Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Dendritic Spine Morphogenesis and Synaptic Transmission by Activity-Inducible Protein Homer1a

The postsynaptic density (PSD) proteins Shank and Homer cooperate to induce the maturation and enlargement of dendritic spines (Sala et al., 2001). Homer1a is an activity-inducible short-splice variant of Homer that lacks dimerization capacity. Here, we show that Homer1a reduces the density and size of dendritic spines in cultured hippocampal neurons in correlation with an inhibition of Shank targeting to synapses. Expression of Homer1a also decreases the size of PSD-95 clusters, the number of NMDA receptor clusters, and the level of surface AMPA receptors, implying a negative effect on the growth of synapses. In parallel with the morphological effects on synapses, Homer1a-expressing neurons show diminished AMPA and NMDA receptor postsynaptic currents. All of these outcomes required the integrity of the Ena/VASP Homology 1 domain of Homer1a that mediates binding to the PPXXF motif in Shank and other binding partners. Overexpression of the C-terminal region of Shank containing the Homer binding site causes effects similar to those of Homer1a. These data indicate that an association between Shank and the constitutively expressed long-splice variants of Homer (e.g., Homer1b/c) is important for maintaining dendritic-spine structure and synaptic function. Because Homer1a expression is induced by synaptic activity, our results suggest that this splice variant of Homer operates in a negative feedback loop to regulate the structure and function of synapses in an activity-dependent manner.
Mixture of gaussian models and bayes error under differential privacy

Gaussian mixture models are an important tool in Bayesian decision theory. In this study, we focus on building such models over statistical database protected under differential privacy. Our approach involves querying necessary statistics from a database and building a Bayesian classifier over the noise added responses generated according to differential privacy. We formally analyze the sensitivity of our query set. Since there are multiple methods to query a statistic, either directly or indirectly, we analyze the sensitivities for different querying methods. Furthermore we establish theoretical bounds for the Bayes error for the univariate (one dimensional) case. We study the Bayes error for the multivariate (high dimensional) case in experiments with both simulated data and real life data. We discover that adding Laplace noise to a statistic under certain constraint is problematic. For example variance-covariance matrix is no longer positive definite after noise addition. We propose a heuristic method to fix the noise added variance-covariance matrix.
Customer engagement persuasion process in online brand communities : social influence theory perspective

Customer engagement persuasion process in online brand communities: social influence theory perspective Customer engagement is becoming a more important area in online brand community management. There are a number of competing theories that underline the importance of different types of community members in order that these members can be positively influenced for the benefit of the brand. This paper shares work in progress, which discusses a review of existing thinking – which indicates that there are a number of weaknesses and gaps in this area of research. A conceptual framework is proposed for studying customer engagement based on the Elaboration Likelihood Model (ELM) as well as a methodology and data collection tools. It also explores Amazon Mechanical Turk as a data collection tool for this kind of research.
Taking Industry Seriously in Information Systems Research

In this essay, we argue that industry receives little attention in information systems research and theory, despite its increasingly important influence on IS activities. This is evident both in the narrow range of industries examined in IS research and the infrequent consideration of industry in theory. We base these observations on an analysis of IS publications in two top-tier journals (MIS Quarterly and Information Systems Research) over eight years. Drawing from institutional theory, we consider various ways industry can be addressed and assess how industry influences IS activities. We conclude that industry provides an important contextual "space" to build new IS theory and to evaluate the boundaries of existing IS theory. We outline a range of strategies for incorporating industry into IS research.
Antigen recognition by MHC-incompatible cells of a human mismatched chimera

Tetanus toxin (TT)-specific T cell clones of donor origin were obtained from a patient with severe combined immunodeficiency (SCID) successfully reconstituted by transplantation of allogeneic fetal liver and thymus cells from two different donors performed 10 yr ago. A series of these clones recognized TT in the context of "allo" class II HLA determinants expressed by recipient APC. The restriction element of two T cell clones with the HLA phenotype of the first donor (HLA-DR1,8) and one T cell clone with the HLA phenotype of the second transplant (HLA-DR3,9) was HLA-DR4 of the recipient, whereas other T cell clones derived from the second transplant recognized TT in the context of HLA- DR5 of the recipient's APC. These latter T cell clones were not able to proliferate in response to TT when autologous APC were used. These data demonstrate that recipient and donor cells having different HLA phenotypes could cooperate across the allogeneic barrier and that MHC restriction of antigen (Ag) recognition is independent from the MHC genotype of the T cells but is influenced by the environment in which the T cells mature. We also isolated T cell clones that were able to recognize processed TT presented by all allogeneic EBV cell lines tested, indicating that the Ag specificity of these clones was not restricted by a particular class II MHC molecule. The Ag-specific proliferative response of one of these clones could be blocked by anti- class II MHC mAbs. These results demonstrate that in addition to Ag recognition in the context of specific class II MHC Ags, other types of Ag-specific responses may occur in this human chimera. It is not clear whether this "allo" plus Ag recognition is the result of education of transplanted fetal cells in the host thymus. Taking into consideration our previous findings indicating that alloreactive T cell clones specific for the recipient cells could be isolated in vitro from the PBL of the same patient, our data suggest that the mechanism for deletion of self-reactive clones and the generation of MHC-restricted responses are different.
Association of improved air quality with lung development in children.

