Transient-mediated fate determination in a transcriptional circuit of HIV

Steady-state behavior and bistability have been proposed as mechanisms for decision-making in gene circuits. However, transient gene expression has also been proposed to control cell fate with the decision arbitrated by the lifetime of the expression transient. Here, we report that transcriptional positive-feedback plays a critical role in determining HIV infected cell-fate by extending the duration of Tat expression transients far beyond what protein half-life modulation can achieve. To directly quantify feedback strength and its effects on the duration of Tat transcriptional pulses, we exploit the noise inherent to gene-expression and measure shifts in the autocorrelation of expression noise. The results indicate that transcriptional positive-feedback extends the single-cell Tat expression lifetime by ~6-fold for both minimal Tat circuits and full-length, actively-replicating HIV-1. Importantly, artificial weakening of Tat positive-feedback shortened the duration of Tat expression transients and biased the probability in favor of latency. Thus, transcriptional positive-feedback appears to modulate transient expression lifetime and thereby control cell-fate in HIV

All Your Data Are Belong to Us: Consumer Data Breach Rights and Remedies in an Electronic Exchange Economy

Consumers navigating the United States\u27 modern electronic exchange economy are uniquely vulnerable to injury from data breaches. Hackers run data breach operations on an industrial scale, with a worldwide underground economy supporting the processing and exploitation of stolen information. Economic damages from data breaches exceed millions of dollars annually in direct and indirect costs for consumers and businesses alike. While existing common law, statutory law, and regulatory law offer consumers affected by a data breach some degree of protection, that protection is largely inadequate in the face of the threat posed by consumer data breaches. This Comment argues that consumers can be better protected from the harm caused by data breaches by importing principles from European data privacy law into American law

Virtual Rituals: Community, Emotion, and Ritual in Massive Multiplayer Online Role-playing Games—A Quantitative Test and Extension of Structural Ritualization Theory

Millions of people worldwide immerse themselves in massive multiplayer online role-playing games (MMORPGs). These games generate large, diverse communities that engage in rituals within the game, completing missions or quests. What role do these MMORPG rituals play in commitment to these gaming communities? To address this question, we extend structural ritualization theory to explain the impact of ritual events and emotion on commitment to community in the game World of Warcraft. Our findings suggest that players focused on inanimate resources are less committed than players who focus on social aspects of the ritual events inside the game. We also find that emotional investment is a good predictor of commitment to community

Exposure of benthic invertebrates to sediment vibration: From laboratory experiments to outdoor simulated pile-driving

Activities directly interacting with the seabed, such as pile-driving, can produce vibrations that have the potential to impact benthic invertebrates within their vicinity. This stimuli may interfere with crucial behaviors such as foraging and predator avoidance, and the sensitivity to vibration is largely unknown. Here, the responsiveness of benthic invertebrates to sediment vibration is discussed in relation to laboratory and semi-field trials with two marine species: the mussel (Mytilus edulis) and hermit crab (Pagurus bernhardus). Sensory threshold curves were produced for both species in controlled laboratory conditions, followed by small-scale pile-driving exposures in the field. The merits of behavioral indicators are discussed, in addition to using physiological measures, as a method of determining reception and measuring responses. The measurement and sensors required for sediment vibration quantification are also discussed. Response and threshold data were related to measurements taken in the vicinity of anthropogenic sources, allowing a link between responsiveness and actual operations. The impact of pile-driving on sediment-dwelling invertebrates has received relatively little research, yet the data here suggest that such activities are likely to impact key coastal species which play important roles within the marine environment

Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice

Prostate cancer is themost frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections

The Hyperfine Splitting in Charmonium: Lattice Computations Using the Wilson and Clover Fermion Actions

We compute the hyperfine splitting $m_{J/\psi}-m_{\eta_c}$ on the lattice, using both the Wilson and $O(a)$-improved (clover) actions for quenched quarks. The computations are performed on a $24^3\times48$ lattice at $\beta = 6.2$, using the same set of 18 gluon configurations for both fermion actions. We find that the splitting is 1.83\err{13}{15} times larger with the clover action than with the Wilson action, demonstrating the sensitivity of the spin-splitting to the magnetic moment term which is present in the clover action. However, even with the clover action the result is less than half of the physical mass-splitting. We also compute the decay constants $f_{\eta_c}$ and $f^{-1}_{J/\psi}$, both of which are considerably larger when computed using the clover action than with the Wilson action. For example for the ratio $f^{-1}_{J/\psi}/f^{-1}_{\rho}$ we find 0.32\err{1}{2} with the Wilson action and $0.48\pm 3$ with the clover action (the physical value is 0.44(2)).Comment: LaTeX file, 8 pages and two postscript figures. Southampton Preprint: SHEP 91/92-27 Edinburgh Preprint: 92/51

