Miracle-dz/UniFAR-FTUs huggingface dataset:
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2

The mammalian target of rapamycin (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. These signaling functions are distributed between at least two distinct mTOR protein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to the selective inhibitor rapamycin and activated by growth factor stimulation via the canonical phosphoinositide 3-kinase (PI3K)→Akt→mTOR pathway. Activated mTORC1 kinase up-regulates protein synthesis by phosphorylating key regulators of mRNA translation. By contrast, mTORC2 is resistant to rapamycin. Genetic studies have suggested that mTORC2 may phosphorylate Akt at S473, one of two phosphorylation sites required for Akt activation; this has been controversial, in part because RNA interference and gene knockouts produce distinct Akt phospho-isoforms. The central role of mTOR in controlling key cellular growth and survival pathways has sparked interest in discovering mTOR inhibitors that bind to the ATP site and therefore target both mTORC2 and mTORC1. We investigated mTOR signaling in cells and animals with two novel and specific mTOR kinase domain inhibitors (TORKinibs). Unlike rapamycin, these TORKinibs (PP242 and PP30) inhibit mTORC2, and we use them to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation. Furthermore, we show that TORKinibs inhibit proliferation of primary cells more completely than rapamycin. Surprisingly, we find that mTORC2 is not the basis for this enhanced activity, and we show that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin. Importantly, at the molecular level, PP242 inhibits cap-dependent translation under conditions in which rapamycin has no effect. Our findings identify new functional features of mTORC1 that are resistant to rapamycin but are effectively targeted by TORKinibs. These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease.
Monitoring and Evaluation of Information Systems Via Transaction Log Analysis

Transaction log analysis represents a powerful methodology which allows examination of both user commands and system responses when conducting an online information search. Machine-readable transaction log tapes from online catalogs are obtained and subsequently analyzed using stochastic pattern developments within parsed user sessions, mathematical models utilizing Markov chain analysis and the development of state transition probability matrices, which illustrate the probability of proceeding from one user or system state to another state. The objective of monitoring information systems and using transaction log analysis is to discover the extent to which systems are used and to determine the actual user patterns when conducting an information search. This in turn can aid in the evaluation of such systems and assist in the improvement of existing and future systems. Such analysis can assist in system design, while the predictive power of the methodology may allow real-time aids to be developed.As examples of the use of the methodology, patron use and system response patterns from several online public catalogs have been obtained by transaction log tapes. This paper presents an overview of the methodology, results obtained, and efforts that are being conducted within OCLC's Office of Research.
On Symplectic Capacities and Volume Radius

In this work we present an improvement to a theorem by C. Viterbo, relating the symplectic capacity of a convex body and its volume. This provides one more step towards the proof of the following conjecture: among all convex bodies in R 2n with a given volume, the Euclidean ball has maximal symplectic capacity. More precisely, the conjecture states that the best possible constant γn such that for any choice of a symplectic capacity c and any convex body K ⊂ R 2n we have
Taste Perception: An Examination of Fat Preference, Sensory Specific Satiety, and the Function of Eating Among Moderately Obese and Normal Weight Women

Abstract : Twenty-seven obese (OB) and sixteen age- and ethnicity-matched normal weight (NW) women were compared on fat preference, functional aspects of food, and sensory specific satiety (SSS). All the women rated the hedonic qualities of high-fat pudding more positively than low-fat pudding. Eating served different functions for the two groups of women. OB women rated "feeling full" and "removing hunger" as more important reasons to eat breakfast, lunch, and dinner than did NW women. The importance of "taste" did not differentiate the groups. Different trends in SSS were seen between the NW and OB women, including faster and more dramatic habituation to sweet tastes among the OB women. Some key aspects of taste perception differed between OB and NW women, but other aspects commonly thought to differ, such as fat preference, did not differentiate these groups. Future research should examine the function that eating in general, and taste in particular, play in the development and maintenance of healthy weight status and obesity.
Tesseract: A 4D Network Control Plane