BACKGROUND Air-pollution levels have been trending downward progressively over the past several decades in southern California, as a result of the implementation of air quality-control policies. We assessed whether long-term reductions in pollution were associated with improvements in respiratory health among children. METHODS As part of the Children's Health Study, we measured lung function annually in 2120 children from three separate cohorts corresponding to three separate calendar periods: 1994-1998, 1997-2001, and 2007-2011. Mean ages of the children within each cohort were 11 years at the beginning of the period and 15 years at the end. Linear-regression models were used to examine the relationship between declining pollution levels over time and lung-function development from 11 to 15 years of age, measured as the increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) during that period (referred to as 4-year growth in FEV1 and FVC). RESULTS Over the 13 years spanned by the three cohorts, improvements in 4-year growth of both FEV1 and FVC were associated with declining levels of nitrogen dioxide (P<0.001 for FEV1 and FVC) and of particulate matter with an aerodynamic diameter of less than 2.5 μm (P= 0.008 for FEV1 and P<0.001 for FVC) and less than 10 μm (P<0.001 for FEV1 and FVC). These associations persisted after adjustment for several potential confounders. Significant improvements in lung-function development were observed in both boys and girls and in children with asthma and children without asthma. The proportions of children with clinically low FEV1 (defined as <80% of the predicted value) at 15 years of age declined significantly, from 7.9% to 6.3% to 3.6% across the three periods, as the air quality improved (P = 0.001). CONCLUSIONS We found that long-term improvements in air quality were associated with statistically and clinically significant positive effects on lung-function growth in children. (Funded by the Health Effects Institute and others.).
Establishment of a simple and practical procedure applicable to therapeutic angiogenesis.

BACKGROUND Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed to establish a simple and practical procedure applicable to therapeutic angiogenesis. METHODS AND RESULTS When cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA was augmented at an optimal-frequency stimulation. This increase of VEGF mRNA was derived primarily from transcriptional activation. Electrical stimulation increased the secretion of VEGF protein into the medium. This conditioned medium then augmented the growth of endothelial cells. The effect of electrical stimulation was further confirmed in a rat model of hindlimb ischemia. The tibialis anterior muscle in the ischemic limb was electrically stimulated. The frequency of stimulation was 50 Hz and strength was 0.1 V, which was far below the threshold for muscle contraction. After a 5-day stimulation, there was a significant increase in blood flow within the muscle. Immunohistochemical analysis revealed that VEGF protein was synthesized and capillary density was significantly increased in the stimulated muscle. Rats tolerated this procedure very well, and there was no muscle contraction, muscle injury, or restriction in movement. CONCLUSIONS We propose this procedure as a simple and practical method of therapeutic angiogenesis.
A new optimization identification method for fault diagnosis

Fault diagnosis of electronic circuit is important for safety of the device and relevant power system. In the study, support vector regression (SVR) classifiers combined with the particle swarm optimization algorithm (POSA) are applied to construct diagnostic model of electronic circuit, and the diagnostic system structure of electronic circuit is presented on the basis of the model. It is powerful for the practical problem with small sampling, nonlinear and high dimension, which is very suitable for online fault diagnosis. Utilizing the character that principal components analysis algorithm can keep the discernability of original dataset after reduction, reduce of the original dataset is calculated and used to train individual SVR for ensemble, and consequently, increase the detection accuracy. The test results show that the proposed method is a promised method owning to its high diversity, high detection accuracy and faster speed in fault diagnosis. The experimental result shows that this fault detection method is feasible and effective.
Lapatinib, a Dual EGFR and HER2 Kinase Inhibitor, Selectively Inhibits HER2-Amplified Human Gastric Cancer Cells and is Synergistic with Trastuzumab In vitro and In vivo

