How Much Information Can Be Extracted from Galaxy Clustering at the Field Level?

We present optimal Bayesian field-level cosmological constraints from nonlinear tracers of cosmic large-scale structure, specifically the amplitude σ_{8} of linear matter fluctuations inferred from rest-frame simulated dark matter halos in a comoving volume of 8  (h^{-1} Gpc)^{3}. Our constraint on σ_{8} is entirely due to nonlinear information, and obtained by explicitly sampling the initial conditions along with tracer bias and noise parameters via a Lagrangian effective field theory-based forward model, leftfield. The comparison with a simulation-based inference of the power spectrum and bispectrum-likewise using the leftfield forward model-shows that, when including precisely the same modes of the same data up to k_{max}=0.

Developmental changes in the perceived moral standing of robots.

Emerging evidence suggests that children may think of robots-and artificial intelligence, more generally-as having moral standing. In this paper, we trace the developmental trajectory of this belief. Over three developmental studies (combined N = 415) and one adult study (N = 156), we compared participants' judgments (Experiments 1-3) and donation choices (Experiment 4) towards a human boy, a humanoid robot, and control targets.

Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors.

Medicinal chemistry has discovered thousands of potent protein and lipid kinase inhibitors. These may be developed into therapeutic drugs or chemical probes to study kinase biology. Because of polypharmacology, a large part of the human kinome currently lacks selective chemical probes.

The Puzzle of Evaluating Moral Cognition in Artificial Agents.

In developing artificial intelligence (AI), researchers often benchmark against human performance as a measure of progress. Is this kind of comparison possible for moral cognition? Given that human moral judgment often hinges on intangible properties like "intention" which may have no natural analog in artificial agents, it may prove difficult to design a "like-for-like" comparison between the moral behavior of artificial and human agents. What would a measure of moral behavior for both humans and AI look like? We unravel the complexity of this question by discussing examples within reinforcement learning and generative AI, and we examine how the puzzle of evaluating artificial agents' moral cognition remains open for further investigation within cognitive science.

Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.

Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding the extent and the time- and dose-response characteristics of drug-regulated PTMs. In this work, we introduce a proteomic assay called decryptM that quantifies drug-PTM modulation for thousands of PTMs in cells to shed light on target engagement and drug mechanism of action. Examples range from detecting DNA damage by chemotherapeutics, to identifying drug-specific PTM signatures of kinase inhibitors, to demonstrating that rituximab kills CD20-positive B cells by overactivating B cell receptor signaling.

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor.

The ephrin type-A receptor 2 (EPHA2) kinase belongs to the largest family of receptor tyrosine kinases. There are several indications of an involvement of EPHA2 in the development of infectious diseases and cancer. Despite pharmacological potential, EPHA2 is an under-examined target protein.

Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity.

Casein kinases 1 (CK1) are key signaling molecules that have emerged recently as attractive therapeutic targets in particular for the treatment of hematological malignancies. Herein, we report the identification of a new class of potent and highly selective inhibitors of CK1α, δ and ϵ. Based on their optimal in vitro and in vivo profiles and their exclusive selectivity, MU1250, MU1500 and MU1742 were selected as quality chemical probes for those CK1 isoforms.

Second primary malignancies induced by radioactive iodine treatment of differentiated thyroid carcinoma - a critical review and evaluation of the existing evidence.

Purpose: Concern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy.

Moderators and Predictors of Response After 36 Weeks of Treatment in the Treatment for Adolescents with Depression Study (TADS).

This study investigated pretreatment variables associated with depression severity in adolescents following maintenance treatment for major depressive disorder (MDD). Data was derived from the Treatment for Adolescents with Depression Study (TADS). Participants received one of three treatments: cognitive behavioral therapy (CBT), fluoxetine (FLX), or combined CBT and fluoxetine (COMB).

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems.

Robust, reproducible and quantitative analysis of thousands of proteomes by micro-flow LC-MS/MS.

Nano-flow liquid chromatography tandem mass spectrometry (nano-flow LC-MS/MS) is the mainstay in proteome research because of its excellent sensitivity but often comes at the expense of robustness. Here we show that micro-flow LC-MS/MS using a 1 × 150 mm column shows excellent reproducibility of chromatographic retention time (<0.3% coefficient of variation, CV) and protein quantification (<7.

Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms.

New drugs are desperately needed to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report screening commercial kinase inhibitors for antibacterial activity and found the anticancer drug sorafenib as major hit that effectively kills MRSA strains. Varying the key structural features led to the identification of a potent analogue, PK150, that showed antibacterial activity against several pathogenic strains at submicromolar concentrations.

ProteomicsDB: a multi-omics and multi-organism resource for life science research.

ProteomicsDB (https://www.ProteomicsDB.org) started as a protein-centric in-memory database for the exploration of large collections of quantitative mass spectrometry-based proteomics data.

Marital and Parent-Child Relationships during Treatment for Adolescent Depression: Child-Driven and Bidirectional Effects.

Adolescent depression can be a stressor for parents and families. This study evaluated how treating adolescent depression affects marital and parent-child relationships. We examined whether marital adjustment and parent-child conflict improved over the course of active treatment of depressed adolescents (36-week visit) and long-term follow-up (one year after discontinuation of treatment) in a sample of 322 clinically depressed youth participating in the Treatment for Adolescents with Depression Study (TADS).

The long-term effect of trauma history on adolescent depression treatment.

Background: Childhood trauma is associated with the development of depression during adolescence. Prior research suggests that traumatic experiences may result in differential acute treatment outcomes for depressed adolescents. However, the long-term effects of trauma on treatment response remain unclear.

Chemoproteomic Selectivity Profiling of PIKK and PI3K Kinase Inhibitors.

Chemical proteomic approaches utilizing immobilized, broad-selective kinase inhibitors (Kinobeads) have proven valuable for the elucidation of a compound's target profile under close-to-physiological conditions and often revealed potentially synergistic or toxic off-targets. Current Kinobeads enrich more than 300 native protein kinases from cell line or tissue lysates but do not systematically cover phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related kinases (PIKKs). Some PIKKs and PI3Ks show aberrant activation in many human diseases and are indeed validated drug targets.

CiRCus: A Framework to Enable Classification of Complex High-Throughput Experiments.

Despite the increasing use of high-throughput experiments in molecular biology, methods for evaluating and classifying the acquired results have not kept pace, requiring significant manual efforts to do so. Here, we present CiRCus, a framework to generate custom machine learning models to classify results from high-throughput proteomics binding experiments. We show the experimental procedure that guided us to the layout of this framework as well as the usage of the framework on an example data set consisting of 557 166 protein/drug binding curves achieving an AUC of 0.

Adaptive Resistance to EGFR-Targeted Therapy by Calcium Signaling in NSCLC Cells.

Targeted therapies against oncogenic receptor tyrosine kinases (RTK) show promising results in the clinic. Unfortunately, despite the initial positive response, most patients develop therapeutic resistance. Most research has focused on acquired resistance occurring after an extensive time of treatment; however, the question remains as to how cells can survive an initial treatment, as early resistance to apoptosis will enable cells to develop any growth-stimulating mechanism.

The target landscape of clinical kinase drugs.

Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs.

Endocrine and Local IGF-I in the Bony Fish Immune System.

A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies.

Trajectories of Functioning Into Emerging Adulthood Following Treatment for Adolescent Depression.

Purpose: It is well established that empirically supported treatments reduce depressive symptoms for most adolescents; however, it is not yet known whether these interventions lead to sustained improvements in global functioning. The goal of this study is to assess the clinical characteristics and trajectories of long-term psychosocial functioning among emerging adults who have experienced adolescent-onset major depressive disorder.

Methods: Global functioning was assessed using the Clinical Global Assessment Scale for children (participants ≤18 years), the Global Assessment of Functioning (participants ≥ 19 years) and the Health of the Nation Outcome Scales for Adolescents among 196 adolescents who elected to complete 3.

Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors.

Human immunodeficiency virus (HIV) type I integrase (IN) active site, and viral DNA-binding residues K156 and K159 are predicted to interact both with strand transfer-selective IN inhibitors (STI), e.g. L-731,988, Elvitegravir (EVG), and the FDA-approved IN inhibitor, Raltegravir (RGV), and strand transfer non-selective inhibitors, e.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400  deg^{2} patch of sky centered on RA 0 h, Dec. -57.