Miracle-dz/UniFAR-FTUs huggingface dataset:
The Oncogenic Protein Kinase Tpl-2/Cot Contributes to Epstein-Barr Virus-Encoded Latent Infection Membrane Protein 1-Induced NF-κB Signaling Downstream of TRAF2

ABSTRACT The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-κB. LMP1 promotes NF-κB activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-κB kinase, the IκB kinases, and their downstream targets, IκBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-κB signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkin's disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-κB signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-κB activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-κB occurs through modulation of both IκBα and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.
Level set based method for simultaneous optimization of material property and topology of functionally graded structures

A level set based method is proposed for simultaneous optimization of material property and topology of functionally graded structures. The objective is to determine the optimal material property (via material volume fraction) and structural topology to maximize the performance of the structure in a given application. In the proposed method volume fraction and structural boundary are considered as design variables, with the former being discretized as a scaler field and the latter being implicitly represented by level set method. To perform simultaneous optimization, the two design variables are integrated into a common objective functional. Sensitivity analysis is conducted to obtain the descent directions. The optimization process is then expressed as the solution to a coupled Hamilton-Jacobi equation and diffusion partial differential equation. Numerical results are provided for the problem of mean compliance optimization in two dimensions.
Capacity of Fading Broadcast Channels With Minimum Rate Requirements

Fading broadcast channels have been studied extensively over the past 30 years and the Shannon capacity of these channels is well established. This paper examines the Shannon capacity of two-user fading broadcast channel using superposition coding and assuming perfect channel information at both the receiver and transmitter with the additional constraint of maintaining minimum data rates for both users in all fading states. We first describe the basic broadcast channel model and set up the problem of finding the Shannon capacity of such a channel with the minimum rate constraint. Then two simple sub-optimal algorithms are proposed to lower bound this capacity. Finally, numerical results are provided for both sub-optimal methods for a number of different fading channels.
GreenHPC: a novel framework to measure energy consumption on HPC applications

Energy consumption on systems that have a continuous power source is tightly-related to both the computing time of an application and its required CPU load. Considering the scope of HPC applications which commonly have a time precision in nano or milliseconds, we observe a lack of systems that combine appropriate sampling rate, low intrusiveness and low cost. In this context, this article presents a model called GreenHPC that uses a hall effect sensor to precisely capture current with an arbitrary timeslice on HPC applications. Its scientific contribution relies on analyzing the energy consumption at a cluster scale, without application intrusiveness, showing the impact of maintaining idle nodes or turning them off for energy saving. Furthermore, considering the use of GreenHPC over the execution of a seismic wave application, we also present the number of employed processors which present the best energy consumption index. Finally, we have used the obtained results to infer a model to estimate energy consumption of HPC applications. All the developed work has a special concern on reproducibility, so all data and hardware schematics are available for download at 1.
Optimal management of sarcopenia

Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs.
Collection Selection for Distributed Web Search: Using Highly Discriminative Keys, Query-driven Indexing and ColRank

Current popular web search engines, such as Google, Live Search and Yahoo! , rely on crawling to build an index of the World Wide Web. Crawling is a continuous process to keep the index fresh and generates an enormous amount of data traffic. By far the largest part of the web remains unindexed, because crawlers are unaware of the existence of web pages and they have difficulties crawling dynamically generated content. These problems were the main motivation to research distributed web search. We assume that web sites, or peers, can index a collection consisting of local content, but possibly also content from other web sites. Peers cooperate with a broker by sending a part of their index. Receiving indices from many peers, the broker gains a global overview of the peers’ content. When a user poses a query to a broker, the broker selects a few peers to which it forwards the query. Selected peers should be promising to create a good result set with many relevant documents. The result sets are merged at the broker and sent to the user. This research focuses on collection selection, which corresponds to the selection of the most promising peers. The use of highly discriminative keys is employed as a strategy to select those peers. A highly discriminative key is a term set which is an index entry at the broker. The key is highly discriminative with respect to the collections because the posting lists pointing to the collections are relatively small. Query-driven indexing is applied to reduce the index size by only storing index entries that are part of popular queries. A PageRank-like algorithm is also tested to assign scores to collections that can be used for ranking. The Sophos prototype was developed to test these methods. Sophos was evaluated on different aspects, such as collection selection performance and index sizes. The performance of the methods is compared to a baseline that applied language modeling onto merged documents in collections. The results show that Sophos can outperform the baseline with ad-hoc queries on a web based test set.Query-driven indexing is able to substantially reduce index sizes against a small loss in collection selection performance. We also found large differences in the level of difficulty to answer queries on various corpus splits.
Comparative physiological, biochemical and molecular thermal stress response profiles for two unionid freshwater mussel species