Purpose: HER2 amplification occurs in 18% to 27% of gastric and gastroesophageal junction cancers. Lapatinib, a potent ATP-competitive inhibitor simultaneously inhibits both EGFR and HER2. To explore the role of HER family biology in upper gastrointestinal cancers, we evaluated the effect of lapatinib, erlotinib, and trastuzumab in a panel of molecularly characterized human upper gastrointestinal cancer cell lines and xenografts. Experimental Design: EGFR and HER2 protein expression were determined in a panel of 14 human upper gastrointestinal cancer cell lines and HER2 status was assessed by fluorescent in situ hybridization. Dose-response curves were generated to determine sensitivity to lapatinib, erlotinib, and trastuzumab. In HER2-amplified cells, the combination of trastuzumab and lapatinib was evaluated using the median effects principal. The efficacy of lapatinib, trastuzumab, or the combination was examined in HER2-amplified xenograft models. Results: Lapatinib had concentration-dependent antiproliferative activity across the panel with the greatest effects in HER2-amplified cells. There was no association between EGFR protein expression and sensitivity to any of the HER-targeted agents. Cell cycle analysis revealed that lapatinib induced G1 arrest in sensitive lines and phosphorylated AKT and phosphorylated ERK were decreased in response to lapatinib as well. The combination of lapatinib and trastuzumab was highly synergistic in inhibiting cell growth with a combination index of <1. The combination also induced greater decreases in AKT and ERK activation, G0-G1 cell cycle arrest, and increased rates of apoptosis. In vivo studies showed that the combination of lapatinib and trastuzumab had greater antitumor efficacy than either drug alone. Conclusion: Together, these data suggest that lapatinib has activity in HER2-amplified upper gastrointestinal cancer and supports the ongoing clinical investigation of lapatinib in patients with HER2-amplified disease. Clin Cancer Res; 16(5); 1509–19
Collective Mind: cleaning up the research and experimentation mess in computer engineering using crowdsourcing, big data and machine learning

Software and hardware co-design and optimization of HPC systems has become intolerably complex, ad-hoc, time consuming and error prone due to enormous number of available design and optimization choices, complex interactions between all software and hardware components, and multiple strict requirements placed on performance, power consumption, size, reliability and cost. We present our novel long-term holistic and practical solution to this problem based on customizable, plugin-based, schema-free, heterogeneous, open-source Collective Mind repository and infrastructure with unified web interfaces and on-line advise system. This collaborative framework distributes analysis and multi-objective off-line and on-line auto-tuning of computer systems among many participants while utilizing any available smart phone, tablet, laptop, cluster or data center, and continuously observing, classifying and modeling their realistic behavior. Any unexpected behavior is analyzed using shared data mining and predictive modeling plugins or exposed to the community at cTuning.org for collaborative explanation, top-down complexity reduction, incremental problem decomposition and detection of correlating program, architecture or run-time properties (features). Gradually increasing optimization knowledge helps to continuously improve optimization heuristics of any compiler, predict optimizations for new programs or suggest efficient run-time (online) tuning and adaptation strategies depending on end-user requirements. We decided to share all our past research artifacts including hundreds of codelets, numerical applications, data sets, models, universal experimental analysis and auto-tuning pipelines, self-tuning machine learning based meta compiler, and unified statistical analysis and machine learning plugins in a public repository to initiate systematic, reproducible and collaborative research, development and experimentation with a new publication model where experiments and techniques are validated, ranked and improved by the community.
Seasonal Variations in Water Quality Parameters of River Yamuna, India

With heavy industrialisation and expanding urbanisation, rivers are under threat worldwide. The freshwater that Indian rivers carry is often so severely polluted due to heavy pollution load of domestic sewage and industrial poisons that river now threaten the very life they once nurtured. The hydrochemical composition including quality of river water is affected by both the anthropogenic activities and natural processes (Carpenter et al., 1998). Natural processes influencing water quality include weathering of soil and rock, erosion, forest fires and volcanic eruptions whereas anthropogenic activities include urban development and expansion, industrial effluents, mining and refining, agricultural drainage and domestic discharges (Zhao et al., 2014; Basu and Lokesh, 2013) in the rivers. Today, freshwater resource is becoming scarcer and more polluted as the stresses on water quality and quantity due to development and increasing climate change increase every year and are as strongly felt in our country, India, as International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 5 (2017) pp. 694-712 Journal homepage: http://www.ijcmas. com
Erection Capability Is Potentiated by Long-Term Sildenafil Treatment: Role of Blood Flow-Induced Endothelial Nitric-Oxide Synthase Phosphorylation

Despite demonstrated clinical efficacy of sildenafil for the temporary treatment of erectile dysfunction, the possibility that sildenafil used long-term durably augments erectile ability remains unclear. We investigated whether continuous long-term administration of sildenafil at clinically relevant levels to aged rats “primes” the penis for improved erectile ability and involves nitric oxide (NO) or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil prolonged erection and increased the protein expressions of phosphorylated endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine-473 in penes. Only in the young rat penis, protein expressions of phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited phosphodiesterase-5 activity in penes of young and aged rats coincident with assayed free plasma levels of the drug equivalent to clinically therapeutic measurements. We conclude that erectile ability can be enhanced under preconditions of erectile impairment by long-term inhibition of phosphodiesterase-5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack of erectile ability enhancement in young rats by long-term phosphodiesterase-5 inhibition may relate to restrained NO signaling by phosphodiesterase-5 up-regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho-kinase signaling in the penis.
Glutamine infusion during ischemia is detrimental in a murine gut ischemia/reperfusion model.

