gebhart/patrepeval huggingface dataset:
Second-Order Inference for the Mean of a Variable Missing at Random (2015)

We present a second-order estimator of the mean of a variable subject to missingness, under the missing at random assumption. The estimator improves upon existing methods by using an approximate second-order expansion of the parameter functional, in addition to the first-order expansion employed by standard doubly robust methods. This results in weaker assumptions about the convergence rates necessary to establish consistency, local efficiency, and asymptotic linearity. The general estimation strategy is developed under the targeted minimum loss-based estimation (TMLE) framework. We present a simulation comparing the sensitivity of the first and second order estimators to the convergence rate of the initial estimators of the outcome regression and missingness score. In our simulation, the second-order TMLE improved the coverage probability of a confidence interval by up to 85%. In addition, we present a first-order estimator inspired by a second-order expansion of the parameter functional. This estimator only requires one-dimensional smoothing, whereas implementation of the second-order TMLE generally requires kernel smoothing on the covariate space. The first-order estimator proposed is expected to have improved finite sample performance compared to existing first-order estimators. In our simulations, the proposed first-order estimator improved the coverage probability by up to 90%. We provide an illustration of our methods using a publicly available dataset to determine the effect of an anticoagulant on health outcomes of patients undergoing percutaneous coronary intervention. We provide R code implementing the proposed estimator.
Supplemental Figure 3 from Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and <i>ESR1</i> mRNA Expression in Breast Tumors (2023)

&lt;p&gt;Supplemental Figure 3. The association between smoking and LS-defined breast cancer subtypes.&lt;/p&gt;
Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain (2021)

Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.
(Invited) Recent Developments in ST-MRAM, Including Scaling (2013)

Spin-torque Magnetoresistive Random Access Memory (ST-MRAM) is the subject of intense investigation since it extends MRAM technology to densities beyond those achieved with the earlier field-switched MRAM technology. This paper reviews recent developments in ST-MRAM MTJ device technology, including exciting progress in scaling MTJs down to dimensions approaching 20 nm. Fabrication issues relevant to development of ST-MRAM, including its integration with CMOS back-end-of-line (BEOL) processing, are also briefly discussed.
Transgenic mice harboring Aujeszky's disease virus gD gene. (1994)

Plasmid pMLP10 gp50.5 (gD) (Eloit et al., 1990) provided the sequence to integrate. The construct has been injected into the male pronucleus of one-cell mouse embryos (CBA/C5B1). A total of 1,567 microinjected embryos were transferred into the oviduct of pseudopregnant females (Hogan et al., 1986). PCR revealed that 3 out of 10 mice were born with an integrated construct; among them, 2 mice have integrated the construct in their gonads because 20 out of 107 (18.7%) of their offspring were also transgenic. This low percentage could be explained by germline mosaicism and/or differential mortality between transgenic and non-transgenic embryos.
T.echnologies in Li.ghtwave Communications: Innovations (and Their Needs) Abound (2013)

Due in large part to the vision and leadership of Tingye Li, optical communications has achieved dramatic growth by a continuous stream of innovations. This presentation will highlight some key trends and advances in the area of high-capacity, multiplexed optical communication systems.
1/f noise measurement in CMOS image sensors (2005)

This paper describes an in-situ pixel source follower power spectral density (PSD) measurement method that does not require any specialized test equipment. This method requires a dual port CMOS image sensor with analog outputs that allow differential time series noise measurements. We describe the sensor circuits and measurement techniques used for collecting data. We derive an estimator for the PSD based on the measured data. We also present a technique for estimating the confidence interval of the PSD based on Bootstrap re-sampling. Using our estimate of the PSD, we derive estimators for the SPICE NLEV3 1/f noise model parameters <i>AF</i> and <i>KF</i>. We also determine confidence intervals for these estimators. Using this method we present the estimated source follower PSD for a CMOS image sensor fabricated in a 0.18&#956;m CMOS process with 3.3&#956;m X 3.3&#956;m pixels. We also present the estimated values of <i>AF</i> and <i>KF</i> based on the estimated PSD.
Joint compression and feedback of CSI in correlated multiuser MISO channels (2016)