We present Tesseract, an experimental system that enables the direct control of a computer network that is under a single administrative domain. Tesseract's design is based on the 4D architecture, which advocates the decomposition of the network control plane into decision, dissemination, discovery, and data planes. Tesseract provides two primary abstract services to enable direct control: the dissemination service that carries opaque control information fromthe network decision element to the nodes in the network, and the node configuration service which provides the interface for the decision element to command the nodes in the network to carry out the desired control policies. Tesseract is designed to enable easy innovation. The neighbor discovery, dissemination and node configuration services, which are agnostic to network control policies, are the only distributed functions implemented in the switch nodes. A variety of network control policies can be implemented outside of switch nodes without the need for introducing new distributed protocols. Tesseract also minimizes the need for manual node configurations to reduce human errors. We evaluate Tesseract's responsiveness and robustness when applied to backbone and enterprise network topologies in the Emulab environment. We find that Tesseract is resilient to component failures. Its responsiveness for intra-domain routing control is sufficiently scalable to handle a thousand nodes. Moreover, we demonstrate Tesseract's flexibility by showing its application in joint packet forwarding and policy based filtering for IP networks, and in link-cost driven Ethernet packet forwarding.
Expression of beta adrenergic receptors in mouse oocytes and preimplantation embryos

Accumulating evidence indicates the role of endogenous catecholamines in mammalian embryogenesis. We searched public databases containing nucleotide sequences derived from mouse preimplantation cDNA libraries and found a partial sequence homology between a cDNA clone from mouse blastocysts and the mouse beta 2‐adrenergic receptor sequence. No significant sequence homology was found for other mouse adrenergic and dopamine receptors. Using RT‐PCR, we showed that beta 2‐adrenoceptor is transcribed not only at blastocyst stage but also at earlier stages of preimplantation development as well as in oocytes. Moreover, we demonstrated that transcripts encoding both isoforms of the beta 3‐adrenoceptor (beta 3a‐ and beta 3b‐) are expressed in mouse oocytes and preimplantation embryos as well. We did not detect the beta 1‐adrenoceptor transcript either in oocytes or in preimplantation embryos. Using an antibody against the mouse beta 2‐adrenergic receptor, we showed that the receptor protein is expressed in oocytes and preimplantation embryos; in blastocysts, the immufluorescence labeling was stronger in the inner cell mass than in throphectodermal cells. The cell number of the in vitro cultured mouse preimplantation embryos exposed to isoproterenol (a potent beta adrenoceptor agonist) was lower than in control embryos, suggesting that activation of beta adrenergic receptors by appropriate agonist concentration can influence cell proliferation in mouse pre‐implantation embryos. Thus, our results indicate that beta adrenergic receptors are expressed in mouse oocytes and preimplantation embryos and that ligands for the receptors can affect the mouse embryo even in the very early stages of development. Mol. Reprod. Dev. 71: 145–153, 2005. © 2005 Wiley‐Liss, Inc.
Multiple human pressures and their spatial patterns in European running waters

Running water ecosystems of Europe are affected by various human pressures. However, little is known about the prevalence, spatial patterns, interactions with natural environment and co‐occurrence of pressures. This study represents the first high‐resolution data analysis of human pressures at the European scale, where important pressure criteria for 9330 sampling sites in 14 European countries were analysed. We identified 15 criteria describing major anthropogenic degradation and combined these into a global pressure index by taking additive effects of multiple pressures into account. Rivers are affected by alterations of water quality (59%), hydrology (41%) and morphology (38%). Connectivity is disrupted at the catchment level in 85% and 35% at the river segment level. Approximately 31% of all sites are affected by one, 29% by two, 28% by three and 12% by four pressure groups; only 21% are unaffected. In total, 47% of the sites are multi‐impacted. Approximately 90% of lowland rivers are impacted by a combination of all four pressure groups.
Emotion and trauma: underlying emotions and trauma symptoms in two flooded populations