Modeling the Pyrochemical Reduction of Spent UO2 Fuel in a Pilot-Scale Reactor

A kinetic model has been derived for the reduction of oxide spent nuclear fuel in a radial flow reactor. In this reaction, lithium dissolved in molten LiCl reacts with UO2 and fission product oxides to form a porous, metallic product. As the reaction proceeds, the depth of the porous layer around the exterior of each fuel particle increases. The observed rate of reaction has been found to be only dependent upon the rate of diffusion of lithium across this layer, consistent with a classic shrinking core kinetic model. This shrinking core model has been extended to predict the behavior of a hypothetical, pilot-scale reactor for oxide reduction. The design of the pilot-scale reactor includes forced flow through baskets that contain the fuel particles. The results of the modeling indicate that this is an essential feature in order to minimize the time needed to achieve full conversion of the fuel

Comparing Maps of Mean Monthly Surface Temperature and Precipitation for Alaska and Adjacent Areas of Canada Produced by Two Different Methods

Maps of mean monthly surface temperature and precipitation for Alaska and adjacent areas of Canada, produced by Oregon State University’s Spatial Climate Analysis Service (SCAS) and the Alaska Geospatial Data Clearinghouse (AGDC), were analyzed. Because both sets of maps are generally available and in use by the community, there is a need to document differences between the processes and input data sets used by the two groups to produce their respective set of maps and to identify similarities and differences between the two sets of maps and possible reasons for the differences. These differences do not affect the observed large-scale patterns of seasonal and annual variability. Alaska is divided into interior and coastal zones, with consistent but different variability, separated by a transition region. The transition region has high interannual variability but low long-term mean variability. Both data sets support the four major ecosystems and ecosystem transition zone identified in our earlier work. Differences between the two sets of maps do occur, however, on the regional scale; they reflect differences in physiographic domains and in the treatment of these domains by the two groups (AGDC, SCAS). These differences also provide guidance for an improved observational network for Alaska. On the basis of validation with independent in situ data, we conclude that the data set produced by SCAS provides the best spatial coverage of Alaskan long-term mean monthly surface temperature and precipitation currently available.On a analysé des cartes représentant les moyennes mensuelles des précipitations et des températures de l’air en surface pour l’Alaska et les zones contiguës du Canada. Ces cartes avaient été établies par le service d’analyse du climat spatial (SCAS) de l’université de l’Oregon et le centre d’échange de données géospatiales de l’Alaska (AGDC). Vu qu’en général le public peut se procurer les deux ensembles de cartes et qu’il les utilise, il est nécessaire de documenter les différences entre les processus et les jeux de données d’entrée utilisés par les deux groupes pour créer leur propre ensemble de cartes, ainsi que de dégager les similarités et les différences entre les deux ensembles de cartes et les raisons possibles de ces différences. Ces dernières n’affectent pas les schémas de variabilité saisonnière et annuelle observés à grande échelle. L’Alaska est divisé en zones intérieures et zones côtières, possédant une variabilité constante mais différente, séparées par une région de transition. Celle-ci possède une grande variabilité interannuelle mais une faible variabilité à long terme de la moyenne. Les deux jeux de données sont compatibles avec les quatre grands écosystèmes et leurs zones de transition que nous avions identifiés dans nos travaux antérieurs. Il y a cependant des différences à l’échelle régionale entre les deux ensembles de cartes; elles témoignent de différences dans les domaines physiographiques et dans le traitement que font les deux groupes (AGDC et SCAS) de ces domaines. Ces différences offrent également une piste pour l’établissement d’un réseau d’observation amélioré pour l’Alaska. En nous basant sur une validation fondée sur des données indépendantes recueillies in situ, nous concluons que le jeu de données produit par SCAS représente actuellement la meilleure couverture spatiale disponible pour les moyennes mensuelles à long terme des précipitations et des températures de l’air en surface en Alaska

Hydrologic Scales, Cloud Variability, Remote Sensing, and Models: Implications for Forecasting Snowmelt and Streamflow

Accurate prediction of available water supply from snowmelt is needed if the myriad of human, environmental, agricultural, and industrial demands for water are to be satisfied, especially given legislatively imposed conditions on its allocation. Robust retrievals of hydrologic basin model variables (e.g., insolation or areal extent of snow cover) provide several advantages over the current operational use of either point measurements or parameter-izations to help to meet this requirement. Insolation can be provided at hourly time scales (or better if needed during rapid melt events associated with flooding) and at 1-km spatial resolution. These satellite-based retrievals incorporate the effects of highly variable (both in space and time) and unpredictable cloud cover on estimates of insolation. The insolation estimates are further adjusted for the effects of basin topography using a high-resolution digital elevation model prior to model input. Simulations of two Sierra Nevada rivers in the snowmelt seasons of 1998 and 1999 indicate that even the simplest improvements in modeled insolation can improve snowmelt simulations, with 10%–20 % reductions in root-mean-square errors. Direct retrieval of the areal extent of snow cover may mitigate the need to rely entirely on internal calculations of this variable, a reliance that can yield large errors that are difficult to correct until long after the season is complete and that often leads to persistent underestimates or overestimates of the volumes of the water to operational reservoirs. Agencie