The potential gains of multiple antennas in wireless systems can be limited by channel state information imperfections. In this context, this paper tackles the limited feedback in multiuser correlated multiple input single output (MU-MISO). We propose a framework to feedback the minimum number of bits with limited performance degradation. This framework is based on decor relating the channel state information by compression and then quantize the compressed (CSI) and feedback it to the base station (BS). We characterize the rate loIEEss resulting from the proposed framework. An upper bound on the rate loss is derived in terms of the amount of feedback and the statistics of the channel. Based on this characterization, we propose an adaptive bit allocation algorithm that takes into the account the channel statistics to reduce the rate loss induced by the quantization. Moreover, in order to maintain a constant rate loss with respect to perfect CSI, it is shown that the number of feedback bits should scale linearly with the SNR (in dB) and to the rank of the user transmit correlation matrix. We validate the proposed framework by Monte-carlo simulations.
Resilient and Coherence Preserving Dissemination of Dynamic Data Using Cooperating Peers (2004)

The focus of our work is to design and build a dynamic data distribution system that is coherence-preserving, i.e. the delivered data must preserve associated coherence requirements (the user-specified bound on tolerable imprecision) and resilient to failures. To this end, we consider a system in which a set of repositories cooperate with each other and the sources, forming a peer-to-peer network. In this system, necessary changes are pushed to the users so that they are automatically informed, about changes of interest. We present techniques 1) to determine when to push an update from one repository to another for coherence maintenance, 2) to construct an efficient dissemination tree for propagating changes from sources to cooperating repositories, and 3) to make the system resilient to failures. An experimental evaluation using real world traces of dynamically changing data demonstrates that 1) careful dissemination of updates through a network of cooperating repositories can substantially lower the cost of coherence maintenance, 2) unless designed carefully, even push-based systems experience considerable loss in fidelity due to message delays and processing costs, 3) the computational and communication cost of achieving resiliency is made to be low, and 4) surprisingly, adding resiliency actually improve fidelity even in the absence of failures.
Solid-Phase and Solution-Phase Parallel Synthesis of Tetrahydro-isoquinolines via Pictet-Spengler Reaction (2002)

An efficient parallel synthesis of 6,7-dimethoxytetrahydroisoquinolines is reported. The key reaction step is 3,4-dimethoxyphenethylimines reacting with acid chlorides to form an N-acyliminium ion intermediate, which undergoes Pictet-Spengler condensation to give the desired products in >80% yield. Both solution-phase and solid-phase synthesis of 6,7-dimethoxytetrahydroisoquinolines are described.
Evaluation of Recombinant Fixfc-Xten Bleeding Efficacy in Hemophilia-B Mouse Models (2016)