11 Chapter 1: Introduction 12 1.0 Disasters and Definitions 12 1.1 Natural Disasters 12 2.0 Post-disaster impact in detail 13 2.1 Posttraumatic reactions 14 2.2 Additional post-event difficulties 14 2.3 Focus on posttraumatic stress symptoms 15 2.4 Focus on disaster predictors 16 2.5 Limitations of focus on disaster variables 18 2.6 Variations / inconsistencies 19 2.7 Specific disaster focus 20 3.0 Flooding 21 3.1 Health effects of flooding 22 3.2 Psychological effects of flooding 23 3.3 Importance of perception 25 4.0 Specific case studies 26 4.1 Specific features of flooding – personal accounts 27 4.2 Stresses in the aftermath 29 5.0 Does distress reflect PTSD? 30 5.1 Understandings of criteria 31
A Generalized Natural Actor-Critic Algorithm

Policy gradient Reinforcement Learning (RL) algorithms have received substantial attention, seeking stochastic policies that maximize the average (or discounted cumulative) reward. In addition, extensions based on the concept of the Natural Gradient (NG) show promising learning efficiency because these regard metrics for the task. Though there are two candidate metrics, Kakade's Fisher Information Matrix (FIM) for the policy (action) distribution and Morimura's FIM for the state-action joint distribution, but all RL algorithms with NG have followed Kakade's approach. In this paper, we describe a generalized Natural Gradient (gNG) that linearly interpolates the two FIMs and propose an efficient implementation for the gNG learning based on a theory of the estimating function, the generalized Natural Actor-Critic (gNAC) algorithm. The gNAC algorithm involves a near optimal auxiliary function to reduce the variance of the gNG estimates. Interestingly, the gNAC can be regarded as a natural extension of the current state-of-the-art NAC algorithm [1], as long as the interpolating parameter is appropriately selected. Numerical experiments showed that the proposed gNAC algorithm can estimate gNG efficiently and outperformed the NAC algorithm.
Blocking artefact free video coding based on a bilinear forward image warping model

In this paper a new very low bit rate video coding scheme is presented. It is based on a forward motion estimation technique using an image warping model, thus delivering the basis for temporal tracking of regions or objects. In order to deal with new or disappearing image contents a new algorithm for the adaptation of a tracked control grid is proposed. To improve the coding efficiency a high quality pixel interpolation in the warping based predictor has to be used, which unfortunately also emphasizes the high frequency coding artefacts. To reduce these artefacts the prediction error is coded by a biorthogonal wavelet transform. The proposed coder yields an improvement of the PSNR of ca. 0.7 dB compared to the advanced H.263 coder. In addition the visual quality is better as any blocking artefacts in the coded images are avoided.
Transthoracic Echocardiography in Pediatric Intensive Care: Impact on Medical and Surgical Management

Objectives: Although transthoracic echocardiography is commonly performed in the PICU, its utility is not specifically known. The purpose of this investigation was to evaluate the clinical impact of echocardiography in the PICU in terms of frequency of unanticipated findings and the frequency and nature of clinical management changes attributed to the results of echocardiography. Design: Prospective cohort study. Setting: Nineteen-bed combined medical-surgical-cardiac PICU at a tertiary care children’s hospital. Patients: All patients in PICU undergoing transthoracic echocardiography. Interventions, Measurements, and Main Results: Data collected included echocardiography indications, pre-echocardiography clinical assessment of anticipated echocardiography findings, height, weight, primary diagnosis, age, and urgency (stat vs routine) of echocardiography. Input of the attending care team (intensivist, cardiologist, and/or cardiovascular surgeon) allowed classification of echocardiography results as either confirming the pre-echocardiography impression, altering the pre-echocardiography clinical impression regarding the indication for which the test was performed, or altering the impression by virtue of new findings unrelated to the specific indication. The nature of the new findings were recorded and categorized. The team recorded clinical management changes made in response to the echocardiography results; the nature of these were listed and categorized. Echocardiograms (n = 416) were performed in 132 patients. Of these, 244 echocardiograms (59%) were ordered on male patients, 31% were under 30 days old, median age was 103 days, 379 (91%) had a primary cardiac diagnosis, and 92 (22%) were ordered stat. Sixty-three percent of echocardiograms confirmed and 24% altered the pre-echocardiography impression regarding the indication for the echocardiography; 13% introduced new findings unrelated to the indication. Cardiac surgical revision was the management change required in 26 patients (6.3%). Stat echocardiography was more likely to alter the pre-echocardiography assessment than routine echocardiography (p < 0.001). Management changes were more commonly associated with stat echocardiograms (p = 0.002) and those with new unexpected findings (p < 0.001) but had no demonstrable association with age less than 30 days (p = 0.332). Conclusions: Unanticipated echocardiography results are common in the PICU, and they often alter the clinical impressions that prompted the echocardiogram or introduce new findings unrelated to the reason for which the echocardiogram was recorded. Clinical management changes attributable to echocardiography findings are frequent in the PICU, including occasional surgical intervention. Echocardiography adds diagnostic value and contributes to the management approach in the PICU, accounting for its frequent use.
Role of Broad-Complex (Br) and Krüppel homolog 1 (Kr-h1) in the Ovary Development of Nilaparvata lugens

