We consider the problem of uncertainty assessment for low dimensional components in high dimensional models. Specifically, we propose a novel decorrelated score function to handle the impact of high ...dimensional nuisance parameters. We consider both hypothesis tests and confidence regions for generic penalized M-estimators. Unlike most existing inferential methods which are tailored for individual models, our method provides a general framework for high dimensional inference and is applicable to a wide variety of applications. In particular, we apply this general framework to study five illustrative examples: linear regression, logistic regression, Poisson regression, Gaussian graphical model and additive hazards model. For hypothesis testing, we develop general theorems to characterize the limiting distributions of the decorrelated score test statistic under both null hypothesis and local alternatives. These results provide asymptotic guarantees on the type I errors and local powers. For confidence region construction, we show that the decorrelated score function can be used to construct point estimators that are asymptotically normal and semiparametrically efficient. We further generalize this framework to handle the settings of misspecified models. Thorough numerical results are provided to back up the developed theory.
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
Summary
We propose a robust method to estimate the average treatment effects in observational studies when the number of potential confounders is possibly much greater than the sample size. Our ...method consists of three steps. We first use a class of penalized $M$-estimators for the propensity score and outcome models. We then calibrate the initial estimate of the propensity score by balancing a carefully selected subset of covariates that are predictive of the outcome. Finally, the estimated propensity score is used to construct the inverse probability weighting estimator. We prove that the proposed estimator, which we call the high-dimensional covariate balancing propensity score, has the sample boundedness property, is root-$n$ consistent, asymptotically normal, and semiparametrically efficient when the propensity score model is correctly specified and the outcome model is linear in covariates. More importantly, we show that our estimator remains root-$n$ consistent and asymptotically normal so long as either the propensity score model or the outcome model is correctly specified. We provide valid confidence intervals in both cases and further extend these results to the case where the outcome model is a generalized linear model. In simulation studies, we find that the proposed methodology often estimates the average treatment effect more accurately than existing methods. We also present an empirical application, in which we estimate the average causal effect of college attendance on adulthood political participation. An open-source software package is available for implementing the proposed methodology.
This paper presents an in-depth study on the new mode of intelligent multidistance teaching of English with the help of virtual scenes of the Internet of Things. The virtual simulation technology is ...integrated into the traditional IoT teaching, and the professional education of IoT application technology is tapped; from the analysis of the current situation of IoT skills teaching and the feasibility of carrying out virtual simulation teaching, the “four-driven” design principle is proposed, and the teaching design is combined with the virtual simulation technology teaching, and the case design of the skill-based virtual simulation technology teaching of experience, demonstration, interaction, and assessment in the virtual environment is given. This paper presents the case design of virtual simulation teaching in a virtual environment with experience, demonstration, interaction, and assessment, and the multidimensional effect evaluation of IoT skills teaching and researches the application of virtual simulation to IoT skills teaching through the above four aspects. In this paper, a framework for distributed collaborative computing is built using an asynchronous message queue MQ, which enables multiple nodes to serve a task through task splitting. The DeepCluster module can effectively cluster the time series by deep representation learning and obtain the typical variation of time series patterns. In the task offloading module of the framework, a task offloading decision algorithm based on a value-constrained multi 0–1 backpacking model is designed to minimize task processing latency with an optimal offloading solution. The system test results show that the proposed distributed computing framework and offloading decision algorithm can significantly reduce the processing latency of large tasks.
* China is now the largest egg production country worldwide * Egg production in China is characterized by diversity in several aspects * China is now capable of breeding new varieties, with more than ...50% of the market share * Policies have been implemented to ensure sustainable development of egg production * Integrating crop-chicken-vegetable production system is established
Eggs are one of the most nutritious and affordable animal products worldwide. From 1985, egg production in China has retained the leading place in the world. A total of 33 Mt of eggs were produced in 2019 representing ˃ 40% of the world total production. Egg production in China is characterized by diversity in several aspects, including layer breeds, products and production systems. New breeds and synthetic lines are developed to improve the genetic potentials of egg production and feed efficiency of layers. In the past, layer farms were run mostly by small households with 100 to 1000 layers per farm. Over the past decades, egg production in China has developed toward standardization and expansion of production systems, and many of these modern intensive farms raise millions of layers. Although the Chinese egg products maintain strong competitiveness over other animal products and imported egg products, the egg industry will grow at a slower pace compared to the past. Chinese consumers are more concerned about the quality and safety of eggs and egg products, as well as the environmental issues related to animal production, which presents challenges for the Chinese egg industry.