Abstract Introduction: Prophylactic treatment for hemophilia has demonstrated clear benefit over on demand treatment in hemophilic patients. Alprolix (rFIXFc) is the first of a new generation of long acting clotting factors we made to reduce the frequency of intravenous infusions (Powell, NEJM, 2013). Nevertheless, intravenous injections can be particularly challenging for young patients and patients with limited venous access and are time consuming. We are developing a novel rFIXFc fusion protein, using XTEN recombinant technology, which is suitable for prophylactic subcutaneous dosing in hemophilia B. In the current studies we explore the in vivo bleeding efficacy of subcutaneously dosed rFIXFc-XTEN in hemophilia B mouse model. Methods: recombinant rFIXFc-XTEN was produced in HEK293 cells and affinity purified. The subcutaneous PK profile of rFIXFc-XTEN was compared to that of intravenously dosed rFIXFc in hemophilia B mice. The prolonged and acute bleeding efficacies were evaluated in HemB mouse tail-vein transection (TVT) and tail-clip bleeding models. Results and conclusions: Subcutaneous dosing of rFIXFc-XTEN shows a tmax around 20 hours post dosing in mice, and improved plasma activity levels compared to similar (IU/kg) intravenously dosed rFIX or rFIXFc. Using the TVT bleeding model in HemB mice we show that at 72 hours post dosing, subcutaneously dosed rFIXFc-XTEN has improved in vivo efficacy compared to intravenously dosed rFIXFc at all tested doses. Similarly, acute efficacy testing in the HemB mouse tail-clip bleeding model showed improved efficacy of intravenously dosed rFIXFc-XTEN compared to rFIXFc. These data support the potential of once weekly or less frequent subcutaneous prophylactic dosing of rFIXFc-XTEN in humans. Disclosures Liu: biogen: Employment, Equity Ownership. van der Flier:Biogen: Employment, Equity Ownership. Ismail:Biogen: Employment, Equity Ownership. Simpson:Biogen: Employment, Equity Ownership. Kurt:Biogen: Employment, Equity Ownership. Schellenberger:Amunix: Employment, Equity Ownership. Loh:Biogen: Employment, Equity Ownership, Other: share holder. Peters:Biogen: Employment, Equity Ownership, Other: share holder.
Grounding Criterion: Toward a Formal Theory of Grounding (2000)

In a conversation, participants establish and maintain their mutual belief that their utterances have been understood well enough for current purposes – a process that has been referred to as grounding. In order to make a contribution to the conversation, participants typically do more than just produce the right utterance at the right time; they coordinate the presentation and acceptance of their utterances until they have reached a sufficient level of mutual understanding to move on, a level defined by the grounding criterion . Recent interest in employing grounding for use in collaborative dialog systems has highlighted difficulties in rendering hitherto qualitative intuitions about grounding into formal terms. In this paper, we propose a formalization of grounding based on decision theory that captures key intuitions about the contribution model while providing an explicit method for determining the grounding criterion. We illustrate the formalization by reviewing interactions between a user and a prototype spoken dialog system called the Bayesian Receptionist .
The potential role of pomegranate and its nano-formulations on cerebral neurons in aluminum chloride induced Alzheimer rat model (2020)

The oxidative stress leading to degenerative changes in the brain of Alzheimer's disease (AD) is evident. Our aim was to evaluate the therapeutic and protective effects of pomegranate extract (PE) and pomegranate extract-loaded nanoparticles (PE nano) in an AlCl 3-induced AD rat model. Nanoparticles were synthesized with a PE load of 0.68% w/w, and 70 male Wistar rats were divided into 7 groups: Group I was the control, Group II received PE., Group III received PE nano for 2 weeks, Group IV received AlCl 3 (50 mg/kg) daily orally for 4 weeks, Group V received PE for 2 weeks, Group VI received PE nano for 2 weeks, and Groups V and VI were started after AlCl 3 administration was stopped. Group VII received PE for 2 weeks and was stopped before AlCl 3 was administered. The Results revealed that the discrimination index in the novel object recognition test was the least in AD rat model but increased in cases protected with PE treated with PE nano. Similar results were shown based on calculating the brain weight/body weight percent. The biomarkers of antioxidant activity (catalase, glutathione and total antioxidant activity) in brain homogenate were significantly increased in groups treated with either PE or PE nano. The thiobarbituric acid reactive substance measured to estimate lipid peroxidation was significantly increased in AD rat model and decreased in groups protected with PE or treated with PE nano. Histopathological studies using hematoxylin and eosin, cresyl violet, and silver stains revealed hyaline degeneration, chromatolysis, and hallmarks of AD; neurofibrillary tangles and the senile plaques in brains of AD rat model. Restoration of the histological architecture, Nissl granules, and minimal appearance of hallmarks of AD characterized brains treated with PE or PE nano. In conclusion, PE was more effective as a protectant than a therapeutic measure in alleviating the antioxidant, lipid peroxidative effects and histopathological hallmarks in AD brains. But, the therapeutic PE-loaded nanoparticles increased the efficacy of active components and produced similar results as the protective PE.
Supplementary Figure 2 from A First-in-Human Phase I Study of INVAC-1, an Optimized Human Telomerase DNA Vaccine in Patients with Advanced Solid Tumors (2023)