Ovarian development plays an important role in the life history of insects and is crucial for control of the insect population. The metamorphosis of an insect is precisely regulated by the interaction of the juvenile hormone and ecdysone. To understand the role of NlBr and NlKr-h1 in ovary development, we used RNA interference (RNAi) to down-regulate the expression of Broad-Complex (Br) and Krüppel homolog 1 (Kr-h1), two important down-stream transcription factors of juvenile hormone and ecdysone signaling. We further investigated their effects on metamorphosis and ovary development. The results showed that both NlBr and NlKr-h1 are induced by ecdysone. The down-regulation of NlBr and NlKr-h1 alone or together by RNAi is more effective than the topical application of ecdysone on the number of ovarioles, suggesting the necessity of NlBr and NlKr-h1 in determining the number of ovarioles. The ovarian grade was significantly increased/decreased by the topical application of ecdysone and down-regulation of NlBr and NlKr-h1. The pre-oviposition period was also increased. When NlBr and NlKr-h1 were down-regulated together, the ovary grade was not significantly different compared to the control (dsGFP), indicating that the development of the ovary is under the control of both NlBr and NlKr-h1. The interaction between the NlBr and NlKr-h1 on the number of ovarioles and the development of the ovary indicates cross-talk between both juvenile hormone and ecdysone signaling at the transcription level in the brown planthopper. Both genes are nuclear transcription factors and may regulate signaling via down-stream genes. These results would help to both enhance the current understanding of the regulatory mechanism of the interaction between juvenile hormone and ecdysone signaling pathways during ovarian development and to design chemicals to control pests.
An Open-Source Tool Set Enabling Analog-Digital-Software Co-Design

This paper presents an analog-digital hardware-software co-design environment for simulating and programming reconfigurable systems. The tool simulates, designs, as well as enables experimental measurements after compiling to configurable systems in the same integrated design tool framework. High level software in Scilab/Xcos (open-source programs similar to MATLAB/Simulink) that converts the high-level block description by the user to blif format (sci2blif), which acts as an input to the modified VPR tool, including the code v p r 2 s w c s , encoding the specific platform through specific architecture files, resulting in a targetable switch list on the resulting configurable analog–digital system. The resulting tool uses an analog and mixed-signal library of components, enabling users and future researchers access to the basic analog operations/computations that are possible.
Towards a framework that promotes integration between the UX design and SCRUM, Aligned to CMMI

This paper proposes a framework to integrate user experience design into the software development cycle. The proposal defines practices, principles, techniques and artifacts of user experience in organizations that use agile methodologies (SCRUM) in association with CMMI process areas and the dimensions prescribed in the maturity model for user experience design recommended by the Human Factors Institute. The evolutionary path is supported by SCRUM practices. The preliminary framework is based on systematic reviews of the integration of design and experience, agile methodologies, SCRUM and CMMI. The framework, as well as future studies, will be validated and refined by panels of experts and case studies.
Critical Vulnerability in Browser Security Metrics