ABSTRACT Freshwater mussels, aquatic keystone species, are in global decline. Long life spans, sedentary lifestyles, and unique reproductive strategies involving obligate parasitic stages make unionid freshwater mussels particularly sensitive to environmental perturbations resulting from global climate change. A greater understanding of the mechanisms by which closely related species differ in their response to thermal challenge is critical for successful conservation and management practices. As such, both an acute heat shock and a chronic warming simulation were conducted in order to evaluate responses between hypothesized thermally tolerant (Villosa lienosa) and thermally sensitive (Villosa nebulosa) freshwater mussels in response to predicted thermal warming. Multiple biological responses were quantified, including mortality, condition index, growth rates, glycogen and triglyceride content, and candidate gene expression. During acute heat shock, both species upregulated HSP90 and HSP70, although V. lienosa showed consistently greater transcript levels during upregulation. This pattern was consistent during the chronic warming simulation, with V. nebulosa showing greater induction of HSP60. Chronic warming stimulated increases in condition index for V. nebulosa; however, declines in growth rates during a recovery period were observed with no concurrent change in tissue glycogen levels. This contrasts with V. lienosa, where tissue glycogen significantly increased during chronic warming, although no response was observed for condition index or growth rates. These biological differences might indicate disparate thermal stress response mechanisms correlated with metabolic demands and resource utilization, and could thus be a factor influencing current ranges of these two species and their ability to cope with future persistent warming in their native habitats. Summary: Comparative response profiling of two freshwater mussels, Villosa lienosa and Villosa nebulosa, under acute and chronic heat conditions indicates disparate thermal response mechanisms that may influence their range and survival under predicted global warming.
Carbon Dots: From Intense Absorption in Visible Range to Excitation-Independent and Excitation-Dependent Photoluminescence

Carbon dots (CDs) were hydrothermally synthesized using citric acid as carbon source and ethylenediamine as additive. The as-obtained CDs were then subjected to ultraviolet (UV) irradiation, resulting in ultraviolet-irradiated CDs (UVCDs). The morphology and size of CDs were characterized by transmission electron microscopy. Elemental analysis (EA) was employed to explore the composition of CDs. The surface functional groups of CDs were investigated with the help of Fourier transformation infrared spectroscopy. Fluorescence spectrometry and ultraviolet-visible (UV-vis) spectrophotometry were used to characterize the optical properties of CDs and UVCDs. The results show that the size of CDs was around 10 nm. C, H, O, and N constituted CDs with the empirical elemental composition CH1.26O0. 52N0.22. Apart from excitation-independent photoluminescence (PL), CDs exhibited two UV-vis absorption peaks at 340 and 451 nm. They also revealed weak near infrared (NIF) emission with excitation at 340 and 360 nm. In addition to excitation-dependent PL, UVCDs showed one UV-vis absorption peak at 340 nm and extension of UV-vis absorption band to visible range, and they also displayed weak NIF emission at 340 and 360 nm excitation. Optical behaviors originated from surface defects and band bending. The as-prepared CDs could be used to harvest solar energy.
Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca2+-Dependent Manner