&lt;p&gt;Kaplan-Meier representation of Overall Survival and Progression Free Survival&lt;/p&gt;
In Situ Fluorescence Imaging of Localized Corrosion with a pH-Sensitive Imaging Fiber (1997)

Abstract A fiber optic pH-sensor capable of both visualizing corrosion sites and measuring local chemical concentrations is applied to real-time corrosion monitoring. The imaging fiber’s distal face containing an immobilized pH-sensitive fluorescent dye is brought into contact with metal surfaces submerged in aqueous buffers and fluorescence images are acquired as a function of time. The observed changes in fluorescence due to increases in pH at cathodic sites and decreases in pH at anodic sites are indicative of localized corrosion rates.
HGF as Angiogenic Factor and Therapeutic Approach (2011)

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator for morphogenic tissue interactions. Although HGF was originally identified as a potent mitogen for hepatocytes, it has also been identified as a member of angiogenic growth factors. Interestingly, the presence of its specific receptor, c-met, is observed in vascular cells and cardiac myocytes. On the other hand, recently, we demonstrated that HGF plasmid DNA transfer significantly improves the size of ulcer in patients with peripheral artery disease (PAD) at Phase III clinical trial, while vascular endothelial growth factor (VEGF) gene therapies for PAD at Phase III have not been succeeded yet. To further investigate this difference between HGF and VEGF, we showed that HGF but not VEGF improves the senescence EPC against oxidative stress through the inhibition of rac1. Moreover, we reported that HGF promotes SHIP-2 translocation from epithelial growth factor receptor (EGFR) to c-Met, and it would protect oxidative stress through EGFR degradation. By this anti-oxidative and anti-senescence effects of HGF would maintain the vessel so long in patients with PAD who receive much oxidative stress in real world. In this report, we discuss a potential therapeutic strategy using HGF in cardiovascular diseases. Keywords: Angiogenesis, gene therapy, peripheral artery disease (PAD), HGF, VEGF, hepatocyte growth factor, vascular endothelial growth factor, epithelial growth factor receptor, c-Met, SHIP-2, plasmid DNA transfer, Phase III clinical trial, EPCs, Cbl, ROS, VSMC, CLI, Ang II, fibroblast growth factor, epithelial growth factor, senescence, GTP binding rac1, Rutherford 5, ERK, Akt, ankle-brachial pressure index, QOL
On the Performance of NOMA-Based Cooperative Relaying Systems Over Rician Fading Channels (2017)

Non-orthogonal multiple access (NOMA) is a promising technique for the fifth generation (5G) wireless communications. As users with good channel conditions can serve as relays to enhance the system performance by using successive interference cancellation (SIC), the integration of NOMA and cooperative relaying has recently attracted increasing interests. In this paper, a NOMA-based cooperative relaying system is studied, and an analytical framework is developed to evaluate its performance. Specifically, the performance of NOMA over Rician fading channels is studied, and the exact expression of the average achievable rate is derived. Moreover, we also propose an approximation method to calculate the achievable rate by using the Gauss-Chebyshev Integration. Numerical results confirm that our derived analytical results match well with the Monte Carlo simulations.
Towards the composition of stateful and independent semantic web services (2008)

Most of the work on automated semantic Web service composition has focused so far on two main levels of composition i.e., functional level and process level composition (respectively FLC and PLC from now). The former level of composition considered Web services as atomic components that can be executed in a single request-response step whereas the latter level studies in more details the protocol and the behavioural features of Web services. Since PLC i.e., a time and particularly space consuming level of composition makes difficult the scalability of composition-based applications, it seems interesting to restrict the composition of stateful but (only) independent Web services. Such a restriction make possible the composition of a large number of Web services in industrial scenarios, the whole with convincing results. In this paper we suggest to study the advantages to apply FLC together with β-composition in order to perform an automated end to end composition of stateful and independent services. In particular we focus on computational complexity results concerning the two models of composition i.e., the well-known PLC vs. the newest FLC+β-composition. Moreover we prove that FLC is an interesting and necessary level of composition to significantly reduce computational complexity not only in space but also in time.
Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical for Colonic Protection (2010)