BACKGROUND Gut ischemia/reperfusion (I/R) frequently occurs in clinical settings as a result of disproportionate splanchnic hypoperfusion during shock. Glutamine (GLN) supplementation of total parenteral nutrition (TPN) before gut I/R improves survival after gut I/R compared with standard TPN. However, it is unknown whether GLN treatment after the occurrence of the insult is beneficial or not. The aims of this study were to examine effects of GLN infusion during gut ischemia on survival, myeloid cell (neutrophils + monocytes) activation, and vascular permeability in organs. METHODS Male Institute of Cancer Research (ICR) mice were randomized to control and GLN groups. After IV cannulation, mice underwent 90 (experiments 1 and 2) or 60 (experiment 3) minutes of gut I/R. Control mice received normal saline infusion at 1 mL/h for 60 minutes during ischemia, whereas the GLN group was given 3% GLN solution. In experiment 1, survival rates were monitored for 72 hours (n = 25). In experiment 2, peripheral blood was obtained at 2 or 4 hours after reperfusion (n = 17). Reactive oxygen intermediate (ROI) production by myeloid cells was determined by flow cytometry using dihydrorhodamine 123 with or without phorbol myristate acetate stimulation. Expression of CD11a and CD11b on myeloid cells was also measured. Myeloperoxidase (MPO) activity in the lung was evaluated. In experiment 3, vascular permeability in organs was measured using Evans blue at 2 or 4 hours. RESULTS In experiment 1, survival time in the GLN group was significantly reduced compared with the control group (p = .02, log-rank test). The survival rates were 92% (12/13) and 42% (5/12) for the control and GLN groups at 12 hours (p = .01) and 38% (5/13) and 0% (0/12) at 48 hours (p = .02), respectively. In experiment 2, ROI production was significantly higher in the GLN group than in the control group after PMA stimulation both at 2 and 4 hours. CD11b expression was significantly higher in the GLN group than in the control group at 4 hours. There was no difference in pulmonary MPO activity at either time point. In experiment 3, GLN infusion significantly increased hepatic vascular permeability compared with saline infusion at 4 hours. CONCLUSIONS GLN infusion during ischemia is detrimental for survival after gut I/R. A possible mechanism is excessive priming of myeloid cells caused by GLN infusion. Timing of GLN administration is critical for outcome after gut ischemic insult.
R&D Investments, Information and Strategy

This paper argues that firms can best realize the value of their investments in R&D by exploiting the associated information asymmetries. Attention is directed away from the physical results of R&D and towards the firm's ability, more generally, to earn rents from the private information emanating from its R&D. Four strategies may be used to exploit the information asymmetries from R&D: (1) publish the details of the innovation in return for legal protection; (2) keep the information inside the firm; (3) make the information selectively, informally available to others; and (4) disseminate the information as widely and rapidly as possible. To implement these strategies, resources may be allocated both to the commercial development of new technologies, and/or to related market opportunities (investing in other companies, assets and technologies). Of critical importance are the innovator's own skills and resources in effectively gathering, understanding, and commercially exploiting R&D-generated information asymmetries, both internally and in relation to other firms. This study should yield new insights to managers in designing strategies (and counter-strategies) to position themselves not only at the technological edge, but more fundamentally, at the 'information edge'.
The Case for Making Tight Control Plane Latency Guarantees in SDN Switches

SDN controllers demand tight performance guarantees over the control plane actions performed by SDN switches. For example, traffic engineering techniques that frequently reconfigure the network require guarantees on the speed of gathering data from the network and the speed of reconfiguring the network. Yet, modern switches provide no guarantees for these control plane actions, e.g., inserting rules or gathering statistics. In fact, initial experiments demonstrate that unpredictability in control plane actions, specifically rule insertion, can inflate application completion times by a factor of 4X! In this paper, we present Mercury, a framework that offers a novel method for efficiently and practically managing switch TCAM to enable strict performance guarantees. Specifically, Mercury builds on the fundamental properties of TCAMs and provides guarantees by trading-off a nominal amount of TCAM space for assured performance. Our preliminary evaluations show that with less than 10% overheads, Mercury provides guarantees of 10ms insertion time and improves application performance by a factor 2X to 5X.