Background: Phosphorylation state of dopamine- and cAMP-regulated phosphoprotein, molecular weight 32kDa (DARPP32) is crucial to understand drug-mediated synaptic plasticity. In this study, mechanisms underlying repeated cocaine-stimulated phosphorylation of DARPP32 at threonine 75 (pDARPP32-Thr75) were determined by investigating the hypothesis that activation of protein kinases and phosphatases coupled to glutamate signaling is necessary for the regulation of pDARPP32-Thr75 after repeated cocaine administration. Methods: Intracaudate drug infusions into the rat dorsal striatum followed by Western immunoblot analysis were mainly performed to test this hypothesis. Results: The results demonstrated that 7 repeated daily intraperitoneal injections of cocaine (20mg/kg) upregulated the expression of pDARPP32-Thr75. Increases in the cytosolic Ca2+ concentrations followed by Ca2+-dependent protein kinase activation through stimulation of Ca2+ channels in striatal neurons were necessary for the phosphorylation. Activation of protein phosphatases further regulated the phosphorylation state by deactivating pDARPP32-Thr75 and upstream protein kinases. Conclusion: These findings suggest that activation of protein kinases and phosphatases coupled to glutamate receptors controls the phosphorylation state of DARPP32-Thr75 after repeated exposure to cocaine in the dorsal striatum in a Ca2+-dependent manner.
Identification of an antithrombotic allosteric modulator that acts through helix 8 of PAR1

G protein-coupled receptors (GPCRs) can assume multiple conformations and possess multiple binding sites. Whereas endogenous agonists acting at the orthosteric binding site stabilize the active receptor conformation, small molecules that act at nonorthosteric sites can stabilize alternative conformations. The large majority of these allosteric modulators associate with extracellular loops of GPCRs. The role of intracellular domains in mediating allosteric modulation is largely unknown. In screening a small-molecule library for inhibitors of platelet activation, we identified a family of compounds that modified PAR1-mediated granule secretion. The most potent inhibitory compound, termed JF5, also demonstrated noncompetitive inhibition of the α2A-adrenergic receptor. Aggregation studies using a battery of platelet GPCR agonists demonstrated that sensitivity to JF5 was limited to GPCRs that possessed a constrained eighth helix, as defined by a C-terminal palmitoylation site and interactions with TM7 and the i1 loop. Inhibition by JF5 was overcome in a PAR1 mutant in which the eighth helix was deleted, confirming a role for helix 8 in JF5 activity. Evaluation of downstream signaling showed that JF5 was selective with regard to G protein coupling, blocking signaling mediated by Gαq but not Gα12. The compound inhibited thrombus formation in vivo following vascular injury with an IC50 of ∼1 mg/kg. These results indicate a role for helix 8 in conferring sensitivity to small molecules, and show that this sensitivity can be exploited to control platelet activation during thrombus formation.
A Network Architecture for Providing Micro-Mobility in MPLS/GMPLS Networks

The Mobile Plane Architecture (MPA) is a network architecture that provides micro-mobility in a network-centric way, that is, the burden of supporting micro-mobility is placed on the network and not on the mobile nodes. MPA employs an overlay network above an IPv4 or IPv6 transport network in order to direct traffic to the mobile nodes. The overlay network is built by establishing point-to-multipoint (P2MP) tunnels through the transport network. This paper presents an implementation of MPA over MPLS/GMPLS networks. It is shown that the combination of P2MP tunneling with label stacking is an effective way for providing mobility services in MPLS/GMPLS transport networks. Results obtained in a lab-sized network are presented as well.
SDX-Based Flexibility or Internet Correctness?: Pick Two!

Software-Defined Internet eXchange Points (SDXes) are recently gaining momentum, with several SDXes now running in production. The deployment of multiple SDXes on the Internet raises the question of whether the interactions between these SDXes will cause correctness problems, since SDX policies can deflect traffic away from the default BGP route for a prefix, effectively breaking the congruence between the control plane and data plane. Although one deflection on a path will never cause loops to occur, combining multiple deflections at different SDXes can lead to persistent forwarding loops that the control plane never sees. In this paper, we introduce SIDR, a coordination framework that enables SDXes to verify the end-to-end correctness (i.e., loop freedom) of an SDX policy. The challenge behind SIDR is to strike a balance between privacy, scalability, and flexibility. SIDR addresses these challenges by: (i) not requiring SDXes to disclose the flow space their SDX policies act on, only the next-hop they deflect to; and (ii) minimizing the number of SDXes that must exchange state to detect correctness problems. SIDR manages to preserve the flexibility of SDX policies by activating the vast majority of the safe policies, the policies that do not create a loop. We implemented SIDR on the SDX platform and showed its practical effectiveness: SIDR can activate 91% of all safe policies while preserving privacy and scalability and can perform correctness checks in about one second.
A prenatal prediction model for total nucleated cell count increases the efficacy of umbilical cord blood banking

