia, and drug resistance. A possible alternative is atovaquone, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity. However, it is not known if atovaquone alters the disposition or adverse effects of antileukemic drugs. Methods: Using a crossover study design, we compared the pharmacokinetics of etoposide and its CYP3A4-formed catechol metabolite when given as a 300 mg/m2 i.v. infusion following daily atovaquone versus trimethoprim/sulfamethoxazole in nine patients. Results: The area under the concentration time curve (AUC) of etoposide, etoposide catechol and the catechol to etoposide AUC ratio were slightly higher (a median of 8.6%, 28.4%, and 25.9%) following atovaquone as compared to trimethoprim/sulfamethoxazole (P=0.055, P=0.031 and P=0.023), respectively. In vitro analysis in human liver microsomes showed modest inhibition of etoposide catechol formation in the presence of atovaquone. Using uptake of 3H-vinblastine in L-MDR1 cells, atovaquone was shown to inhibit P-glycoprotein with an apparent Ki of 95.6 µM. Conclusions: Although the effect of atovaquone on etoposide disposition was modest, in light of the fact that the risk of etoposide-related secondary acute myeloid leukemia has been linked to minor changes in schedule and concurrent therapy, we suggest caution with the simultaneous administration of atovaquone and etoposide, particularly if used with other CYP3A4/P-glycoprotein substrates.