Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.

HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein

Econometric Analysis of Production Networks with Dominant Units

This paper builds on the work of Acemoglu et al. (2012) and considers a production network with unobserved common technological factor and establishes general conditions under which the network structure contributes to aggregate fluctuations. It introduces the notions of strongly and weakly dominant units, and shows that at most a finite number of units in the network can be strongly dominant, while the number of weakly dominant units can rise with N (the cross section dimension). This paper further establishes the equivalence between the highest degree of dominance in a network and the inverse of the shape parameter of the power law. A new extremum estimator for the degree of pervasiveness of individual units in the network is proposed, and is shown to be robust to the choice of the underlying distribution. Using Monte Carlo techniques, the proposed estimator is shown to have satisfactory small sample properties. Empirical applications to US input-output tables suggest the presence of production sectors with a high degree of pervasiveness, but their effects are not sufficiently pervasive to be considered as strongly dominant

A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye

Regulated cell death and survival play important roles in neural development. Extracellular signals are presumed to regulate seven apparent caspases to determine the final structure of the nervous system. In the eye, the EGF receptor, Notch, and intact primary pigment and cone cells have been implicated in survival or death signals. An antibody raised against a peptide from human caspase 3 was used to investigate how extracellular signals controlled spatial patterning of cell death. The antibody crossreacted specifically with dying Drosophila cells and labelled the activated effector caspase Drice. It was found that the initiator caspase Dronc and the proapoptotic gene head involution defective were important for activation in vivo. Dronc may play roles in dying cells in addition to activating downstream effector caspases. Epistasis experiments ordered EGF receptor, Notch, and primary pigment and cone cells into a single pathway that affected caspase activity in pupal retina through hid and Inhibitor of Apoptosis Proteins. None of these extracellular signals appeared to act by initiating caspase activation independently of hid. Taken together, these findings indicate that in eye development spatial regulation of cell death and survival is integrated through a single intracellular pathway

Technology In The Classroom Versus Sustainability

The use of technology in universities and colleges is an issue of interest and speculation. One issue related to technology use in the classroom is sustainability of resources that support the technology. This paper explores faculty perceptions about technology use and sustainability in an east coast university. This university has initiated a new program that has been charged with the objective of creating and maintaining a sustainability program. The program is still being developed, but a few of the key goals are to look at recycling campus-wide, printing costs in the computer labs and library, and exploring what the faculty perceptions are about using technology in the classroom. This paper focuses on the last goal; and in order to explore this objective, a survey was administered to the Schools of Business, Health Professions, Arts & Sciences and the Library. The research question addressed in this paper is the relationship between the use of technology in the classroom and the course discipline of the faculty teaching the class. The faculty participants in the survey included four of its academic schools - Business, Health Professions, Arts & Sciences, and the Library. Consequently, there are four different faculty affiliations based on their school. The research questions related to school assignments presented in this paper: · Are there significant differences in the use of technology based on the school in which the faculty member is associated? · Do technology-driven programs in the schools of business and library science tend to perceive the use of technology in the classroom differently than other schools? · Are differences in the school of affiliation reflected in faculty views of importance of technology to the learning process? · Are differences in the school of affiliation reflected in faculty perceptions in the use of technology devices, including the desktop computers, iPad/Tablets, Laptops, Smartphones, or E-Readers? · Do faculty affiliations with schools impact their view of the importance moving toward the use of electronic documents? · Do faculty affiliations impact whether technology devices are viewed as distractions? · Are sustainability enthusiasts also technology enthusiasts

Structural Econometric Estimation of the Basic Reproduction Number for Covid-19 Across U.S. States and Selected Countries

This paper proposes a structural econometric approach to estimating the basic reproduction number ($\mathcal{R}_{0}$) of Covid-19. This approach identifies $\mathcal{R}_{0}$ in a panel regression model by filtering out the effects of mitigating factors on disease diffusion and is easy to implement. We apply the method to data from 48 contiguous U.S. states and a diverse set of countries. Our results reveal a notable concentration of $\mathcal{R}_{0}$ estimates with an average value of 4.5. Through a counterfactual analysis, we highlight a significant underestimation of the $\mathcal{R}_{0}$ when mitigating factors are not appropriately accounted for

Physician attitudes towards-and adoption of-mobile health

OBJECTIVE: Smartphone apps and mobile devices are an emerging method of healthcare data collection. This study sought to understand how physicians currently view mobile health (mHealth) technologies and use them in patient care. METHODS: A total of 186 physicians affiliated with Washington University School of Medicine in St. Louis, Missouri, USA completed a survey in 2016 regarding their current implementation of mHealth technologies for patient care and support for further development. RESULTS: More than half of respondents were willing to discuss health apps and mobile devices with patients. However, most were not currently recommending them to patients. Apps/devices that encouraged a healthy diet and weight or tracked heart rate received the highest satisfaction ratings. Apps/devices that accessed the EMR (electronic medical record) remotely, provided medication reminders, or enrolled research subjects garnered the most interest despite respondents lacking prior experience. A majority agreed that collected biometrics are useful for promoting a healthy lifestyle (68%), tracking medical treatment (64%), or conducting research (56%); and agreed that proof of accuracy and precision (81%) and the efficient integration of collected data (68%) are necessary improvements. Uploading data automatically and updating physicians in real-time was the most preferred method of data integration into the EMR. CONCLUSIONS: Physicians show interest in using mHealth technologies for patient care but have limited experience, usually with those specific to their specialties. Proof of quality and a method to integrate data into the EMR are necessary for a mainstream role in healthcare

Is It Easier to Count Communities Than Find Them?

Random graph models with community structure have been studied extensively in the literature. For both the problems of detecting and recovering community structure, an interesting landscape of statistical and computational phase transitions has emerged. A natural unanswered question is: might it be possible to infer properties of the community structure (for instance, the number and sizes of communities) even in situations where actually finding those communities is believed to be computationally hard? We show the answer is no. In particular, we consider certain hypothesis testing problems between models with different community structures, and we show (in the low-degree polynomial framework) that testing between two options is as hard as finding the communities. In addition, our methods give the first computational lower bounds for testing between two different "planted" distributions, whereas previous results have considered testing between a planted distribution and an i.i.d. "null" distribution