The cytokine, interleukin (IL)-19, is a member of the IL-10 family that includes IL-20, IL-22, IL-24, and IL-26. Recent studies have shown that IL-19 is produced by keratinocytes, epithelial cells, macrophages, and B-cells. Little is known about the exact biological role of IL-19 in immunological regulation, although there is an increasing body of data demonstrating that IL-19 is associated with the development of Th2 responses and the pathogenesis of psoriasis. In this review, I shall attempt to discuss current knowledge about the role of IL-19 on macrophages and the potential role in inflammatory bowel disease.
Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency (2021)

Forkhead box (Fox) transcription factors play important roles in mammalian development and disease. However, their function in mouse somatic cell reprogramming remains unclear. Here, we report that FoxD subfamily and FoxG1 accelerate induced pluripotent stem cells (iPSCs) generation from mouse fibroblasts as early as day4 while FoxA and FoxO subfamily impede this process obviously. More importantly, FoxD3, FoxD4 and FoxG1 can replace Oct4 respectively and generate iPSCs with germline transmission together with Sox2 and Klf4. On the contrary, FoxO6 almost totally blocks reprogramming through inhibiting cell proliferation, suppressing the expression of pluripotent genes and hindering the process of mesenchymal to epithelial transition (MET). Thus, our study uncovers unexpected roles of Fox transcription factors in reprogramming and offers new insights into cell fate transition.
Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs. (1991)

U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dominant (gain-of-function), compensatory mutations in U6 results in wild-type growth. Cold-insensitive growth can also be restored by two classes of recessive (loss-of-function) suppressors: (1) mutations in PRP24, which we show to be a U6-specific binding protein of the RNP-consensus family; and (2) mutations in U6, which lie outside the interaction domain and identify putative PRP24-binding sites. Destabilization of the U4/U6 helix causes the accumulation of a PRP24/U4/U6 complex, which is undetectable in wild-type cells. The loss-of-function suppressor mutations inhibit the binding of PRP24 to U6, and thus presumably promote the release of PRP24 from the PRP24/U4/U6 complex and the reformation of the base-paired U4/U6 snRNP. We propose that the PRP24/U4/U6 complex is normally a highly transient intermediate in the spliceosome cycle and that PRP24 promotes the reannealing of U6 with U4.
Effect of an Asparagine-to-Serine Mutation at Position 294 in Neuraminidase on the Pathogenicity of Highly Pathogenic H5N1 Influenza A Virus (2011)

Like the histidine-to-tyrosine substitution at position 274 in neuraminidase (NA H274Y), an asparagine-to-serine mutation at position 294 in this protein (NA N294S) confers oseltamivir resistance to highly pathogenic H5N1 influenza A viruses. However, unlike viruses with the NA H274Y mutation, the properties of viruses possessing NA N294S are not well understood. Here, we assessed the effect of the NA N294S substitution on the replication and pathogenicity of human H5N1 viruses and on the efficacy of the NA inhibitors oseltamivir and zanamivir in mouse and ferret models. Although NA N294S-possessing H5N1 viruses were attenuated in mice and ferrets compared to their oseltamivir-sensitive counterparts, one of the infected ferrets died from systemic infection, demonstrating the potential lethality in ferrets of oseltamivir-resistant H5N1 viruses with the NA N294S substitution. The efficacy of oseltamivir, but not that of zanamivir, against an NA N294S-possessing virus was substantially impaired both in ferrets and in vitro. These results demonstrate the considerable pathogenicity of NA N294S substitution-possessing H5N1 viruses and underscore the importance of monitoring the emergence of the NA N294S mutation in circulating H5N1 viruses.