A novel radical 1,2‐formylfunctionalization of alkenes involving 1,2(4,5)‐formyl migration triggered by addition of various carbon‐ and heteroatom‐centered radicals to alkenes has been developed for ...the first time, thus providing straightforward access to diverse β‐functionalized aldehydes with good efficiency, remarkable selectivity, and excellent functional group tolerance. Analogous transformations mediated by a keto‐carbonyl migration have also been effected under similar conditions. This method was used to access ring systems including various benzannulated nine‐, ten‐, and eleven‐membered rings, complex 6‐5(6,7)‐6(5) fused rings, and bridged rings with diverse functionalities.
The old 1,2: A novel 1,2‐formyl functionalization of unactivated alkenes involving formyl migration and addition of radicals to alkenes has been developed for access to synthetically important β‐functionalized aldehydes. The analogous keto‐carbonyl migration has been performed to synthesize challenging medium‐sized diketones, which were additionally transformed into complex fused rings.
The indicator displacement assay (IDA) is for the first time performed within a metal-organic framework (MOF) to achieve ultrasensitive fluorescence turn-on sensing. A Zr(iv) ion MOF (UiO-67-DQ-PsO) ...furnished with electron-deficient diquat units (DQ
, as the receptor) on the wall and electron-rich 1-pyrenesulfonate anions (PsO
, as the fluorescent indicator) in the pores was prepared by postsynthetic anion exchange. The MOF is capable of sensing alkylamines owing to the competing PsO
-DQ
and alkylamine-DQ
charge-transfer interactions, the former interaction causing a fluorescence OFF state and the latter displacing PsO
to trigger its emission. Significant advantages have been demonstrated for the IDA inside the MOF. The turn-on assay exhibits much higher sensitivity and anti-interference than the turn-off sensing using the MOF without indicators (the sensitivity is enhanced by as much as six orders of magnitude to the subnanomolar level). The integration of both the receptor and indicator in the porous solid enables facile regeneration and recyclability of the IDA ensemble. Furthermore, we show that the confined space provided by the MOF significantly enhances the supramolecular interactions to make possible the IDA impossible in solution. This work not only demonstrates a novel conceptual approach to fabricate superior fluorescence turn-on sensors using porous materials but also has important implications for supramolecular chemistry in porous materials.
Ionic metal–organic frameworks (IMOFs) that integrate synergistic Lewis‐acid sites (intrinsic metal centers of the frameworks) and nucleophilic anions (halides encapsulated within pores) are ...intriguing platforms for the design of fully heterogeneous catalytic systems for cycloaddition of CO2 to epoxides. A new, facile and versatile synthetic approach has been used to fabricate triazolium‐based IMOFs for the first time. The approach makes use of azide–alkyne click chemistry and subsequent N‐alkylation to post‐synthetically create a cationic triazolium ring and introduce exchangeable counteranions at the same time. The IMOFs are efficient and recyclable heterogeneous catalysts for CO2 conversion under mild and cocatalyst‐free conditions. In particular, the click‐accessible triazolium ring provides a handle to incorporate further functionality. The MIL‐101‐tzmOH‐Br catalyst, which integrates hydrogen‐bonding hydroxy groups besides metal centers and bromide anions, shows superior catalytic performance under mild conditions.
Click here to convert CO2! An ionic metal–organic framework (IMOF) bearing a CrIII center at the node, a hydroxy group grafted to the cationic linker and a bromide anion encapsulated within the pore is fabricated by facile azide–alkyne click chemistry. The multifunctional IMOF presents superior heterogeneous catalytic activity for cycloaddition of CO2 to epoxides under mild and cocatalyst‐free conditions.
The development of selective sensing materials for amine detection has received considerable attentions because amines have high toxicity and exist widely. In this article, we demonstrate for the ...first time that a degree of discriminative detection of alkylamines can be achieved by a metal–organic coordination material. The material is derived from CdII and 4,4′-bipyridinium-1,1′-bis(phenylene-3-carboxylate), shows 1D channels lined with electron-deficient viologen chromophores, and exhibits different colors upon contact with amine vapors of different molecular sizes and types (primary, secondary, and tertiary). The vapochromism is attributable to electron transfer from the amine group to viologen. The discrimination between amines is because the analyte–receptor interactions, which either directly mediate or indirectly affect electron transfer, are influenced by the number of the N–H bonds in the amine molecule, the size of the amine molecule relative to the receptor channel and the steric hindrance for the electron donor–acceptor contacts. The material also shows reversible photo- and hydrochromism owing to stimuli-induced reversible electron transfer. The compound can be deposited in paper simply by spraying the mixture solution of the starting metal salt and the ligand. The paper can be used as portable test strips for visual and differentiable detection of amines and as erasable inkless printing medium.
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