Every time a browser vendor releases a patch for a critical vulnerability, the popular news media publishes a slew of negative press article detailing the security holes that have been announced in the product. Users who read these articles often decide to switch to a “safer” browser. The negative press associated with security patch releases has a number of unhealthy effects on the industry. We challenge the conventional wisdom of the current browser security evaluation paradigm: that browsers that receive infrequent security patches are safer than browsers that receive frequent patches, that browsers with a lower bug count are safer, and that reducing browser vulnerabilities is the only path that a browser vendor can follow to improve security. We argue that patch deployment matters vastly more than patch frequency, that bug count fails to take into account differences in severity and vendor reporting methodologies, and that the security features that matter most are ignored by negative news articles. We propose methods for evaluating browser security that take into account new industry best practices such as silent patch deployment and sandboxing.
A Reinforcement Learning Solution for Allocating Replicated Fragments in a Distributed Database

Debido a la complejidad del problema de la distribucion de los datos, la mayoria de las propuestas de solucion presentadas hasta la fecha han coincidido en dividir el proceso de diseno de la distribucion en dos fases seriadas: la fragmentacion y la ubicacion de los fragmentos en los sitios de la red. Este trabajo aborda el problema de ubicacion de fragmentos partiendo de un modelo matematico que en su forma general es NP–Completo y propone un metodo metaheuristico basado en Q–Learning de Aprendizaje Reforzado que minimiza el costo total en un tiempo aceptable. Esta propuesta integra la replicacion de fragmentos
Detection and Genomic Characterization of Enterovirus D68 in Respiratory Samples Isolated in the United States in 2016

ABSTRACT The genomic sequences of three 2016 enterovirus D68 (EV-D68) strains were obtained from respiratory samples of patients from Florida, Texas, and New York. These EV-D68 sequences share highest nucleotide identities with strains that circulated in North America, Europe, and Asia in 2014–2015.
Bisexuality and the Challenge to Lesbian Politics

The subject of bisexuality continues to divide the lesbian and gay community. At pride marches, in films such as Go Fish, at academic conferences, the role and status of bisexuals is hotly contested. Within lesbian communities, formed to support lesbians in a patriarchal and heterosexist society, bisexual women are often perceived as a threat or as a political weakness. Bisexual women feel that they are regarded with suspicion and distrust, if not openly scorned. Drawing on her research with over 400 bisexual and lesbian women, surveying the treatment of bisexuality in the lesbian and gay press, and examining the recent growth of a self-consciously political bisexual movement, Paula Rust addresses a range of questions pertaining to the political and social relationships between lesbians and bisexual women. By tracing the roots of the controversy over bisexuality among lesbians back to the early lesbian feminist debates of the 1970s, Rust argues that those debates created the circumstances in which bisexuality became an inevitable challenge to lesbian politics. She also traces it forward, predicting the future of sexual politics.
Organizational Legitimacy of Multinational Enterprises in the Pearl River Delta

Currently, more and more Multinational Enterprises (MNEs) conduct foreign direct investments (FDI) in Pearl River Delta (PRD). This study is designed to research empirically organizational legitimacy typology of MNEs as compared with that of domestic companies at the perspective of local public audience in PRD. Telephone survey was applied to collect data in Zhuhai, Shenzhen and Guangzhou. The findings of this article suggest that (1) compared with domestic companies, MNEs have higher pragmatic legitimacy and moral legitimacy, but have lower cognitive legitimacy; (2) the local public audience’ s general legitimacy attitude depends more on pragmatic element and moral element and less on cognitive one; and (3) MNEs have higher general legitimacy than domestic companies. This study is expected to give foreign and domestic managers in PRD practical implication about specific legitimacy management in terms of three legitimacy elements and suggest how they can be really accepted by the PRD’ s society.