The most important factor for the selection of an umbilical cord blood unit (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count as a surrogate marker for stem cell content in the CBU. At present, about one in five donors can provide a CBU with a sufficient TNC count for umbilical cord blood (UCB) banking. It is labor‐intensive to obtain consent of all eligible donors and optimization of the selection is needed. The purpose of this study was to investigate prenatal clinical predictors for TNC count that would help to identify successful UCB donors already on admission to the delivery unit.
Strained Ge1-xSnx thin film on Ge (100) with low temperature Ge buffer layer

Alloys of germanium (Ge) and tin (Sn) get much research attention because of possible direct band gap semiconductors. In this paper, we report the growth of Ge1-xSnx thin film deposited on Ge (100) with different Sn compositions ranging from 4% to 20% by Molecular Beam Epitaxy (MBE). Different experimental techniques are employed to characterize the film including, Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), and Raman scattering measurement. From the analysis, it shows that high quality film can be obtained which is desired for optoelectronic devices.
Evolution in agriculture: the application of evolutionary approaches to the management of biotic interactions in agro-ecosystems

Anthropogenic impacts increasingly drive ecological and evolutionary processes at many spatio‐temporal scales, demanding greater capacity to predict and manage their consequences. This is particularly true for agro‐ecosystems, which not only comprise a significant proportion of land use, but which also involve conflicting imperatives to expand or intensify production while simultaneously reducing environmental impacts. These imperatives reinforce the likelihood of further major changes in agriculture over the next 30–40 years. Key transformations include genetic technologies as well as changes in land use. The use of evolutionary principles is not new in agriculture (e.g. crop breeding, domestication of animals, management of selection for pest resistance), but given land‐use trends and other transformative processes in production landscapes, ecological and evolutionary research in agro‐ecosystems must consider such issues in a broader systems context. Here, we focus on biotic interactions involving pests and pathogens as exemplars of situations where integration of agronomic, ecological and evolutionary perspectives has practical value. Although their presence in agro‐ecosystems may be new, many traits involved in these associations evolved in natural settings. We advocate the use of predictive frameworks based on evolutionary models as pre‐emptive management tools and identify some specific research opportunities to facilitate this. We conclude with a brief discussion of multidisciplinary approaches in applied evolutionary problems.
δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function

Significance We systematically dissect the structural elements of the δ subunit of the coat protein I (COPI) vesicle coat. We demonstrate that the µ-homology domain is dispensable for essential COPI functions. We map a key helix, positionally analogous to a helix observed in clathrin adaptor (AP) structures but without assigned function in AP, let alone COPI. This helix shows all features of an amphipathic helix that can enable interactions of a protein with the membrane. Indeed, the residues on its hydrophobic surface were specifically required for its function. Both findings substantially refine current models of coat formation and restrict the mechanisms of how the coat polymer is constructed or how HDEL cargo is recognized by COPI. Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential. We map a previously uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents. It is positionally analogous to an unstructured linker that becomes helical and membrane-facing in the open form of the AP2 clathrin adaptor complex. Based on the amphipathic nature of the critical helix it may probe the membrane for lipid packing defects or mediate interaction with cargo and thus contribute to stabilizing membrane-associated coatomer.
The Allocation of Attention to Learning of Goal-Directed Actions: A Cognitive Neuroscience Framework Focusing on the Basal Ganglia

The present paper builds on the idea that attention is largely in service of our actions. A framework and model which captures the allocation of attention for learning of goal-directed actions is proposed and developed. This framework highlights an evolutionary model based on the notion that rudimentary functions of the basal ganglia have become embedded into increasingly higher levels of networks which all contribute to adaptive learning. Supporting the proposed model, background literature is presented alongside key evidence based on experimental studies in the so-called “split-brain” (surgically divided cerebral hemispheres), and selected evidence from related areas of research. Although overlap with other existing findings and models is acknowledged, the proposed framework is an original synthesis of cognitive experimental findings with supporting evidence of a neural system and a carefully formulated model of attention. It is the hope that this new synthesis will be informative in fields of cognition and other fields of brain sciences and will lead to new avenues for experimentation across domains.